A Comprehensive Review on the Antioxidant and Anti-Inflammatory Bioactives of Kiwi and Its By-Products for Functional Foods and Cosmetics with Health-Promoting Properties

Featured Application

The valorization of kiwi and kiwi by-products’ bioactives as ingredients in the application of functional foods and cosmetics with anti-inflammatory and antioxidant health benefits.

Abstract

Kiwi’s increased popularity as a healthy fruit with several agro-food applications has increased the amount of bio-waste produced like leaf, peel, and seed by-products, usually combined to form a kiwi pomace, which increases the environmental footprint of kiwi fruit and waste management costs. The aim of the present study is to thoroughly review and outline the nutritional content and bioactive components of both kiwi fruit and its by-products, as well as the innovative approaches to obtain and valorize kiwi’s bioactives, phytochemicals, vitamins, and nutrients in several functional food products, nutraceuticals, and cosmetics applications with health-promoting properties. The antioxidant and anti-inflammatory properties and mechanisms of action of the extracted polyphenols, flavonoids, flavones, organic acids, and other bioactive components in both the fruit and in its functional products are also elucidated. Emphasis is given to those bioactive ingredients and extracts from kiwi by-products that can be valorized in various functional foods, supplements, nutraceuticals, nutricosmetics, cosmeceuticals, and cosmetics-related applications, with antioxidant and anti-inflammatory health-promoting properties. Characteristic examples with reported health benefits are the functional kiwi fruit jelly (FKJ),fermented kiwi fruit products like wine, starchy kiwi fruit flour (SKF), and kiwi-derived functional protein bars, cheese and flour, as well as several nutraceuticals and functional cosmetics with kiwi bioactives improving their antioxidant, antiaging, and photoprotective properties, collagen synthesis, skin density, hydration, elasticity, and the wound healing process, while beneficially reducing skin roughness, wrinkles, hyperpigmentation, keratinocyte death, and DNA and cell damage. The limitations and future perspectives for these kiwi bioactive-based applications are also discussed.

1. Introduction

According to the World Health Organization (WHO), people in developed and developing countries are affected by inflammation-related chronic disorders, including cancer, diabetes, and renal, liver, and cardiovascular disease [1]. Several risk factors like age, obesity, and cigarette smoking, as well as non-healthy dietary habits, are implicated in the onset and development of such disorders, through the continuous induction of inflammation and oxidative stress manifestations [2,3]. Addressing inflammatory pathways, therefore, holds enormous promise for both the prevention of and therapy for these life-threatening illnesses [4,5]. Meanwhile, oxidative stress can be induced by inflammation and/or can induce inflammation and, thus, also plays a vital role in the occurrence of chronic diseases, by detrimentally affecting almost all classes of biomolecules, including plasma and membrane proteins, and lipids and lipoproteins, while it can also reach and damage DNA in the cell nucleus [6]. Apart from the classical pharmaceutical approaches against these disorders, which are usually accompanied by negative side effects [4], a promising and viable solution is the adoption of healthy habits, which includes the daily consumption of nutritious fruits and vegetables.

However, successfully integrating healthy eating habits into the daily life of the average person, with a modern stressful way of life, is a difficult endeavor, considering their limited free time and occupied mental capacity, which may limit their ability to keep up with such a lifestyle change [7,8]. Furthermore, there are increasing sustainability issues related to the daily intake of such healthy foods, while the daily cost of obtaining such products is continuously increasing due to several factors, including the transportation cost of imported fruit from other countries, which also further increases the environmental footprint of these foods. Thus, alternative solutions are needed to supplement the daily diet of the population with bioactive ingredients from healthy fruits, including kiwi fruit, which can reduce both the sustainability and cost issues related to such fruits, on the one hand, and the risk of inflammation and oxidative stress-associated disorders, on the other.

Currently, a lot of research has been conducted on the bioactives present in bio-waste from fruit processing, including kiwi fruit by-products, which encompasses large quantities of by-products in the agricultural sector, to reduce the related environmental footprint and waste management costs, in the context of the design of a circular economy, according to UN directives. Kiwi peel, seeds, pomace, leaves, and other inedible parts, are sources of untapped nutrients and bioactives worldwide [9]. In the context of green growth and the circular economy, the solution to the dual problem of chronic diseases and the large volume of bio-waste could be the incorporation of bioactives from the said kiwi by-products into new health-promoting functional products that can supplement healthy diets with important dietary bioactives and provide additional health benefits [10], including functional foods, nutraceuticals, supplements, and cosmetics.

Even though the kiwi fruit is a tropical fruit endemic to northern China, it can now be cultivated in several other locations, including European countries located in the Mediterranean, including Italy and Greece. There are around 60–70 species in the family of Actinidia, also known as the Actinidiaceae family. The ones that stand out for their popularity among consumers are the yellow—Actinidia chinensis, the green—A. deliciosa, and the resistant—A. arguta [11,12] varieties. Regarding kiwi fruit production, based on recent statistical research (2021), the dominant country is China (2380.79 TMT), followed by New Zealand (628.5 TMT) and Italy (416.06 TMT) [13]. Consequently, the industrial processing of kiwi fruit generates a large quantity of by-products, estimated to be one million tons per year, globally [11,12,13].

Like most healthy fruits, kiwi provides a variety of nutrients and dietary bioactives that promote several health benefits for the human body after ingestion. Kiwi is ingested either in the form of a processed product, such as concentrated juice, or through the direct consumption of fresh fruit. Vitamins (E and C), polyphenols, minerals, and carotenoids, as well as bioactive molecules like ascorbic, folic, citric, and glutamic acid, and several phenolic and lipid bioactives are contained in kiwi fruit and its by-products, making it both an interesting source of antioxidant and anti-inflammatory bioactives [11,12,14]. Interestingly, such bioactives are usually found in considerable amounts in kiwi by-products too, while research is being conducted on obtaining these kiwi bioactives from bio-waste through green methodological approaches to utilize them as bio-functional ingredients in several applications.

Within this comprehensive review, the valorization of such bioactives from kiwi fruit and its by-products in several functional products, including functional foods, supplements, nutraceuticals, nutricosmetics, cosmeceuticals, and cosmetics, with antioxidant and anti-inflammatory health-promoting properties, are thoroughly reviewed.

2. Methods

The Scopus database was utilized to find the relevant literature. The following keywords were used: “kiwi” “by-products”, “kiwi pomace”, “food”, “sustainability”, “tocopherols”, “vitamin”, ”phenolic”, ”carotenoid”, “fatty acid”, “polar lipid”, “flavonoid”, “bioactive”, “health benefits”, “antioxidant”, “antiaging”, “antimicrobial”, “anti-inflammatory”, “skin protection”, “cardio-protective”, “anti-tumor”, “anti-cancer”, “cardiovascular diseases”, “diabetes”, “cancer”, “applications”, “functional foods”, “supplements”, “nutraceuticals”, “cosmetic”, “sunscreen”, “sun oil”, “nutricosmetics”, “cosmeceuticals”, “pharmaceuticals”. This included the use of combinations of these keywords by using AND and/or OR terms. This query was applied to the title, abstract, and keywords of the articles, and the search process was carried out during March–May 2024, for the period covering the last 15 years.

2.1. Inclusion Criteria

The selection criteria were determined by considering the metadata available on the Scopus database, with eligible studies meeting the following criteria: (i) must be a research article; (ii) written in English; and (iii) published between 2010 and 2024. A limited number of important articles before 2010 were also included, since they had not been previously reviewed, thoroughly.

2.2. Exclusion Criteria

Conference papers, books, and short surveys, as well as publications written in languages other than English, were excluded.

2.3. Quality Assessment

To evaluate the articles’ quality and relevance, we first reviewed their titles and abstracts, excluding those unrelated to the topic. Subsequently, the remaining articles were thoroughly read to determine whether they met the predefined inclusion criteria and provided pertinent information for this review.

2.4. Intended Audience

The findings of this study are targeted toward academic and industrial scientists in the general fields of functional foods, cosmetics, chemistry, drugs, pharmaceutics, medicine and pharmaceutical chemistry, biochemistry, environmental chemistry, waste management, biology, and even molecular biology, as well as toward healthcare professionals and policymakers. This research offers insights into the potential multifaceted use(s) of kiwi fruit by-products, such as kiwi pomace, as functional ingredients of novel foods and cosmetics with health-promoting properties, and their role(s) against inflammation, since they exhibit significant anti-inflammatory, antithrombotic, and antioxidant activities.

3. Bio-Functional Compounds and Health Benefits of Kiwi Fruit and Its Juice

3.1. Some Historical Aspects of Kiwi Fruit

Up until the previous century, some of the beneficial properties of exotic fruits were initially proposed in relation to their flowers and their seeds, including those of kiwi fruit, without however linking these benefits to its dietary bioactive components, rather than in relation to pharmaceutical compounds from these parts of the fruits. The flowers of these plants were also used in a decorative role and in products providing beauty. The beginning of worldwide kiwi fruit production was marked by Isabel Fraser, the director of a New Zealand ladies’ college, who imported kiwi fruit seeds from China to her country. However, the “Golden Age” of Actinidia production began after 1922 and after the intervention of the gardener Hayward Wright, in which the kiwi fruit was presented as “a wonderful fruiting climber” and was highlighted as a winter fruit with unique properties. At the time, a small number of similar fruit varieties existed and, thus, he managed to promote it in the market to a great extent. The name of the best-known species, Hayward, was used to honor him, while the “kiwi fruit” was established by Turner and Grower in 1959, referring to the national bird of New Zealand [15,16].

3.2. Kiwi Nutritional Value and Bioactive Composition

To fully evaluate the nutritional value and benefits of kiwi fruit, it is essential to describe its composition in terms of its bioactive compounds. The bioactive molecules and, thus, their composition in kiwi fruit can be affected by several factors, such as ripening, the place, and the development of the weather, etc. However, most of the nutritional components that are noteworthy for examination, including proteins, lipids, vitamins, carbohydrates, and minerals, are constantly present in the fruit. More precisely, kiwi is a major provider of beneficial substances for human health, like vitamins, phenolics, minerals, pigments, and plant fibers. Moreover, kiwi is not only rich in polar compounds like ascorbic, folic, citric, and glutamic acids, and in several amphiphilic bioactive compounds, including phenolics, but it also has low lipid content, while it does not contain cholesterol [14,17]. An overview of the most well-known bioactives in kiwi is provided in

Table 1. Physicochemical properties of bioactives in kiwi.

Bioactives	Molecular Formula	Molecular Weight	log Kow
Vitamins
Ascorbic acid	C6H8O6	176.13	−1.880
Alpha tocopherol	C29H50O2	430.72	12.179
Beta tocopherol	C28H48O2	416.69	11.631
Gamma tocopherol	C28H48O2	416.69	11.631
Delta tocopherol	C27H46O2	402.67	11.084
Alpha tocotrienol	C29H44O2	424.67	11.923
Beta tocotrienol	C28H42O2	410.65	11.375
Gamma tocotrienol	C28H42O2	410.65	11.375
Delta tocotrienol	C27H40O2	396.62	10.828
Folic acid	C19H19N7O6	441.41	−1.950
Carotenoids
Beta-carotene	C40H56	536.89	17.623
Lutein	C40H56O2	568.89	14.823
Violaxanthin	C40H56O4	600.89	11.976
9′-cis neoxanthin	C40H56O4	600.89	11.940
Phenolic compounds
Polyphenols
Neochlorogenic acid	C16H18O9	354.32	−1.014
Flavan-3-ols
Kaempferol	C15H10O6	286.24	1.959
Epicatechin	C15H14O6	290.27	1.175
Catechin	C15H14O6	290.27	1.175
Flavonoids
Luteolin	C15H10O6	286.24	2.364
Procyanidins	C30H26O12	578.53	1.882
3, 4-dihydroxybenzoic acid	C7H6O4	154.12	0.914
Catechol	C6H6O2	110.11	1.033
Pyrogallol	C6H6O3	126.11	0.974
Quercetin	C15H10O7	302.24	1.479
Phenolic acids
Syringic acid	C9H10O5	198.18	1.044
Ferulic acid	C10H10O4	194.19	1.415
Ellagic acid	C14H6O8	302.2	−2.046
Gallic acid	C7H6O5	170.12	0.855
Caffeic acid	C9H8O4	180.16	1.110
P-coumaric acid	C9H8O3	164.16	1.590
Chlorogenic acid	C16H18O9	354.32	−1.014
Protocatechuic acid	C7H6O4	154.12	0.914
P-hydroxybenzoic acid	C7H6O3	138.12	1.394
Cryptochlorogenic acid	C16H18O9	354.32	−1.014
Flavonol glycosides
Quercetin 3-rutinoside	C27H30O16	610.53	−1.109
Kaempferol 3-rutinoside	C27H30O15	594.53	−0.629
Fatty acids
Alpha-linolenic acid	C18H30O2	278.44	7.299
Linoleic acid	C18H32O2	280.45	7.514

. It is evident that the bioactives belong to polar, semi-polar, and non-polar compounds, resulting in the differentiation of their accumulation in the human body after consumption.

3.2.1. Kiwi Vitamins

With respect to the nutrients present in kiwi-derived juices, vitamin C, vitamin E, and folate are present in high percentages in these kiwi products (Figure 1). Vitamin C, commonly known as ascorbic acid, is a vital vitamin for humans, which is obtained from various plants and animal products that can synthesize it. Our need for the daily intake of vitamin C stems from the fact that we cannot produce it, due to a gene mutation of an enzyme that is essential in the series of reactions for its formation. The raw material, sugars, and relatively simple chemical synthesis process make understandable, the increased concentration of this vitamin in fruits and vegetables, and in quantitatively large amounts compared to other types of vitamins, especially in kiwi fruit. Its main properties, and according to which it is extremely useful for humans, are its involvement as a co-enzyme in collagen formation, as well as its potent antioxidant capacity, that is, the neutralization of free radicals and particularly reactive oxygen and/or nitrogen species (ROS/RNS), which offers protection from oxidative stress damage. Its deficiency in humans is reported to be associated with signs of fatigue and lethargy, while its additional properties as a co-factor in enzymes have also been reported in dopamine neurotransmission and hormone synthesis pathways [15,18,19,20].

Another important vitamin present in kiwi is vitamin E. This vitamin encompasses a group of fat-soluble compounds referred to as tocochromanols, specifically chroman-6-ols. These can be further classified into tocopherols (α-, β-, γ-, and δ-tocopherols) and tocotrienols (α-, β-, γ-, and δ-tocotrienols). Vitamin E consists of each or of all these eight forms, which are produced by plants like kiwi through the utilization of homogentisic acid. It can be defined as a robust chain-breaking antioxidant, which hampers the generation of ROS molecules both when lipid oxidation occurs and in the midst of the dissemination of free radical reactions. The primary effect of α-tocopherol is to capture and counteract the free radicals present. Consequently, vitamin E can protect against the onset of chronic diseases that are linked to oxidative stress [21].

For some years, it was widely believed that the primary source of vitamin E in kiwi fruit was the seeds, which were thought to contain a significant amount of the vitamin due to their high lipid content. However, the seeds were known to be resistant to digestion, making the vitamin E in them largely unavailable. Fiorentino and colleagues demonstrated that α-tocopherol is present in the flesh of the kiwi too, potentially linked to the cellular membranes of the fruit cells, with potentially higher bioavailability compared to that of the seeds. The presence of vitamins in the flesh of kiwi has a significant role, as it enhances the organization of membrane lipids, resulting in a more tightly packed membrane. This increased stability of the cell membrane is crucial for the overall health and functioning of the cells in kiwi fruit. Vitamin E plays a vital role in promoting membrane repair in mammalian cells too, by preventing the occurrence of oxidized phospholipids [11,15,21].

Last, but not least, another important vitamin in kiwi is folate and its derivatives. Folates are an indispensable constituent of the human diet, serving as a crucial form of water-soluble vitamin B (Vitamin B6). They play a vital role in numerous metabolic pathways, particularly in carbon transfer reactions like the synthesis of purines and pyrimidines, as well as the interconversion of amino acids. In 2002, the WHO and FAO stated that the daily recommended intake was 400 μm/day for adults. The same quantities were given by the IOM in 2004 and so, the EU also approved this amount. The term folate encompasses the whole pack of folic acid derivatives, which includes naturally occurring polyglutamates found in food, as well as the synthetic form of folic acid, commonly used for fortifying food and as a nutritional supplement. It is important to note that mammalian cells are incapable of synthesizing folate, and its deficiency has been linked to a wide range of disorders [22]. Women of childbearing age and who are planning for pregnancy, are advised to consume 600 μg/day of folate, since it has been shown to potentially safeguard against developmental complications, including neural tube defects, which may arise within the fetus [15,23]. Kiwi is often acknowledged as a valuable source of dietary folate, as it is contained in high proportions in many kiwi varieties compared to other fruits. The contribution of folate in kiwi can also substitute for the loss of this vitamin due to heating, namely through the cooking of the green foliage of other vegetables [15].

3.2.2. Kiwi Phenolics

Another important class of dietary bioactives present in kiwi are several phenolics, and especially flavonoids. Kiwi fruit exhibits antioxidant activity, thanks to the phenolics and polyphenols that it contains. The intake of these compounds, from fruits or other foods, acts on different metabolic pathways of the human body, providing protection from various diseases associated with inflammation and oxidative stress. Nevertheless, the bioavailability of phenolics through the intestine in in vivo conditions has been characterized as a slow process, while after ingestion from the intestine, phenolics are usually bound in human serum albumins (blood protein carriers). Both of these processes significantly affect the concentration of phenolics in the blood after ingestion and, thus, their effect on lipoproteins and cell membranes. These protein carriers also act as markers for thrombo-inflammatory cardiovascular complications caused by fibrinogen, while kiwi fruit ingestion seems to reduce this thrombotic glycoprotein complex, thus minimizing fibrinogen-induced thrombosis and any subsequent complications. In addition, phenolics provide protection against lipid oxidation, and hydrogen peroxide, etc. [24,25].

In vitro experimental procedures for scavenging free radicals facilitate the evaluation of the antioxidant activity of polyphenols found in kiwis. The chemical structure and spatial arrangement of phenolic compounds make them good donors of electrons and protons, resulting in the stabilization of uncoupled electrons and the creation of metal-chelating ions [26]. Kiwi-derived juice has been found to contain coumaric (p-coumaric) and caffeic acid as a matrix, as well as chlorogenic acid, protocatechuic acid, and a derivative of 3, 4-dihydroxybenzoic acid. Such substances constitute strong acidic phenolic compounds. Other important phenolic bioactives are also present in kiwi juice, including epicatechin, catechin, and procyanidins [14,27]. Moreover, a freeze-dried aqueous kiwi extract contained all these phenolics, along with syringic acid, ferulic acid, catechol, ellagic acid, p-hydroxybenzoic acid, pyrogallol, gallic acid, α-tocopherol, and quercetin [11]. The above compounds are divided into different classes of phenolics, such as flavonols, flavonoids, flavan-3-ols, and phenolic acids. The classifications are shown in Figure 2, together with the structure of the main bioactive phenolics mentioned.

3.2.3. Kiwi Pigments

Another class of natural bioactives in kiwi are pigments. These compounds are divided into carotenoids, chlorophylls, and anthocyanins, and are mainly responsible for the external appearance of fruits and vegetables, i.e., their color. However, some of them are also detected inside the fruit, as in the case of kiwi, which further supports the antioxidant potential and benefits of kiwi and its products [16,28].

Carotenoids, while only expected to be present in natural edible fruits with a red or yellowish color, also appear to occur in green fruits. They are lipophilic antioxidants, with a dual function in terms of attractiveness and nutritional value. In green kiwi fruit, the carotenoids that are present are closely linked to chlorophyll tissues, i.e., beta-carotene, lutein, violaxanthin, and 9′-cis neoxanthin, with the highest concentration being that of beta-carotene. It is noted that the first two compounds are potent antioxidants and are bio-accessible [17,29].

The chlorophylls in kiwi fruit vary in proportion in different species. Chlorophylls are classified as hydrophobic lipid-soluble compounds, with their two main classes being a and b chlorophylls, with chlorophyll a being in higher concentrations in all chlorophyllous organisms, including kiwi, while their ratio (a/b) determines the color of the fruit. In the case of kiwi’s flesh green color, its content in terms of chlorophylls, and especially α chlorophylls, is not diminished during ripening, resulting in the preservation of the kiwi’s green color. The carotenoids present in kiwi flesh are in the non-esterified form, as often happens when they are related to tissues containing chlorophylls that have not been transited and stored in chromoplasts as esterified carotenoids and, thus, the green color is retained [11,17,29].

Finally, a special category of pigments, related to the metabolic pathway of flavonoids, is anthocyanins. These include compounds derived from pelargonidin, peonidin, and, in the case of kiwi, cyanidin. Their synthesis occurs at the end of the flavonoid pathway, which is why it is often considered a subcategory of them, while they seem to function in a complementary fashion to many flavonoids in metabolic pathways. For example, in the green kiwi, the 3-O-glycoside cyanidin appears, as shown in Figure 3, inside a ring and around the central part of the fruit flesh [11,17,30].

3.2.4. Other Important Kiwi Nutrients

Apart from their richness in bioactive components, kiwi fruit also contains a plethora of essential nutrients. As a protein source, like other fruits, kiwi also contains some considerable amounts of protein, including a moderate amount of actinidin. Actinidin is an enzyme of the protease family, playing a decisive role in the digestion of food by hydrolyzing other proteins. Its role is, therefore, the process of breaking down large protein molecules into smaller ones or even into amino acids, with the aim of enabling their absorption by the body and, thus, enabling the digestibility of protein foods [15,17,23]. Concerning kiwi’s lipid content, it has been characterized as a healthy fat-free snack, as it contains low amounts of lipids. Nevertheless, the majority of kiwi lipids, even in low amounts, are healthy ones, present mainly in the spores inside the flesh of the fruit, with the main representatives being unsaturated fatty acids, especially the omega-3 alpha-linolenic acid (C18:3; n-3) [17]. Kiwi fruit is rich in minerals and trace elements too. Calcium, iron, potassium, magnesium, manganese, copper, phosphorus, zinc, and selenium are the most frequently occurring metals and elements present in several kiwi varieties (

Table 2. Characteristic nutritional content and composition of dietary bioactives in kiwi.

Proximate (g/100 g)	Nutritional Value	Reference
Water	81.07–83.49	[32]
Energy (kcal/KJ)	61/255	[32]
Total Fat	0.5–0.52	[32]
Sugar	8.99–9	[32]
Fiber	3	[32]
Total carbohydrate	14.66–14.7 (15)	[32]
Total protein	1.1–1.14	[32]
Nutrients (g/100 g)
Vitamin C	92.7	[32]
Vitamin E	1.46	[32]
Folate	25	[32]
Pigments (μg/100 g)
Beta-carotene	52, 170	[29,32]
Lutein	122, 160	[29,32]
Violaxanthin	nd, 110	[29,32]
9′-cis neoxanthin	nd, 120	[29,32]
Total carotenoids	nd, 590	[29,32]
Chlorophyll a	nd, 550	[29,32]
Chlorophyll b	nd, 440	[29,32]
Total chlorophylls	nd, 990	[29,32]
Minerals (mg/100 g)
Calcium	34	[30,32]
Iron	0.31	[30,32]
Magnesium	17	[30,32]
Phosphorus	34	[30,32]
Potassium	312	[30,32]
Sodium	3	[30,32]
Zinc	0.14	[30,32]
Copper	013	[30,32]
Manganese	0.098	[30,32]
Selenium	0.2	[30,32]
Phenolics	Juice = mg/L Whole fruit = mg/100 g
Total phenolics	180–220 mg/100 g, 96 mg/100 g, 700 mg/L (for juice) and 78–103 mg/g (fresh weight)	[27,33,34]
Protocatechuic acid	0.24 (mg/L), 2634.27 (mg/kg)	[27,35]
Catechin	nd, 411.24 (mg/kg)	[27,35]
Chlorogenic acid	0.71(mg/L), 243.10 (mg/kg)	[27,35]
Caffeic acid	0.09 (mg/L), 8.14 (mg/kg)	[27,35]
Epicatechin	2.62 (mg/L), nd	[27,35]
P-coumaric	0.06 (mg/L), nd	[27,35]
Quercetin 3-rutinoside	0.41 (mg/L)	[27]
Quercetin 3-glucoside	0.20 (mg/L)	[27]
Kaempferol 3-rutinoside	0.20 (mg/L)	[27]
Quercetin 3-rhamnoside	0.45 (mg/L)	[27]
Kaempferol 3-rhamnoside	0.05 (mg/L)	[27]

) [31]. It is also worth highlighting the actinide fibers in kiwi and their beneficial role in the management of gastrointestinal complications [16].

4. Health Benefits and Composition of Kiwi By-Products

Kiwi and its products are included among the healthy fruits highly demanded by consumers, due to their nutritional value and proposed health benefits. Nevertheless, the processing of such products contribute significantly to the increased amount of by-products available, which further advances the related environmental issues and waste management costs of such agri-food bio-waste. On the other hand, it seems that a considerable amount of highly valuable kiwi nutrients and bioactives remain in its by-products after processing. Thus, the recovery and valorization of such valuable bioactive compounds from kiwi by-products, via several applications, is of paramount importance for the sustainable development of this fruit, in the context of the design of a circular economy. Promising kiwi by-products, that are not considered edible and are not used for juice production, and which are now considered more as sustainable natural resources rather than bio-waste, are the set of different peels, the residual pulp/pomace, the seeds, and the leaves of the kiwi, which represent up to 30% of total kiwi fruit production. These by-products constitute substantial sources of the nutritionally important bioactive compounds found in kiwi, mainly phenolics, vitamins, and pigments, which are retained in such by-products, as shown in Figure 4 [34,36,37].

4.1. Kiwi Seeds

In addition to its green flesh, kiwi contains small seeds inside the flesh, embedded in the edible part of the fruit. However, when the fruit is not intended for raw consumption but for industrial processing to produce juice, these small black seeds are not ground and are eventually discarded. Thus, they can be considered as part of kiwi by-products, mainly from industry, with a strong nutritional value profile. It is reasonable that the fruit flesh does not provide the same amount of components as the whole fruit, but this does not mean that what it has to offer should be lost. By approximation, the oiliness of the seeds is what makes them particularly special. A lipid content of 28.3–35% reflects their fatty nature, information useful for oil production. Linoleic acid and linolenic acid play a leading role, as two of the polyunsaturated fatty acids in the seeds. Vegetable fats show antioxidant and anti-inflammatory activity, with the composition of omega-3 and omega-6 fatty acids giving them special nutritional value. Thus, oil produced from these seeds protects the proper functioning of the brain, heart, and lipid metabolism, and is also reported in the literature to inhibit the appearance of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Despite their small contribution to the total fruit, constituting 33–46 g per Kg of kiwi, the protein and phenolic content is remarkable. Of the 329 mg/g of phenolics occurring in Hayward’s kiwi seeds, catechin (45 mg/g), p-coumaric acid (53 mg/g), and p-hydroxybenzoic acid (63 mg/g) stand out in regard to the corresponding amounts. Natural extracts’ antioxidant capabilities are often measured in equivalents of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox; TE = Trolox equivalents). They are assessed using specific antioxidant assays, including the metal ion-based ferric reducing antioxidant power (FRAP) assay and organic radical production tests for scavenging free radicals, such as 2,2′-azinodis (3-ethylbenzothiazolam-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) tests, as well as the oxygen radical absorption capacity (ORAC) assay. Concerning the antioxidant capacity of seeds, spectrophotometric analysis revealed values of 107 mg TE/kg through the FRAP assay, 2 mg TE/kg in the ORAC assay, and an IC50 of 35 mg/mL, as observed in the DPPH test.

Concerning the protein content of kiwi seeds, a protein content of 12.72–14.94% permeate the seeds, thus they are a good aid in the digestion process. A survey reported that plant-derived seed proteins meet the FAO and WHO preferred limits in terms of their contribution to digestion and amino acid supply. This fact makes seeds an interesting substitute protein source, which can be industrially developed, so that they are no longer considered a simple waste product but a nutritious product with good digestive properties. The variation in the percentage of the components can be attributed to the differences of the fruits in relation to the place of origin, the variety, and the growing conditions [11,34,38,39].

4.2. Kiwi Eaves

Agricultural waste accounts for a portion of kiwi garbage, i.e., flowers, leaves, stalks, and branches, which are not consumed by humans, but can be applied and utilized in other sectors, such as the fertilizer industry, as biofuels (in the case of branches, stems, and leaves), as well as in the medical/pharmacological field (mainly leaves and flowers). Thus, instead of being burned or composted, their content in terms of vitamins, metals, and various bioactives can be made available in other food products, medicines, and other products, which are much more exploitable. The recycling of these types of plant waste can be compared to the reuse of by-products of industrial origin, with the biomass from kiwi cultivation reaching as high as 3 Mg dw per hectare, making it apparent that agricultural waste requires its fair share of attention as well. By its nature, kiwi is a plant that discards its leaves in the winter, thus arbitrarily a form of biomass is created. The kiwi plant is strengthened through the pruning process during the growth stages, which aims to achieve cultivation optimization.

The leaves have garnered a significant amount of bioactive interest, which was discovered long ago, having already penetrated ancient Chinese medicinal traditions. Inflammation and diseases were treated with extracts of kiwi leaves, thus revealing their anti-inflammatory action. Such traditions are still observed today, as kiwi leaves are considered edible in China and South Korea. The bioactivity, however, is scientifically different in each extraction, depending on the solvent applied. Regarding the nutritional value of the leaves, the main role is played by phenolic compounds and, in particular, by organic acids, such as neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, and caffeic acid, and also by quercetin and its derivatives, kaempferol, catechin, and procyanidin B-type dimers. Their values reach up to 200 mg/g leaf. Depending on the study, different types of phenolics and health-promoting properties of the leaves exist. Their anti-inflammatory activity was overlooked in a study where nitric oxide formation from lipopolysaccharides in mouse blood macrophage cells was reduced due to the presence of caffeic acid producers. These compounds were able to suppress the inflammation created by lipopolysaccharides. Another piece of research provided detailed commentary on quantitative analysis of the phenolic compounds found in the leaves of the A. arguta variety and their antioxidant properties in leaf extracts. It is reported that an extract with 50% methanol provides protection to red blood cells from UVB and UVC radiation, while an extract with 50% ethanol shows increased reducibility and anti-radicality when compared to water extracts and other ethanol concentrations, of which the DPPH antioxidant assay, which showed the elimination of reactive oxygen species, was lower. In addition, the above extracts, as well as hydroalcoholic ones, show antimicrobial properties due to the phenolics and flavonoids present, such as hydroxycinnamic derivatives, flavan-3-ol, and flavonol derivatives. Finally, it is reported that catechins contained in kiwi leaves reduce the fragility of erythrocytes [11,34]. Overall, in addition to their antioxidant and anti-inflammatory effects, kiwi leaves are not commonly consumed as they are, but their components can be valorized into various products with kiwi leaf extracts as bioactive ingredients to enrich functional products, including functional foods, cosmetics, and pharmaceuticals.

4.3. Kiwi Peel/Skin

As a fruit, kiwi fruit is commonly eaten without its peel, which ends up in household waste, and the waste of juice-producing companies and other kiwi fruit producers. However, discarding the skin can and should be avoided as it is a nutritious part of the fruit, but unfortunately it is unusable. Depending on the variety, the peel can be green, brown, yellow, or orange, while its texture is usually fluffy–hairy. Throughout the literature, the content of phenolic compounds in the peel is consistently reported, which indicates high antioxidant capacity. For the variety A. deliciosa, a phenolic content of 13 mg GAE/g dw and 0.91 mg GAE/g fw was reported and, specifically, the compounds protocatechuic acid, chlorogenic acid, caffeic acid, rutin, p-hydroxybenzoic acid, and quercetin, were observed [34,36]. These compounds are also present in the pulp, but not at such high values. Epicatechin, with a concentration of 163 µg/g, quantitatively takes the highest position among the polyphenolic compounds. This phenolic superiority, especially flavonoids that appear in kiwi fruit skin, supports all of its aforementioned antioxidant, antibacterial, and anticancer properties. Their activities can be quantified and compared to those of other parts of the fruit, by subjecting such extracts to a series of assays (DPPH, ABTS). Furthermore, the type of solvent, its solubility, and its content are considered to be important factors in the reported occurrence of antioxidants. After measuring the antioxidant potential of kiwi fruit peel with DPPH (107 g/mL) and ABTS (258 g/mL) assays, the ethanolic extracts were determined to be excellent antioxidants. Many studies have been carried out specifically on the phenolics of the different kiwi fruit peels, mostly reaching the aforementioned conclusion. For example, in another study, the values varied depending on the ethanol percentage, thus 96% ethanol extracts had a phenolic concentration of up to 1.54 CtE mg/g, while for 50% ethanol extracts, the concentration decreased to 0.55 CtE mg/g [11,37].

Moreover, metals appear in small quantities, but they do not cease to exist and add nutritional value. The most important percentages are given by manganese, potassium, calcium, and sodium (820 mg/100 g, 230 mg/100 g, 230 mg/100 g, and 90 mg/100 g, respectively) [34]. Comparing the aforementioned values with those in Table 3, it is made apparent that the different peels are more enriched in metals than the juice/flesh of the fruit.

Carotenoids are also present, with a total amount of approximately 5.70 mg/g DW, with the main representative, as expected, being beta-carotene. In the same survey, the presence of lycopene is mentioned, a red pigment, mainly found in tomatoes, which is rarely found in kiwi fruit, especially in the species A. deliciosa. Based on the USDA, kiwi fruit has lycopene content that is non-negative [36,40]. Chlorophylls were extensively tested in a project, which used extracts of peel and pulp from two species of the A. deliciosa family, to make flour. The amount that was found in the peel extracts was 2–12 mg/100 g of the flour. The wide range of the amount is due to the growing conditions of the fruit and the stage of ripening, as the composition of the peel is time sensitive and changes phytochemically with the passage of days [41]. The category of pigments also includes, as mentioned, anthocyanins, with cyanidin-3-O-sambubioside standing out in the skin of kiwi [12].

The last, but most important of the two components that remain to be analyzed, are vitamin E and plant/dietary fibers. The fiber content of kiwi is mainly due to its skin, rather than its flesh. That is, when kiwi juice or the raw part of the fruit without the peel is consumed, the fibers that were expected to pass through the body do not even reach the oral cavity, as they are discarded together with the peel. The main source of fiber is the carbohydrates contained and, especially the polysaccharides, in the skin, which help in the development of insoluble and soluble fibers. The first category of insoluble fibers appears as cellulose and hemicellulose products, while the second is pectin. However, due to the abovementioned sensitivity to ripening, these carbohydrates are constantly changing in terms of quantity and quality. These variations directly affect the contribution of dietary fibers to the body and, especially, the intestine. The main property of fiber is the retention of water, through which the digestion process and intestinal products are optimized [15]. Last, but not least, vitamin E shows a 24–25% DPPH rate and α-tocopherol content of 2.4 mg/100 g fw. Specifically, the vitamin through the three isomers retained in the skin of kiwi, α-, γ-, and δ-tocopherol, and the newly researched δ-tocomonoenol, promotes an extremely strong antioxidant profile, with high bioavailability. Given the high vitamin E content of kiwi peel, the food sector might benefit from them as an all-natural ingredient, with beneficial properties capable of influencing consumer health [11,12].

4.4. Kiwi Pomace

The pomace of kiwi fruit, like any fruit, essentially consists of a set of by-products, i.e., the skin, leaves, and seeds condensed into a form of residue pulp. Pomace is enriched with a series of bioactives derived from its components and can be an important source of nutrients. The main starting point for the production of pomace is the kiwi fruit industries that discard a high amount of the abovementioned by-products, during the processing of the fruit. However, as a naturally produced form of bio-waste, it is a shame that it is not exploited, as it can be used for the creation of new functional products in the fields of cosmetics, food products, and pharmaceuticals. A wide range of phenolics are hidden in pomace and are mainly compounds, such as chlorogenic acid, p-coumaric acid, catechin, protocatechuic acid, and derivatives of caffeic acid (Table 3). These types of bio-waste are also characterized by a high water and sugar content. In research carried out on extracts of kiwi pomace and pears, a composition of 12.8% polysaccharides was found in kiwi pomace, while dietary fiber did not fail to make an appearance, with a value of 25.8% on a dry weight basis. Here, the primary exponent of soluble fiber is pectin, in the form of oligosaccharides, and with a total percentage of 7% DW, which, if reached through an enzymatic breakdown process, might aid antiaging, cause a reduction in arteriosclerosis, and cause the prevention of diabetes via its prebiotic effects. Insoluble fibers, on the other hand, are represented by protopectin, in the order of 18.7%. Specialized food items tailored for individuals dealing with diabetes, heart issues, and obesity can be enhanced with both soluble and insoluble dietary fiber sourced from the often overlooked kiwi fruit. Another research paper suggested that by employing acid, alkaline, and enzymatic extraction methods, it is possible to obtain 33 g/100 g of soluble and 72 g/100 g on a dry weight basis of insoluble dietary fiber. In this scenario, an ultrafine powder derived from insoluble dietary fiber found in a by-product kiwi fruit beverage was incorporated as a replacement in low-fat meat, which led to an improvement in its physicochemical quality and textural traits [34,37,42,43]. Hence, the beneficial properties offered by a simple extract of one of the bio-products of this small fruit are apparent.

Table 3. The composition of bioactives in Kiwi by-products.

Composition	Amount	By-Product
Total phenolics	329 mg/g	Seeds [38]
Total proteins	12.62% 12.72–14.94%	Peels [34] Seeds [38]
Total lipids	3.7% 28.3–35%	Peels [34] Seeds [11]
Total carotenoids	5.70 ± 0.033 mg/g DW 1.55 ± 0.093	Peels [34] Pomace [34]
Phenolic profile
Total phenolics	14.3–24.6 (GAE) 9.71 ± 0.28 mg GAE/g DW 3.79 ± 0.15 mg GAE/g DW 200 mg/g	Peels [34,35] Pomace [34] Leaf [11]
Chlorogenic acid	0.40 mg/g	Peels [44]
Catechin	45 mg/g 0.36 mg/g	Seeds [11] Peels [44]
P-coumaric acid	53 mg/g	Seeds [11]
Hydroxybenzoic acid	63 mg/g	Seeds [11]
Caffeic acid	0.15 mg/g	Peels [44]
Epicatechin	0.32 mg/g	Peels [44]

Table 3. The composition of bioactives in Kiwi by-products.

Composition	Amount	By-Product
Total phenolics	329 mg/g	Seeds [38]
Total proteins	12.62% 12.72–14.94%	Peels [34] Seeds [38]
Total lipids	3.7% 28.3–35%	Peels [34] Seeds [11]
Total carotenoids	5.70 ± 0.033 mg/g DW 1.55 ± 0.093	Peels [34] Pomace [34]
Phenolic profile
Total phenolics	14.3–24.6 (GAE) 9.71 ± 0.28 mg GAE/g DW 3.79 ± 0.15 mg GAE/g DW 200 mg/g	Peels [34,35] Pomace [34] Leaf [11]
Chlorogenic acid	0.40 mg/g	Peels [44]
Catechin	45 mg/g 0.36 mg/g	Seeds [11] Peels [44]
P-coumaric acid	53 mg/g	Seeds [11]
Hydroxybenzoic acid	63 mg/g	Seeds [11]
Caffeic acid	0.15 mg/g	Peels [44]
Epicatechin	0.32 mg/g	Peels [44]

5. Valorization of Bioactive Compounds from Kiwi By-Products in the Application of Health-Promoting Functional Foods, Supplements, and Nutraceuticals

5.1. Kiwi Bioactives: From the Fruit’s Bio-Waste to Functional Products Promoting Wellness

Fruits, vegetables, and other nutritionally important foods are known contributors to wellness, as represented by their low position in the nutritional pyramid, pointing to their necessary frequent and/or daily consumption. Kiwi has received a lot of attention in recent years due to its therapeutic benefits, which are constantly being discovered by research. Its consumption is also linked, in the present work, to contributing in a multifaceted way not only to the proper maintenance of organism homeostasis, but also to the development of protection against chronic diseases. However, due to its nutritional profile, the fruit is not only intended for raw consumption as a simple food. Of course, its introduction into a person’s diet should be promoted, but the maximization of its utilization is also necessary, aiming to enhance other foods, supplements, medicines, and cosmetics via the integration of its bioactive components. These bioactive compounds are not only found in kiwi flesh and juice, but also in the products exported from both industry and agricultural activities as waste. The peel, seeds, leaves, and pomace have an equally interesting composition, which does not seem to have been noticed by functional product companies. First, however, answers must be given to two basic questions that arise: “What are the main properties of these compounds?” and “How transferable are they through different sources?”.

Starting with the vitamins, specifically vitamin C, a good antioxidant, it is ideal for incorporation into face creams and cosmetic products, as it protects the skin from damage that can occur due to the sun’s radiation, pollution, and aging. Its antiaging effects are correlated with increased collagen production in the body, as a result of the increased intake of this vitamin. In essence, collagen is a protein product that keeps the skin youthful and also regenerates it in cases of wounds and scars. Furthermore, with the production of collagen, the skin regains its firmness and a uniform soft texture, since the protein penetrates the tissues and acts as an emollient. Similarly, vitamin E and kiwi’s amino acids also contribute to the improvement and regeneration of the skin. These vitamins appear both in the interior of the fruit and in the peel [31,45].

The fatty acids of actinium seeds, in particular, find applications in foods aimed at reducing cardiovascular diseases. Strokes and coronary heart disease are known to be delayed or even prevented with proper exercise and a healthy diet. Thus, the intake of good fatty acids, such as omega-3, found in seeds is guaranteed to have positive results to protect against heart diseases. These fatty acids, through extracts, can be applied to a series of foods and supplements that will act directly where needed [11,31,45]. In the same category for the protection against cardiovascular diseases, potassium can strengthen prevention attempts. Potassium seems to be obtained mainly from the peel, as it is one of the minerals contained in them. Its main action is essentially the removal of sodium that the body receives from other foods, thus, ensuring the proper functioning of the heart, which can be disturbed by the intake of sodium in our diet [45].

In combination with potassium, plant fibers also play a role in reducing heart disease by minimizing cholesterol and sugar levels. On the other hand, dietary fibers help the body in a lot of different ways, with the most important effect being protection against cancer. The anticancer property is mainly specialized in the intestine, due to the absorption of cellulose, hemicellulose, and pectin. Antimutagens prevent the change in genomes before the initiation of cancer. Kiwi, thus, performs a cytotoxic function on malignant cells that tend to differentiate. In addition, due to their antimicrobial actions, these fibers also contribute to the prevention of bacterial colonization in the intestinal space. Mutagenesis, which could be caused by bacterial infections, is also controlled in this way. In addition to cancer, simpler disorders, such as constipation, are also regulated [45,46].

The phenolic profile of both the fruit and its by-products provides the greatest number of beneficial actions, since they are natural antioxidants and anti-inflammatory agents. The main sources of these actions are the peel of the kiwi fruit and other by-products. Thus, the enrichment of new products with their extracts will lead to increased levels of antioxidant and anti-inflammatory abilities. These actions have been tested in in vivo and in vitro models. In a study, it was found that the polyphenols of the seeds helped eliminate the pro-inflammatory cytokines IL-1β and TNF-α, which polysaccharides create in macrophage cells. The above test showed their anti-inflammatory action, since phenolic components protect against the appearance of inflammation in the cells of the organism they have entered. Polyphenols derived from fruit skin can replace synthetic antioxidants. Various phytochemical factors cause the formation of free radicals that destroy cell wall membranes. For the preservation of food or other oxidation-sensitive products, the use of additives is recommended. An extract of kiwi peel can act as a natural antioxidant additive, ideal for protecting food, for e.g., from lipid oxidation [11,46]. In addition, a class of anthocyanins contained in the fruit may be applied to cosmetic and skin care products, due to its tyrosinase-inhibiting property. Tyrosinase is an enzyme that contributes to the process of melanin production. However, hyperpigmentation, i.e., the appearance of increased levels of melanin, is a phenomenon that causes skin irregularities, such as spots and bruises [46,47].

The proteins, mainly actinidin, in kiwi fruit, also have important applications, especially in the meat industry. The main ability of actinidin, as far as meat optimization is concerned, is the change in myofibrillar components. The sarcomere is a muscle functional unit that consists of four proteins: myosin, actin, tropomyosin, and troponin. The system involves myofibrils. Actinidin, therefore, affects this system and helps make the meat tender. Also, this ability of the enzyme is due to water retention, with a parallel increase in nitrogen solubility. Other researchers have commented on how the presence of actinidin enhanced the aroma of the food, while in milk products, it dissolves as a volatile that forms a casein clot, which undergoes serum separation. Thus, a kiwi extract, for example from its seeds, can increase the nutritional value of dairy products, the tenderness of meat, and the aromatics of other products [11,46,48].

To achieve these applications, the recovery of each component is required, through a process specific to each one, to form an extract that contains each of the compounds that are to be used. In regard to the phenolic components, the most observed extraction is the subcritical water-soluble extraction. It is an ecological and efficient technique that leads to obtaining the best antioxidant activity in relation to conventional processes. The use of organic solvents does not need to cease, but it can be considered certain that solvents such as water and ethanol are not only more effective but are indicated as preferred when the extracts are intended for applications in food, cosmetics, and pharmaceutical products. Moreover, for compounds with antioxidant actions, a low temperature of 30–37 °C during the extraction is observed. Anti-inflammatory properties are obtained mainly through ethanol–water extracts, which are intended to be used in medical procedures. The temperatures during the extraction process vary, as extraction can happen at 25 °C with a longer extraction time. If fast rates are required, boiling is not prohibited. Acetone and methanol or ethanol solutions, as well as separate solvents, are used to recover compounds from kiwi peel with antimicrobial activity at 30 °C [11,12,34].

5.2. Overview of Kiwi’s Rich Content in Phenolics and Novel Protein Discoveries Associated with ITS Antioxidant Health Benefits

Several in vitro and in vivo studies have been conducted on the antioxidant activities of kiwi bioactives. The majority of the in vitro studies have demonstrated that kiwi, particularly gold kiwi, exhibits strong antioxidant effects, due to its ability to inhibit lipid oxidation, eliminate hydrogen peroxide (H₂O₂), mimic superoxide dismutase (SOD) activity, and exhibit peroxyl radical scavenging activity. These effects are attributed to the presence of various bioactive compounds, including polyphenols, supported by in vivo experiments. In a clinical trial involving healthy volunteers, kiwi consumption was suggested to decrease oxidative stress markers, such as 8-OHdG and hexanoyl-lysine adduct (HEL) in urine, indicating potential benefits for reducing oxidative stress and preventing associated diseases [49,50].

Kiwi berries, highlighted for their rich vitamin C content and diverse phytochemicals, including polyphenols, offer additional antioxidant benefits. Notably, the skin of kiwi berries, with its smooth texture and high phytochemical content, presents an opportunity for consumption without removal [51]. Moreover, kiwi berry extracts are implicated in regulating the VIP-cAMP-PKA-AQP3 signaling pathway, improving gut microbial composition and enhancing intestinal health. Additionally, fermented beverages derived from kiwi exhibit antioxidant capacity and stability, with potential benefits for nematode health [52].

In the realm of pharmaceutical applications, kiwi fruit-derived extracellular vesicles (KEVs) show promise as drug carriers for liver cancer treatment, demonstrating hepatic targeting and enhanced drug bioavailability in regard to their uptake by HepG2 cells [53]. Building upon the investigation into KEVs for liver cancer treatment, the subsequent characterization of these vesicles, particularly STAT3/EKEVs, reveals their potential in advancing therapeutic approaches for non-small-cell lung cancer (NSCLC). This study revealed the favorable properties of KEVs, including good colloidal stability, an average particle size of 198 nm, and a negative surface charge. They exhibited excellent serum stability and biocompatibility, outperforming cationic liposomes in terms of cytotoxicity. Further characterization of STAT3/EKEVs highlighted their stability, smaller size (~187 nm), and efficient internalization in cancer cells. In vitro studies have demonstrated enhanced antitumor activity of STAT3/EKEVs, leading to significant inhibition of tumor growth and the induction of tumor cell apoptosis. In vivo biodistribution studies have confirmed the targeted accumulation of STAT3/EKEVs at tumor sites, resulting in substantial tumor growth inhibition, without evident toxicity to blood cells or organs. These findings suggest that STAT3/EKEVs have potential for NSCLC treatment, offering a safe and effective therapeutic option, with little toxicity. Further research and clinical trials are warranted to explore the full therapeutic possibilities [54].

Meanwhile, animal studies in diabetic mice hint at kiwi’s potential in managing type 2 diabetes mellitus (T2DM) and related complications by alleviating hyperglycemia, improving insulin resistance, and preventing cardiovascular complications. These findings are the result of tests involving kiwi extracts, which found increasing serum adiponectin levels and decreasing HOMA-IR, suggesting improved insulin sensitivity; meanwhile, a reduction in triglyceride accumulation in the liver was observed, and lower serum triglyceride and total cholesterol levels were reported at the same time, potentially preventing cardiovascular complications. Moreover, daraesoon (the shoot of hardy kiwi, Actinidia arguta) extract leads to reduced serum glucose and glycated hemoglobin levels in db/db mice, indicating improved long-term blood glucose control. Specifically, daraesoon extract reduces hepatic MCP-1 and TNF-α levels in diabetic obese mice [55].

Furthermore, a study specializing in long-term colonic fermentation revealed that kiwi fruit functional groups (FFGs) positively influence gut microbial communities. While the initial effects were modest, with reductions in certain bacterial populations, metabolite analysis showed increased butyrate production. In dynamic experiments, Kiwi FFGs demonstrated a dose-dependent influence, boosting beneficial bacteria like Roseburia and A. muciniphila. Overall, Kiwi FFGs appear to have a beneficial impact on the gut microbiota [56]. In a separate survey, researchers explored the potential of Actinidia deliciosa aqueous extract (ADAE) in protecting against streptozotocin-induced diabetic nephropathy, again in rats. The results demonstrate that ADAE effectively reduces oxidative stress, scavenges free radicals, and alleviates inflammation, thereby improving renal function and mitigating lipid peroxidation-related damage. ADAE’s potent antioxidant and antiradical properties contribute to lowering blood glucose levels and mitigating changes in hematological parameters, renal function biomarkers, kidney tissue structure, and gene expression affected by lipid peroxidation. These findings underscore ADAE’s potential as a therapeutic agent for preventing and treating diabetic nephropathy, offering hope for individuals seeking natural remedies for diabetes-related complications [57].

Special attention should be directed to an attempt that was carried out experimentally to enhance the stability and bioavailability of polyphenol-rich kiwi extracts—purified kiwi leaf proanthocyanidins (PKLPs)—by ultrasound-assisted nanoencapsulation. Various factors, such as lecithin mass ratios, ultrasonic power and time, the storage conditions, and simulated gastrointestinal digestion, play crucial roles in modulating the properties of nanoliposomes loaded with PKLPs. Higher lecithin mass ratios were apparent, albeit enhancing encapsulation efficiency, resulting in larger particle sizes and reducing the stability. Ultrasonic treatment can improve nanoliposome stability and homogeneity, enhancing the bioavailability of PKLPs. Moreover, in vitro digestion studies indicate altered nanoliposome properties and improved bioaccessibility of PKLPs, with in vivo studies demonstrating enhanced plasma concentration and bioavailability. However, it is noteworthy that the antioxidant capacity of loaded nanoliposomes is lower compared to free PKLPs, suggesting potential formulation challenges [58].

As mentioned in the third chapter, the utilization of kiwi fruit residues has garnered attention for its rich phenolic content, with 10 phenolics identified, encompassing benzoic acids, cinnamic acids, flavan-3-ols, and flavonols. Notably, caffeic acid emerged as the predominant phenolic compound, followed by p-hydroxybenzoic acid, epicatechin, ferulic acid, and catechin. These five key phenolics collectively constitute 86% of the total identified phenolics in kiwi fruit pomaces [59]. Further exploration into kiwi seed polyphenols (KSPs) revealed strong antioxidant and anti-inflammatory properties, attributed to the synergistic effects of the five identified polyphenolic compounds. Notably, KSPs exhibited superior radical scavenging activity compared to synthetic antioxidants, showcasing their potential for suppressing the expression of pro-inflammatory cytokines.

Additionally, the development of tunable fluorescent carbon dots from kiwi biowaste introduces a novel avenue for fluorescence imaging applications. This innovation underscores the growing significance of natural fluorescein in cellular imaging, hinting at broader applications for such environmentally friendly materials [60].

Moreover, specific proteins in kiwi fruit, such as the peptide kissper, have been linked to beneficial effects on gastrointestinal physiology, inflammation modulation, and oxidative stress reduction. Kissper’s resistance to proteolysis suggests its potential therapeutic role, supported by its ability to control calcium levels and mitigate reactive oxygen species (ROS) production [61].

Last, but not least, the high phenolic extract obtained from kiwi peel through ultrasonic extraction technology suggested the presence of natural active substances, like polyphenols and flavonoids. These compounds contribute to the antioxidant and anti-inflammatory properties observed in the extract. Moreover, chromatographic analysis has confirmed the presence of phenolic compounds in kiwi leaf extracts, contributing to their antioxidant activity, being safe for human cells at certain concentrations, of course. Additionally, kiwi fruit exhibits diverse biological activities, such as antioxidant, antimicrobial, and anticancer effects. This connection underscores the potential health benefits derived from the bioactive compounds present in kiwi fruit, particularly in its peel, highlighting its importance in both food and pharmaceutical industries [12,41,60].

5.3. Kiwi Bioactives in Functional Foods Applications

The shift towards healthier eating habits in developed economies has led to increased demand for high-quality products, with multiple nutritional and functional benefits. This has given rise to the concept of functional foods.

The concept of functional foods originated in Japan in 1998. More specifically, a non-alcoholic beverage enriched with fiber was the first functional food to be introduced by Otsuka Pharmaceutical. This initiative aimed to improve dietary habits and promote longevity, while reducing healthcare costs. Subsequently, Japan established a category of foods known as FOSHU (food for specified health use), which is approved by the Ministry of Health and Welfare. In Europe, the definition of functional foods was formalized between 1995 and 1998, emphasizing their beneficial effects on specific bodily functions, beyond basic nutrition [62].

Functional foods, i.e., foods and beverages that have added health benefits beyond their nutritional value, can improve health and well-being indicators [63]. Functional food products have the potential to offer multiple nutrients that are often difficult to obtain, including additional fiber, protein, vitamins, minerals, and antioxidants, and can improve overall well-being [62]. Furthermore, the mechanism of functional foods is capable of improving the availability of several essential fatty and amino acids, probiotics and prebiotics [64]. These products may contribute to achieving optimal nutrition in older individuals, thereby supporting healthy aging. Therefore, functional foods also promote optimal health and reduce the risk of noncommunicable diseases and improve overall well-being. Thus, functional foods are now considered to be an accessible food therapy to eliminate health problems, since many medications have disagreeable side effects, aiming to affect multiple systems in the body, such as the immune, nervous, and skeletal systems [62,64,65,66].

The Actinidia genus holds prominent status globally due to its substantial commercial and nutritional significance, and contains approximately 60 species, with kiwi fruit being the most consumed member, due to its plentiful health advantages. Currently, individuals gravitate toward convenient foods that offer sufficient nutritional value. Kiwi fruit exhibits potent antioxidant properties and immune-boosting effects, both in vitro and in vivo [67,68,69]. Kiwi fruits can be stored fresh for weeks, even months, without compromising the quality, in controlled temperatures. On an industrial scale, innovative kiwi products are manufactured and marketed. However, beyond consumption in its natural state, kiwi fruit is commonly incorporated into a variety of functional food products. These kiwi-based functional foods have the potential to fulfill the nutritional and health requirements of consumers, while also encouraging the utilization of natural resources (

Table 4. Applications of kiwi pomace and its bioactive compounds in functional foods.

Functional Food	Bio-Functional Ingredients	Amount	Aims	Results	References
	(Kiwi pomace and/or its Bioactives)
Functional kiwi fruit jelly (FKJ)	Kiwi fruit juice	35%	⮚ Nutritional evaluation	Prevention of fat accumulation Low in calories Increase in phenolic content Capacity for antioxidant and anti-inflammatory activity	[71]
Wine	Fermented kiwi fruit juice	A glass of wine for sensory assessment	⮚ Volatile compounds and sensory evaluation	Capacity for antioxidant, antidiabetic, and anticancer activities Rich in vitamins, amino acids, polyphenols, and other bioactive compounds Notable increase in total flavonoid and total phenolic content of low-ethanol kiwi wines Beneficial impact on organic acids, primarily by decreasing the concentration of malic acid	[73]
Starchy kiwi fruit flour (SKF)	Kiwi fruit pulp	66.63–80.42%	⮚ Physicochemical and nutritional evaluation	Lower pH and transparency, but higher swelling power than potato and corn starches Considerable amounts of minerals and total polyphenol content, showcasing strong antioxidant capacity Enzymes do not easily hydrolyze SKF and do not induce a fast rise in blood glucose levels	[72]
Protein bars	Powder from kiwi fruit pomace and peel	6%	⮚ Phytochemical constitution, antioxidant activity, and cell viability evaluation	Increase in flavonoid content, polyphenol content, carotenoid content, and antioxidant activity Capacity for beneficial impact on consumer health, with a prebiotic influence on lactic acid bacteria	[36]
Cheese	Kiwi fruit pulp	80 mg of powder rich in actinidin	⮚ Physicochemical, nutritional, and volatile compound constitution evaluation	Higher concentrations of polyphenols and phytosterols	[74]
Flour	Skin and bagasse from two varieties (Bruno and Monty)	Extracts of 5 g each	⮚ Physicochemical, microbiological, and nutritional evaluation	The flour made with kiwi fruit peel from both varieties showed higher levels of bioactive compounds and antioxidant activity than the flour made with bagasse from both varieties Bruno variety had higher DPPH values and levels of phenolic compounds Monty variety showed higher FRAP values, vitamin C, flavonoids, chlorophylls, and carotenoids Holding dietary fiber and bioactive compounds with antioxidant action	[41]

) [68,70]. The development of kiwi-derived products is based on their nutritional and biological properties, attributed to its high content in terms of dietary fiber and bioactive compounds, including vitamins (C, E, and A), phenolic compounds, and minerals [36,71,72].

Furthermore, the industrial processing of kiwi fruits results in a large amount of by-products, including peel, seeds, and residual pulp, estimated at approximately one million tons annually. Thus, with the food industry grappling with the disposal of thousands of tons of kiwi by-products annually, there is a pressing need to recognize kiwi by-products as valuable sources of functional ingredients. Nowadays, efforts from both a scientific and practical perspective, are being made to explore the functional potential of these materials as sources of essential chemical compounds with considerable added value for human and animal well-being. Indicatively, these compounds encompass polyphenols, carotenoids, and triterpenes, exhibiting plenty of biological activities, such as antioxidative, anti-inflammatory, antimicrobial, and antidiabetic effects, and many more [36,67,68,69,70].

In the industrial sphere, innovative kiwi products are processed and commercialized, such as protein bars, jelly, wine, and flour, among others. To elaborate further, the bioactive effects of functional kiwi fruit jelly (FKJ) were investigated in vivo in a mouse model. More precisely, forty male mice, aged seven weeks, were purchased and accommodated in a controlled environment, with access to food and water. After the eight-week experiment, blood samples were obtained from the orbital sinus of each mouse, and samples from the liver, subcutaneous adipose tissues (SAT), abdominal adipose tissues (AAT), and perirenal adipose tissues (PEAT) were collected and weighed. The findings indicate that FKJ can help prevent fat accumulation and is rich in phenols and flavonoids, low in calories, with antioxidant and anti-inflammatory capacity [71]. Kiwi wine was produced through the fermentation of kiwi fruit juice with indigenous Zygosaccharomyces rouxii (Zr) and Saccharomyces cerevisiae (Sc), without adding sugars. The results indicate that consecutive fermentations led to a notable increase in the total flavonoids and total phenols of low-ethanol kiwi wines. Additionally, they had a beneficial impact on organic acids, primarily by decreasing the concentration of malic acid. Moreover, kiwi wine is rich in vitamins, amino acids, polyphenols, and other bioactive compounds, which offer antioxidant, antidiabetic, and anticancer activities [73]. Starchy kiwi fruit flour (SKF) was investigated in vitro. The outcomes show that SKF has a lower pH and transparency and a higher swelling power compared to potato and corn starch. Moreover, SKF contains considerable amounts of mineral elements and total polyphenol content, showcasing strong antioxidant capacity. Furthermore, SKF is not easily hydrolyzed by enzymes and does not induce a fast rise in blood glucose levels [72]. Powder from kiwi fruit pomace and peel was added to protein bars. The protein bars were tested for phytochemicals, antioxidant activity, and cell viability. Kiwi peel powder led to a different phytochemical profile of the protein bar, with higher flavonoid content, polyphenol content, carotenoid content, and antioxidant activity when compared with the control sample. The results validate the potential of kiwi pomace as a functional food component, offering beneficial impacts on consumer health and a prebiotic influence on lactic acid bacteria [36]. At the same time, kiwi pulp was used to make cheese from sheep and buffalo milk and was compared to calf rennet. Higher concentrations of polyphenols and phytosterols were found in the kiwi cheese, which was 4.5 times (buffalo) and 3 times (sheep) higher than in cheese made with calf rennet. This could mean that the production of nutraceutical cheese is possible, since beneficial compounds can be added to it [74].

Lastly, kiwi flour is made from the skin and bagasse from two varieties (Bruno and Monty) of kiwi fruit (Actinidia deliciosa) at two stages of maturation. The flour made with kiwi fruit peel from both varieties showed higher levels of bioactive compounds and antioxidant activity than the flour made with bagasse from both varieties. The flour made with green kiwi fruit skin from the Bruno variety had higher DPPH values and levels of phenolic compounds, while the Monty variety showed higher FRAP values, vitamin C, flavonoids, chlorophylls, and carotenoids. This flour is a promising ingredient for the enhancement of products with dietary fiber, and bioactive compounds with antioxidant action [41]. Since flour had been made, it was expected that baking enriched gluten-free bread should be tried with polyphenols and related antioxidants derived from a natural aqueous extract from green-fleshed kiwi fruit (Actinidia deliciosa). The aqueous extract that was used showed good stability, so was proven to contain beneficial health-related constituents and can be perceived as a functional ingredient for gluten-free bread formulation [75].

5.4. Health-Promoting Properties of Kiwi Fruit-Based Nutraceuticals

Nutraceuticals are products utilized as medicine that have nutritional value. The term “nutraceutical” was coined from “nutrition” and “pharmaceutical” in 1989 by Stephen DeFelice. A nutraceutical can be identified as, “a food, or part of a food, that provides medical or health benefits, including the prevention and/or treatment of a disease”. Nutraceuticals may be used to ameliorate health, delay the aging process, prevent chronic diseases, increase life expectancy, or support the structure or function of the body. Today, nutraceuticals are under the spotlight because of their potential nutritional, safety, and therapeutic effects. Recent studies have exhibited encouraging findings for these compounds in various cases [76]. The compounds found in kiwi fruit have been linked with various health problems, because of their potential as a cure for them. Since kiwi is composed of multiple substances, individual research has been conducted on many of them and their effects on different health matters.

Quercetin is a substance found in kiwi and is a promising dietary component exhibiting antioxidant and anti-inflammatory properties. A study showed the effect of quercetin supplementation on markers of oxidative stress and inflammation in sarcoidosis. One group of non-smoking and untreated patients with sarcoidosis were divided into two, with matching age and gender. One group was given quercetin orally within 24 h, the other was given a placebo. Quercetin supplementation enhanced the antioxidant defense, hinted at by the higher total plasma antioxidant capacity. In addition, the markers of oxidative stress and inflammation in the blood of the sarcoidosis patients were lowered. Thus, it was concluded that quercetin can be beneficial for patients with sarcoidosis [77]. In another study, participants who consumed bread enriched with flavonoids with 0.05% of a 1:1 mixture of (−)-epicatechin and quercetin for three months were found to have less total cholesterol, LDL cholesterol, triglycerides, and fasting plasma glucose than before. Nuclear abnormalities in buccal epithelium cells also dropped, indicating a genoprotective effect. The antioxidant activity of these substances was observed by monitoring changes in the cytoplasmic redox tone of intact Caco-2 cells expressing HyPer, a fluorescent redox biosensor. The combination of (–)-epicatechin and quercetin changes the cytoplasmic ambient redox in living cells, significantly improves biochemical parameters related to metabolic syndrome, and reduces the number of cell abnormalities in the buccal epithelium cells of patients [78].

Today, network pharmacology and molecular docking techniques can be used to analyze the key components, gene targets, protein–protein interactions, biological functions, signaling pathways, and possible mechanisms of different reactions. The major compounds of kiwi root were screened out, such as quercetin, β-sitosterol, and aloe-emodin, and the major targets of kiwi root against non-small-cell lung cancer were TP53, AKT1, and TNF. It was concluded that kiwi root may stop the growth of NSCLC through PI3K-Akt and MAPK signaling pathways, which suggests that kiwi fruit root might exert its anti-NSCLC effect through multiple components, multiple pathways, and multiple targets. These results show that kiwi roots might have anticancer properties [79].

Hardy kiwi fruits were extracted and tested against five different human cancer cells to study their anticancer properties. The hardy kiwi fruit extracts showed anti-proliferative effects in regard to Hep3B and HeLa cells, but not HT29, HepG2, and LoVo cells. In an MTT assay, hardy kiwi fruit extracts displayed the most inhibition in regard to Hep3B viability, among the tested cancer cells. These properties are the outcome of the high nutritional value of ascorbic acid and phenolic compounds, which show good antioxidant potential and might be utilized in the future to stop cancerous growth [80]. A hardy kiwi was used in a pill to study its effects on atopic dermatitis (AD) in dogs. The study had two phases, with the first one being a randomized, double-blind, placebo-controlled study and the second phase being an open, non-placebo-controlled study. The results were promising for mild-to-moderate cases of AD. The effectiveness was most noticeable after 2 months of continued utilization. Long-term therapy is advised to evaluate the clinical benefits of this treatment in individual clinical cases [81].

Kiwi fruit peels were converted into valuable kiwi fruit peel carbon dots (KFP-CDs), and their anticancer properties were tested on human breast cancer cells lines and human thyroid cancer cell lines. The findings indicate excellent biocompatibility; synthesized KFP-CDs are nontoxic to both normal cells and cancer cells, which provides safe and sustainable development of cellular imaging. Additionally, the KFP-CDs were capable of being utilized as a cell labeling agent for both in vitro and in vivo imaging for MSCs, breast cancer cells, and thyroid cancer cells [60].

The combination of catechin, rutin, and epicatechin, was used in regard to Swiss albino mice, to study their anti-diabetic, antioxidant, and anti-inflammatory properties. The single and combined effect of the three molecules was measured using the oral glucose tolerance test. The three compounds demonstrated excellent antihyperglycemic activity, both separately and in different combinations, involving single, binary, and ternary mixes, and were compared to positive and normal controls. Nonetheless, the determination of the optimal combination was concluded using a preset goals for each response. Among the substances tested, EP exhibited the most effective inhibition of hyperglycemia. Utilizing mixture design experimentation, efforts were made to maximize the formulation that best achieved the desired effect. The predicted formulation comprised a binary combination of RU and EP in a ratio of 25:75. This combination was then administered to alloxan-induced diabetic mice over a 28-day period, resulting in remarkable outcomes, without any observed signs of toxicity. Given its confirmed antidiabetic, antioxidant, and anti-inflammatory properties, along with its diverse modes of action, this formulated combination could be considered a safe and versatile alternative for the treatment of diabetes [82].

The potential of the cacao flavonoid (−)-epicatechin (Epi), a substance found in kiwi, to cancel out oxidative stress (OS), by positively influencing mitochondrial structure/function endpoints and redox balance control systems in the skeletal and cardiac muscles of dystrophic, δ-sarcoglycan (δ-SG) null mice, was investigated. Male mice, both wild type and δ-SG null, aged 2.5 months, were orally administered either water (as control) or Epi for 2 weeks. The findings revealed a significant normalization of the total protein carbonylation, restoration of the reduced/oxidized glutathione (GSH/GSSG ratio), and enhancement in the activities of superoxide dismutase 2, catalase, and citrate synthase, with Epi treatment. These effects were accompanied by elevations in the protein levels for thioredoxin (TRX), glutathione peroxidase, superoxide dismutase 2, catalase, and mitochondrial endpoints. Additionally, a reduction was observed in fibrosis in both heart and skeletal muscles, along with an improvement in skeletal muscle function, following treatment. These results underscore the potential of Epi as a therapeutic candidate for mitigating muscle degeneration associated with muscular dystrophy (MD) [83].

The acute and chronic effects of ellagic acid on pentylenetetrazole and picrotoxin-induced convulsions were investigated in young male Swiss albino mice. Ellagic acid and diazepam were given either as a single dose for acute treatment or for 14 consecutive days for chronic treatment. Pentylenetetrazole induced both tonic and clonic convulsions, while picrotoxin induced tonic convulsions only. The higher dose of ellagic acid administered acutely, and both doses administered chronically, significantly delayed the onset of convulsions, reduced the duration of clonic and tonic convulsions, and decreased mortality compared to the control groups treated with pentylenetetrazole and picrotoxin. Ellagic acid also reversed the decrease in brain GABA levels induced by pentylenetetrazole and picrotoxin. Acute and chronic administration of diazepam showed excellent anticonvulsant activity and increased brain GABA levels. These findings indicate that ellagic acid possesses significant antiepileptic activity in mice, likely mediated through the enhancement of GABAergic transmission in the brain [84].

Kiwi is rich in vitamin C, which has been linked with greater feelings of vitality. Kiwi fruit was tested in order to find whether the properties of vitamin C are effective. Young adults with a plasma vitamin C < 40 µmol/L were assigned to three conditions: kiwi fruit, vitamin C, or the placebo. The trial consisted of a 2-week lead-in, a 4-week intervention, and a 2-week washout. Plasma vitamin C levels were saturated within two weeks for both the kiwi fruit and vitamin C groups. Participants who consumed the kiwi fruit exhibited a trend of improvement in mood disturbance, considerably decreased fatigue, and radically improved well-being after two weeks of the intervention. Advances in well-being remained elevated through the washout. Participants who consumed vitamin C tablets showed improvement in their well-being after two weeks. The participants with low vitamin C levels from the start showed improved mood and less fatigue. It was also found that subjects who ate kiwi fruit did not gain fat during the study. No changes were reported in the placebo group. Kiwi fruit consumption ameliorated vitality in adults with low vitamin C status. Vitamin C tablets performed similarly, but not as efficiently as the kiwi fruit, indicating that the fruit has more beneficial properties Analogous results were found in a similar study from the same authors [85,86].

The cardioprotective effect of chlorogenic acid (CGA) on isoproterenol (ISO)-induced myocardial infarction (MI) in male albino Wistar rats was studied. ISO-induced myocardial damage was indicated by the elevated levels of marker enzymes, such as creatine kinase (CK), creatine kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and cardiac troponin T and I (cTnT, cTnI) in serum. The levels of lipid peroxidation products, such as thiobarbituric acid reactive substances (TBARSs), conjugated dienes (CDs), and lipid hydroperoxides (LHPs), rose remarkably in the plasma and heart tissue. Enzymatic antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), as well as the non-enzymic antioxidants like vitamin C, vitamin E, and reduced glutathione (GSH), experienced a decline in activity, as seen in the erythrocytes, plasma, and heart tissue of the ISO-induced rats, suggested by the myocardium infarct size staining with triphenyltetrazolium chloride (TTC). Thus, orally administered CGA at different doses for 19 days was found to be beneficial, for the reasons stated above [87].

The positive effects of vitamin C and Ε on oxidative stress in women with endometriosis were measured through a clinical trial, as well. Sixty women of reproductive age with pelvic pain and laparoscopic-proven endometriosis from stages 1–3 were studied. Half of the participants were given vitamin C and vitamin B, and the other half were given placebo pills, daily for 8 weeks. Subjects who took the vitamins showed a decrease in MDA and ROS in comparison with the placebo treatment. No significant decline in the total antioxidant capacity was found. Nevertheless, the severity of the pelvic pain was improved, as well as dysmenorrheal and dyspareunia after 8 weeks of the vitamin intake. These results support the potential role of antioxidants in the management of endometriosis [88].

Vitamin E was investigated for its potential to treat chronic insomnia in a clinical study. The participants were 160 postmenopausal women with chronic insomnia disorder, and they were divided into two groups. The group who received vitamin E got 400 units of mixed tocopherol daily, while the placebo group was given an identical oral capsule. After one month of daily intake, the PSQI (Pittsburgh Sleep Quality Index) score was significantly lower, indicating better sleep quality, in the vitamin E group in comparison to the placebo group. In addition, there was a remarkable decrease in the percentage of participants using sedative drugs in the vitamin E group, with the placebo group exhibiting a statistically insignificant decrease. This study demonstrates vitamin E’s potential as an alternative treatment for chronic insomnia disorder, which improves sleep quality and reduces sedative drug use [89].

In conclusion, the diverse array of bioactive compounds present in kiwi fruit highlights its profound potential as a source of functional ingredients for dietary interventions. From flavonoids, like quercetin and catechin, to essential vitamins, such as vitamin C, E, and B, each offers a unique mechanism of action that contributes to physiological health and homeostasis. As ongoing research continues to elucidate the interplay between these compounds and their impact on cellular pathways, the integration of kiwi fruit-derived nutraceuticals into functional foods emerges as a compelling avenue for enhancing human health and mitigating disease risk. Leveraging the innate bioactivity of kiwi fruit in tailored nutritional strategies holds promise for optimizing metabolic health, strengthening the immune system, and combating chronic diseases.

6. Kiwi Bioactives in Cosmetics Applications

6.1. Kiwi as a Sustainable Natural Source of Bioactives for Healthy Natural Cosmetics

The continuous growth of the cosmetics industry is mainly due to the responsive attitude of consumers toward the trends and standards of promoting and maintaining a youthful appearance. These attitudes have been shaped and promoted by social media, resulting in the continuous development of the sector over the last 100 years. In addition, the terms well-being and prosperity include not only cosmetic products, but any goods that promote beauty, health, and protection against pollution (an aspect of cosmetics that is receiving enormous attention and is being researched continuously in the 21st century). The first efforts to develop better products, aimed at improving both the skin all over the body and hair, were made with the use of pharmaceutical composites [90]. However, their repeated use, as expected, brought to the surface various disadvantages, which led to the interest of consumers and companies in finding naturally derived products. Thus, due to this new trend and the constant competition between industries to make available for sale new innovative products that would attract customers due to their herbal origin, research into the use of plant extracts was initiated. So-called “green cosmetics” or “bio-cosmetics” is a revolutionary idea of ecological interest, with positive effects on the health of the person using them. The applied plant extracts contain a range of bioactive ingredients, such as those present in both kiwi and its derivatives. Naturally, factors such as the methods and time of extraction vary according to the ingredients required, thus the composition of each extract varies. However, they all contain substances derived from fruits, flowers, plants, and other products of the earth that promote human health. Great attention seems to be being paid to the process of antiaging and skin tightening, i.e., the attempt to slow down the appearance of wrinkles, blotches, spots, and general scars, as well as photoprotection from solar radiation, which is directly related to the previous processes [90,91,92].

Exposure to ultraviolet radiation and other damage leads to skin aging and skin disorders [93]. Aging is an irreversible, continuous process of natural change that begins pretty early in life. During this process, many bodily functions begin to dysfunction and reactive oxygen species accumulate, which is the main occurrence affecting this process. Skin aging results from intrinsic and extrinsic factors, leading to reduced skin functionality and structure. UV radiation also generates reactive oxygen species (ROS) that damage lipids, proteins, and DNA. ROS-induced DNA damage and the activation of enzymes like collagenase and elastase contribute to skin photoaging, leading to collagen breakdown, elastin abnormalities, wrinkles, and the loss of elasticity. Consequently, consuming natural, nutrient-rich diets with antioxidant properties, such as fruits and vegetables and products based on them, has a significant role in the delay of the aging process. Moreover, fruits and vegetables have the capacity to transfer moisture to the skin of the consumer [94].

Kiwi fruit, and also its by-products, such as peel, branches, and leaves, can be used in the cosmetics industry. The application of the bioactives of kiwi in cosmetic products has many benefits, including antioxidant, anti-inflammatory, and antibacterial effects (

Table 5. Bioactive compounds in kiwi fruit and its by-products with potential health-promoting applications in cosmetics.

Bioactive Compounds	Potential Functional Cosmetic Product	Activity	References
Phenolic compounds	Sunscreens and sunblocks	Antioxidant and photoprotective properties against UV (UVR, UVA, and UVB) radiation	[96,97,98,99]
		Improvement to skin density, reduction of wrinkles, increase in skin elasticity, hydration, and antiaging	[96,100,101,102]
		Expedited healing process	[44,103,104,105,106]
		Control of overexposure to oxidative stress in the wound bed (chlorogenic acid)	[44,103,104,105,106]
Vitamin C	Anti-hyperpigmentation, wound and scar healing formulations	Antioxidant and anti-inflammatory activities, with wound healing properties	[107]
		Shielding against UV-induced oxidative stress, providing regenerative benefits	[108,109]
		Enhancement of aged skin’s microstructure attributed to increased collagen synthesis	[108,109]
		Capacity to address hyperpigmentation	[108,109]
Vitamin E	Photoprotective and antioxidant formulations	Antioxidant, anti-tumorigenic, and photoprotective activities, with skin barrier stabilizing properties	[110]
		Reduction of DNA damage and keratinocyte death in sunburn	[110]
		Enhancement of stratum corneum hydration	[110]
		Diminishes skin roughness	[110]
		Protection against skin aging, due to its excellent moisturizing properties	[111]
Vitamin C and vitamin E	Stabilized antiaging action	Enhancement of sunscreen in preventing DNA damage and inflammation, promoting cell renewal	[109]
Carotenoids	Greater skin health and regeneration. Collagen and elastin stimulatory formulation	Strong antioxidant and anti-glycosylation properties	[112]
		Collagen degradation protection potential	[112]
		Boosting cell proliferation and reducing oxidative stress	[112]
		Photoprotection against UV radiation, increasing microcirculation, diminishing skin roughness, protection against skin cancer, and prevention of skin aging and cell damage	[113,114]

). Through experiments, a kiwi extract was used in moisturizing and antiaging creams [95]. The incorporation of a kiwi extract into sunscreen was also performed, since sunlight is considered one of the most harmful environmental hazards for the skin, leading to premature skin aging, inflammation, and a higher risk of skin cancer. Kiwi’s antiaging activity was studied in vivo with C. elegans as the animal model, which has plenty of homologous genes with humans. Wild-type C. elegans were cultured at room temperature, while being fed with E. coli, in order to perform assays that showed the influence of fermented kiwi beverages. Specifically, lifespan assays, an assessment of acute toxicology, a fertility assay, and body bending frequency, the determination of antioxidant enzyme activity, and MDA content in vivo, and the study of oxidative stress and heat stress, were executed [94]. Moreover, collagen, phenolic compounds, carotenoids, and vitamin C and E were also isolated from the kiwi extract, which displayed many positive effects on the skin when applied in the form of a cream [95].

6.2. Kiwi Bioactives and Skin Health

6.2.1. Phenolic Compounds

Phenolic compounds can be found easily in plants. Consequently, multiple phenolic acids, such as coumaric (p-coumaric), caffeic, chlorogenic, protocatechuic, gallic, syringic, ferulic, ellagic, and p-hydroxybenzoic acid, etc., are detected in kiwi. In addition, other compounds that belong to the latter group (phenolic) are located in kiwi fruit, including epicatechin, catechin, procyanidins, catechol, quercetin or rutin, kaempferol, and luteolin, etc. [12,46,59,68,70]. Many studies, both in vitro and in vivo, have taken place and they have shown that the majority of these compounds have multiple assets that can be used in cosmetic products. The information available today comes from various sources. Mainly, the information that we possess comes from studies and experiments that have been conducted specifically on kiwi fruit. Other fruits and plants that have been studied can also provide information on this matter, since they contain many polyphenols that are found in kiwi too. What is more, research has been conducted for each substance separately by isolating them, for a better understanding of their bioactivity. As a result, it was discovered that the action of the phenolic substances in kiwi on skin can have an antioxidative effect, as they protect the body from external oxidizing agents, such as UV electromagnetic radiation. They can act as photoprotectants, since they protect the skin from photo-aging and photo-oxidative damage induced by UV radiation, including UVR, UVA, and UVB [96,97,98,99]. Some substances have also been found to improve the density of the skin, they can reduce wrinkles and increase skin elasticity, as well as moisturize it, promoting an antiaging effect [96,100,101,102].

Additionally, there is evidence from several experiments on rats that show the wound-healing effects of kiwi. A dressing that contained kiwi fruit paste was placed on inflicted burn wounds. The dressing moisturized the wounds and, since kiwi fruit extracts are rich in antibacterial agents and enzymes, it allowed the enzymes to digest the hard eschar in full-thickness burns, making the healing process faster than normal (Table 6) [44,103,104,105,106]. Another study highlighted the promising antioxidant and free radical scavenger effects of chlorogenic acid, a phenolic compound found in kiwi, in wound healing, since it can control overexposure to oxidative stress in the wound bed [107].

6.2.2. Vitamin C

Vitamin C (a.k.a. ascorbic acid) is included in plenty of cosmetic products, especially in antiaging focused products. The topical application of vitamin C has also exhibited both promising anti-inflammatory and wound healing properties that further suggest its clinical use in such a way. However, oral supplementation of ascorbate as a supplement and/or as a nutricosmetic does not have the same effects [108]. Vitamin C is a natural antioxidant. The application of this compound onto the skin has demonstrated efficacy in shielding against UV-induced oxidative stress and in providing regenerative benefits. Clinical studies have revealed an enhancement in the microstructure of aged skin attributed to increased collagen synthesis stimulated by the topical application of vitamin C and its capacity to address hyperpigmentation [108,109].

6.2.3. Vitamin E

Vitamin E (a.k.a. α-tocopherol) has been widely used as an additive in cosmetics and has various benefits, including anti-tumorigenic, photoprotective, and skin barrier stabilizing properties. Whether taken orally or topically it has the same effect, unlike vitamin C. Vitamin E TPGS (a water-soluble derivative of vitamin E) undergoes intracellular hydrolysis, releasing α-tocopherol after crossing cell membranes, making it suitable for incorporation into personal care and cosmetics products [93]. Furthermore, vitamin E acetate serves as an antioxidant, effectively scavenging free radicals to reduce DNA damage and keratinocyte death, as a result of sunburn cell formation, while also enhancing stratum corneum hydration and diminishing skin roughness [110]. Vitamin E is classified as a water-insoluble vitamin and is known for its capacity to protect the skin from harmful oxidative stress, a leading cause of skin aging, and its excellent moisturizing properties [111].

Ultimately, the combination of vitamin C and vitamin E can notably enhance the efficacy of sunscreen in preventing DNA damage and inflammation, while also promoting cell renewal. Consequently, this combination has the prospect of being the main ingredient in photoprotective formulations with antiaging attributes [109].

6.2.4. Collagen

Collagen is the most abundant protein in the body, used as an adjunct wound therapy to promote healing [115]. It is an important substance in the extracellular matrix, well known for its role in the regulation of the phases of wound healing, either in natural, fibrillar conformation, or as soluble components in the wound milieu. Collagen synthesis in our bodies gradually changes as we age; as collagen fibers become thicker and shorter, the synthesis of collagen in deep skin layers alters from a tightly organized network of fibers to an unorganized maze. Excess sun exposure can damage collagen fibers, reducing their thickness and strength, leading to wrinkles on the skin’s surface. Research has shown that UV radiation can affect collagen and alter its molecular structure [116,117]. This contributes to the appearance of skin aging, with a reduction in skin elasticity and tone, giving way to the increased appearance of wrinkles, sagging eyelids, and bags under the eyes [118].

From experiments with rats that had burn wounds dressed with a kiwi fruit extract, it was discovered that the self-debridement procedure could increase collagen deposition in the wound healing process [103,106]. The latter is of great significance, since collagen has all these positive effects that can ameliorate wound healing. Similarly, there are findings from in vitro studies on kiwi polysaccharides, showing that they can increase metabolic activity and the synthesis of collagen in dermal equivalents, and potentially be used in products to promote skin health and regeneration. Hence, kiwi fruit polysaccharides have promising stimulatory effects on cell proliferation and collagen synthesis, implying future applications in skin care and tissue engineering (Table 6) [95]. All in all, the above findings are distinctive, considering the fact that the natural synthesis of collagen wears out over time.

6.2.5. Carotenoids

Carotenoids are considered high-value ingredients in cosmeceutical industries. Carotenoids have shown strong antioxidant and anti-glycosylation properties and hold promise for preventing collagen degradation. Moreover, they can significantly boost cell proliferation and reduce oxidative stress [112]. Other benefits of carotenoids include photoprotection against UV irradiation, increasing microcirculation, diminishing skin roughness, protection against skin cancer, and the prevention of skin aging and cell damage [113,114]. Both topically applied and orally administered natural supplements, rich in carotenoids, show the same significance [113].

6.3. Other Cosmetics’ Applications

In the last decades, several attempts to introduce fruit extracts in secular products and creams have been made, since, as mentioned above, they undoubtedly have numerous positive effects [119,120,121]. The application of kiwi extracts in creams has been achieved through a few methods [44,122,123]. Firstly, kiwi was analyzed and then the extraction of kiwi compounds took place with different methods based on processes found in the literature [121]. Then, the extract was placed in a regular formulation found in creams, but because the concentration of the compounds was high, the formulation needed to be diluted [122]. The final product was found to be a promising source of bioactive ingredients for skin care and for the possible development of safe and effective cosmeceuticals. In the future, it would be interesting to further evaluate the beneficial properties of kiwi extracts on the skin and to study the development of new cosmetic formulations incorporating it as a bioactive ingredient for further in vivo study.

Table 6. Natural origin bioactive compounds with potential health-promoting applications in cosmetics, which can potentially be harvested from kiwi and its by-products.

Bio-Functional Ingredient of Kiwi or Its By-Products	Bioactive Compounds	Potential Functional Cosmetic Product	Activity	References
Kiwi extract (solution of peeled kiwi powder in distilled water)	Antibacterial agents and enzymes	Nanofibers—PCL/CA/KE (1%)	Expedited healing process via higher collagen deposition	[103]
Kiwi paste	Proteolytic enzymes	Burn wound dressing (debridement agent)	Enhanced enzymatic debridement via eschar enzymatic digestion Smooth healing and wound contracture	[104]
Raw kiwi piece (cut from the fleshy part)	Proteolytic enzymes	Burn wound dressing (debridement agent)	Kiwi-treated wounds exhibited spontaneous debridement significantly faster than fibrinolysin-treated wounds	[105]
Raw kiwi piece (cut from the fleshy part)	Antibacterial, scavenger agents, and proteolytic enzymes	Cutaneous wound dressing	Kiwi-treated wounds exhibited faster healing time, shorter wound length, and greater wound tensile strength than the control group	[106]
Kiwi peel extract	Catechin, epicatechin, chlorogenic acid, and caffeic acid	Moisturizing cream (antioxidant and antibacterial agent)	The absence of microorganisms was observed in the formulation exhibiting antioxidant activity against ABTS and DPPH radicals	[44]
Kiwi	Purified polysaccharides (rhamnose, arabinose, xylose, mannose, galactose, glucose, uronic acid)	Physiological engineering agents	Keratinocytes exhibited an increase in energy metabolism, cell proliferation, and ATP synthesis Fibroblasts exhibited similar proliferation effects, albeit were less sensitive to them	[95]

Table 6. Natural origin bioactive compounds with potential health-promoting applications in cosmetics, which can potentially be harvested from kiwi and its by-products.

Bio-Functional Ingredient of Kiwi or Its By-Products	Bioactive Compounds	Potential Functional Cosmetic Product	Activity	References
Kiwi extract (solution of peeled kiwi powder in distilled water)	Antibacterial agents and enzymes	Nanofibers—PCL/CA/KE (1%)	Expedited healing process via higher collagen deposition	[103]
Kiwi paste	Proteolytic enzymes	Burn wound dressing (debridement agent)	Enhanced enzymatic debridement via eschar enzymatic digestion Smooth healing and wound contracture	[104]
Raw kiwi piece (cut from the fleshy part)	Proteolytic enzymes	Burn wound dressing (debridement agent)	Kiwi-treated wounds exhibited spontaneous debridement significantly faster than fibrinolysin-treated wounds	[105]
Raw kiwi piece (cut from the fleshy part)	Antibacterial, scavenger agents, and proteolytic enzymes	Cutaneous wound dressing	Kiwi-treated wounds exhibited faster healing time, shorter wound length, and greater wound tensile strength than the control group	[106]
Kiwi peel extract	Catechin, epicatechin, chlorogenic acid, and caffeic acid	Moisturizing cream (antioxidant and antibacterial agent)	The absence of microorganisms was observed in the formulation exhibiting antioxidant activity against ABTS and DPPH radicals	[44]
Kiwi	Purified polysaccharides (rhamnose, arabinose, xylose, mannose, galactose, glucose, uronic acid)	Physiological engineering agents	Keratinocytes exhibited an increase in energy metabolism, cell proliferation, and ATP synthesis Fibroblasts exhibited similar proliferation effects, albeit were less sensitive to them	[95]

7. Conclusions, Limitations, and Future Perspectives

Kiwi, or as many call it, the king of fruits, aside from its attractive interior due to the intense and lively green color of its flesh, hides a rich nutritional profile, worthy of the beauty of its internal presentation. The available compounds and elements that it offers to the human body have been analyzed at the level of raw consumption and the processing of the fruit for the production of its juice. However, its many facets are overshadowed, as its nutritional value is not found exclusively in its fleshy part. The peel, seeds, leaves, and all of them combined in a pomace, present an equally interesting option in terms of their nutritional value. The above parts of kiwi are called by-products and, unfortunately, it is a common phenomenon that they are treated as waste, both by humans and by companies. The non-utilization and accumulation of these forms of bio-waste create a major ecological problem.

On the other hand, there seem to be constant concerns about the scourge of chronic diseases and the inability to treat them. Chronic inflammation seems to easily turn into diseases that afflict people throughout their life and also put them in danger of losing it. Oxidative stress, inflammation, and thrombosis seem to promote these diseases, so it becomes clear where the fight against such disease should begin. Over the years various drugs and supplements have been proposed, however none can compare to the natural origin of the necessary bioactive ingredients required. These components are contained in an abundance of fruits and vegetables, including in kiwi. The intake of nutrients from the consumption of a fruit that has antioxidant and anti-inflammatory effects is a good start; however, it is not enough, as often people find it difficult to follow a healthy diet and also because many of the good elements of this particular fruit are not consumed, but are discarded together with the by-products.

The antioxidant and anti-inflammatory abilities of the bioactive ingredients in extracts can be used in new products, resulting in their optimization. Compounds from the categories of polyphenols, carotenoids, vitamins, dietary fibers, and others, show a high percentage of such actions. Essentially, through the stabilization of free radicals and the reduction of oxidative stress, disturbances occur that impacts the proper functioning of the human body. Cancer, cardiovascular disease, diabetes, and certain autoimmune diseases have been directly linked to oxidative stress and the pathways it affects. In addition, the phenolic components, as well as the dietary fiber in kiwi and its by-products, have made contributions to the better functioning of the digestive system, as they act against inflammation due to polysaccharides.

Therefore, the extraction of the bioactive substances present in the juice, seeds, and skin, etc., and their application in new functional products and cosmetics that promote human health are at the center of the attention of researchers. A large range of opportunities can be developed through the enrichment of goods with kiwi extracts in sectors such as food, pharmaceuticals, and cosmetics. Based on this information, a new world of functional goods may unfold in the hands of researchers. This chemical composition and quantitative availability make kiwi ideal for the discovery of new ways for humans to obtain bio-functional nutrients for several health-promoting products with added value, including functional foods, nutraceuticals, and cosmetics.

Nevertheless, a proof of concept for a possible application to valorize extracts from kiwi by-products, applying the principles of sustainability and the circular economy to the food and cosmetics industries, is needed. Despite promising results, other studies are needed to evaluate safety and other properties. Thus, safety issues and other limitations, including in regard to sustainability, also exist and need to be considered for such applications.

For example, while kiwi fruit offers numerous health benefits due to its rich bioactive content, several limitations must be considered when incorporating kiwi bioactives into functional products. The primary limitation is its allergenic potential, as kiwi fruit can cause allergic reactions, ranging from mild oral allergy syndrome (OAS) to severe anaphylaxis, restricting its use in functional foods for the general population. Additionally, kiwi bioactives, such as vitamins, antioxidants, and enzymes, can degrade during processing and storage, affecting the efficacy and nutritional value of functional products, making it challenging to ensure these compounds remain stable and bioavailable. Furthermore, kiwi fruit allergens can cross-react with other common allergens like latex and birch pollen, necessitating clear labeling of functional products to inform consumers of the potential risks. In regions with a high incidence of these related allergies, the use of kiwi bioactives may need to be limited to avoid adverse reactions among sensitive populations. Addressing these limitations requires innovative approaches in food technology and allergen management to safely and effectively incorporate the health benefits of kiwi bioactives into functional products. Diagnosis relies on skin prick tests (SPTs), specific IgE tests, and the prick-by-prick method, using fresh fruit for higher sensitivity. Component-resolved diagnostics (CRDs) aid in identifying allergens like Actinidin (Act d 1), associated with severe reactions, even in non-pollen allergic individuals. Thaumatin-like protein (Act d 2) contributes to cross-reactivity with mold allergens. Regional differences exist in symptom presentation, with systemic reactions more frequent in central and southern Europe, contrasting with milder oral symptoms in central/western Europe. Children often exhibit mono-sensitization to kiwi fruit, while adults commonly display multiple sensitizations, reflecting demographic variability in allergy patterns [124].

Some allergic reactions to kiwi fruit have been reported, but the mechanisms behind the reaction are still unclear. Nevertheless, very scarce information is available in the literature about this topic.

Thus, more research is necessary on the toxicity of kiwi bioactives and extracts to ensure consumer safety when they are added to a new product. For example, cytotoxicity studies of extracts must be performed to confirm their security for human applications. The stability of cosmetic formulations should be analyzed for longer periods, ideally six months, and their moisturizing properties must also be assessed. Finally, a sustainability assessment should also be performed prior to such an application, to analyze factors such as the carbon footprint, resource consumption, and end-of-life disposal, to clearly understand the impact of the production of novel functional foods and cosmetic products, in comparison to commercial ones.