Avocado and Its By-Products as Natural Sources of Valuable Anti-Inflammatory and Antioxidant Bioactives for Functional Foods and Cosmetics with Health-Promoting Properties

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Valorization of bioactives from avocado and its by-products as ingredients of functional foods and cosmetics applications with health-promoting properties.

Abstract

Avocado (Persea americana) is a unique fruit with exceptional nutritional and technological characteristics, as well as proposed health benefits. Moreover, the commercial utilization of avocado to make guacamole and/or to extract its oil for several applications generates massive amounts of avocado bio-wastes, including peels and seeds by-products, which further impact the environment and waste management costs. Within this article, the proposed health benefits of moderate avocado consumption, as a functional component of a balanced diet against inflammation-related chronic disorders, and its potential applications are fully addressed. The numerous bioactive compounds present in avocado fruit and its by-products, such as its bioactive phenolics, dietary fiber, and lipid bioactives like unsaturated fatty acids and polar lipids, are also thoroughly outlined. The functional anti-inflammatory, antithrombotic, and antioxidant properties of each of these bioactives and avocado extracts, are then thoroughly reviewed. Emphasis is given to these avocado-derived bioactives and extracts that have the potential to be utilized in various industrial applications, such as in functional foods, supplements, nutraceuticals, and cosmetics related health-promoting applications. The limitations and future perspectives of these applications based on avocado bioactives are also discussed.

1. Introduction

According to the World Health Organization (W.H.O.), inflammation-related chronic disorders like cardiovascular diseases (CVD), cancer, chronic respiratory diseases, diabetes, and diabetes-related kidney disease have increased the mortality rate in developed and developing countries [1], while they also negatively impact daily activities and global health economy profiles [2,3]. The presence of several risk factors, modifiable and non-modifiable ones, may continuously trigger unsolved, chronic thrombo-inflammatory manifestations and concomitant oxidative stress complications, which are implicated in the onset and the development of these disorders [4,5].

Appropriate medical treatment is the golden standard, while possible side-effects and other financial and cultural issues may hinder their use [6]. On the other hand, establishing a healthy lifestyle by the inclusion of healthy dietary habits like the daily consumption and/or use of products from healthy fruits and vegetables, such as avocado fruit, seems to provide notable protection against such chronic disorders, without any observed side-effects [7]. Nevertheless, not everyone is capable of following this dietary pattern in the long term due to the high cost of such food choices, lack of time to appropriately prepare such meals, etc. Therefore, the intake of supplements, nutraceuticals, bio-functional foods, nutricosmetics, and cosmeceuticals rich in bioactives from these healthy fruits in a sustainable and environmentally friendly way is highly desirable and must further be supported [8,9,10].

The increasing demand for the introduction of healthy fruits like avocado and for their valuable components for several products has increased the amount of co-produced bio-wastes derived from avocado processing. Nevertheless, based on a circular economy design, according to UN and EU directives, considering by-products of fruits like avocado as sustainable sources of valuable bioactives seems to yield both the reduction of the environmental footprint of these bio-wastes and waste management costs, as well as several low-cost functional ingredients for the development of novel products with health-promoting properties and, thus, of added value [8,9,10].

Succinctly, the aim of the present study is to outline the anti-inflammatory and antioxidant activities, as well as the various health benefits, of the bioactives from avocado fruit and its by-products. Plus, a review of their potential valorization as bio-functional ingredients in several functional foods, supplements, nutraceuticals, nutricosmetics, cosmeceuticals, and cosmetics-related applications and products with health-promoting properties is thoroughly analyzed.

Avocado has been advocated as one of the most nutritious fruits and is nowadays increasingly included in several healthy dietary patterns. Research has also proposed its potential as a superfood due to it being rich in several important nutrients and bioactive compounds. Avocado, otherwise known as Persea americana, is a flowering plant native to Mexico and Central America, which belongs to the Lauraceae family [11]. Avocado fruit can be divided into three parts: the central seed, which accounts for 20% of the whole fruit, the pulp, which accounts for its bulk majority (65%), and the outside peel (15%). It must be noted that this fruit is commonly referred to as “vegetable butter” due to the fact that it comprises of a significant amount of lipids and especially a high concentration of unsaturated fatty acids [12,13]. Persea americana is rich in a variety of vitamins (with vitamin C and D being the predominant), minerals (mainly copper), and phytochemicals (in which flavonoids are the prevalent), and it is known to possess antioxidant activities, as well as to improve immunological function and to reduce inflammation, which can lead to the overall decrease of the risk for chronic diseases [14,15].

Avocados reportedly have high antioxidant properties because they consist of secondary metabolites and other active molecules like flavonoids, phenolics, tannins, tocopherols, fatty alcohols, carotenoids, and anthocyanins [13]. Due to these components and owing to their content being full of highly bioavailable carotenoids, low energy density, viscous prebiotic fiber, and high unsaturated-to-saturated fatty acid ratio, their consumption contributes to a plethora of health benefits.

Specifically, the primary health effects avocado promotes are related to the cardiovascular systems’ well-being, since the consumption of this fruit enhances blood lipids’ profiles and endothelial blood flow, improves cognitive performance, contributes to a healthier body mass index and composition, provides colonic microbiota health, and induces accompanying cardiometabolic and brain advantages [16,17]. Several avocado-derived bioactive compounds, such as carotenoids and xanthophylls like carotene, lycopene, lutein, zeaxanthin, and cryptoxanthin have exhibited anticancer benefits against several types of cancer, including breast, larynx, and mouth tumors [11]. Moreover, P. Americana’s phytochemicals have shown benefits for diabetes management, while avocado intake enables inhibition of several diabetes-related enzymes’ action (alpha-glycosidase and alpha-amylase) that downregulate glucose’s fast metabolism [18].

More than 3 million tons of avocado are produced around the world each year, where only the pulp is consumed, while the seeds and peel are thrown away. Making use of the waste, by utilizing the phytochemical composition of avocados’ by-products, will consequently lead to embracing the importance of the avocado industry and will possibly contribute to the creation of new, more efficient products [11,19,20]. Avocado by-products contain lipid bioactives and vitamins, such as monounsaturated fatty acids like oleic acid, phytosterols, tocopherols, tocotrienols, and carotenoids, as well as some more amphiphilic polar bioactive compounds like polyphenols. All these bioactives have shown anti-inflammatory and antimicrobial activities with potential health-promoting properties. Thus, avocado’s by-products that consist of such a wide range of bioactive compounds can be exploited for several nanotechnological, agro-industrial, pharmaceutical, tissue engineering, and other health-related applications, many of which are synopsized in Figure 1. Furthermore, caffeoylquinic acid obtained from avocado may be a part of an innovative drug delivery method that is believed to improve the bioavailability of those substances and, as a result, their therapeutic efficacy. Additionally, polysaccharides existing in the avocado seeds and peels could be transformed from waste to biomaterials, such as polylactic acid (PLA) [20,21,22]. Cellulosic avocado biomass is a possible attributor to bioethanol’s greener production through fermentation [20,21].

2. Methods

The Scopus database was utilized for finding the related literature. The following keywords were used: “avocado”, “oil”, “by-products”, “avocado pomace”, “avocado peel”, “avocado pulp”, “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”, “hypertension”, “neurodegenerative diseases”, “applications”, “functional foods”, “supplements”, “nutraceuticals”, “cosmetic”, “sunscreen”, “sun oil”, “nutricosmetics”, “cosmeceuticals”, and “pharmaceuticals”, with the use of combinations of these keywords by using the AND and/or OR terms in each query in order to retrieve information from relevant scientific databases, including Scopus, Science Direct, PubMed, Research Gate, and Google Scholar.

This search process was concluded in March–May 2024 for the last 5 years, and the selection criteria were determined by considering the metadata available from these databases, with the eligible studies meeting the following criteria: (i) be exclusively research articles; (ii) be written in English; and (iii) be published between 2020 and 2024.

To evaluate the articles’ quality and relevance, we first reviewed their titles, abstracts, and keywords, excluding duplicates retrieved from different databases and those articles that were deemed unrelated to the topic.

Subsequently, the remaining articles were thoroughly analyzed so as to determine whether they met the predefined inclusion criteria and provided pertinent information for this review. Also, conference papers, books, previous reviews, and short surveys, as well as publications written in languages other than English, were excluded. A limited number of important articles prior to 2020 were also included since they were not previously reviewed thoroughly.

3. Avocado’s Composition in Nutrients and Bioactives

3.1. General Composition/Chemical Composition

The fruit of avocado has three structural parts: peel, pulp, and seed, and it is categorized into different types based on the geographical area it is domesticated in. Under these circumstances, avocado belongs either in Guatemalan (quilaoacatl), Mexican (aoacatl), and West Indian (tlacacolaocatl) varieties [23]. Each variety has individual characteristics such as color and texture of the peel features, size and shape of the fruit, ripening time, oil composition, salinity, and frost tolerance. The commercially dominant cultivated variety is Hass avocado, a hybrid of Guatemalan and Mexican varieties, due to its coarseness and firmness of the peel, as well as its richness in bioactive oils that can be harvested [24].

The compositional analysis of avocado clarifies this fruit as a nutritional powerhouse. In particular, it is high in fiber, vitamins, minerals, monounsaturated fatty acids, and other compounds that are indicated to promote valuable health effects. In this review, data of five types of different cultivars were selected (Haas, Fuerte, Bacon, Ettinger, Pinkerton) and displayed in

Table 1. Proximate nutritional composition of avocado’s fruit and its by-products.

Nutrients *	Avocado Fruit 1	Avocado By-Products 1
Ash	0.57–10.80	1.6
Carbohydrates	4.77–8.89	67.5
Lipids	51.83–72.34	1.41–4.12
Protein	4.80–8.61	3.4
Total dietary fiber	6.03–7.24	21.6
Total insoluble fiber	-	18.7
Vitamins	0.02–0.04	1.3–6
References	[25,26,27,28,29,30]	[26,31]

* Data are a combination of the ones presented in [25,26,27,28,29,30,31]. ¹ Estimation of typical gross composition expressed as grams of total compound per 100 g of avocado weight (g 100 g⁻¹)

.

3.1.1. Avocado Fruit Composition

Avocado’s nutritional composition has been proposed to provide several health benefits on consumers, and it consists mainly of a high lipid content and considerable amounts of proteins, dietary fiber, and minerals, while it is a fruit that owns a relatively low content in carbohydrates [32,33]. C7 sugars, such as D-mannoheptulose and perseitol, were identified as the dominating sugars in specific avocado cultivars. These cultivars displayed higher quantities of C7 sugars rather than fructose and glucose and were associated with a sweet sensory attribute. Current studies suggest that C7 sugars play a significant role in carbohydrate storage and translocation in avocados [34]. Moreover, the most used part of the fruit, the pulp, has a low content of carbohydrates as shown in Table 1 (4.77–8.89 g/100 g), while avocado by-products have the highest content of carbohydrates (67.5 g/100 g).

Avocados are known to possess an extremely low glycemic index and load because of their low carbohydrate content. Such characteristics are associated with enhanced metabolic health, especially in terms of glycemic response. Numerous studies that have been conducted that show that avocado consumption improves weight management and metabolic health. Furthermore, the observed correlation between avocado intake and diabetes prevention in various studies could be ascribable to a plethora of possible causes, but mainly due to low levels of glucose and sucrose. In addition, avocado’s principal sugar known as D-mannoheptulose, which is a unique seven-carbon sugar, that could assist blood glucose regulation, could lead us to fully elucidate this fruit’s association to diabetes management and/or diminishment [35]. However, studies emphasize the significance of balancing lipids, sugars, and carbohydrates for avocados’ sensory flavor profile, a factor that should be taken into serious consideration beforehand [36].

3.1.2. Avocado Oil Composition

Currently available bibliography focuses on the oil composition of avocado owing to the technological convenience it provides. Avocado oil is usually extracted via various methods from the pulp of avocado fruit. Different approaches have noted inconsistent results regarding the chemical composition of the fruit after processing, a fact that implies that we should take more steps towards improving the efficacy of each method. Avocado oil’s versatile applications are nowadays gaining popularity, as this oil is used in many ways including functional foods, cosmetics, and product development [37]. More specifically, the principal fatty acids of avocado oil consist of oleic acid, a crucial omega-9 fatty acid, as well as linoleic acid, and palmitic acid. This oil contains α-tocopherols, which are strongly effective towards the prevention of free radical chain reactions and high levels of fat-soluble vitamins A and D [15]. Thus, all bioactives contained both in avocado and its oil are further thoroughly outlined below.

3.2. Avocado Bioactive Compounds

Bioactive compounds are traced in minuscule amounts in various plants and foods, including avocado, and are considered extra-nutritional constituents, some of which are tannins, carotenoids, fatty acids, polar lipids, and polyphenols, with an important biological role. These compounds may differ chemically and structurally, but their positive pharmacological effect categorizes them as functional compounds [38,39]. The importance of bioactive compounds not only “lies” in their ability to act as a protective agent but in their ability to do so without any additional side-effects, while reducing economic or environmental costs, especially when retrieved from the bio-wastes of avocado fruit, as a large quantity of these compounds is treated as waste by food industries, especially regarding the peel and seed part of the avocado, which account for the 15–16% of the whole avocado fruit [40,41]. Thus, the anti-inflammatory, antioxidant, anti-thrombotic, neuroprotective, and cardioprotective properties of these compounds from avocado and its by-products against inflammation-related chronic diseases are explored in this section (

Table 2. Proximate composition of phenolic and flavonoids compounds and the antioxidant capacity of avocado’s fruit, by-products, and oil *.

Phenolic and Flavonoids Compounds (GAE) *1	Avocado Fruit	Avocado By-Products
TPC	0.825–5.6	66.1–4.250
Chlorogenic acid	0–10.77	0–34.96
p-hydrobenzoic acid	18.25–25.34	0–11.19
Caffeic acid	4.63–10.19	0–4.53
Benzoic acid	-	128.51–147.73
Catechin	58.67–121.61	2.58–2.62
Epigallocatechin	-	0.82
Rutinoside–3–O–quercetin	-	0.35–0.45
Glycoside–3–O–kaempferol	-	0.87–0.93
Quercetin	5.06–8.84	2.72–2.9
Gallic acid	0.007–32.75	0.004–9.22
References	[26,42,43,44,45]	[26,31,42,45]
Antioxidant Capacity *	Avocado Fruit	Avocado By-Products
TAAc 2	0.24–0.27	22.01–63.54
ABTs 3	0.23–0.44	63.67–155.04
DPPH 4	0.09–0.58	94.56–182.66
FRAP 4	0.05–0.18	1.74–4.38
References	[26,46]	[47]

* Data are a combination of the presented references in the table above. ¹ Expressed in mg GAE g⁻¹ of FW, GAE: Gallic Acid Equivalent; ² Expressed as mg of Ascorbic Acid Equivalent g⁻¹ of FW; ³ Expressed as ABTs values; ⁴ Expressed as trolox equivalent values: TAAc: Total Antioxidant Activity; ABTs: 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid); DPPH: 2,2-diphenyl-1-picrylhydrazyl; FRAP: ferric-reducing antioxidant power assay.

and

Table 3. Composition of lipid bioactives, fatty acids, and lipophilic vitamins of avocado fruit and oil, and their processing by-products *.

Lipid Composition 1	Avocado Fruit	Avocado By-Products		Avocado Oil
Total lipids	15.04–18.61	0.38–1.595		99.88–99.89
Fatty acid Composition 1	Avocado fruit/pulp	Avocado by-products (s/p)		Avocado oil (g/100 g)
		(peel)	(seed)
SFA	19.55–24.89	17.27–25.198	16.88–34.99	12.54–30.51
UFA	61.94–80.12	66.43–82.508	56.539–95.28	53.18–76.86
MUFA	51.91–68.99	47.67–66.478	22.735–45.76	45.39–86.93
PUFA	10.03–20.06	10.97–27.48	30.4–49.52	7.05–67.95
Palmitic acid (16:0)	19.33–26.51	16.42–23.66	16.78–26.21	11.79–29.84
Stearic acid (18:0)	0.47–0.73	0.62–1.583	0.10–5.79	0.053–3.7
Cis-Oleic acid (18:1)	48.5–57.45	48.29–60.06	27.04–42.87	33.33–68.14
Linoleic acid (18:2)	11.12–19.04	10.97–24.84	22.21–39.12	7.05–17.15
Palmitoleic acid (16:1)	8.48–13.25	7.684–9.938	3.519–6.430	1.22–14.58
GLA (18:3 ω6)	9.57–19.2	16.93–27.04	10.97–43.05	-
ALA (18:3 ω3)	0.38–1.17	0.92–1.62	0.50–6.47	0.69–1.18
References	[27,42,43,48]	[42,43]		[15,49,50,51,52,53]
Vitamins Composition 1	Avocado fruit mg kg−1	Avocado by-products (mg/kg)		Avocado oil (mg/kg)
		(peel)	(seed)
a–carotene	- 2	2.7 (FW)	- 2	0.7–0.9(DW)
b-carotene (pro-vitamin A)	- 2	1.35 (FW)	- 2	0.7–0.9(DW)
Lutein	- 2	0.322–0.324	0.322–0.324	0.99–1.25(DW)
Total carotenoids	6.47–9.34 (FW)	13.50–17.90 (FW)	1.37–7.2 (FW)	15.21–32.78 (FW) 33.3–35.8 (DW)
α-tocopherols	17.31–58.07	30.32–777.8	301.7–309.1	86.13–885.4
β-tocopherols	- 2	- 2	- 2	2.44–126.5
γ-tocopherols	25.89–27.43	42.19–44.27	- 2	8.93–151.1
δ-tocopherols	6.28–6.86	78.04–769.7	709.4–721.6	26.03–110.3
Total tocopherols	55.34–59.48	2302.6–2310.4	662–1380	125.57–1273.3
References	[28,42,45,54]	[31,42,45,54,55,56]		[30,42,49,50,57,58,59] *
Vitamins composition 1	Avocado fruit	Avocado by-products(%/DW)		Avocado oil(mg/kg)
Tannins	-	0.15–0.17		-
References	-	[31]		-

* Data are a combination of the presented references in the table above. ¹ Estimates of typical gross composition (percentage weight) %. The data collected are a composition of different experimental conditions; in the case of a control sample, the values were extracted from it. Ripeness was not a parameter in the presented data while drying and extraction methods were. ² Research papers included in the reference do not differentiate between each compound and present the total content of each compound family.

).

3.2.1. Phenolic Content

Due to its ubiquity and wide accessibility, the Hass avocado variety has been widely researched for its antioxidant properties. These properties exist primarily because of the presence of phenolics and flavonoid acids, which consist of functional groups that exhibit eliminating actions on free radicals, enzyme inhibition or activation, metal chelating activities, modifications in gene expression patterns, and reactions with cell signaling pathways, in addition to various bioactivities, depending on the structure of each phenol [60]. Phenolic compounds are abundant in both avocado fruits and their by-products and have been associated with immunoregulatory functions, as well as preventive effects against a variety of diseases including diabetes, cancer, and neurodegenerative diseases [61,62,63,64,65]. The overall phenolic content identified in avocado fruit pomace ranges from 0.825 to 5.6 GAE as shown in Table 2, and in avocado oil, it ranges from 24.49 to 31.68 mg g⁻¹ DW [49]. Phenolic compounds exhibit properties that allow them to combat free radicals and, therefore, decrease degenerative diseases associated with oxidative stress, such as cardiovascular and neurological disorders or UV-induced skin aging. They are additionally acknowledged for their antifungal and antibacterial effects, especially against Gram-positive bacterial strains [60,62,64]. As a result, phenolic compounds are recognized as the primary kind of antioxidants that can neutralize free radicals by single electron transfer (SET) or hydrogen atom transfer (HAT). According to published research, the amount and arrangement of hydroxyl groups in phenolics compounds places a significant impact on avocado’s antioxidant activity [62].

At the same time, avocado industries face a huge issue in managing the large amount of generated waste, which consists of seeds and peels, representing 21–30% of the total raw material. These by-products are knowingly rich in polyphenols that can be utilized for diverse biological activities mainly because of their antibacterial, antimicrobial, anti-inflammatory, anticarcinogenic, epigenetic, and chemo-preventive properties [63]. In avocado’s by-product extracts, the total phenolic compounds that have been identified, as shown in Table 2, range from 4.250 to 66.1 mg g⁻¹. Some of the phenolic compounds identified in avocado’s by-product extracts are epicatechin, procyanidin B2, 5-O-caffeoyl-quinic acid, procyanidin B trimmers, kaempferol O-glucosyl rhamnoside, myricetin 3-rhamnoside, kaempferol, gallic acid, chlorogenic acid, p-hydrobenzoic acid, caffeic acid, benzoic acid, catechin, epigallocatechin, rutinoside-3-O-quercetin, glycoside-3-O-kaempferol, and quercetin [66]. Remarkably, the peel and seed of avocados contain higher concentrations of these phenolic compounds compared to the pulp, with the avocado peel extracts exceeding the phenolic quantities of the seed extracts. More particularly, seeds, except for their high starch content, also have a high polyphenol content, causing a bitter taste and harm if consumed in excess. Fruit peels, on the contrary, are valued for their profusion of polyphenols and antioxidants, which function as barriers to prevent oxidative stress caused by high temperatures and sunshine. [65]. Several studies in different varieties of P. americana leaf extracts have demonstrated strong antioxidant activity, while purified leaf extracts have a concentration-dependent antibacterial effect. Plant phenolics are primarily attached to plant cell walls, and their effectiveness depends on both availability and chemical composition. Fermentative bacteria in the human gut convert these dietary phenolics and, hence, improve absorption and regulate health-promoting properties [64]. Moreover, limited studies suggest that avocado by-products could produce phenolic-rich extracts with antiproliferative effects, which possess valuable prospects for cancer prevention and treatment. The peel of avocado extracts have been shown to induce apoptosis in MDA–MB–231 cells through promoting the activation of caspase 3 and its target protein PARP [62]. Consequently, these residues provide a low-cost source of phenolic acids and flavonoids via extracts that have substantial functional potential [62].

In avocado peel extracts, seed coat, and seed, 72 district compounds were identified. Peel extract have the greatest amount of compound variety, with 69 phenolics noted, followed by seed coat and seed extracts, both with 58 compounds. Among the seed coat and seed extracts, the first consists of higher amounts of trans-cinnamic acid derivatives. In the peel extract, epicatechin and type B procyanidin dimers are the prevalent flavonoids, while seed coat extracts consist of type B procyanidin dimers and trimmers, along with type A procyanidin dimers and trimmers. Sakuranetin and luteolin are the only flavonoids detected in greater quantities in seed extracts than in peel and seed coat extracts. In contrast, penstemide, a terpene, is detected in all the parts of avocado’s by-products. Notably, the seed, seed coat, and peel extracts contain a high concentration of feruloylquinic and caffeoylquinic acid, which are isomeric forms of chlorogenic and have antioxidant properties. Additionally, epicatechin and catechin derivatives, which include procyanidins, were the major flavonoids, with potential physiological properties that promote homeostasis. Penstemide, an isovaleroyl-type iridoid glucoside, which is found only in avocados, has been linked to a variety of health benefits including anti-inflammatory, hepatoprotective, and antidepressant properties. Phenolics compounds have also shown pro-oxidant effects, most notably in tumor cells, where they have been associated with pro-apoptotic activities [65]. The most important phenolic compounds are displayed in Figure 2.

3.2.2. Tannins

Tannins are a chemical family of compounds, mostly detected in some foods and plants. Tannins, especially the condensed type, are reported to have a correlation with possible antioxidant activities and beneficial health effects in humans. They are considered a sub-group of polyphenols because of the phenolic rings in their structure, which make them natural anti-oxidants that reduce CVD’s, diabetes, and cancer risks [67,68]. In the cultivars examined, the quantity of tannins ranged from 0.15 to 0.17%DW in seed and pulp samples, as reported in [31].

Green tea tannins are naturally occurring polyphenols that have significant radical scavenging properties, efficiently trapping and neutralizing free radicals without harming the skin. These properties make them ideal for skincare applications. Numerous studies that tested in vitro tannins/avocado oils, especially from avocado peel creams, identified UV protection, antifungal and antibacterial activity, and phytochemical characteristics, including spreadability, viscosity, and distribution of particles size. Green tea tannins of avocado such as epicatechin, catechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate are natural antioxidants and radical scavengers. These tannins stabilize radicals by delocalizing or terminating electrons, which increases their antioxidant activity. Notably, Epigallocatechin gallate (EGCG) has been found to increase the activity of ROS-scavenging enzymes. Green tea tannins, because of their biologically active flavan–3–ol groups, can operate as radical scavenging antioxidants, fighting photoaging and functioning as natural sunscreens against sunburns and wrinkles [69,70].

In addition, avocado seed extracts have been proven to reduce triglycerides, blood pressure, and glycemic levels, helping to prevent cardiovascular disease and lower cholesterol. They also possess antioxidant and antibacterial characteristics, which can be utilized in dermatology. Avocado seed oil, on the other hand, which is also high in antioxidants, has pharmacological benefits in preventing diseases, including hypertension, diabetes, hypercholesterolemia, and fatty liver disease, by lowering cardiometabolic risk and exhibiting hepatoprotective effects. All these advantages of avocado by-products are related to the presence of a variety of polyphenols, which include tannins like procyanidins and catechins, as well as hydroxybenzoic and hydroxycinnamic acid derivates, alkaloids, and flavonoids [70,71].

3.2.3. Carotenoids

Carotenoids and chlorophylls are the main pigments in avocado oils, with lutein and β-carotene being the most common carotenoids of the fruit and pheophytin a and b being the most common chlorophylls, respectively. The terpenoid pigments known as carotenoids range in color from yellow to orange-red and are produced by bacteria, fungi, and photosynthetic organisms. There are two groups of carotenoids: carotenes, which are just hydrocarbons and do not include oxygen, and xanthophylls, which do have the presence of oxygen. By scavenging and neutralizing free radicals, they can function as antioxidants [72]. Beyond their function as naturally occurring colors, carotenoids are beneficial to human health because they function as bioactive substances with provitamin-A properties (β-carotene and β-cryptoxanthin) and strong antioxidant activity. Similarly, chlorophylls possess antimutagenic and antioxidant properties in addition to being responsible for giving the green coloration, which aids the prevention of degenerative diseases. Notably, because carotenoids have a positive association with antioxidant activity, they can function as defenses against photosensitive oxidation [17,73,74,75,76,77,78].

Fruits and vegetables’ carotenoid content varies depending on ripeness, genetic diversity, and processing techniques [79]. In avocado seeds, the dried sample of the Hass variety had the highest total carotenoid concentration, with 6.47–9.34 mg/kg, as shown in Table 3, while the carotenoids found in avocado were mainly neoxanthin, violaxanthin, neochrome, 9″-cis-neoxanthin, lutein-5,6-epoxide, chrysanthemaxanthin, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, and β-carotene [15,80]. Xanthophylls lutein (all-trans-lutein), β-carotene, zeaxanthin, and cryptoxanthin make up about 90% of the carotenoids in avocado. Avocados provide an ideal dietary matrix for increasing zeaxanthin and lutein bioavailability, as these carotenoids are absorbed better when ingested with lipids and entire foods, rather than as supplements. Carotenoids are considered to linger within small intestinal enterocytes, until long-chain fatty acids become available to encapsulate and transfer them via the lymphatic system. Avocados serve an important function in stimulating chylomicron production and delivering lutein throughout the body, making them a good dietary option for increasing zeaxanthin and lutein intake, which improves cognitive health. Moreover, several studies have found a link between lutein and zeaxanthin consumption and beneficial cognitive profiles, particularly among people with obesity or those who are overweight [75,81].

In various studies [14,17,77,81], a randomized controlled trial was conducted so as to assess the effect of avocado consumption on cognition in older adults via the intake of a high-lutein-content food source. The results showed that avocado consumption significantly increased serum lutein levels and macular pigment optical density (MPOD) [77]. As result, individuals showed significant improvements in spatial working memory within three months. More particularly, a study by Edwards et al. [81] evaluated the effect of avocado consumption on cognitive function in overweight and obese adults using dietary intervention rather than supplementation. Participants aged 25–45 were randomly allocated to either a daily meal comprising fresh avocado or an isocaloric meal as a control for 12 weeks. The avocado group had substantially greater serum lutein levels and demonstrated improved accuracy in the Flanker task (measure of attentional inhibition). However, there was no significant association between cognitive enhancement and serum lutein levels, while there was also no difference in macular pigment optical density. The structures of the most vital carotenoid compounds present in avocado are illustrated in Figure 3.

3.2.4. Fatty Acids

Avocado is rich in several health-promoting fatty acids, including both the main categories of unsaturated fatty acids (UFAs), the polyunsaturated fatty acids (PUFAs) and the monounsaturated fatty acids (MUFAs) [82], with both types being reported to act against thrombogenesis and atherogenicity and to be protective agents in many diseases like CVDs, neurodegenerative disorders, and cancer [26,33,82]. Avocado’s content in fatty acids has been presented with a focus being on the amounts of omega-3 (ω-3) and omega-6 (ω-6) valuable PUFA, like the α-linoleic acid (ALA), eicosapentaenoic acid (EDA), and docosahexaenoic acid (DHA), since these PUFAs cannot be synthesized from the human body, suggesting that they can also be ingested by avocado fruit.

Avocado fruit is renowned for its oil extraction, which is high in lipids, especially monounsaturated fatty acids, with oleic acid being the prevalent [26,33,35,83,84,85,86,87,88]. Avocado oil’s health benefits are mostly due to its high quantity of monounsaturated fatty acids, phytosterols, and other bioactive substances with antioxidant effects. Despite the fact that saturated fatty acids like palmitic acid have various health effects, they also help to stabilize oxidation [33,89,90]. The avocado oil derived from ripe avocado pulp is highly valued for its food and cosmetic applications. It has a high concentration of oleic acid, a beneficial omega-9 fatty acid, as well as linoleic and palmitic acids. Additionally, it consists of α-tocopherol (a subset of lipid compounds, known as vitamin E) and the fat-soluble vitamins A and D. α-tocopherol, with a concentration ranging from 17.31 to 58.07 mg/kg as shown in Table 3, is a powerful antioxidant that prevents oxidative damage. Avocado oil’s omega-3 (ω-3), omega-6 (ω-6), and omega-9 (ω-9) fatty acids are important in eicosanoid signaling, while an optimal balance could reduce inflammatory risks linked with disorders like obesity [15,83,84]. When it comes to avocado by-products, as shown in Table 3, with a concentration of 27.04–60.06% of total fatty acids, oleic acid is also the major fatty acid in avocado seeds, followed by linoleic, stearic, palmitic, and arachidonic acids. Palmitic and stearic acids are the major saturated fatty acids identified, while linoleic and arachidonic are the major polyunsaturated fatty acids. While certain studies have shown variances in fatty acid composition, notably in the preponderance of specific acids, the overall profile highlights the richness of ω-6 fatty acids in seeds [26,33,83,84,85,86,87].

The lipid extract of avocado seeds comprises two types of lipids: long-chain fatty acids and fatty acid derivates, which are predominantly composed of unsaturated chains and saturated long-chain fatty acids. Avocatins and polyhydroxylated fatty alcohols are some of the major fatty acid derivatives. The long-chain fatty acids contained in avocado have been reported in several studies to have anticancer activities against colon cancer cell lines and are being considered as possible chemotherapy adjuvants. Numerous bioactive substances, especially long-chain lipid molecules such as avocatins and persenins, have been found to exhibit anti-cancer properties independently. This demonstrates the potential for natural chemical combinations to target therapeutic pathways and induce apoptosis in cancer cells [91]. More specifically, avocado seeds’ lipid extract inhibits fatty acid oxidation, increases reactive oxygen species (ROS) production, and induces caspase-dependent death in Caco-2 cells, as well as regulates inflammation related to cytokine release. Similar studies have discovered that avocado lipids include apoptosis in oral and breast cancer cells. More specifically, these extracts induce a decrease in the mitochondrial membrane potential in Caco-2 cells, resembling the actions of the derivates of avocado fatty acids in oral cancer cells [74,88,91]. The release of intracellular calcium from the endoplasmic reticulum may cause mitochondrial membrane depolarization, which facilitates the activation of pro-apoptotic proteins. Fatty acids, acting through G-protein coupled receptors, can cause calcium release, whilst acetogenins have been demonstrated to modulate cell cycle progression and cell death. However, in Caco-2 cells, lipid seed extracts did not affect intracellular calcium levels, presumably due to the short treatment period. Additionally, fatty acid binding proteins (FABPs) can impact the control of interleukin-6 (IL-6), which connects inflammation to metabolic problems and diseases [91].

The study by FD Krumreich et al. [33] examined avocado variety’s lipid profile, measuring atherogenic and thrombogenic indices to determine its potential contribution to the prevention of dyslipidemia. The connection between hypercholesterolemia and hypocholesterolemia was also examined with a focus on the function of fatty acid content. The ratio between hypocholesterolemic and hypercholesterolemic fatty acids (h/H ratio) that was measured reflected the functional activity of fatty acids in lipid metabolism and was critical for determining the risk of cardiovascular disease. Avocado was found to have a promising fatty acid content, with an h/H ratio that indicated possible heart health advantages, aligning with values associated with lower cardiovascular risk.

In [91], when Caco-2 cells were treated with the avocado seed lipid extract, the glycolytic rate decreased significantly in comparison to the positive control. Moreover, the effect of this extract on fatty acids oxidation (FAO) revealed a 45% reduction in cellular respiration, indicating FAO inhibition. These findings indicate that seed lipid extracts could impact cancer cell metabolism, impeding glycolysis and FAO processes. Limiting lipid metabolism, particularly FAO, has been suggested as a therapeutic method against cancer cells, since changes in mitochondria associated with lipid accumulation can affect cell proliferation. According to studies, inhibiting FAO might be a viable approach to colorectal cancer.

M. Lara-Márquez’s et al. [92] emphasized the connection between avocado consumption and improved glycemic control, especially in people with type II diabetes. This association might be attributable to bioactive chemicals found in avocados, such as the avocatin B lipid, which has been demonstrated in animal studies to improve glucose tolerance and lower insulin resistance. Furthermore, avocados’ high monounsaturated fatty acid (MUFA) content has been proposed as another possible reason for their positive benefits on glycemia, particularly in people who already have dysglycemia. Moreover, avocation-B (composed of avocadene and avocadyne) can improve glucose tolerance, regulation, and sensitivity to insulin [74,88,91].

Similar patterns were followed by S. V. Thompson et al. [87], where for over a duration of 12 weeks, the effects of avocado consumption on metabolite concentrations and fecal microbiota in adults who were overweight or obese were examined. Participants who continuously followed the avocado intervention had more diverse fecal microbiota and higher amounts of specific microbial metabolites, particularly acetate. Despite the consumption of greater total fat, the avocado group exhibited lower fecal bile acid contents, with substantial decreases in cholic and chenodeoxycholic acid. These changes could be connected to variations in the dietary fat content and consequent changes in fecal fatty acid and bile acid compositions. Notably, avocado consumption increased the number of Faecalibacterium and Lachnospira, both of which have been pointed out as health-promoting metabolic factors. Avocado consumption has been linked to many health advantages, including better lipid profiles and decreased obesity.

Potential advantages of avocado’s intake on insulin sensitivity were reported by X. Zhang’s et al. [93], which were connected to its combination of unsaturated fats and newly identified lipid compounds such as avocatin B (Avo-B). The observed decrease in hsCRP (high-sensitivity c-reactive protein) levels following avocado consumption, compared to the control intervention, suggests a possible connection between increased polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) intake and lower hsCRP levels. In particular, the avocado group’s increased MUFA and PUFA consumption could have changed plasma fatty acid profiles, which subsequently impacted inflammatory pathways.

Finally, G. James-Martin et al. [94] reported that avocado consumption has the potential to improve cardiovascular health due to its high content of unsaturated fats. Because of their beneficial effects on lipid profiles, it is proposed that one could substitute saturated fats with monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids, such as those found in avocado. According to this study, avocado consumers showed healthier overall diets that include fiber, MUFA, polyunsaturated fatty acids, minerals, and vitamins. In addition, avocado consumers had lower body mass index (BMI) and waist circumference than non-consumers.

4. Health-Promoting Effects of Avocado and Its Bioactives

4.1. Antioxidant Activity

Avocados are rich in antioxidative chemicals, which have scientifically been proven to have a positive impact on overall health and well-being. Remarkably, abundant polyphenol content—especially in terms of phenolic and tannin compounds—has a strong correlation with avocados’ antioxidant function. These polyphenols increase avocados’ total antioxidant activity, which raises their nutritional content and may hold positive effects on health. Knowing this relationship can help people make educated food decisions that promote general health and well-being, and avocado has been in the spotlight of research over the past few years [47]. A series of mechanisms underline polyphenols’ antioxidant qualities. In detail, the phenolic hydroxyl group can donate one hydrogen atom or an electron to the reactive oxygen species (ROS), which results in their decomposition. Also, the activity and synthesis of enzymes that are essential for neutralizing oxidants can be controlled from polyphenols. The main oxidase enzymes that are responsible for this are SOD1 and SOD2 because of their ability to convert superoxide into hydrogen peroxide. Afterward, CAT or GSH-Px deactivates hydrogen peroxide to produce water and oxygen. Moreover, in the Nrf2 pathway, Nrf2 is a transcriptional factor that regulates the expression of detoxifying enzymes like SOD, GPx1, NQO1, GST, and HO-1 and is in turn regulated by polyphenols via their binding to antioxidant response elements (AREs) in the promoter regions of enzyme genes. This process increases the antioxidant activity of cells. Resveratrol has the ability to break down the Nrf2-Keap complex in the cytosol, which permits Nrf2 to go into the nucleus and attach itself to the 5ʹ-promoter region of NQO1 that contains AREs, thus activating transcription [95].

The quantification of antioxidant activity (AA) can be achieved with a series of tests. The DPPH free radical is a long-lived organic nitrogen radical with a deep purple color, while when a DPPH solution is mixed with an antioxidant, its color turns from purple to yellow of the corresponding hydrazine, and, thus, the reducing ability of antioxidants toward DPPH is usually evaluated by monitoring the decrease in its absorbance at 515–528 nm, with the results usually expressed as half the maximum inhibitory concentration (IC50 value) or as a % scavenging of DPPH^• at a fixed antioxidant concentration for all the tested compounds, or even as Trolox equivalent antioxidant capacity (TEAC) after normalizing with the respective Trolox equivalent IC50 value [96]. Many studies have utilized the in vitro assay to investigate and validate the antioxidant properties of avocado fruit [18,46,47,64,71,79,97,98,99,100,101,102,103,104]. Moreover, the reduction of ferric-tripyridyltriazine to a unique blue ferrous-tripyridyltriazine complex that displays a noticeable absorption peak at 593 nm is a common step in the FRAP assay that is utilized to evaluate antioxidant activity [105]. This assay has proven to be useful in determining the antioxidant capacity of different avocado constituents [18,46,47,63,64,71,98,99,100,102]. In order to validate the statements made about avocados’ antioxidant activity (AA), further tests such as ABTS ([18,46,47,63,100,101]), RPA ([46,47,99]), TAC ([46,47]), OH—RSA ([46,47,99]), FICA ([46,47]) were conducted. These studies contributed to our full understanding of the health benefits of avocados by shedding more light on the antioxidant potential of various avocado segments, as displayed in Table 2.

4.2. Anti-Inflammatory Activity

The Persea Americana fruit is reported to have anti-inflammatory effects both through in vivo and in vitro experiments. The existence of phenolics, tannins, and carotenoids is strongly linked to the anti-inflammatory characteristic of avocado fruit [106]. Inflammation is the product of a response from the human body when its homeostasis and normal function are disrupted by an irregularity, namely, pathogens, wounds, injuries, and allergies. Chronic inflammation is linked to several serious diseases including cancer, CVDs, and thrombosis [107]. In the event of such a response, chemical mediators called chemokines, cytokines, eicosanoids, and vasoactive amines are triggered, signaling the human defense system to start combating the issue. In this process, some mediators cause collateral damage in the organism, leading to the prementioned diseases.

In an in vivo study on rats [108], a correlation between lowering intestinal inflammation effects and avocado fruit pulp without unwanted side effects was reported. By introducing a rising quantity of avocado fruit pulp to the rats before the TNBS induced inflammation, a significantly milder response from cytokines, precisely interleukin-1β (IL-1Β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), which caused the observed inflammation. Specifically, a 20% dietary interference with avocado pulp reduced IL-1Β and IFN-γ by 53.7% and 41.38%, respectively.

Another previously conducted study by D. F. Elmaghraby et al. [109] on ovariectomized rats found that avocado bioactive constitutes, such as oleic acid and phenolics, mimic the effect of estrogens, which suppress the inflammatory mediators of IL-6 and TNF-α in the liver. An administration of 1 mL/250 g/day of Persea americana for one month reduced the value of these mediators by threefold. This observation is due to the fact that phytosterols like β-sitosterol, which is considered a polyphenolic, are structurally similar to estrogen.

R. Goudarzi et al. [110] reported that avocado soy unsaponifiables (ASU) showed beneficial effects against neuroinflammation. The study, after inflicting an artificial stroke on mice through the permanently double ligations of the right common carotid artery, examined values and mechanisms that differed from the control group. In detail, they found that post-op tests that examined depression in rodents had better results if they were treated with ASU. The mechanism proposed was that ASU significantly lowered the IL-10 (Interleukin 10) and TNF-α expressions in the hippocampal region by 35% with an oral dose of 50 mg/kg per day, meaning that ASU can provide us with a neuroprotective, anti-inflammatory, and antioxidant role.

Additionally, there is evidence that P. americana extracts provide beneficial effects in regulating inflammatory responses caused by diseases, particularly coccidiosis. Jumping on that hypothesis, T. Al–Otaibi et al. [111] examined and assessed the benefits of a plant-based treatment as opposed to synthetic anticoccidial drugs in affected mice. The study design allowed for the comparison between the non-treated, plant-treated, and drug-treated mice by three tests. Firstly, a parasitic score and a goblet cell response; secondly, an antioxidant activity test; and lastly, a quantitative real-time polymerase chain reaction. This research study concluded that animals treated with PAFE (P. americana fruit extract) had more goblet cells than untreated mice, while significantly upkeeping glutathione levels. At the same time, the antioxidant agents in the avocado could reduce the levels of MDA (lipid peroxidation) and NO (nitric oxide), which cause oxidative stress damage. In the last test, after the infection-induced augmentation in inflammatory cytokines, PAFE showed downregulation in the expression of IL-1β, TNF-α, and IFN-γ. These test results, with a dosage of 500 mg kg⁻¹, decreased by 85.41% the number of oocysts in the feces of mice and gravitated towards the fact that avocado fruit plays a serious antioxidant, anticoccidial, and anti-inflammatory role.

A huge and important role of the anti-inflammatory bioactives of avocado is to prevent inflammation-induced cancer, namely, (DEN)/2—acetylaminofluorene (2AAF)-induced hepatocarcinogenesis [112]. In this study, a group of rats were treated with avocado seeds and avocado fruit extract and went through many tests. One test was the determination of enzymes that show liver functionality and cancer marker assessments, namely, ALP (Alkaline Phosphatase), GGT (Gamma—Glutamyl Transferase), ALT (Alanine Aminotransferase), and bilirubin levels. Activities of such markers were elevated in comparison to the control group while the avocado-treated mice had a downward trend with regard to them, while serum protein levels increased. In addition to that, this treatment downregulated the increase in the serum compounds, AFP (Alpha-Fetoprotein), CEA (Carcinoembryonic Antigen), CA19.9 (Carbohydrate Antigen 19-9), and miR-122 (microRNA-122), in contrast to the untreated group, while LPO levels decreased and GSH (glutathione) levels increased. Lastly, inflammation markers were lowered through the reduction of COX-2, NF-κB, and Ki-67, which are linked to inflammation. This study also concluded that p53 and BAX levels increased, meaning that apoptosis pathways were enabled to maintain tissue homeostasis.

In addition, another study by T. M. K. Motawi et al. [113] examined an agent used to treat cancer as it counteracts human tumors and autoimmune diseases but, unfortunately, with unwanted side effects. By examining the pharmacokinetics of Cyclophosphamide (CPA), this study established that its products inside the human body disrupt homeostasis and induce toxicity in urological and pulmonary systems as they instigate fibrosis, necrosis, hemorrhagic cystitis, and peroxidative damage. Three groups of mice control, CPA-treated and CPA + AE-treated, were studied with reference to several biochemical and enzymatic parameters. In more detail, it is speculated that administering AE helped keep Glutathione S-transferase (GST) levels at an adequate level via augmenting the activity of regulative enzymes of oxidative stress. In addition, avocado constituents such as persin, acetogenins, persenone A, carotenoids, and vitamin E, are reported to prevent oxidative damage in tissues by suppressing CYP2B6-mediated CPA metabolism. It is reported that the main mechanism proposed for inflammatory protection is the inhibition of myeloperoxidase (MPO) by avocado acetone extract acetogenins.

A. H. Elosaily et al. [25] studied the determination of the anti-inflammatory effect of avocado in carrageenan-induced edema in rats. The outcome of the study was attributed to the content of the avocado cultivars that contain certain bioactives such as β-sitosterol, α-tocopherol, and palmitoleic acid, which possess an anti-inflammatory activity. It is speculated that avocado oil interacts with COX-2 enzymes. In the end, the study pointed out a clear relationship between edema reduction and avocado oil dosage. Both oils with a dosage of 15 mg/kg had a similar inhibition in the rat paw edema of 35%.

4.3. Cardiovascular Diseases

Poor nutrition and excess weight are common risk factors for noncommunicable illness, such as cardiovascular disease (CVD), which impacts millions of people globally. Avocado intake, high in unsaturated fatty acids, can reduce modifiable dietary risk factors for CVD by substituting saturated fats with monounsaturated fatty acids [94].

According to studies, avocado consumers follow better diets, with greater intakes of fiber, vitamins, minerals, MUFA, and PUFA, as well as exhibit a lower BMI and waist circumference than non-consumers. However, systematic reviews have shown inconsistent results regarding the impact of avocado intake on blood lipids. Some studies show a decrease in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides, while others show insignificant alterations in TC, LDL-C, and triglyceride concentrations, but an increase in high-density lipoprotein cholesterol (HDL-C) [94].

A follow–up study to an experiment on an avocado per day as a usual habitual diet was conducted so as to determine if consuming one avocado per day for six months results in an improvement in visceral adiposity, rather than consuming fewer avocados per month. This study displayed high potential as a rigorous assessment of the prospective health advantages of avocado intake on cardiometabolic risk factors, lower fat, and overall diet quality. Given the prevalence of obesity and health-related concerns, such as CVD and diabetes diseases, finding effective nutritional therapies is critical. These studies’ strengths include their large randomized controlled design, high recruitment and retention rates, and the application of a multi–center method, which improves their external validity. Despite the limitations caused by the COVID-19 epidemic, the study aimed to document any changes in dietary habits and identify the connection between avocado consumption, visceral adiposity, and cardiometabolic disease risk. In addition, the trial findings have the potential to influence individuals about the limitation of the high risk of cardiometabolic disorders via the consumption of one avocado per day [114].

In recent studies, researchers investigated the effect of three dosages of herbs and spices, including avocado, on gut bacterial composition in individuals who followed an average American diet, regarding the risk for cardiovascular disease. Such studies claimed that consuming culinary amounts of those herbs and spices as part of a consistent background diet resulted in changes in gut bacterial composition. The diversity and taxonomic enrichment of gut bacteria differed across the low-, medium-, and high-spice dosages as compared to the baseline. Moreover, it was found that consuming avocado resulted in decreased levels of bile acids, notably chenodeoxycholic and cholic acids. These findings emphasized the complex connections between gut and host bacteria, which are impacted by the nutrients of certain diets. Hence, it was concluded that including avocado into a diet may affect the gut bacteria composition, which allowed the development of a panel of fecal bacteria biomarkers indicating food constitution [115,116].

Following this train of thought, more trial studies proved that both vegan and vegetarian diets that include avocado consumption have significantly reduced CVD risk factors that promote type 2 diabetes, as well as indicators like high-sensitivity C-reactive protein and IL-6. A vegan diet’s advantages are most likely due to its ideal macro- and micronutrient composition, which contains lower dietary cholesterol and saturated fats and lower total caloric intake. Moreover, the reduced amounts of carnitine and choline in vegan diets leads to decreased levels of proatherogenic-N-oxide (TMAO), which is related to CVD morbidity and death. A vegan diet comprising of avocado may initiate adverse cardiovascular consequences, like an increased risk of ischemic stroke, due to reduced intakes of key nutrients such as amino acids, which dietary fortification can reduce [117,118,119].

In general, avocados high in saturated fat and fiber have been investigated in clinical studies for their possible impact on metabolic diseases. Individuals’ reactions to avocado consumption vary, possibly due to genetic variances. According to research, avocado may help control dyslipidemia in individuals who are overweight or obese but can be influenced by different genetic profiles. Avocado components, such as monounsaturated fatty acids and soluble fiber, have separately been found to improve blood lipid profiles. Clinical trials have shown that avocados have varying impacts on lipid outcomes, commenting on the comparison diet and the individuals’ baseline metabolic health [120].

Last but not least, MacKenzie K. Senn and X. Zhang et al., respectively [91,92], by studying avocado consumption in overweight or obese people with insulin resistance, observed promising effects on glucose management and cardiometabolic risk factors after 12 weeks. Participants who replaced carbohydrate energy with avocado energy reported improved dietary patterns and tendencies toward better glucose management and lower indicators of cardiometabolic risk. Avocado consumption led to lower levels of high-sensitivity C-reactive protein (hsCRP), a marker of inflammation linked to chronic disorders such as CVD and obesity. Avocados are reported to contain high concentrations of MUFA and PUFA, which can alter inflammatory pathways. In addition, including fresh avocado in the diet may improve metabolic health and help people fulfill dietary requirements of essential nutrients like folate, potassium, and fiber.

4.4. Benefits against Neurodegenerative Disorders

In the reviewed literature, many studies and clinical trials exhibited a connection between avocado fruit and neuroprotection. By an in-silico approach, S. Angum et al. evaluated the positive health effects of avocado against Cadmium-induced toxicity. Cadmium interferes with the proper functioning of cells by disrupting cellular redox balance, causing apoptosis, and leading to hepatocellular damage, neurotoxicity, pulmonary edema, cancer, and cardiac and neurodegenerative diseases. It was observed that avocado juice treatment successfully reduced Cd accumulation and lipid peroxidation in the liver, kidney, and hippocampal tissues, while it beneficially upregulated the expression of the genes for important antioxidant enzymes, such as the SOD (Superoxide Dismutase), CAT (Catalase), and GPx (Glutathione Peroxidase), and it also showed considerable active potential for improving memory and learning. These results suggest that a diet containing papaya and avocado can help treat the lethal effects caused by Cd due to the beneficial effects of their bioactives that can improve health at the cellular and molecular levels [121]. Moreover, an in vivo study of the neuroprotective effects of P. americana extracts based on a D. melanogaster model was followed by G. G. da Silva et al. [122]. The flies after a rotenone-induced neurotoxicity had their survival rate evaluated. It was found that seed extracts, in comparison with peel extracts, had a much more significant result in preventing neurodegenerative diseases. In conclusion, introducing a flavonoid- and polyketides-rich diet through avocado extracts showed both a preventive and a therapeutic role, while the preventive approach exhibited a better survival rate.

To continue, the effects of P. Americana in rats with AlCl₃-induced Alzheimer’s were thoroughly examined [123]. Many parameters were tested, and it was found that avocado can treat neurological damage. In more detail, xanthophylls and flavonoids, constituents of avocado, are proposed to possess antioxidant and DNA-protective capabilities. In addition to that, ellagic acid is a tannin that can protect the membrane of the cell by binding into it and preventing cell death, apoptosis, DNA fragmentation, and oxidative stress. Another mechanism of neuroprotection was tested by a decrease in caspase 3 levels that induce apoptosis and upregulation of dopamine, an important parameter of the pathogenically physis of Alzheimer’s, by omega-3 fatty acids [123]. At the same time, in a recently published in vitro study, neuroprotective and antioxidant activities of avocados were also suggested. In this case, a rich-in-phenolics extract derived by a pressurized liquid extraction process with an environmental-friendly practice exhibited a strong antioxidant capacity of 3350 µmol Trolox equivalent/g dry extract and 0.14 µg/mL in both ABTS and ORAC assay procedures, respectively, which also suggested antioxidant neuroprotection [124]. Prior to that, a clinical trial on adults who were introduced to an avocado diet showed no correlation between avocado consumption and cognitive function except an increase in serum lutein concentration in the order of 33% after testing in comparison to the control group which was given daily avocado intake for 12 weeks. In the end, the increased lutein is uncorrelated with cognitive ability [81].

One group of researchers, J. R. Motta et al. [125], proposed that avocado oil could protect neuro cells that are damaged by oxidative stress. This protective effect is attributed to PUFA like omega-3, which can decrease risk factors in neurodegenerative disorders. This in vitro experiment examined oxidative and apoptotic markers while focusing on the toxic effect of hydrocortisone in neuroblastoma cells (SH-SY5Y). The antioxidant effect of the avocado oil (AO) increased BDNF (Brain-Derived Neurotrophic Factor) by 28% in the 5 μg/mL dosage, which is important for brain development. Similarly, AO prevented the oxidation of DNA and had a diverse result in oxidative stress markers. Higher levels of NO, LPX, and PCAR and lower levels of ROS were observed and, thus, AO had an influence on the modulation of oxidation pathways.

Finally, the circle of reviewed trials ends with an examination of the ability of phenolic extracts of an avocado peel to prevent neurodegeneration by neurotoxins like paraquat and maneb. These chemicals are linked to the induction of apoptosis in neuronal-like cells and the upregulation of certain apoptotic proteins (DJ-1, PUMA, CASP-3, LRRK2 kinase), while avocado peel extracts disrupt the oxidation mechanism. In detail, it prohibits the phosphorylation of the LRRK2 kinase that dictates the apoptosis pathways by blocking the damage from the oxidative stress [126].

A synopsis of the individual revised parts, as well as the most important properties each part is connected with, is displayed in Figure 4.

5. Applications

5.1. Functional Foods

Functional foods are considered as products of which at least one compound has been added in order to obtain enhanced nutritional value. Avocado fruit has been examined in how it influences numerous of products such as bread and yogurt.

A research based on bread showed that the enrichment with 5%, 10%, 15%, 20%, and 25% avocado pulp powder (APP) has an important nutritional impact. As the APP’s concentration increases in the final product, the protein amount and phenolic and antioxidant activities follow suit. The main observation in the 25% addition is that carbohydrates and lipids are replaced by APP and a significant increase in phenolic content and antioxidant activity, which could be theorized as a healthier substitute [127]. Similar findings were exported from an experiment of producing cookies enriched with avocado puree instead of butter. The 100% substitution of butter by avocado puree was ranked top overall across all examined measurements. The final functional food also had better bulk density of wheat flour, swelling index, and oil absorption capacity [128].

Another research that focuses on the enrichment of bread with avocado waste powder (AWP) showed that there is a positive correlation between the concentration of AWP and antioxidant activity. Larger amounts of AWP in the bread result in greater antioxidant content.

In particular, bread enriched with 5% w/w with AWP showed a tremendous increase in the Total Phenolic Content (TPC), which is interlinked with the antioxidant activity. The scale of the increase is 675% in relation to the control bread. The experimental 10% w/w with AWP bread did not follow the double size of TPC but had a minor change of 3.69% in comparison to the 5% w/w AWP bread. These results reveal that a minimum quantity of AWP has a major increase in the antioxidant content of the product [129].

Similarly, a research based on the seed of avocado tried to figure out how this waste as powder could be beneficial in stirred yogurt. The 1%, 2%, and 3% addition of nano-avocado seed powder (nano-ASP) constituted correspondingly to an increase in ash, carbohydrate, and crude fiber, as well as a noteworthy supply of polyphenols, with reasonable antioxidant activity, which aided in the growth of some probiotic strains and regulated their antibacterial action against certain infections. One extra benefit which highlights the nutritional impact of nano-ASP is that it provides a good source of minerals (K, P, Ca, and Mg) and crude fibers [130].

A study conducted to define the freeze-dried avocado seed powder as a source of fiber in designed snacks led to extremely positive findings. When the snack was enriched with 6%, 12%, and 18% of this powder, there was observed a rise in fiber concentration (54%, 109%, 163%) and polyphenolic content (382%, 891%, 1247%) accordingly. This increase of phenolic compounds is responsible for the enhanced antioxidant activity (273%, 625%, 881%), and for this reason, avocado seed powder could be indicated as a supplement of wheat flour for several snacks such as cereal products [31]. Concordantly, research where the insertion of ASP in beverages was examined-showed that polyphenols do not have the same stability in different conditions. The most efficient environment consists of pH 5.5 and a dark storage spot. In the same study, scientists reported the fact that baked products enriched with ASP due to high temperatures lost approximately 85% of the total phenolic compounds because of their denaturation [131].

Other researchers investigated a technical way of producing yogurts fortified with avocado oil in order to obtain a balanced ratio of saturated/unsaturated fatty acids in the final product. This attempt was judged applicable because the entire procedure of inserting the avocado oil into the yogurt did not modify the important fatty acids of the oil. In this way, they maintained their capability through the boosted nutritional profile to decrease Atherogenic Index (AI) and Thrombogenic Index (TI) [132].

Lastly, the sustainability of inserting 0.5% and 1% avocado peel extract in mayonnaise as a substitute for synthetic preservatives was examined. The results showed that the physiochemical properties of the final product remained immutable during its storage time, and that antimicrobial and antioxidant factors operated at an equivalent level in relation to the synthetic ones. The only drawback of this fortification was the slight number of discrepancy of sensory parameters between control and modified samples [62,133]. All applications of avocado pomace or recovered functional compounds as ingredients in functional foods are analyzed in

Table 4. Applications of avocado pomace or recovered functional compounds as ingredients in functional foods.

Functional Food	Bio-Functional Ingredients	Amount	Aims	Results	References
Bread	Avocado Pulp Powder	5–25%	➢ Physicochemical and nutritional evaluation	Increase in APP’s concentration favors protein, phenolic, and antioxidant profiles	[127]
				Capacity for carbohydrates and lipids substitution
	Avocado Waste Powder	5%	➢ Nutritional and sensory evaluation	Significant increase in TPC (675% to the control) and antioxidant profiles	[129]
Cookies	Avocado Puree	25%, 50%, 75% 100%	➢ Quality and sensory evaluation	Enhancement of bulk density of wheat flour, swelling index, and oil absorption capacity	[128]
	Avocado Seed Powder	6%, 12%, 18%	➢ Physicochemical evaluation, chemical composition	Five-fold increase in phenolic content and four-fold increase in antioxidant profile, compared to the control	[31]
				Capacity for wheat flour supplementation
Yogurt	Nano-Avocado Seed Powder	1.0, 2.0, and 3.0%	➢ Physicochemical, sensory, and antimicrobial evaluation	Showcasing phenolic and mineral contents and antioxidant activity	[130]
				Supporting probiotic action, aiding against infections
	Avocado Oil	n.d. *	➢ Nutritional balancing of end product	The balanced ratio of unsaturated/saturated fatty acids decreases both Atherogenic Index (AI) and Thrombogenic Index (TI)	[132]
Beverages	Avocado Seed Powder Extract	n.d.	➢ Shelf-life evaluation	Protection of phenolic profile higher in pH = 5.5 and refrigerated conditions	[131]
Baked Products	Avocado Seed Powder	15, 30, or 50%	➢ Nutritional and sensory evaluation	Loss of phenolic content due to high temperatures
Mayonnaise	Avocado Peel Extract	0.5% and 1.0% of extract	➢ Physicochemical, sensory, antioxidant, and antimicrobial evaluation	Reciprocation of desired stability and antimicrobial and antioxidant profiles	[133]
				Sensory differentiation between modified samples and control
Pork sausages	Avocado Waste Water Powder	0.2%	➢ Chemical and proximate evaluation	Inhibition of lipid oxidation Equal antioxidant capacity compared to sodium erythorbate (E316)	[65]

* n.d. = not defined.

.

5.2. Cosmetics

Customers’ preferences for sustainable and natural components in cosmetics have grown in the last few years. The cosmetic industry is paying more and more attention to avocados, which are well-known for their nutritional advantages, because of their ability to improve the appearance and health of the skin. Avocados and their by-products have a rich composition of bioactive substances that constitute a great opportunity for the formulation of cosmetics with many advantages. The fruit, with its abundance of antioxidant and anti-inflammatory properties, is a perfect fit for this trend. Because of its capacity to fight oxidative stress, lessen inflammation, and supply vital nutrients for skin nourishment, it is effective in promoting skin health.

Exposures to various external factors such as solar radiation from the ultraviolet [UV], visible light, infrared [IR] wavelengths, pollution from the environment, and smoke, as well as internal factors like eating, drinking, stress, and lack of sleep, can cause oxidative stress by producing free radicals (ROS), (RNS), (RCS).

Matrix Metalloproteinases (MMPs) are enzymes that break down molecules like collagen, elastin, and hyaluronic acid, which make up the extracellular matrix (ECM) in the dermis and can be activated by free radicals [134]. Recent scientific investigations, including in vivo and ex vivo experiments, have demonstrated that the addition of (8–10%) avocado oil to cosmetic formulas greatly increases the formation of vital skin proteins like collagen and elastin fibers, while also improving the moisture content of the skin. As a consequence, these advantageous outcomes result in increased skin hydration, successfully averting problems like dryness and chapped lips, and diminishing the apparent indications of aging, particularly wrinkles. The major components of avocado oil that contribute to these amazing skin benefits include vitamin A, which is essential for the formation of collagen. Additionally, the abundance of polyphenols in avocado oil serves as a barrier against matrix metalloproteinases (MMPs), which are enzymes that break down collagen, keeping skin firm and supple over time. In summary, avocado oil’s exceptional qualities support a holistic approach to skin care by successfully addressing issues with moisture and anti-aging [135,136,137,138].

Other studies that delved into the various benefits of avocado extract when incorporated into skincare products unveiled a plethora of fascinating findings. First of all, it was found that avocado extract has skin-rejuvenating qualities. It not only improves skin moisture, but also greatly accelerates the creation and growth of the epithelial tissue. This leads to a noticeable enhancement of the skin’s general appearance, which is crucial for fortifying the body’s natural epidermal barrier. Moreover, research has revealed avocado extract’s other beneficial qualities, in addition to its beauty benefits. Its remarkable antibacterial and anti-inflammatory properties have been helpful in the treatment of infections and skin wounds [135,139]. Furthermore, the extract’s potential to help speed up wound healing is demonstrated by its capacity to reduce bleeding, mature scar tissue, and stimulate collagen synthesis. In summary, avocado extract’s complex qualities make it an intriguing component with a range of advantages for skincare formulas, providing a comprehensive strategy for promoting and preserving skin health and vitality (2% addition of avocado oil) [135,136,140]. The fatty acid content of avocado contributes to its positive effect on the skin. They have well-known roles in energy production and storage, as well as in the synthesis of membrane lipid bilayers, but they also play important roles in other aspects of epidermal function. First, the permeability barrier depends on fatty acids and ceramides, one of the complex lipids made from fatty acids. Second, the complex lipids in sebum—which is secreted by sebaceous glands—are constructed by fatty acids. Thirdly, fatty acids are crucial for keratinocyte signaling that control epidermal homeostasis. Fatty acids, for instance, have the ability to bind to peroxisome proliferator-activated receptors, which enhances the permeability barrier and encourages keratinocyte development. Furthermore, they can alter skin signaling molecules. For example, they can control hair follicle development and epidermal homeostasis by palmitoylation proteins [141].

Beyond just directly benefitting the skin, avocado’s bioactive components extend their effects through antibacterial, anti-inflammatory, and antioxidant properties, making them a versatile ingredient for overall skin health, protection against external aggressors, and preservative agents. The preservation qualities of avocados help skincare products last longer, maintaining their stability and effectiveness over time (0.5% addition of avocado oil) [139,142]. All activities of avocado’s bio-functional ingredients and their applications in cosmetic uses are summarized in

Table 5. Activities of avocado’s bio-functional ingredients and their applications in cosmetic uses.

Bio-Functional Ingredients	Activity	Application	References
Avocado Oil	Increase in collagen synthesis, reduction in the number of inflammatory cells, accelerating coagulation and regeneration of epithelium	Wound healing	[135]
	Reduction in wound area compared to control group
Avocado oil	One-grade improvement in GIAS (Global Aesthetic Improvement Scale) in 30% and 45% of participants after 6 and 12 weeks, respectively	Anti-wrinkle cream	[136]
	Significant increase in net elasticity (R5) and gross elasticity (R2) after 12 weeks
Avocado oil	Improvement in skin barrier function	Two cosmetic creams for restoring the epidermal barrier	[140]
	Increase in hydration level and transepidermal water loss (TEWL)
Avocado Peel Extracts	Antioxidant and antibacterial agents	Moisturing cream formulations	[139]
	Capacity of integration in both oil-in-water and water-in-oil formulations
	Substitution potential of synthetic preservatives
Avocado leaf essential oils	Moderate antibacterial and antioxidative action	Active ingredient in cosmetics	[142]
	Potential source of bioactive phytochemicals for medical and cosmetic use
Avocado seed oil	Potential moisture-increase properties via unsaturated fatty acids profile	Lip balm	[137]
Avocado oil	Lowest peroxide and IC50 value and highest antioxidative activity in this study	Nano-emulsions	[138]
	Moderate anti-aging activity
	Formulation achieved small droplet size and high zeta potential
Avocado oil	Possible increase of structure in the system with an oily phase of vegetable oil	Conditioners	[143]
Avocado bio-oil (HTC-derived)	Constitution of ethanolic extracts and liquid phase with the highest antioxidant ability	Sustainable cosmeceuticals	[144]
	Higher inhibition effect on tyrosinase and elastase activities in its heavy bio-oils than the control
	Capacity for hyperpigmentation and skin flaccidity management
Avocado leaf extract	Formulated gel (3% ALE) prevented the UVB irradiation-induced mechanical allodynia after the 2nd and 3rd day post irradiation.	Post-sunburn pain relief	[145]

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6. Conclusions

This appraisal of the nutrition composition and bioactive potential of avocado fruit and its by-products is, in fact, comprehensive and incisive, since it has pointed out their anti-inflammatory, antioxidant, antithrombotic, and anticancer activities. This paper articulates the bioactive applications in the formulations of the products industries: food sector, nutraceuticals, cosmeceuticals, and pharmaceuticals, thus presenting their contribution in the present scenario of the world health of consumers and the cure for non-communicable diseases. The other green issues like the environmental and economic benefits of reusing avocado’s by-products and their connection with the sustainability concept and circular economy are also reviewed in this article. This review likewise underscores the potential of avocado’s by-products in various sectors of the health care industry in a thorough manner.

Avocado fruit, rich in bioactive compounds such as carotenoids, tocopherols, polyphenols, and unsaturated fatty acids, offers substantial health benefits, including antitumor, anti-inflammatory, and anti-oxidative effects. Its consumption can mitigate oxidative stress and chronic inflammation conditions linked to diseases like atherosclerosis and cancer. Beyond their dietary advantages, avocados’ by-products, particularly the peel and seed, hold untapped potential in various industries. These by-products contain valuable nutrients and bioactive compounds, enabling their use in cosmetics, nutraceuticals, supplements, and even in nano-emulsions. Even though avocado’s bioactives are rather promising health-promoting agents, studies on their recovery, feasibility, and application in cosmetics are scarce. The anti-aging and anti-inflammatory properties of the by-products of avocado’s bioactives are the key factors for its application in cosmetics, pharmaceuticals, and nutraceuticals, with the aim of improving skin protection and skin care health. This multifaced utility not only enhances the sustainability of avocado production but also supports economic growth by expanding applications in several health sectors. The exploration of these bioactive compounds and their mechanisms continues to open new avenues for research and development, emphasizing the avocados’ broad-ranging benefits and applications.