Actinidia arguta (Sieb. et Zucc.) Planch. ex Miq.: A Review of Phytochemistry and Pharmacology

Actinidia arguta (Siebold & Zucc.) Planch ex Miq. (A. arguta) is a highly valued vine plant belonging to the Actinidia lindl genus. It is extensively utilized for its edible and medicinal properties. The various parts of A. arguta serve diverse purposes. The fruit is rich in vitamins, amino acids, and vitamin C, making it a nutritious and flavorful raw material for producing jam, canned food, and wine. The flowers yield volatile oils suitable for essential oil extraction. The leaves contain phenolic compounds and can be used for tea production. Additionally, the roots, stems, and leaves of A. arguta possess significant medicinal value, as they contain a wide array of active ingredients that exert multiple pharmacological and therapeutic effects. These effects include quenching thirst, relieving heat, stopping bleeding, promoting blood circulation, reducing swelling, dispelling wind, and alleviating dampness. Comprehensive information on A. arguta was collected from scientific databases covering the period from 1970 to 2023. The databases used for this review included Web of Science, PubMed, ProQuest, and CNKI. The objective of this review was to provide a detailed explanation of A. arguta from multiple perspectives, such as phytochemistry and pharmacological effects. By doing so, it aimed to establish a solid foundation and propose new research ideas for further exploration of the plant’s potential applications and industrial development. To date, a total of 539 compounds have been isolated and identified from A. arguta. These compounds include terpenoids, flavonoids, phenolics, phenylpropanoids, lignin, organic acids, volatile components, alkanes, coumarins, anthraquinones, alkaloids, polysaccharides, and inorganic elements. Flavonoids, phenolics, alkaloids, and polysaccharides are the key bioactive constituents of A. arguta. Moreover, phenolics and flavonoids in A. arguta exhibit remarkable antioxidant, anti-inflammatory, and anti-tumor properties. Additionally, they show promising potential in improving glucose metabolism, combating aging, reducing fatigue, and regulating the immune system. While some fundamental studies on A. arguta have been conducted, further research is necessary to enhance our understanding of its mechanism of action, quality evaluation, and compatibility mechanisms. A more comprehensive investigation is highly warranted to explore the mechanism of action and expand the range of drug resources associated with A. arguta. This will contribute to the current hot topics of anti-aging and anti-tumor drug research and development, thereby promoting its further development and utilization.


Introduction
The Actinidia lindl genus belongs to the Actinidiaceae family and comprises more than 54 species, including deciduous, semi-deciduous, and evergreen vines.Actinidia arguta (Sieb.et Zucc.)Planch.ex Miq.(A. arguta), which is commonly known as kiwiberry (Figure 1), is a large deciduous vine found in China, Korea, Japan, and Russia.It thrives in mixed forests and well-watered environments, particularly at altitudes ranging from 500 to 1500 m [1].Another noteworthy plant within this genus is Actinidia chinensis Planch., which contributes to China's role as the world's leading kiwifruit producer [2].These two species display distinct morphological characteristics, making them easily distinguishable.The primary difference lies in the size and appearance of the fruit.A. arguta produces relatively smaller, smooth, green-skinned fruit, while Actinidia chinensis bears larger, brown-skinned fruit covered in fuzz [3].

Materials and Methods
To ensure the reliability and integrity of the information gathered for this review, we meticulously collected data from numerous databases including Web of Science, Pub-Med, ProQuest, and the China National Knowledge Infrastructure (CNKI).Our literature search encompassed articles published in peer-reviewed journals, Ph.D. dissertations, master's theses, conference papers, and classic texts of Chinese herbal medicines.To maximize the breadth of our research, we employed specific keywords during the literature search, such as Actinidia arguta, phytochemistry, secondary metabolites, pharmacology, biological activity, safety, toxicology, medicinal uses, and other related terms.This enabled us to retrieve a comprehensive range of relevant studies published between 1970 and November 2023.

Phytochemistry
Given the successful isolation and identification of numerous bioactive compounds from the roots, stems, leaves, and fruit of A. arguta, there is a growing interest in utilizing the fruit of A. arguta as raw materials for health food and the roots, stems, and leaves of A. arguta as medicinal resources [2][3][4][5][6][7][8][9][10][11]. A. arguta contains a diverse range of compounds, The roots of A. arguta possess significant medicinal properties [4].Its benefits have been documented in the "Dietary Materia Medica" of the Tang Dynasty and the "Compendium of Materia Medica" of the Ming Dynasty.Traditionally, the roots have been used to quench thirst, relieve heat, stop bleeding, promote blood circulation, reduce swelling, dispel wind, and alleviate dampness.In modern clinical practice, it is employed in the treatment of ailments such as rheumatism, lymphoid tuberculosis, esophageal cancer, gastric cancer, and breast cancer.Additionally, A. arguta is valued both as an ornamental tree species and a fruit tree.Its leaves contain polyphenolic compounds suitable for tea preparation [5].The fruit, which is known for its potent antipyretic and astringent effects, is also highly nutritious and widely consumed [6].Its small size and seeds make it ideal for fresh consumption, as well as for making jam, canned food, and wine [7][8][9].The flesh is tender and juicy, offering a delightful sweet and sour flavor.Abundant in amino acids, vitamins, and minerals, particularly vitamin C, which surpasses other fruits by severalfold, the A. arguta fruit is a valuable ingredient for the development of functional health foods [10,11].
While studies summarizing the phytochemistry and pharmacological effects of A. arguta exist, certain information gaps and inadequacies need to be addressed.These include an incomplete listing of chemical components and insufficient details regarding their chemical structures.Additionally, the description of the pharmacological mechanism of A. arguta lacks thoroughness.A previous report discussed the chemical components and pharmacological effects of A. arguta [13].However, this previous review only provided brief introductions to the names of over 60 chemical components, their total extracts, and a concise overview of the anti-tumor, antioxidant, and hypoglycemic effects.In contrast, our review encompasses a total of 539 components, complete with structural information for each compound.Furthermore, our review delves into distinct classifications of pharmacological research, providing an up-to-date and comprehensive observational perspective on A. arguta.
Therefore, we conducted a comprehensive literature review to address the aforementioned gaps by offering a comprehensive examination of the phytochemistry and pharmacological effects of A. arguta.We aimed to inspire future research on A. arguta while providing valuable references for the rational utilization of its resources and the efficient development of related products.

Materials and Methods
To ensure the reliability and integrity of the information gathered for this review, we meticulously collected data from numerous databases including Web of Science, PubMed, ProQuest, and the China National Knowledge Infrastructure (CNKI).Our literature search encompassed articles published in peer-reviewed journals, Ph.D. dissertations, master's theses, conference papers, and classic texts of Chinese herbal medicines.To maximize the breadth of our research, we employed specific keywords during the literature search, such as Actinidia arguta, phytochemistry, secondary metabolites, pharmacology, biological activity, safety, toxicology, medicinal uses, and other related terms.This enabled us to retrieve a comprehensive range of relevant studies published between 1970 and November 2023.

Phytochemistry
Given the successful isolation and identification of numerous bioactive compounds from the roots, stems, leaves, and fruit of A. arguta, there is a growing interest in utilizing the fruit of A. arguta as raw materials for health food and the roots, stems, and leaves of A. arguta as medicinal resources [2][3][4][5][6][7][8][9][10][11]. A. arguta contains a diverse range of compounds, with over 500 compounds isolated from the plant according to literature reports [12].These compounds can be broadly categorized into eight types, including terpenoids, flavonoids, phenolics, phenylpropanoid and lignin compounds, organic acids, and volatile compounds.This emphasizes the abundant potential of A. arguta as a source of bioactive ingredients that can be further explored in drug development, functional food production, and nutritional applications [13].

Phenylpropanoid and Lignin Compounds
Phenylpropanoid and lignin compounds primarily function in regulating plant growth and resistance against viruses [33].For the first time, researchers isolated and

Volatile Compounds
All volatile compounds, except for n-docosane, were identified using gas chromatographymass spectrometry (GC-MS) analysis.So far, 327 volatile compounds have been analyzed and identified from A. arguta (Table 6, Figure 7), primarily from fruit, with a smaller portion from roots and seeds.Matich et al. (2003) identified over 200 volatile components from flowers and fruit, mainly including linalool derivatives and sesquiterpenoids [41].Yang et al. (2012) also identified 32 volatile components from the fruit, mainly phenolics, alcohols, and alkenes [42].Other researchers isolated 12 components from the fruit, predominantly lipids and alcohols.Notably, ethyl butyrate accounts for a significant relative content of 86.89%, which gives the fruit its strong aroma.Although ethyl butyrate is widely used in the food, spice, and tobacco industries, the synthetic form raises concerns about its toxicity.Given the current preference for natural spices, the high relative content of ethyl butyrate in A. arguta volatile oil presents an excellent opportunity for natural extraction [43].Xin et al. (2009) utilized a solid-phase microextraction device and employed GC-MS to identify 21 volatile components in A. arguta [44].Sun et al. (2012) isolated 10 volatile components from the fruit [45].Recently, Wang et al. (2022) discovered 33 volatile components from the fruit [46].Additionally, 13 volatile components were extracted from the fruit and seeds of A. arguta [47][48][49].Yang et al. (2000) identified 17 compounds from the roots, mainly consisting of aliphatic compounds [50].

Volatile Compounds
All volatile compounds, except for n-docosane, were identified using gas chromatography-mass spectrometry (GC-MS) analysis.So far, 327 volatile compounds have been analyzed and identified from A. arguta (Table 6, Figure 7), primarily from fruit, with a smaller portion from roots and seeds.Matich et al. (2003) identified over 200 volatile components from flowers and fruit, mainly including linalool derivatives and sesquiterpenoids [41].Yang et al. (2012) also identified 32 volatile components from the fruit, mainly phenolics, alcohols, and alkenes [42].Other researchers isolated 12 components from the fruit, predominantly lipids and alcohols.Notably, ethyl butyrate accounts for a significant relative content of 86.89%, which gives the fruit its strong aroma.Although ethyl butyrate is widely used in the food, spice, and tobacco industries, the synthetic  GC-MS: Gas chromatography-mass spectrometry.

Inorganic Elements
The report indicates that A. arguta contains 29 inorganic elements (Table 8), many of which have beneficial effects on the human body [55].FPD: flame photometric detector; AAS: atomic absorption spectroscopy; ICP: inductively coupled plasma; AFS: atomic fluorescence spectrometry.

Pharmacological Activities
As both a medicinal and edible plant, A. arguta not only bears edible fruit but its entire plant can also be employed for medicinal purposes.Modern pharmacological studies verified various pharmacological effects of A. arguta, including antioxidant, antiinflammatory, anti-tumor, anti-aging, anti-fatigue, hypoglycemic, lipid-lowering, antibacterial, anti-glycation, anti-radiation, and immune regulation activities.

Antioxidant Activity
The continuous generation of reactive oxygen species (ROS) during oxidative metabolism is regarded as a major contributor to human aging [56].Excessive accumulation of ROS in organisms may lead to oxidative stress, causing immune injury, rheumatoid arthritis, and atherosclerosis [57].However, there is growing evidence suggesting that synthetic antioxidants can result in liver damage and even cancer [58].Consequently, the search for natural antioxidants from plants has gained prominence in recent years [59][60][61][62].
An et al. ( 2016) extracted total flavonoids and polyphenols from three varieties of A. arguta and assessed their antioxidant capacities using DPPH, 2,2 -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and oxygen radical absorbance capacity (ORAC) methods.The results indicated that every 100 g of fresh fruit possessed an antioxidant capacity equivalent to containing 203.4 mg, 135.5 mg, and 115.0 mg of vitamin C, respectively [63].Additionally, the addition of citric acid was observed to enhance the extraction rate of total polyphenols from A. arguta, thereby augmenting its antioxidant activity [64].The flavonoids of A. arguta effectively scavenge DPPH at relatively low concentrations, with the EC 50 value reached at a concentration of 174.2 mg/L, which is similar to vitamin C. Additionally, at a concentration of 750 mg/L, the scavenging rate of DPPH exceeds 90%.Furthermore, A. arguta demonstrates a certain ability to scavenge hydroxyl radicals and superoxide anion free radicals, which increases with the concentration of flavonoids [65].
A separate study extracted quercetin from A. arguta and evaluated its antioxidant capacity.The results show no significant difference in the total antioxidant capacity between quercetin and vitamin C at the same molar concentration in vitro.However, the IC 50 of quercetin and vitamin C in the anti-lipid peroxidation assay was 0.79 mg/mL and 1.41 mg/mL, respectively, indicating the former's superior strength.Moreover, when combined, quercetin and vitamin C exhibited synergistic antioxidant effects.Quercetin's antioxidant capacity was further evaluated in vivo using a carbon tetrachloride-induced mouse oxidative liver injury model experiment.The results demonstrated that quercetin had significantly better antioxidant capacity in vivo compared with vitamin C. At the same time, combining quercetin with vitamin C resulted in enhanced antioxidant abilities [66].This could be attributed to quercetin being a lipophilic antioxidant that is primarily distributed near the biofilm's surface, while vitamin C, which is a hydrophilic antioxidant, is located outside the membrane where it can scavenge ROS that diffuse outside the membrane [67].Lee et al. (2014) analyzed the antioxidant activities of different solvent extracts from the stem of A. arguta.The ethyl acetate fraction (IC 50 , 14.28 µg/mL) and n-butanol fraction (IC 50 , 48.27 µg/mL) exhibited high DPPH scavenging activity.In addition, the ethyl acetate fraction (200 µg/mL) effectively inhibited nitric oxide (NO) production in RAW 264.7 cells induced by LPS, in contrast with other fractions [68].Gao et al. (2019) measured the antioxidant capacities of different solvent extracts (ethyl acetate, n-butanol, water, methanol, and ethanol) from the adventitious roots of A. arguta.The ethyl acetate extract showed the strongest antioxidant capacity, with a DPPH scavenging rate of 88.09% at a concentration of 0.1 mg/mL.The ABTS scavenging rate at a concentration of 1.0 mg/mL was 95.62%.The chelating ability of iron ions was positively correlated with the concentration of the extract [69].Khromykh et al. (2022) studied the antioxidant activities of components such as polyphenols in the peels and pulps of A. arguta.The results indicated that the peels had stronger reducing power and total antioxidant capacity compared with the pulps [70].The best processing extract of A. arguta exhibited exceptional antioxidant and antiradical activities, including ABTS, ferric-reducing antioxidant power (FRAP), superoxide anion radical, hypochlorous acid, and peroxyl radical scavenging [71].
Plant polysaccharides, in addition to multifunctional compounds, such as flavonoids, phenolics, and anthraquinones, also possess significant antioxidant capacity [72].Polysaccharides from A. arguta fruit exhibited a strong scavenging ability for DPPH and alkyl radicals, with IC 50 values of 0.497 mg/mL and 0.547 mg/mL, respectively.At a concentration of 1 mg/mL, the polysaccharides showed scavenging rates of 86.4% and 87.1% for DPPH and alkyl radicals, similar to vitamin C [73].Moreover, polysaccharides from A. arguta fruit demonstrated the ability to scavenge hydroxyl radicals [74], indicating their strong antioxidant potential and promising prospects for development.Polysaccharides extracted from A. arguta leaves and stems also exhibited DPPH scavenging activities, with IC 50 values of 0.71 mg/mL and 0.72 mg/mL, respectively.These findings suggest that polysaccharides derived from A. arguta leaves and stems could be further developed and utilized as natural antioxidants [75].
The alkaloids found in A. arguta show scavenging effects on DPPH, hydroxyl radicals, and superoxide anion radicals.These alkaloids were also found to inhibit lipid peroxidation and possess a strong iron ion reduction ability [51].The volatile components of A. arguta demonstrated certain antioxidant activity.The essential oil of A. arguta exhibited strong scavenging activity with DPPH (IC 50 = 117.60µg/mL), which was comparable with the synthetic antioxidant butylated hydroxytoluene (BHT) [46].Furthermore, the storage temperature was found to impact the antioxidant activity of A. arguta.Storage at 0 • C significantly inhibited the browning and respiratory intensity of A. arguta compared with 5 • C and 10 • C. Additionally, storage at 0 • C maintained higher fruit hardness and vitamin C, glutathione (GSH), and flavonoid contents while inhibiting relative conductivity; malondialdehyde (MDA) content; and peroxidase, and polyphenol oxidase activities.Storage at 0 • C also maintained higher superoxide dismutase (SOD), catalase, and glutathione reductase activities [76].

Anti-Inflammatory Activity
Inflammatory reactions can protect the human body from bacteria and tumors.However, chronic inflammation resulting from the continuous activation of macrophages can lead to serious health issues, including heart disease, gastrointestinal problems, and a sore throat.A. arguta contains various anti-inflammatory compounds, such as (+)-catechin, chlorogenic acid, (−)-epi-catechin, quercetin, rutin, and caffeic acid.Experimental results suggest that the chloroform layer of A. arguta stems exerts anti-inflammatory effects by inhibiting mitogen-activated protein kinase phosphorylation and the nuclear translocation of NF-κB [77].In vitro experiments showed that the methanol extract of A. arguta leaves (12.5, 25, and 50 µg/mL) specifically inhibits NLRP3 ubiquitination, thereby suppressing the secretion of caspase-1 and IL-1β.This conclusion was also confirmed in in vivo experiments on a mouse model of peritonitis [78].The results of anti-inflammatory activity research showed that when the total triterpenoid concentration of A. arguta branches reached 4 mg/mL, the inhibition rates of hyaluronidase activity and bovine serum albumin denaturation reached 81.48% and 71.09%, respectively.The anti-inflammatory activity was slightly lower than that of the positive control, namely, diclofenac sodium.The results confirmed the anti-inflammatory activities of total triterpenoids in A. arguta branches, which can effectively reduce the production and development of inflammation and maintain normal physiological functions [79].However, the mechanism of its anti-inflammatory effect still needs to be studied.The anti-inflammatory effects of the fruit of A. arguta were investigated using an LPS-stimulated RAW 264.7 murine macrophage cell line.The polyphenols and flavonoids in the fruit of A. arguta can effectively inhibit the release of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and their effects on the release of NO are dose-dependent.Therefore, inhibition of this pathway could be a possible mechanism of the anti-inflammatory effects of the fruit of A. arguta [63].

Anti-Tumor Activity
The anti-tumor effect is mainly reflected in inhibiting the proliferation and growth of tumor cells, promoting tumor cell apoptosis, enhancing the body's immunity, and alleviating symptoms.A. arguta exhibits a significant anti-tumor effect, with its roots, stems, leaves, and fruit containing various anti-tumor active ingredients, such as flavonoids, anthraquinones, and polysaccharides.A mouse model of reduced bone marrow function was created using a single intravenous injection of 5-fluorouracil at a dose of 150 mg/kg.Methanol extract from A. arguta stems (100 mg/kg/d) promotes the proliferation of mouse bone marrow cells, in which (+)-catechin and (−)-epi-catechin play a role [80].(+)-catechin (1 and 10 mg/kg/d) was found to be effective in promoting bone marrow cell proliferation and combating the hematotoxicity of 5-fluorouracil in mice [81].Five types of human cancer cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum in a 5% CO 2 -humified incubator at 37 • C. It was observed that A. arguta fruit exhibits anti-proliferative activities against Hep3B and HeLa cell lines but has no effect on HT-29, HepG2, and LoVo cells [82].The inhibitory effect of extracts on leukemia cells was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay.
Anthraquinone compounds extracted from A. arguta roots exhibited significant inhibitory effects on four leukemia cell lines, namely, JARKET, RAJI, L1210, and K562.The inhibitory rate shows a positive correlation with the concentration of the extract [83].Furthermore, the polysaccharide derived from A. arguta stems (20 mg/mL) inhibited the proliferation of transplanted S180 tumor cells in Swiss mice, and this anti-tumor effect might be attributed to the enhanced immune function of the body [84]. A. arguta juice has the ability to block the formation of N-nitroso morpholine (a known carcinogen) under simulated gastric juice conditions, with a blocking rate of 79.52%.This rate is higher than that of an equivalent amount of vitamin C solution, indicating the strong anti-tumor effects of A. arguta juice [85].The volatile components of A. arguta also exhibit cytotoxic activities.The cytotoxicity of A. arguta essential oil was studied using the MTT assay, yielding IC 50 values of 6.067 mg/mL, 11.905 mg/mL, and 13.646 mg/mL for the A549, HT-29, and PC-3 cell lines, respectively [46].The antiproliferative activities of A. arguta extract against HepG2 and HT-29 cells (0-100 mg/mL and 0-200 mg/mL, respectively) were found to be 1.44-4.25 times higher than that of Actinidia kolomikta or Actinidia chinensis extracts, likely due to the higher flavonoid content in A. arguta extract.Therefore, A. arguta extract shows potential as a chemotherapeutic agent against HepG2 and HT-29 cells [86].

Anti-Aging Activity
Modern medicine recognizes skin aging as a physiological or pathological change influenced by various factors and is categorized as either endogenous aging or exogenous aging [87].Endogenous aging is influenced by genetic or endocrine factors, while exogenous aging is influenced by external environmental factors that can lead to skin laxity, roughness, and deepening wrinkles [88].Traditional Chinese medicine contains active ingredients, such as saponins, polysaccharides, and flavonoids, that possess anti-aging effects by scavenging free radicals, regulating immunity, reducing mitochondrial DNA damage, improving substance metabolism, and enhancing microcirculation [89].
In one study, 14-month-old TA 1 pure-strain mice were fed A. arguta juice for 50 d [90].The results showed that male and female mice had 75.17% and 76.25% inhibition rates of MAO-B activity in the brain, indicating that A. arguta juice can modulate the central aging clock by regulating brain monoamine levels and exerting anti-aging effects.A. arguta juice also significantly reduced lipofuscin content in mouse myocardial cells, demonstrating its antioxidant effect and ability to inhibit free radical production.Moreover, it reduced the hydroxyproline content in the tail tendons of 14-month-old TA 1 pure-strain mice, suggesting its potential to delay aging.Additionally, A. arguta juice decreased the levels of total bile acid (TBA) and increased SOD activity.However, further research is needed to determine the specific mechanisms behind its anti-aging effects [91].In another study, Gan et al. (2004) administered A. arguta juice to elderly Wistar rats aged 20-22 months with a weight of 400 ± 30 g at doses of 3 g/kg and 6 g/kg for 30 d.The measurements of red blood cell and liver SOD, whole blood glutathione peroxidase (GSH-Px) activity, serum MDA, and lipofuscin content in brain and heart tissues revealed a significant increase in red blood cell SOD, liver SOD, and whole blood GSH-Px activity.Additionally, the levels of serum MDA and lipofuscin in brain and heart tissues were significantly reduced.These findings indicate that A. arguta juice could enhance the activities of antioxidant enzymes, reduce lipid peroxidation, and delay the aging process in the bodies of elderly rats [92].

Anti-Fatigue Effect
Effervescent tablets were produced using A. arguta fruit through spray drying and tablet pressing technologies in certain studies.The dose was divided into low-, medium-, and high-dose groups, with an administration of 0.2 mL per 20 g weight of medication for 20-22 g Kunming male mice.Compared with the control group, the effervescent tablet low-, medium-, and high-dose groups exhibited significant differences in terms of prolonged exhaustive swimming time in mice, with increases of 35.03%, 61.15%, and 89.81%, respectively.Similarly, the fatigue rotation time of mice increased by 58.10%, 122.86%, and 157.14% in the low-, medium-, and high-dose groups, respectively.While the low-dose group displayed a significant difference, the medium-and high-dose groups showed extremely significant differences.Furthermore, effervescent tablets were found to enhance exercise endurance and improve parameters such as lactate dehydrogenase activity, liver glycogen, and muscle glycogen content in mice.Additionally, they reduced serum urea nitrogen and blood lactate content, demonstrating significant anti-fatigue effects [93].In another experiment, 28 Kunming mice were randomly allocated into four groups and administered doses of 0, 50, 100, and 200 mg/kg/d of crude alkaloid extract from A. arguta for 28 d raised in an SPF barrier system.The evaluation of exercise abilities included forelimb strength training and weight-bearing swimming time, while anti-fatigue abilities were assessed by measuring the glycogen content in the liver and muscles, as well as observing morphological changes in the longitudinal profiles of striated and skeletal muscles.The results indicated that the crude alkaloid extract improved the endurance and grip strength of mice and prolonged their swimming time under load, with the 100 mg/kg/d group displaying the most significant prolongation.Compared with the control group, the experimental group showed significant decreases in the levels of lactate, ammonia, and creatine kinase, accompanied by an increase in tissue glycogen content.Moreover, no changes were observed in the morphology of striated and skeletal muscles [94].

Hypoglycemic Activity
Plant polysaccharides have the beneficial effect of reducing blood sugar levels.They are safe, with minimal toxic and side effects, and show positive effects in individuals with hyperglycemia.As a result, an increasing number of researchers are dedicated to utilizing plant polysaccharides in the development of safe, affordable, and effective natural medications for blood sugar reduction [95,96].A. arguta polysaccharides exhibit hypoglycemic effects, and studies indicate that the main active compounds responsible for this effect in A. arguta are flavonoids and polysaccharides [97,98].In one study, mice induced with type II diabetes through a high-fat and high-sugar diet, combined with streptozocin (STZ), were administered low, medium, and high doses of A. arguta flavonoids at 90, 180, and 270 mg/kg/d, respectively.The results show a significant improvement in the symptoms of the diabetic mice, specifically in reduced fasting blood glucose levels and serum insulin levels.The fasting blood glucose level decreased correspondingly as the dose increased.Additionally, it was observed that the expression level of the glucokinase gene in the liver of the diabetic mice increased, thereby enhancing the glucokinase activity.The hypoglycemic effect of flavonoids on type II diabetic mice is thought to be mediated by upregulating the expression of the glucokinase gene, repairing damaged pancreatic islet β cells, improving serum insulin levels, inhibiting α-glucosidase activity, and enhancing glucokinase activity, thus maintaining glucose homeostasis in the liver [98].
The polyphenol fraction of A. arguta, which contains quercetin-3-O-glucoside and quercetin-3-O-galactoside, exhibits inhibitory activity against α-glucosidase and maltase.Male KK-A y mice, which is a type II diabetic model, and C57BL/6J mice, which is a nondiabetic control model of KK-A y mice, in addition to male Sprague Dawley (SD) rats, were used for a single-dose test.In an oral glucose tolerance test conducted on KK-A y mice fed with quercetin-3-O-glucoside for 4 weeks, blood glucose levels tended to be lower 60 min after glucose administration.These findings suggest that A. arguta possesses antidiabetic effects, and quercetin-3-O-glucoside, which is a component of A. arguta, may be useful in the prevention of type II diabetes by suppressing gluconeogenesis and enhancing lipid β-oxidation [99].
To explore the hypoglycemic effect of polysaccharides, a model of type II diabetic mice was established by feeding them with a high-fat and high-sugar diet and intraperitoneal injection of a low-dose STZ.Polysaccharides derived from A. arguta branches were orally administered to mice in low-, medium-, and high-dose groups at 10, 20, and 40 mg/kg, respectively.Another group of mice was administered 40 mg/kg of metformin as a positive control.After 28 d of continuous administration, there was a significant decrease in total cholesterol, total triglycerides, and low-density lipoprotein cholesterol, while high-density lipoprotein cholesterol levels significantly increased.This indicates an improvement in the abnormal blood lipid profile found in diabetic mice.Moreover, the content of MDA in serum significantly decreased, while the content of SOD increased, suggesting that polysaccharides may have a hypoglycemic effect by inhibiting peroxidation reactions in the body.An examination of organ indices and histomorphology revealed that the high-dose polysaccharide group exhibited a protective effect on the pancreas and liver of STZ-induced diabetic mice.Therefore, it can be inferred that polysaccharides regulate blood sugar levels and lipid metabolism in diabetic mice while also reducing insulin resistance [100].
A. arguta fruit polysaccharide has a reparative effect on the islets of the pancreas in diabetic mice induced by intraperitoneal injection of alloxan.It increases insulin secretion, improves glucose and lipid metabolism, significantly reduces fasting blood sugar, increases glucose tolerance, boosts liver glycogen, and lowers blood lipid levels [101].However, the exact mechanism still requires further exploration.Compared with the control group, rats with STZ-induced diabetes that were fed with the 70% ethanol extract (400 mg/kg) of A. arguta experienced a significant reduction in postprandial blood glucose by inhibiting α-glucosidase activity [102].Additionally, in a study using mice fed with a high-fat and high-sugar diet, an extract of A. arguta not only reduced barbituric acid reactive substances but also increased GSH levels [103].Another study showed that a polyphenol extract in the fruit of A. arguta also inhibited α-glucosidase activity [103].Furthermore, an aqueous extract of A. arguta stem exhibited appreciable inhibitory activity against the α-glucosidase enzyme, with an IC 50 of 1.71 mg/mL [68].

Hypolipidemic Activity
In recent years, the incidence rate of hyperlipidemia has been increasing.Hyperlipidemia is a sign of a lipid metabolism disorder and one of the main triggers for atherosclerosis, heart disease, and fatty liver [104].Preventing the occurrence and development of hyperlipidemia is of great significance for reducing the incidence rate of cardiovascular and cerebrovascular diseases [104].The search for lipid-lowering drugs from natural plants is currently a prominent research topic [105,106].Leontowicz et al. (2016) investigated the protective effects of A. arguta fruit on the aorta and liver of hypercholesterolemic rats.They fed 71 male Wistar rats with 1% cholesterol to induce a model and then randomly divided them into groups.In the A. arguta group, the levels of total cholesterol, low-density lipoprotein cholesterol, the total cholesterol/high-density lipoprotein cholesterol atherosclerosis index, and triglyceride in the liver serum were reduced, accompanied by an increase in high-density lipoprotein cholesterol.Additionally, the serum's antioxidant capacity became stronger.Rat liver fibrosis decreased, the prothrombin time was prolonged, and serum peroxidase decreased.This suggests that A. arguta can effectively reduce the probability of hyperlipidemia [107].
There are also reports of a study that selected 36 male mice and randomly divided them into three groups: blank control, high-fat model, and high-fat+polysaccharide groups, each containing 12 mice.The high-fat+polysaccharide group was fed a high-fat diet daily, while A. arguta fruit polysaccharide (300 mg/kg) was administered via gavage.The results demonstrated that polysaccharides significantly reduced the content of total cholesterol and triglycerides in both the serum and liver of mice while increasing the level of high-density lipoprotein cholesterol in the liver.Pathological observations of liver tissue indicated that polysaccharides significantly improved and alleviated the symptoms of liver fat and hyperlipidemia.Determining the lipid levels in mouse feces revealed that polysaccharides significantly increased the total fat, cholesterol, and triglyceride contents in the feces of high-fat mice, suggesting that the polysaccharide's effect on reducing cholesterol levels is achieved by promoting the cholesterol excretion pathway [108].

Other Pharmacological Effects
A. arguta also exhibits other pharmacological effects, such as antibacterial, antiglycated, anti-radiation, and immune-regulation properties.Studies have reported the in vitro antibacterial activity of A. arguta.The results indicate that A. arguta volatile oil has significant antibacterial activity against Staphylococcus aureus and Saccharomyces cerevisiae, with inhibition zones of 19.5 mm and 20.5 mm, respectively.The antibacterial activities against Bacillus subtilis and Microsporum canis are moderate, with inhibition zones of 17.2 mm and 16.8 mm, respectively.However, A. arguta shows weak antibacterial activities against Escherichia coli and Pseudomonas aeruginosa, with inhibition zones of 8.5 mm and 10 mm, respectively [46].Additionally, studies indicate that A. arguta fruit polysaccharides have inhibitory effects on Bacillus subtilis, Escherichia coli, Staphylococcus aureus, and other bacteria.The antibacterial effect increases as the concentration of polysaccharides increases, with a minimum inhibitory concentration (MIC) ranging from 10 to 25 mg/mL.However, no antibacterial effect was observed against Candida tropicalis.Temperature and pH values also impact the antibacterial effect of polysaccharides, with a higher temperature resulting in a more pronounced effect.Polysaccharides exhibit a better antibacterial effect within a pH range of 4-5 [109].The total flavonoids of A. arguta have inhibitory effects on Escherichia coli, Staphylococcus aureus, Rhizopus, Aspergillus oryzae, Candida tropicalis, and Saccharomyces cerevisiae.The inhibitory effect increases as the concentration of total flavonoids increases, with an MIC ranging from 25 to 50 mg/mL.No inhibitory effect was observed against Aspergillus niger.Similar to polysaccharides, temperature and pH values also affect the antibacterial effect of total flavonoids, with a higher temperature having a more pronounced effect.Total flavonoids exhibit a better antibacterial effect within a pH range of 5-6 [110].Another study investigated the antibacterial activity of A. arguta fruit and leaves.The crude extracts of A. arguta fruit and leaves notably inhibited clinical strains of Pseudomonas aeruginosa and Escherichia coli, which were resistant to the action of ofloxacin.The inhibitory effects of the plant extracts on clinical strains of Klebsiella pneumoniae and Acinetobacter baumannii were comparable with the effect of ofloxacin [70].In addition, Macedo et al. (2023) studied an extract of A. arguta, which displayed antimicrobial activities against Staphylococcus aureus (MIC = 32 mg/mL) and Pseudomonas gingivalis (MIC = 64 mg/mL) and reduced the growth rate of Escherichia coli [71].
A novel cell wall polysaccharide (AAPs) was extracted from A. arguta fruit and separated into four parts, namely, water-eluted polysaccharide, salt-eluted polysaccharide (SPS)-1, SPS-2, and SPS-3.All four types of polysaccharides exhibited the ability to scavenge free radicals, chelate iron ions, inhibit lipid peroxidation, and inhibit protein glycation.However, SPS showed significantly stronger effects compared with the water-eluted polysaccharide.Particularly, SPS-3 demonstrated the highest antioxidant and anti-glycated activities.Furthermore, the inhibitory effect of AAPs on advanced glycation end product formation can be attributed to their ability to inhibit the production of protein carbonyl groups and protect protein thiol groups.This effect is not related to the scavenging capacity of dicarbonyl compounds.These findings suggest that the mechanisms underlying the antiglycated effects of AAPs may be linked to their antioxidant activities [111].Moreover, more than 20% of A. arguta fruit polysaccharides significantly enhanced the survival rate of yeast cells after ultraviolet radiation, indicating the radiation-protective effects of these polysaccharides on cells [112].
Studies also demonstrated that A. arguta stem polysaccharides have a notable immunepromoting effect and act as effective immune regulators in mice (20 ± 2 g).These polysaccharides enhance the proliferation of T and B lymphocytes both in vivo and in vitro, with the most significant effect observed at a dose of 100 mg/kg.Additionally, they promote mitosis and stimulate the production of lymphokines in mice.Furthermore, A. arguta stem polysaccharides enhance the primary response of B cells to SRBC antibodies and improve the phagocytic ability of macrophages [113].Other research indicates that A. arguta fruit polysaccharides briefly increase the proportion of total T cells and helper T cells in 6-week-old female mouse peripheral blood, have a long-term inhibitory effect on the proportion of B cells and toxic T cells in mouse peripheral blood, and exhibit delayed and instantaneous promotion of the proportion of NK cells in mouse peripheral blood [114].Moreover, high doses of A. arguta fruit polysaccharides promote the growth of SD rats and significantly increase their spleen index.The medium-and high-dose groups also exhibit significant increases in the thymic index, phagocytic index, and concanavalin A (Con A)-induced splenic lymphocyte transformation index in rats.These findings confirm that polysaccharides enhance the immune system by promoting the growth of immune organs, enhancing cellular immune function, and improving the phagocytic ability of monocytes and macrophages [115].In terms of safety, three solvent extracts (water, water:ethanol (50:50), and ethanol) of A. arguta leaves showed no adverse effects on caco-2 and HT29-MTX cells at concentrations below 100 µg/mL and 1000 µg/mL, respectively.This suggests that A. arguta leaves are relatively safe for consumption [116].

Discussion
We conducted a comprehensive review of the phytochemistry and pharmacological research of A. arguta, which is a traditional medicinal plant.A total of 539 compounds were reported, showing that A. arguta contains a variety of phytochemicals, including terpenoids, flavonoids, phenolics, phenylpropanoids, lignin, organic acids, volatile components, alkanes, coumarins, anthraquinones, alkaloids, polysaccharides, and inorganic elements.We also elucidated the various pharmacological studies on these compounds and various extracts of A. arguta.This thorough literature review indicates that A. arguta has excellent antioxidant, anti-inflammatory, and anti-tumor properties.Furthermore, it has broad application prospects for improving glucose metabolism, anti-aging, anti-fatigue, and immune regulation.In particular, flavonoids, phenolics, and polysaccharides, which were identified as the main components responsible for mediating these pharmacological effects, were extensively studied and reported multiple times.
Additionally, the roots of A. arguta have long been known for their unique anticancer effects and are highlighted in the "Dietary Materia Medica", along with the "Compendium of Materia Medica".Therefore, a significant amount of academic research is dedicated to revealing the active ingredient of its anticancer efficacy.In recent years, A. arguta, as a new fruit, has gradually been accepted by more and more people due to its excellent taste and rich nutritional value.It is used to prepare jam, canned food, and wine, making it an emerging resource for research and processing in the food industry.This has driven a surge in demand in both domestic and international markets, leading to the large-scale planting of A. arguta.Consequently, researchers have been inspired to explore the different medicinal parts of the plant and strive to broaden their research scope.Amongst these sections, the leaves of A. arguta have received attention due to their unique characteristics similar to tea.However, current research on the chemical composition of A. arguta mainly focuses on the isolation and identification of individual compounds, with limited research on the changes in component content in different regions and plant parts.Additionally, further exploration is needed to establish quality standards for A. arguta.It is important to highlight future research in these areas, as it is crucial for enhancing the standardized application and quality control of A. arguta.
Of particular interest in A. arguta are flavonoids and phenolics.Researchers discovered a total of 52 compounds from these categories in A. arguta, which showed extensive clinical efficacy in clinical studies regarding anti-aging and hypoglycemic effects.It is noteworthy that A. arguta contains compounds with specific structures, such as (2R,6R,9R)-trihydroxymegastigmane-4,7E-dien-3-one-9-O-β-D-glucopyranoside, which is a methylcyclohexenetype sesquiterpenoid glycoside compound that has not been reported in the literature.These unique chemical characteristics make A. arguta a promising subject for further exploration of the biological activity of these novel terpenoids and the potential discovery of safe and effective compounds with therapeutic applications.
Moreover, numerous studies revealed the various pharmacological activities of A. arguta, mainly focusing on its antioxidant, anti-inflammatory, and anti-tumor effects.However, it is important to note that some studies only utilize extracts from different parts or solvents of A. arguta, rather than pure compounds.Additionally, the research on other pharmacological activities of A. arguta is not comprehensive enough, with many mechanisms of action remaining unidentified.Currently, research on the pharmacokinetics of A. arguta is limited, despite its significant role in elucidating metabolic pathways.Therefore, further exploration of the pharmacological activity and pharmacokinetics of A. arguta is necessary.
This review, however, has certain limitations.First, the methods used for collecting literature and data were limited, which may lead to the omission of relevant studies.Second, the quality of some collected research literature may have flaws, potentially affecting the reliability of the review's results.Another significant limitation was the lack of research on the toxicity and clinical reports of A. arguta, especially regarding its significant therapeutic effect on gastrointestinal tumors.Further studies should address these limitations and delve into unexplored areas, such as toxicity, pharmacokinetics, and clinical research.

Conclusions
However, there is currently a dearth of comprehensive and detailed documentation on the phytochemistry and pharmacology of A. arguta.As a result, the main objective of this review was to thoroughly explore the existing research on A. arguta by examining multiple databases and addressing these aforementioned aspects.Additionally, this review aimed to establish a strong foundation for further exploration of the potential uses of A. arguta, as well as providing guidance for future research.First, it was demonstrated that the roots of A. arguta exhibit remarkable efficacy as an anti-tumor agent, particularly in the treatment of gastrointestinal tumors.This finding suggests its potential as a valuable addition to the arsenal of anti-cancer drugs.Second, given the deep-rooted love for tea culture in East Asian countries, products such as health teas derived from the leaves of A. arguta hold tremendous potential for development.These teas could cater to the growing demand for natural and beneficial beverages, offering unique flavors and potential health benefits.Furthermore, the fruit of A. arguta is not only nutritionally rich but also boasts an appealing taste, making it increasingly popular among consumers.As awareness of the fruit's health benefits spreads, it is expected that more and more individuals will embrace and enjoy the fruit of A. arguta.Building upon this extensive review, further investigations into A. arguta are likely to lead to the isolation and identification of additional chemical components.Additionally, ongoing research will undoubtedly uncover more effective and practical pharmacological effects, ultimately benefiting humanity and contributing to the advancement of medical science.

Figure 2 .
Figure 2. Chemical structures of terpenoids isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.

Figure 3 .
Figure 3.Chemical structures of flavonoids isolated from Actinidia arguta.Chemical struct were drawn using Chemdraw Professional 15.0 software.

Figure 3 .
Figure 3.Chemical structures of flavonoids isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.

Figure 4 .
Figure 4.Chemical structures of phenolic compounds isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.

Figure 4 .
Figure 4.Chemical structures of phenolic compounds isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.

Figure 5 .
Figure 5.Chemical structures of phenylpropanoid and lignin compounds isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.

Figure 5 .
Figure 5.Chemical structures of phenylpropanoid and lignin compounds isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.

Figure 6 .
Figure 6.Chemical structures of organic acids (esters) isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.

Figure 6 .
Figure 6.Chemical structures of organic acids (esters) isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.

Figure 7 .
Figure 7.Chemical structures of volatile components isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.

Figure 7 .
Figure 7.Chemical structures of volatile components isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.

Figure 8 .
Figure 8.Chemical structures of other compounds isolated from Actinidia arguta.Chemical structures were drawn using Chemdraw Professional 15.0 software.