Advances in Research on Chemical Constituents and Their Biological Activities of the Genus Actinidia

Kiwi, a fruit from plants of the genus Actinidia, is one of the famous fruits with thousand years of edible history. In the past twenty years, a great deal of research has been done on the chemical constituents of the Actinidia species. A large number of secondary metabolites including triterpenoids, flavonoids, phenols, etc. have been identified from differents parts of Actinidia plants, which exhibited significant in vitro and in vivo pharmacological activities including anticancer, anti-inflammatory, neuroprotective, anti-oxidative, anti-bacterial, and anti-diabetic activities. In order to fully understand the chemical components and biological activities of Actinidia plants, and to improve their further research, development and utilization, this review summarizes the compounds extracted from different parts of Actinidia plants since 1959 to 2020, classifies the types of constituents, reports on the pharmacological activities of relative compounds and medicinal potentials.


Introduction
With the development of natural product research, a huge number of chemical constituents have been identified from natural resources. There is no doubt that the research on the chemical composition of fruits, including trace elements, has greatly improved the application prospects of these fruits. With no exception, it is the same to kiwifruit, one of the most prestigious fruits with a long history of eating [1,2]. Kiwi belongs to plants of the genus Actinidia comprising more than 70 species around the world [3]. Some of these plants are proven to have a wide range of medicinal activities. For example, A. valvata, whose root is known as ''Mao-Ren-Shen" in traditional Chinese medicine, exhibits antitumor and anti-inflammatory activities and has been used for the treatment of hepatoma, lung carcinoma and myeloma for a long time [4,5]. The roots of A. chinensis Planch, called "Teng-Li-Gen" usually, were used as a traditional Chinese medicine for the treatment of various cancers, such as esophagus cancer, liver cancer, and gastric cancer [6]. In the past two decades, great research had been accomplished about exploring the chemical composition of Actinidia plants. These studies have greatly promoted the understanding of the chemical components and functions of the Actinidia plant. According to literature survey, 12 Actinidia species including A. valvata, A. chinensis, A. argute, A. polygama, A. kolomikta, A. eriantha, A. macrosperma, A. deliciosa, A. chrysantha, A. rufa, A. indochinensis, and A. valvata were reported for their natural products. This review systematically summarizes the chemical components and their biological activities from different parts of 12 Actinidia species from 1959 to 2020. According to structure types, a total of 325 molecules have been collected including terpeniods, phenols, and other small groups (Fig. 1). Names and isolation information were listed in the tables, while the biological activities of the extracts or compounds were discussed in the text.

Terpenoids
In recent years, a large number of terpenoids were isolated from many Actinidia species. Among them, triterpenes account for the vast majority that are mainly composed by several normal frameworks including ursane-type, oleanane-type, and lupane-type. Of the total 325 compounds in this review, 104 are triterpenoids. From the literature review, ursolic acids and their saponins are undoubtedly the most abundant in Actinidia species.

Other Terpenoids
A total of 19 other terpenoids including iridoids, diterpenoids, and their glycosides have been found from Actinidia plants (105 − 123, Fig. 5, Table 4). None of these compounds have good biological activities, only compound 120 showed certain anti-angiogenesis activity [77].
In addition to phytosterols, seven normal ergosterols (132-137, Fig. 6, Table 5) were obtained from peel or rhizomes of kiwifruit plants. It is well known that ergosterols should be fungal products. Compounds 132-137 may be produced by fungal infected kiwifruit plants.

Xanthones
Three xanthones were isolated from n-butyl alcohol fraction of A. arguta  Table 8). They were isolated from this plant for the first time [108]. Compound 203 showed extensive biological activities, including inhibiting α-Glycosidase, NO production inhibition and NF-κB inhibition and PPAR activation [116,117]. It has been demonstrated the inhibitory effects on NF-κB transcriptional activation in HepG2 cells stimulated with TNFα with an IC 50 value of 0.85 ± 0.07 μM, which was more potent than the positive control of sulfasalazine (IC 50 = 0.9 μM) [118].

Phenylpropionic Acids
A total of 38 phenylpropionic acid derivatives have been identified from kiwifruit plants (220-257. Fig. 10, Table 9), while most of them were glycosides or quinic acid derivatives. Phytochemical examination of the fruits of A. arguta led to the isolation of two organic acids including caffeic acid 220 and caffeoyl-β-d-glucopyranoside 221, which were tested for their nitric oxide production inhibitory activity in LPS-stimulated RAW 264.7 cells and DPPH radical scavenging activities. Compared with positive control (L-NMMA), they were potently reduced nitric oxide productions and showed anti-oxidative activities [135]. Nine succinic acid derivatives (228-236), eleven quinic acid (245-255) derivatives and two shikimic acid derivatives (256 and 257) were isolated from the fruits of A. arguta. The NF-κB transcriptional inhibitory activity of the compounds was evaluated using RAW 264.7 macrophages cells induced by lipopolysaccharide. Among the groups of
In summary, this review focused on the biological components and related pharmacological activities of various    Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.