key: cord-0834155-piw6qnhg authors: Ji, Tao; Ji, Wei Wei; Wang, Juan; Chen, Hong Jiang; Peng, Xin; Cheng, Ke Jun; Qiu, Dan; Yang, Wei Jie title: A comprehensive review on traditional uses, chemical compositions, pharmacology properties and toxicology of Tetrastigma hemsleyanum date: 2020-08-12 journal: J Ethnopharmacol DOI: 10.1016/j.jep.2020.113247 sha: e84a4a3f9cbc59fd534ec888bdab9e38dd9a472f doc_id: 834155 cord_uid: piw6qnhg ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg (T.hemsleyanum), a rare herbal plant distributed in subtropical areas of mainland China, has become a focus of scientific attention in recent years because of its high traditional value, including uses for treatment of children with fever, pneumonia, asthma, rheumatism, hepatitis, menstrual disorders, scrofula, and pharynx pain. AIM OF THE STUDY: This systematic review aims to provide an insightful understanding of traditional uses, chemical composition, pharmacological effect and clinical application of T. hemsleyanum, and lay a foundation for the further study and for the utilization of T. hemsleyanum resource. MATERIALS AND METHODS: A domestic and overseas literature search in known databases was conducted for published articles using the relevant keywords. RESULTS: One hundred and forty-two chemical constituents identified from T. hemsleyanum have been reported, including flavonoids, phenolic acids, polysaccharide, organic acids, fatty acids, terpenoids, steroids, amino acid and others. Among these components, flavonoids and polysaccharides were the representative active ingredients of T. hemsleyanum, which have been widely investigated. Modern pharmacological studies have shown that these components exhibited various pharmacological activities, such as anti-inflammatory, antioxidant, antivirus, antitumor, antipyretic, anti-hepatic injury, immunomodulatory, antibacterial etc. Moreover, different toxicological studies indicated that the clinical dosage of T. hemsleyanum was safe and reliable. CONCLUSIONS: Modern pharmacological studies have well supported and clarified some traditional uses, and T. hemsleyanum has a good prospect for the development of new drugs due to these outstanding properties. However, the present findings did not provide an in-depth evaluation of bioactivity of the extracts, the composition of its active extracts was not clear. Moreover, they were insufficient to satisfactorily explain some mechanisms of action. Data regarding many aspects of T. hemsleyanum, such as links between the traditional uses and bioactivities, pharmacokinetics, quality control standard and the clinical value of active compositions is still limited which need more attention. 1 Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanum), mostly known as "San 2 ye qing", is a kind of folk plant. Because of its slow growth, it usually takes 3-5 years 3 to meet the requirements of commercial medicinal materials, so it is a precious 4 perennial medicinal resource. It mainly grows in the eastern, central, southern and 5 south-western provinces of China, such as Zhejiang, Jiangsu Guangxi, Fujian and 6 Yunnan provinces (Peng and Wang, 2018) . T. hemsleyanum is known worldwide as 7 sources of phytotherapeutics, which have been used for the treatment of conditions 8 related to inflammatory and immune response, and been recorded based on clinical 9 trials or the use of animal models . As an edible plant, the leaves of T. lanceolate, oblong or ovate lanceolate. The leaflets are 3-10 cm long and 1.5-3 cm 74 wide, with a tapered tip and a wedge-shaped or round base. The flowers of T. 75 hemsleyanum are small, yellow green and ovate. The flowering stage of T. 76 hemsleyanum ranges from April to June, and the fruit phase is normally from August 77 to November. When the flower withered, it will form a small green round fruit with 78 the size of millet. When it is mature, the fruit will turn from green to red, the berries 79 are spherical and soft spherical. hemsleyanum until now. The information about compound name, molecular weight, 121 compound formula, detection method, analysis sample is summarized in Table 1 . Cyt-c and apoptosis activator, such as caspase-8, caspase-9 and caspase-10 could 443 activate the downstream apoptosis executor enzymes, such as caspase-3 and caspase-6, 444 and that finally lead apoptosis. Besides, ROS can produce many kinds of free radicals, 445 which cause cell stress reaction and trigger cell apoptosis. However, many types of 446 antioxidant enzymes can scavenge excessive ROS, such as SOD, catalase (CAT) and 447 glutathione peroxidase (GSH-Px). As shown in Table 4 Ethanol extract of T. Tumor volume↓, Treg ratio↓, COX-2↓, PGE2↓ Zhonggan mixture in the treatment of 58 cases of 691 advanced primary liver cancer Study on the inhibitory effect of effective part of 693 Tetrastigma Hemsleyanum on tumor proliferation and migration Toxicological study on Tetrastigma Hemsleyanum Long term toxicological study of Tetrastigma 698 Inhibition Effect of the Ethylacetate Extract of 700 Tetrastigma hemsleyanum on C57BL /6J Mice with Lewis Lung Cance Inhibitory effect of ethyl acetate 703 extract of Tetrastigma Hemsleyanum on transplanted tumor of Lewis lung cancer 704 and its immune function Investigation on apoptosis of human cervical cancer Hela cells 706 induced by extracts from Tetrastigma hemsleyanum diels et Gilg. Chin Mod 707 Doctor Study on the Tetrastigma Hemsleyanum Anti-induced liver injury in mice. Chin Mod Doctor Components in Tetrastigma Hemsleyanum of Different Months PGE2-dependent mechanisms Effect of Tetrastigma Hemsleyanum flavone on TIMP-2mRNA expression 761 in H22 Tumor Bearing Mice Study on germplasm identification, suspension culture and effects on 763 apoptosis of human hepatocarcinoma HepG2 cells induced by the active 764 components of Tetrastigma hemsleyanum Germplasm Research and Utilization of Tetrastigma 766 hemsleyanum, A Chinese-specific Medicinal Plant Transcriptome 769 profiling reveals candidate flavonol-related genes of Tetrastigma hemsleyanum 770 under cold stress Tetrastigma hemsleyanum from its adulterant species using ISSR, CAPS, and 773 ITS2 barcode Ethylacetate extract from Tetrastigma 775 hemsleyanum induces apoptosis via the mitochondrial caspase-dependent 776 intrinsic pathway in HepG2 cells Influence of Rare Earth Elements on 778 Metabolism and Related Enzyme Activity and Isozyme Expression in 779 Archives of 72 cases of infantile exogenous fever treated with Sanye qing gypsum 895 Rapid simultaneous determination of ten major flavonoids in Tetrastigma 898 hemsleyanum by UPLC-MS/MS Qualitative and quantitative study on the main components of Tetrastigma 901 hemsleyanum by HPLC-Q-TOF and UPLC-QqQ-MS Treatment of 72 cases of exogenous fever in children with sanyeqing 904 and gypsum decoction Anti-tumor Effects of Different Processed Tetrastigma Hemsleyanum Diels et Gilg on Lewis Lung Cancer and H22 Liver Cancer in Mice Comparative 910 study on the growth inhibition of human lung cancer A549 transplanted tumor in 911 nude mice with different preparation of Tetrastigma Hemsleyanum UFLC-DAD Simultaneous Determination of Procyanidins Catechin in Tetrastigma Hemsleyanum Total flavonoid extracts of Tetrastigma hemsleyanum inhibit growth and 935 migration of colorectal cancer through Wnt/β-catenin signaling pathway Total flavonoids 938 of Tetrastigma hemsleyanum inhibits the cycle and proliferation of colon cancer 939 cellsthrough the Wnt/β-catenin pathway Clover Extract on Human Colon Cancer Cellular A549 Apoptosis Tetrastigma hemsleyanum on Caspase-3 expression in A549 lung carcinoma cells Tetrastigma hemsleyanum by UPLC-Triple -TOF/MS. Chin Tradit Herbal Drugs. 948 Experimental study on apoptosis of 950 SMMC-7721 hepatoma cells induced by Tetrastigma hemsleyanum flavones