[Chemical constituents from roots of Kadsura heteroclita].

The dichloromethane fraction of Kadsura heteroclita roots was separated and purified by chromatographic techniques(e.g., silica gel, Sephadex LH-20, ODS, MCI column chromatography) and semi-preparative HPLC. Twenty compounds were isolated from K. heteroclita, and their structures were identified by NMR, MS, UV, and X-ray single crystal diffraction techniques. Twenty compounds were isolated from K. heteroclita, which were identified as xuetongdilactone G(1), mallomacrostin C(2), 3,4-seco(24Z)-cychmrt-4(28),24-diene-3,26-dioic acid 3-methyl ester(3), nigranoic acid(4), methyl ester schizanlactone E(5), schisandronic acid(6), heteroclic acid(7), wogonin(8),(2R,3R)-4'-O-methyldihydroquercetin(9), 15,16-bisnor-13-oxo-8(17),11E-labdadien-19-oic acid(10), stigmast-4-ene-6ß-ol-3-one(11), psoralen(12),(1R,2R,4R)-trihydroxy-p-menthane(13), homovanillyl alcohol(14), 2-(4-hydroxyphenyl)-ethanol(15), coniferaldehyde(16),(E)-7-(4-hydroxy-3-methoxyphenyl)-7-methylbut-8-en-9-one(17), acetovanillone(18), vanillic acid(19) and vanillin(20). Compound 1 is a new compound named xuetongdilactone G. Compounds 2-3 and 8-20 are isolated from K. heteroclita for the first time.

Kadsura heteroclita stem ethanol extract protects against carbon tetrachloride-induced liver injury in mice via suppression of oxidative stress, inflammation, and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Kadsura heteroclita stem (KHS) is a well-known hepatoprotective Tujia ethnomedicine (folk named Xuetong), has long been used for the prevention and treatment of hepatitis and liver diseases. AIM OF THE STUDY: To explore the protective effects of KHS against carbon tetrachloride (CCl4)-induced liver injury and the underlying mechanism, particularly antioxidative, anti-inflammatory, and anti-apoptotic potentials. MATERIALS AND METHODS: The acute toxicity of KHS was measured by the method of maximum tolerated dose (MTD). Liver injury in mice was induced by intraperitoneal injection of 25% carbon tetrachloride (olive oil solubilization) 2 times every week. After modeling, mice in KHS groups were treated with KHS at 100, 200, 400 mg/kg/d, mice in positive control group were treated with bifendate (30 mg/kg/d), and mice in normal and model groups were given ultrapure water. After 4 weeks of treatment, blood of mice was taken from the orbital venous plexus before mice euthanized, the liver, spleen, and thymus of mice were weighed by dissecting the abdominal cavity after mice euthanized. Moreover, the liver of mice was selected for histological examination. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in mice serum were measured using the automatic biochemical analyzer. The levels of superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione peroxidase (GPX-2), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), Bcl-2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), Caspase-3, and Caspase-8 in mice liver were measured by Elisa kits. Furthermore, the protein expression of Bcl-2 and Bax in mice liver tissue was detected by Western blot. RESULTS: The MTD of KHS was determined to be 26 g/kg in both sexes of mice. Treatment with KHS dose-dependently protected the liver and other main organs against CCl4-induced liver injury in mice. The ALT and AST levels in mice liver were significantly reduced after treatment with KHS at the dose of 100, 200, and 400 mg/kg. In addition, the liver histopathological analyses revealed that KHS markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl4. Further assay indicated that KHS significantly suppressed the production of MDA and MPO, while markedly increased the level of SOD and GPx-2. The TNF-α and IL-6 level in mice liver tissue were decreased by KHS, whereas the IL-10 level was increased. KHS also inhibited hepatocyte apoptosis by significantly reducing the expression of Bax, Caspase-3, Caspase-8, as well as increasing the expression of Bcl-2. Besides, the Western blot results strongly demonstrated that KHS inhibited hepatocyte apoptosis, as evidenced by reducing the expression of Bax protein and increasing the expression of Bcl-2 protein in liver injury tissues. CONCLUSIONS: This research firstly clarified that KHS has a significant protective effect against CCl4-induced liver injury, which might be closely related to alleviating oxidative stress, reducing inflammatory response, and inhibiting hepatocyte apoptosis.

Triterpenoids from stems of Kadsura heteroclita.

In the present work, we reported the triterpenoids isolated from n-butanol fraction of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name "Xuetong". This effort resulted in the isolation of six unpresented triterpenoids xuetongsu A-F (1-6), along with five known triterpenoids (7-11). The structures of the reported compounds were established on the 1D, and 2D NMR and HRESIMS spectra, along with CD spectroscopic analysis. Moreover, the absolute stereochemistry of compound 7 was determined by X-ray diffraction analysis. Antioxidant and cytotoxic activities were evaluated for all isolated compounds, compound 7 shown weak cytotoxic activity against HL-60 with IC50 value of 50.0 µM.

Schinortriterpenoids from Tujia ethnomedicine Xuetong-The stems of Kadsura heteroclita.

In the present work, we take advantage of the characteristic NMR signal (δC-10 = 96.0-99.9) for guiding the isolation of schinortriterpenoids (SNTs) from n-butanol fraction of stems of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name "Xuetong". This effort resulted in the identification of three unreported 3,4:9,10-disecocycloartane triterpenoids xuetongdilactones A-C and three undescribed SNTs xuetongdilactones D-F, along with two known SNTs, namely, wuweizidilactone B and micrandilactone B. The structures of the unreported compounds were established based on 1D, and 2D NMR, HRESIMS, and ECD spectroscopic data analysis. The absolute stereochemistry of xuetongdilactone A was determined by X-ray diffraction analysis along with ECD calculation. The antioxidant and cytotoxic activities were evaluated for all the isolated compounds.

Tujia ethnomedicine Xuetong suppresses onset and progression of adjuvant-induced arthritis in rats / 中国药理学通报

Aim Kadsuraheteroclita ( Roxb ) Craib ( Schizandraceae) is a medicinal plant termed Xuetong in Chinese Tujia ethnomedicine. Xuetong possesses therapeutic effects of, in the terms of Chinese medical theories, reinforcing vital energy, promoting blood cir-culation, expelling wind-evil, and removing damp-e-vil, and has been long used for the prevention and treatment of rheumatic and arthritic diseases, especial-ly in the southern China. The HPLC analysis has iden-tified that the ethanol extract of Xuetong contains large-ly biologically active lignans and triterpenoids. Our previous studies have shown that KHS exhibits very fa-vorable safety profile and potent anti-inflammatory and analgesic activities. In the present study, we investiga-ted anti-arthritic effects and the possible mechanisms of Xuetongon adjuvant-induced arthritis ( AIA ) in rats. Methods AIA was established in male Sprague-Daw-ley ( SD ) rats as described previously, and animals were daily treated by gavage with Xuetong ethanol ex-tract ( 1. 0 g · kg-1 ) or vehicle ( 0. 3% CMC-Na ) throughout the 30-day experiment. The incidence and severity of arthritis were evaluated using clinical pa-rameters. On day 30, bone destruction of the arthritic joints was assessed by computed tomography( CT) and histopathological analyses. The serum levels of pro-in-flammatory cytokines TNF-α, IL-1β, and IL-6 were measured by ELISA. Results Treatment with 1. 0 g/kg Xuetong significantly inhibited the onset and pro-gression of AIA. The vehicle-treated rats all developed severe arthritis, while the incidence of AIA in the Xue-tong-treated rats was as low as 55%( P=0. 035 ) . The Xuetong -treated rats exhibited 1. 8 to 2. 3 fold reduc-tion of paw swelling, and gained 10 to 20% more body weight than the vehicle-treated AIA rats throughout the experiment. CT and histopathological examinations re-vealed that Xuetong markedly protected AIA rats from cartilage and bone destruction of joints. Moreover, the serum levels of TNF-α, IL-1β, and IL-6 were signifi-cantly decreased in the Xuetong-treated rats than the vehicle-treated AIA rats. Conclusions These data strongly support the clinical use of Xuetong for rheu-matic and arthritic diseases, and suggest that Xuetong is a valuable candidate for further investigation to be a new anti-arthritic drug with favorable safety profile.