ABSTRACT
Objective: To study the active triterpenoid saponins of Tujia ethnomedicine Kouziqi (Panax japonicus var. major). The antitumor activity was screened and the relationship between the structure and activity of the compounds was discussed. Methods: The ethanol extract of Kouziqi was isolated by Silica gel, ODS and MCI column chromatograph and purified by preparative HPLC. The structures were elucidated on the basis of spectroscopic analysis and compared with literatures. Using MTT assay to detect the cytotoxicity of 14 compounds in BGC-823, HCT-116, Hela, HepG-2 cells. Results: A total of 14 known compounds were isolated from Tujia ethnomedicine Kouziqi and determined as chikusetsusaponin IVa methyl ester (1), chikusetsusaponin IVa butyl ester (2), chikusetsusaponin IV (3), chikusetsusaponin IVa (4), 28-desglucosylchikusetsusaponin IVa (5), oleanolic acid-3-O-β-D-(6'- methylester)-glucuronopyranoside (6), (24R)-majonoside R1 (7), (24R)-pseudoginsinoside F11 (8), (20S)-notoginsinoside-R2 (9), (20S)-ginsenoside Rg2 (10), ginsenoside Rg1 (11), ginsenoside Re (12), ginsenoside Rd (13) and chikusetsusaponin-V methyl ester (14). Among the 14 compounds, compounds 5 and 6 showed dose-dependent cytotoxicity to BGC-823, HCT-116, Hela and HepG-2 cells. Compound 5 had cytotoxicity in BGC-823 and HCT-116 cells with IC50 values of 9.94 and 14.17 μmol/L, respectively. Compound 6 had the best cytotoxicity in HepG-2 cells with IC50 value of 12.70 μmol/L. Conclusion: Compound 6 is isolated from Kouziqi for the first time and its spectral data were reported. The antineoplastic activity of Tujia ethnomedicine Kouziqi is based on the oleanolic acid-type triterpenoid saponins and related to the substituents of C-28, but the mechanism still needs to be deeply studied.
ABSTRACT
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.