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Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional formula that has long been used for treatment of inflammatory diseases in Traditional Chinese Medicine. In this study, we examined its protective effect against sepsis in an experimental septic model induced by cecal ligation and puncture (CLP) in rats. The results demonstrated that prophylactic administration of HLJDT protected rats from CLP-induced lethality and ameliorated CLP-induced liver and lung injury. HLJDT treatment suppressed the production of proinflammatory cytokines, including TNF-α, IL-1, IL-6, and IL-17A, indicating HLJDT could limit excessive inflammatory responses in septic condition. In addition, HLJDT facilitated bacterial clearance by increasing phagocytic activities of peritoneal macrophages. Furthermore, HLJDT treatment reversed CLP-induced suppression of IFN-γ expression and blocked CLP-induced increase in IL-4 expression in spleens of rats at 24 h after CLP, indicating that HLJDT could reverse the shift from Th1 to Th2 response and promote Th1/Th2 balance toward Th1 predominance in septic rats. Moreover, HLJDT also inhibited the expression of IL-17A and ROR-γt in spleens of septic rats, indicating HLJDT is able to inhibit Th17 activation in septic condition. In conclusion, the present study demonstrated the protective effects of HLJDT against sepsis and highlighted the potential of HLJDT as a medication for septic patients.

Background: Rabdosia japonica has been historically used in China as a popular folk medicine for the treatment of cancer, hepatitis, and gastricism. Glaucocalyxin A (GLA), an ent-kaurene diterpene isolated from Rabdosia japonica, is one of the main active ingredients showing potent inhibitory effects against several types of tumor cells. To the best of our knowledge, studies regarding the structural modification and Structure-Activity Relations (SAR) of this compound have not yet been reported. Objective: The aim of this study is to discover more potent derivatives of GLA and investigate their SAR and cytotoxicity mechanisms. Methods: Novel 7-O- and 14-O-derivatives of GLA were synthesized by condensation of acids or acyl chloride. The anti-tumor activities of these derivatives against various human cancer cell lines were evaluated in vitro by MTT assays. Apoptosis assays of compound 17 (7,14-diacylation product) were performed on A549 and HL-60 cells by flow cytometry and TUNNEL. The acute toxicity of this compound was tested on mice, at the dose of 300mg per kg body weight. Results: Seventeen novel 7-O- and 14-O-derivatives of GLA (1-17) were synthesized. These compounds show potent cytotoxicity against the tested cancer cell lines, and almost all of them were found to be more cytotoxic than GLA and oridonin. Of the synthesized derivatives, compound 17 presents the greatest cytotoxicity, with IC50 values of 0.26μM and 1.10μM in HL-60 and CCRF-CEM cells, respectively. Furthermore, this compound induces weak apoptosis of A549 cells but has great potential in stimulating the apoptosis of HL-60 cells. Acute toxicity assays indicate that compound 17 is relatively safe. Conclusion: The results reported herein indicate that the synthesized GLA derivatives exhibit greater cytotoxicity against leukemia cells than against other types of tumors. In particular, the 7,14-diacylation product of GLA is an effective anti-tumor agent. However, the cytotoxicity mechanism of this product in A549 cells is expected to be different than that in other tumor cell lines. Further research is needed to confirm this hypothesis.

The study of Ervatamia yunnanensis Tsiang, growing in Yunnan and Guangxi provinces of China, has focused on the isolation of alkaloids [1][2][3][4][5][6], which are demonstrated to have significant anti-addictive, anti-malarial, anti-reproductive, and anticancer activities [7,8]. About 30 indole alkaloids have been isolated from E. yunnanensis Tsiang. Continuing our investigations into the biologically active constituents of nonalkaloid parts of Ervatamia yunnanensis by chromatographic and spectroscopic methods, we have isolated two lignans (1 and 2), five flavonoids (6, 9, 11, 13, and 14), two triterpenoids (7 and 8), three organic or fatty acids and derivatives (3, 4, and 12), vanillin (10), and one aromatic ketone (5).The plant material was collected in May 2003 at Xishuangbanna, Yunnan province and identified as the stems of Ervatamia yunnanensis Tsiang by Senior Engineer Wang Hong, Xishuanbanna Tropical Plant Garden of the Chinese Academy of Sciences. The air-dried and powdered stems and branches (5 kg) were extracted with 95% EtOH (10 L) by reflux. The percolate was evaporated in vacuum to yield the EtOH extract (425 g), which was suspended in 2% HCl solution. The precipitate in the lower layer after centrifugation, which was deplete of alkaloids, was dissolved in distilled water; then the solution was chromatographed over macroporous adsorptive resin AB-8, eluting with a gradient mixture of water and alcohol. The compositions of fractions were analyzed by TLC. Similar fractions were combined to afford fraction A, 60.0 g (30% alcohol); fraction B, 40.0 g (60% alcohol), and fraction C, 15.0 g (90% alcohol). Fractions A, B, and C were subjected to repeated chromatography on silica-gel columns eluting with a gradient mixture of petroleum ether-ethyl acetate or chloroform-methanol, Sephadex LH-20 eluting with chloroform-methanol, methanol, or a gradient mixture of methanol-water, and C-18 reverse silica-gel columns eluting with a gradient mixture of methanol-water. A total of fourteen compounds (1-14) was isolated and identified based on NMR and mass spectrum, and by direct comparison with authentic samples and the literature. All the identified compounds are known compounds and are reported for the first time from Ervatamia yunnanensis. (+)-Isolariciresinol-9-O-E-D-glucopyranoside (1), white crystalline powder, C 26 H 34 O 11 , ESI-MS: m/z 521 [M -H] -, 545 [M + Na] + .