Modulation of Xiongdanjiuxin pills on the gut-liver axis in high-fat diet rats.

AIM: Xiongdanjiuxin pill (XP) is a traditional Chinese medicine formula for the prevention and treatment of hyperlipidemia (HLP) and related complications. In this study, the gut-liver axis was used as the breakthrough point to analyze the therapeutic effect and potential mechanism of XP on HLP model rats and related complications. MAIN METHODS: We used high-fat diet (HFD) to establish the HLP model of rats and treated them with XP. The 16S rRNA sequencing method was used to explore the effect of XP on the gut microbiota of HFD rats, and the effects of XP on ileum pathology, intestinal barrier and circulatory inflammation in HFD rats were also investigated. We further explored the molecular mechanism of XP treating liver inflammation in rats with HFD by regulating toll-like receptor 4 (TLR4) signaling. KEY FINDINGS: We found that XP could regulate the imbalance of gut microbiota in HFD rats, and up-regulate the expression of tight junction protein in intestinal epithelium of HFD rats, thereby improving the intestinal barrier damage and intestinal inflammatory response. In addition, XP could significantly reduce the levels of inflammatory cytokines in HFD rats, and inhibit TLR4 signaling pathway, thereby reducing liver inflammation in HFD rats. SIGNIFICANCE: XP can effectively improve the imbalance of gut-liver axis in hyperlipidemic rats and alleviate the inflammatory damage of liver. Its mechanism may be related to regulating the disorder of gut microbiota and inhibiting TLR4 signal pathway, so as to achieve the therapeutic effect on hyperlipidemic fatty liver in rats.

Pharmacological characterization of a novel gastrodin derivative as a potential anti-migraine agent.

Migraine is a highly prevalent neurovascular disorder in the brain. An optimal therapy for migraine has not yet been developed. Gastrodin (Gas), the main effective constitute from Gastrodiae Rhizoma (Tianma in Chinese), has been indicated for migraine treatment and prophylaxis more than 30 years, with demonstrated safety. However, Gas is a phenolic glycoside, with relatively low concentrations and weak efficacy in the central nervous system. To develop more effective anti-migraine agents, we synthesized a novel Gas derivative (Gas-D). In the present study, comparative pharmacodynamic evaluations of Gas and Gas-D were performed in a model of nitroglycerin (NTG)-induced migraine in rats and the hot-plate test in mice. Following behavioral testing in this migraine model, external jugular vein blood and the trigeminal nucleus caudalis (TNC) were collected to analyze plasma nitric oxide (NO) and calcitonin gene-related peptide (CGRP) concentrations and c-Fos expression in the TNC. The acute oral toxicity of Gas and Gas-D was also examined. We found that Gas-D had potent anti-migraine effects, likely attributable to inhibition of both trigeminal nerve activation at central sites and the peripheral release of CGRP following NO scavenging. Additionally, Gas-D exerted significant anti-nociceptive effect in response to thermal pain compared with Gas. Furthermore, a single dose of 2.048 g/kg Gas or Gas-D presented no acute oral toxicity in mice. Altogether, the potent anti-migraine and anti-hyperalgesic effects of Gas-D suggest that it might be a potentially novel drug candidate for migraine treatment or prophylaxis.

Pennogenyl saponins induce cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Pennogenyl saponins, the characterized components of Rhizoma Paridis, have been reported to have anticancer activity through induction of apoptosis or anti-metastasis in cultured cells or animal models. The aim of the study was to evaluate the anticancer properties of four pennogenyl saponins (PS1-PS4) on a panel of human cancer and normal cell lines, and explore the potential mechanisms underlying the selective anticancer effects of the steroidal saponins in cancer cells. MATERIALS AND METHODS: Differences in the anticancer activity of pennogenyl saponins were examined by MTT assay in human cancer cell lines (HepG2 hepatocellular carcinoma cells, UACC-257 melanoma cells, MCF-7 breast and PC-3 prostate cancer cells) and normal human cell lines (L-02 liver cells and HEK293 kidney cells). Flow cytometry analysis, JC-1 staining and western blot analysis were applied to detect the effects of anticancer pennogenyl saponins on apoptosis, cell cycle, and expression and/or activation of main effectors involved in the potential signaling pathways. RESULTS: Among the tested four saponins, only PS1 and PS2 selectively inhibited cell growth in HepG2, MCF-7 and PC-3 cells. Moreover, PS1 and PS2 could significantly induce apoptosis and cell cycle G2/M arrest in HepG2 cells, which were at least associated with activation of mitochondrial caspase-dependent and -independent apoptotic cascades, inhibition of cyclin-dependent kinase 1 and PI3K/Akt signaling pathway, and modulation of mitogen-activated protein kinases. CONCLUSIONS: PS1 and PS2 had potent and selective anticancer activity to breast, liver and prostate cancer cells. Furthermore, the anticancer effects of PS1 and PS2 were associated with induction of apoptosis and blockage of cell cycle progression through multiple targets in HepG2 cells. These findings suggest that PS1 and PS2 can be considered as potential agents for the treatment of some cancers such as hepatoma.