Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells.

The potential antitumor effects of sempervirine (SPV), an alkaloid compound derived from the traditional Chinese medicine Gelsemium elegans Benth., on different malignant tumors were described in detail. The impact of SPV on glioma cells and the basic atomic components remain uncertain. This study aimed to investigate the activity of SPV in vitro and in vivo. The effect of SPV on the growth of human glioma cells was determined to explore three aspects, namely, cell cycle, cell apoptosis, and autophagy. In this study, glioma cells, U251 and U87 cells, and one animal model were used. Cells were treated with SPV (0, 1, 4, and 8 µM) for 48 h. The cell viability, cell cycle, apoptosis rate and autophagic flux were examined. Cell cycle, apoptotic, autophagy, and Akt/mTOR signal pathway-related proteins, such as CDK1, Cyclin B1, Beclin-1, p62, LC3, AKT, and mTOR were investigated by Western blot approach. As a result, cells induced by SPV led to G2/M phase arrest and apoptosis. SPV also promoted the effect of autophagic flux and accumulation of LC3B. SPV reduced the expression of p62 protein and induced the autophagic death of glioma cells. Furthermore, SPV downregulated the expressions of AKT and mTOR phosphorylated proteins in the mTOR signaling pathway, thereby affecting the onset of apoptosis and autophagy in U251 cells. In conclusion, SPV induced cellular G2/M phase arrest and blockade of the Akt/mTOR signaling pathway, thereby triggering apoptosis and cellular autophagy. The in vivo and in vitro studies confirmed that SPV inhibits the growth of glioma cancer.

Anti-osteoporotic effects of alisol C 23-acetate via osteoclastogenesis inhibition.

Alismatis rhizoma (AR) is the dried rhizome of Alisma orientale (Sam.) Juz. (Alismataceae). This traditional Chinese formula is diuretic, hypoglycemic, and hypolipidemic. Alisol C 23-acetate (AC23A) from AR is anti-inflammatory and ameliorates certain metabolic diseases. However, the mechanism by which AC23A mitigates osteoporosis is unknown. The present study investigated the anti-osteoporotic effects of AC23A in vivo and in vitro. In an ovariectomized (OVX) rat model, AC23A ameliorated OVX-induced organ coefficients and trabecular bone loss. In OVX rats, AC23A treatment lowered serum TRAP5b, CTK, ß-CTX, TNF-α, IL-6, and IL-1ß, raised serum E2, and did not significantly change serum OCN or BALP. AC23A inhibited osteoclast formation in a rat co-culture system without affecting osteoblast activity. RANK (receptor activator of nuclear factor kappaB) signaling channels are vital osteoclastogenesis transcription elements. AC23A inhibited RANK ligand (RANKL)-induced TRAP, c-Fos, MMP9, NFATc1, and CTK expression and JNK phosphorylation. Therefore, AC23A is anti-osteoclastogenic in vitro and in vivo by inhibiting RANKL-induced osteoclast differentiation and function. Moreover, AC23A could help prevent or limit osteoclast-mediated bone diseases by inhibiting osteoclastogenesis.

Alismatis Rhizoma Triterpenes Alleviate High-Fat Diet-Induced Insulin Resistance in Skeletal Muscle of Mice.

Alismatis rhizoma (AR), which is the dried rhizome of Alisma orientale (Sam.) Juz. (Alismataceae), is an important component of many famous Chinese formulas for hypoglycemic. This study aimed to evaluate the insulin resistance (IR) alleviating effects of AR triterpenes (ART) and ART component compatibility (ARTC, the mixture of 16-oxo-alisol A, 16-oxo-alisol A 23-acetate, 16-oxo-alisol A 24-acetate, alisol C, alisol C 23-acetate, alisol L, alisol A, alisol A 23-acetate, alisol A 24-acetate, alisol L 23-acetate, alisol B, alisol B 23-acetate, 11-deoxy-alisol B and 11-deoxy-alisol B 23-acetate) in high-fat diet-induced IR mice and plamitate-treated IR C2C12 cells, respectively. A dose of 200 mg/kg of ART was orally administered to IR mice, and different doses (25, 50, and 100 µg/ml) of ARTC groups were treated to IR C2C12 cells. IPGTT, IPITT, body weight, Hb1AC, FFA, TNF-α, MCP-1, and IR-associated gene expression (p-AMPK, p-IRS-1, PI3K, p-AKT, p-JNK, and GLUT4) were measured in IR mice. Glucose uptake, TNF-α, MCP-1, and IR-associated gene expression were also measured in IR C2C12 cells. Results showed that ART alleviated high-fat diet-induced IR in the skeletal muscle of mice, and this finding was further validated by ARTC. This study demonstrated that ART presented a notable IR alleviating effect by regulating IR-associated gene expression, and triterpenes were the material basis for the IR alleviating activity of AR.