Neferine inhibits the development of lung cancer cells by downregulating TGF-ß to regulate MST1/ROS-induced pyroptosis.

Non-small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF-ß and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial-mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus-mediated gain-of-function studies of TGF-ß and MST1 were applied to validate the roles of TGF-ß and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF-ß expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF-ß in either in vitro or mouse-transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF-ß to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.

Sangguayin preparation prevents palmitate-induced apoptosis by suppressing endoplasmic reticulum stress and autophagy in db/db mice and MIN6 pancreatic ß-cells.

Sangguayin preparation (SGY-P) is refined from the traditional Chinese medicinal compound Sangguayin, which "clears heat and promotes fluid" and "tonifies kidney and spleen" for "Xiaoke", commonly known as 'Diabetes mellitus' in clinics. Previous studies have shown that SGY-P could reduce insulin resistance and repair damaged pancreas in db/db mice, but the underlying mechanisms were unclear. Here, we investigated whether treatment with SGY-P could protect pancreatic ß-cells from apoptosis and uncovered the underlying mechanisms. db/db mice were used to observe the hypoglycemic and islet protective effect in vivo. Apoptosis was induced in mouse insulinoma 6 (MIN6) cells by palmitate, following which the cells were treated with SGY-P for elucidating the anti-apoptotic mechanism in vitro. Cell viability and nuclear morphology were detected by CCK-8 assay and Hoechst 33258 staining. The expression levels of apoptosis-, endoplasmic reticulum (ER) stress-, and autophagy-related proteins were measured by western blot. The results showed that SGY-P reduced fasting blood glucose, pancreatic pathological changes, and islet ß-cell apoptosis in db/db mice. Palmitate-induced apoptosis in MIN6 cells was decreased by SGY-P treatment. Hence, SGY-P therapy exhibited a protective effect on pancreatic ß-cells by decreasing the expression of cleaved caspase-3, cleaved PARP and Bax, and increasing Bcl-2 by suppressing ER stress (Bip/XBP1/IRE1α/CHOP/Caspase-12) and autophagy (LC3/p62/Atg5) pathways.2/Atg5) pathways.

Corrigendum to "The Effect of Sanggua Drink Extract on Insulin Resistance through the PI3K/AKT Signaling Pathway".

[This corrects the article DOI: 10.1155/2018/9407945.].

The Effect of Sanggua Drink Extract on Insulin Resistance through the PI3K/AKT Signaling Pathway.

Treating type 2 diabetes mellitus (T2DM) using thiazolidinediones and biguanides can present several challenges for patients. Sanggua Drink (SGD) is a commonly used agent in traditional Chinese medicine, and it consists of Folium Mori, Fructus Momordicae Charantiae, Radix Puerariae Lobatae, and Rhizoma Dioscorea. The hypoglycemic effects and mechanisms of SGD extracts on insulin resistance in diabetic rats were investigated. SGD (1.24 g/kg orally) was verified in T2DM rats induced by a high-fat diet and streptozotocin. The results showed that SGD treatment was observed to reduce fasting blood glucose, water and food intake, total cholesterol triglycerides, and LDL, OGTT, FINS, HOMA-IR, GHb, and MDA and increase hepatic glycogen, HDL, SOD, CAT, and GSH-Px in diabetic rats. Simultaneously, SGD treatment by T2DM showed significantly ameliorated pathological changes and reduced inflammation in the pancreas. Treatment was also observed to increase gene and protein expressions of InsR, IRS-2, PI3K, AKT, and Glut4 in the livers of diabetic treated rats. These results suggest that SGD extracts have hypoglycemic properties and may alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Therefore, SGD appears to be a promising insulin sensitizer.