A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1

Abstract Purpose: To investigate the specific molecular mechanisms and effects of curcumin derivative J147 on diabetic peripheral neuropathy (DPN). Methods: We constructed streptozotocin (STZ)-induced DPN rat models to detected mechanical withdrawal threshold (MWT) in vivo using Von Frey filaments. In vitro, we measured cell viability and apoptosis, adenosine 5'-monophosphate-activated protein kinase (AMPK) and transient receptor potential A1 (TRPA1) expression using MTT, flow cytometry, qRT-PCR and western blot. Then, TRPA1 expression level and calcium reaction level were assessed in agonist AICAR treated RSC96cells. Results: The results showed that J147reduced MWT in vivo, increased the mRNA and protein level of AMPK, reduced TRPA1 expression and calcium reaction level in AITCR treated RSC96 cells, and had no obvious effect on cell viability and apoptosis. Besides, AMPK negative regulated TRPA1 expression in RSC96 cells. Conclusions: J147 could ameliorate DPN via negative regulation AMPK on TRPA1 in vivo and in vitro. A curcumin derivative J147might be a new therapeutic potential for the treatment of DPN.

Ginsenoside Rg1 inhibits dietary-induced obesity and improves obesity-related glucose metabolic disorders

Obesity and its consequent type 2 diabetes are significant threats to global health. Emerging evidence indicates that ginsenosides from ginseng (Panax ginseng) have anti-diabetic activity. We hypothesized that ginsenosides Rg1 could suppress dietary-induced obesity and improve obesity-related glucose metabolic disorders. Our results showed that ginsenoside Rg1 attenuated dietary-induced body weight gain and fat accumulation in white adipocyte tissue of mice fed a high-fat diet. Furthermore, we found that ginsenosides Rg1 not only decreased fasting glucose concentration and the 2-h postprandial glucose concentration, but also improved insulin resistance and glucose intolerance in those mice. Ginsenoside Rg1 also activated the AMPK pathway in vitro and in vivo and increased plasma membrane translocation of GLUT4 in C2C12 skeletal muscle cells. In conclusion, our observations suggested that ginsenoside Rg1 inhibited dietary-induced obesity and improved obesity-related insulin resistance and glucose intolerance by activation of the AMPK pathway.

Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5

Chemotherapy response rates in patients with cholangiocarcinoma remain low, primarily due to the development of drug resistance. Epithelial-mesenchymal transition (EMT) of cancer cells is widely accepted to be important for metastasis and progression, but it has also been linked to the development of chemoresistance. Salinomycin (an antibiotic) has shown some potential as a chemotherapeutic agent as it selectively kills cancer stem cells, and has been hypothesized to block the EMT process. In this study, we investigated whether salinomycin could reverse the chemoresistance of cholangiocarcinoma cells to the chemotherapy drug doxorubicin. We found that combined salinomycin with doxorubicin treatment resulted in a significant decrease in cell viability compared with doxorubicin or salinomycin treatment alone in two cholangiocarcinoma cell lines (RBE and Huh-28). The dosages of both drugs that were required to produce a cytotoxic effect decreased, indicating that these two drugs have a synergistic effect. In terms of mechanism, salinomycin reversed doxorubicin-induced EMT of cholangiocarcinoma cells, as shown morphologically and through the detection of EMT markers. Moreover, we showed that salinomycin treatment downregulated the AMP-activated protein kinase family member 5 (ARK5) expression, which regulates the EMT process of cholangiocarcinoma. Our results indicated that salinomycin reversed the EMT process in cholangiocarcinoma cells by inhibiting ARK5 expression and enhanced the chemosensitivity of cholangiocarcinoma cells to doxorubicin. Therefore, a combined treatment of salinomycin with doxorubicin could be used to enhance doxorubicin sensitivity in patients with cholangiocarcinoma.

Potential role of marine algae extract on 3T3-L1 cell proliferation and differentiation: an in vitro approach

BACKGROUND: From ancient times, marine algae have emerged as alternative medicine and foods, contains the rich source of natural products like proteins, vitamins, and secondary metabolites, especially Chlorella vulgaris (C. vulgaris) contains numerous anti-inflammatory, antioxidants and wound healing substances. Type 2 diabetes mellitus is closely associated with adipogenesis and their factors. Hence, we aimed to investigate the chemical constituents and adipo-genic modulatory properties of C. vulgaris in 3T3-L1 pre-adipocytes. RESULTS: We analysed chemical constituents in ethanolic extract of C. vulgaris (EECV) by LC-MS. Results revealed that the EECV contains few triterpenoids and saponin compounds. Further, the effect of EECV on lipid accumulation along with genes and proteins expressions which are associated with adipogenesis and lipogenesis were evaluated using oil red O staining, qPCR and western blot techniques. The data indicated that that EECV treatment increased differentiation and lipid accumulation in 3T3-L1 cells, which indicates positive regulation of adipogenic and lipogenic activity. These increases were associated with up-regulation of PPAR-γ2, C/EBP-α, adiponectin, FAS, and leptin mRNA and protein expressions. Also, EECV treatments increased the concentration of glycerol releases as compared with control cells. Troglitazone is a PPAR-γ agonist that stimulates the PPAR-y2, adiponectin, and GLUT-4 expressions. Similarly, EECV treatments significantly upregulated PPAR-γ, adiponectin, GLUT-4 expressions and glucose utilization. Further, EECV treatment decreased AMPK-α expression as compared with control and metformin treated cells. CONCLUSION: The present research findings confirmed that the EECV effectively modulates the lipid accumulation and differentiation in 3T3-L1 cells through AMPK-α mediated signalling pathway.