DPHC From Alpinia officinarum Ameliorates Oxidative Stress and Insulin Resistance via Activation of Nrf2/ARE Pathway in db/db Mice and High Glucose-Treated HepG2 Cells

(R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC) from the natural plant Alpinia officinarum has been reported to have antioxidation and antidiabetic effects. In this study, the therapeutic effect and molecular mechanism of DPHC on type 2 diabetes mellitus (T2DM) were investigated based on the regulation of oxidative stress and insulin resistance (IR) in vivo and in vitro. In vivo, the fasting blood glucose (FBG) level of db/db mice was significantly reduced with improved glucose tolerance and insulin sensitivity after 8 weeks of treatment with DPHC. In vitro, DPHC ameliorated IR because of its increasing glucose consumption and glucose uptake of IR-HepG2 cells induced by high glucose. In addition, in vitro and in vivo experiments showed that DPHC could regulate the antioxidant enzyme levels including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby reducing the occurrence of oxidative stress and improving insulin resistance. Western blotting and polymerase chain reaction results showed that DPHC could promote the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), the heme oxygenase-1 (HO-1), protein kinase B (AKT), and glucose transporter type 4 (GLUT4), and reduced the phosphorylation levels of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) on Ser307 both in vivo and in vitro. These findings verified that DPHC has the potential to relieve oxidative stress and IR to cure T2DM by activating Nrf2/ARE signaling pathway in db/db mice and IR-HepG2 cells.

Microbial Transformation of Galangin Derivatives and Cytotoxicity Evaluation of Their Metabolites

Galangin (1), 3-O-methylgalangin (2), and galangin flavanone (3), the major bioactive flavonoids isolated from Alpinia officinarum, were biotransformed into one novel and four known metabolites (4–8) by application of the fungal strains Mucor hiemalis and Absidia coerulea as biocatalysts. Their structures were characterized by extensive spectroscopic analyses including one- and two-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry. Compounds 1–7 were evaluated for their cytotoxic activities against cancer cell lines using the MTT assay. The new compound 3-O-methylgalangin-7-O-β-D-glucopyranoside (6) exhibited the most potent cytotoxic activity against MCF-7, A375P, B16F10, B16F1, and A549 cancer cell lines with the IC50 values at 3.55–6.23 μM.

Quantification of Flavonoids in Alpinia officinarum Hance. via HPLC and Evaluation of its Cytotoxicity on Human Prostate Carcinoma (LNCaP) and Breast Carcinoma (MCF-7) Cells

Background: Various plant species have been shown to be effective in prevention or adjuvant therapy of cancer. Alpinia officinarum and its main phytochemicals have also been the subject of several studies for their anti-cancer properties. Objective: The objective of this study is to analyze the extracts of A. officinarum to quantify flavonoids, and to evaluate the growth inhibitory effects of the extracts on MCF-7 and LNCaP cells. Methods: A. officinarum aqueous and hydroalcoholic extracts were analyzed using high-performance liquid chromatography (HPLC) for quantification of three flavonoid compounds. Then MCF-7, LNCaP, and fibroblast cells were treated with several concentrations (25, 50, 100, 200, and 400 μg/mL) of extracts (24, 48 and 72h). Cell viability was assessed using MTT assay. Flow cytometry was conducted to evaluate apoptosis. Results: Galangin and kaempferol (3.85 and 1.57 mg/g dry extract) were quantified respectively in hydroalcoholic and aqueous extracts using a validated method. The hydroalcoholic extract significantly decreased the viability of MCF-7 (IC50: 43.45μg/mL for 48h) and LNCaP cells (IC50: 168μg/mL for 48h). The aqueous extract reduced cancer cell viability by more than 50% only at 200 and 400 μg/mL (72h). Treatment of primary fibroblasts with both extracts showed no significant decrease in cell viability (25-100 μg/mL; 24 and 48h). The hydroalcoholic extract induced a significant increase in apoptotic cells in both MCF-7 and LNCaP cells. Conclusion: Obtained results demonstrated the cytotoxicity of A. officinarum through apoptosis induction in two cancer cell lines. Further investigations are required to determine the underlying apoptotic cell death mechanisms induced by A. officinarum in cancerous cells.