Anti-Diabetic Effect of a Shihunine-Rich Extract of Dendrobium loddigesii on 3T3-L1 Cells and db/db Mice by Up-Regulating AMPK-GLUT4-PPARα.

The stems of Dendrobium loddigesii, a Chinese herb, are often used to treat diabetes and its polar extract is rich in shihunine, a water-soluble Orchidaceae alkaloid, but little is known about the anti-diabetes effects and mechanism of shihunine. This study investigated the anti-diabetic effect of a shihunine-rich extract of D. loddigesii (DLS) based on 3T3-L1 cells and db/db mice. The underlying mechanisms were primarily explored using Western blot analysis and immunohistochemical staining. The 3T3-L1 cell experiments showed that DLS can reduce the intracellular accumulation of oil droplets as well as triglycerides (p < 0.001) and promote the 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2deoxyglucose (2-NBDG) uptake of 3T3-L1 cells (p < 0.001). The animal experiments confirmed that after 8 weeks of DLS treatment, the body weight, fasting blood sugar, and serum lipid levels of mice were significantly lowered, and the oral glucose tolerance test and serum insulin level were significantly improved compared to the no-treatment diabetes mellitus group. Further histomorphology observation led to the conclusion that the quantities of islet cells were significantly increased and the increase in adipose cell size was significantly suppressed. The immunohistochemical test of pancreatic tissue revealed that DLS inhibited the expression of cleaved cysteine aspartic acid-specific protease 3 (cleaved caspase-3). Western blot experiments showed that DLS had agonistic effects on adenosine monophosphate (AMP)-activated protein kinase phosphorylation (p-AMPK) and increased the expression levels of peroxisome proliferator-activated receptor α (PPARα) and glucose transporter 4 (GLUT4) in liver or adipose tissues. These data suggest that the shihunine-rich extract of D. loddigesii is an anti-diabetic fraction of D. loddigesii. Under our experimental condition, DLS at a dose of 50 mg/kg has good anti-diabetic efficacy.

Study on the Polar Extracts of Dendrobium nobile, D. officinale, D. loddigesii, and Flickingeria fimbriata: Metabolite Identification, Content Evaluation, and Bioactivity Assay.

The polar extract of the Dendrobium species or F. fimbriata (a substitute of Dendrobium), between the fat-soluble extract and polysaccharide has barely been researched. This report worked on the qualitative and quantitative studies of polar extracts from D. nobile, D. officinale, D. loddigesii, and F. fimbriata. Eight water-soluble metabolites containing a new diglucoside, flifimdioside A (1), and a rare imidazolium-type alkaloid, anosmine (4), were identified using chromatography as well as spectroscopic techniques. Their contents in the four herbs were high, approximately 0.9⁻3.7 mg/g based on the analysis of quantitative nuclear magnetic resonance (qNMR) spectroscopy. Biological activity evaluation showed that the polar extract of F. fimbriata or its pure component had good antioxidant and neuroprotective activity; compounds 1‒4 and shihunine (8) showed weak α-glucosidase inhibitory activity; 4 and 8 had weak anti-inflammatory activity. Under trial conditions, all samples had no cytotoxic activity.