Glycolipids Derived from the Korean Endemic Plant Aruncus aethusifolius Inducing Glucose Uptake in Mouse Skeletal Muscle C2C12 Cells.

Aruncus spp. has been used as a traditional folk medicine worldwide for its anti-inflammatory, hemostatic, and detoxifying properties. The well-known species A. dioicus var. kamtschaticus has long been used for multifunctional purposes in Eastern Asia. Recently, it was reported that its extract has antioxidant and anti-diabetic effects. In this respect, it is likely that other Aruncus spp. possess various biological activities; however, little research has been conducted thus far. The present study aims to biologically identify active compounds against diabetes in the Korean endemic plant A. aethusifolius and evaluate the underlying mechanisms. A. aethusifolius extract enhanced glucose uptake without toxicity to C2C12 cells. A bioassay-guided isolation of A. aethusifolius yielded two pure compounds, and their structures were characterized as glycolipid derivatives, gingerglycolipid A, and (2S)-3-linolenoylglycerol-O-ß-d-galactopyranoside by an interpretation of nuclear magnetic resonance and high-resolution mass spectrometric data. Both compounds showed glucose uptake activity, and both compounds increased the phosphorylation levels of insulin receptor substrate 1 (IRS-1) and 5'-AMP-activated protein kinase (AMPK) and protein expression of peroxisome proliferator-activated receptor γ (PPARγ). Gingerglycolipid A docked computationally into the active site of IRS-1, AMPK1, AMPK2, and PPARγ (-5.8, -6.9, -6.8, and -6.8 kcal/mol).

Beneficial Effect of Paeonol on Antibiotic-Associated Inflammatory Response in Mice with Diarrhea.

Diarrhea is a common adverse effect of antibiotics particularly that acts on anaerobes. Moutan Radicis Cortex (MRC) is an herbal medicine used for its anti-inflammatory and antibacterial actions. The purpose of this study was to analyze the active components of MRC to determine their effect on antibiotic-associated diarrhea (AAD) and anti-inflammatory effects. Of the various components of MRC, seven compounds (gallic acid, oxypaeoniflorin, paeoniflorin, ethyl gallate, benzoic acid, benzoylpaeoniflorin, paeonol) were identified and assessed for anti-inflammation effects. Paeonol was found to effectively reduce nitric oxide production and levels of IL-6 and TNF-α in a concentration-dependent manner. Paeonol also effectively reduced the mRNA expression level of IL-6, IL-1ß, and TNF-α. Western blotting analysis confirmed the reduction of COX-2 and NF-κB levels; p-p38 MAPK levels increased in the presence of a low concentration (25 µM) of paeonol but decreased in the presence of a high concentration (50 µM). In the mouse model of lincomycin-induced AAD, all experimental groups treated with paeonol (25, 50, and 100 mg/kg concentrations) showed diminished diarrhea status scores. Finally, the expression levels of TNF-α and IL-4 were reduced compared with those in the control group. Therefore, paeonol may have active compounds of MRC to alleviate the diarrhea symptoms of AAD and reduce inflammatory mediators. Other components of the MRC extract could contribute to its known anti-inflammatory and antibacterial activity and should be tested for their possible activity.

Investigating the Systems-Level Effect of Pueraria lobata for Menopause-Related Metabolic Diseases Using an Ovariectomized Rat Model and Network Pharmacological Analysis.

This study was conducted to evaluate the biological activities of Pueraria lobata (PL) on menopause-related metabolic diseases and to explore the underlying mechanism of PL by network pharmacological analyses. We used ovariectomized (OVX) rats as a postmenopausal model and administered PL at different doses (50, 100, and 200 mg/kg). In OVX rats, decreased uterine weights and PPAR-γ (peroxisome proliferator-activated receptor-gamma) mRNA expression in the thigh muscle were significantly recovered after PL administration. PL also significantly alleviated OVX-induced increases in total cholesterol, triglyceride, alanine aminotransferase (ALT/GPT), and aspartate aminotransferase (AST/GOT) levels. To identify the systems-level mechanism of PL, we performed network pharmacological analyses by predicting the targets of the potential bioactive compounds and their associated pathways. We identified 61 targets from four potential active compounds of PL: formononetin, beta-sitosterol, 3'-methoxydaidzein, and daidzein-4,7-diglucoside. Pathway enrichment analysis revealed that among female sex hormone-related pathways, the estrogen signaling pathways, progesterone-mediated oocyte maturation, oxytocin signaling pathways, and prolactin signaling pathways were associated with multiple targets of PL. In conclusion, we found that PL improved various indicators associated with lipid metabolism in the postmenopausal animal model, and we also identified that its therapeutic effects are exerted via multiple female sex hormone-related pathways.