ABSTRACT
Objective: Corydalis bungeana (CB) is a well-used medicinal herb in Mongolian folk medicine and has been traditionally applied as an antiobesity agent. However, the evidence-based pharmacological effects of CB and its specific metabolic alterations in the obese model are not entirely understood. This study aimed to utilize untargeted metabolomic techniques to identify biomarkers and gain mechanistic insight into the serum metabolite alterations associated with weight loss and lipid metabolism in obese rats. Methods: A high-fat high-sugar (HFHS) diet was used to induce obese models in rats. CB extract was orally gavaged at 0.18, 0.9 and 1.8 g/kg doses for six weeks, and feed intake, body weight, fat pad weight, and blood indexes were measured. Blood serum metabolites were evaluated by gas chromatography/quadrupole time-of-flight tandem mass spectrometry (GC-TOF/MS). Results: The results showed that compared with the obese group, the administration of CB extract caused significant decreases in body weight (P < 0.05), feed intake, Lee's index, and perirenal, mesenteric, epididymal fat weight. CB extract also reduced blood triglyceride and total cholesterol levels (P < 0.05) of obese rats. Metabolomic findings showed that nine differential metabolites, including pyruvic acid, D-glucuronic acid, malic acid, dimethylglycine, oxoglutaric acid, pantothenic acid, sorbitol acid, fumaric acid and glucose 6-phosphate were identified under CB treatment and altered metabolic pathways such as TCA cycle, pantothenate and CoA biosynthesis, and glycolysis/gluconeogenesis. Conclusion: This study demonstrated weight loss and lipid lowering effects of CB on HFHS diet-induced obese rats and identified nine metabolites as potential biomarkers for evaluating the favorable therapeutic mechanism of CB via regulation of lipid and glucose metabolism.
ABSTRACT
DaHuangWan (DHW) is a traditional herbal medicine used by Mongolian to treat liver cancer for many years. Clinical application of the drug has been shown to help control tumor progression, prolong survival and improve quality of life. However, the underlying mechanisms and side effects of this drug remain unclear, which greatly limits the clinical application and further optimization of DHW. In this study, we found that DHW inhibits the proliferation of hepatoma cells by modulating the epithelial growth factor (EGF) signaling pathway. Berberine and Costunolide are the main active ingredients in DHW. Interestingly, the combination of Berberine and Costunolide has a dramatic synergistic effect on inhibiting the proliferation of hepatoma cells. Neither Berberine nor Costunolide directly block EGFR phosphorylation. Berberine promotes endocytosis of activated EGFR, while as Costunolide increases ubiquitination of EGFR and reduces EGFR recycling to cell membrane distribution, thereby inhibiting EGF signaling. Berberine and Costunolide target two different steps in regulating the EGF signaling, which explains the synergistic anti-cancer effect of DHW. Since Berberine and Costunolide do not directly target EGFR phosphorylation, DHW could be a supplementary medicine to tyrosine kinase inhibitors in cancer therapy.
