Potential Molecular Mechanisms and Metabolic Networks in Red Ginseng-induced “<i>Shanghuo</i>” (上火)

Objective: To comprehensively uncover potential molecular mechanisms and metabolic networks in RG-induced “ Shanghuo”. Red ginseng (RG) could bring out the manifestations of “ Shanghuo”, which mostly presents as redness, swelling, fever, and pain. Methods: The compounds of RG were obtained from the TCMSP and SymMap databases. The putative targets of RG were determined based on the obtained compounds by STITCH. The potential targets of “ Shanghuo” were retrieved from the literature. Those interacted targets of RG and “ Shanghuo” were screened by STRING and conducted networks of RG and “ Shanghuo”. The RG-influenced “ Shanghuo” targets were further analyzed by the STRING and proved by molecular docking. Afterwards, water extract of RG was given to 6 weeks-old rats for 15 days. Observations were carried out to confirm the establishment of “ Shanghuo” model. Gas chromatography-mass spectrometry (GC-MS) were utilized to identify the differential metabolites. Results: Apolipoprotein B and Serum albumin (ALB) were the co-acting targets, while Transient Receptor Potential Channel Vanilloid 1 was a vital target of RG jointing “ Shanghuo” and RG together through the connection via ALB. Ginsenoside Rb1 was the most influential compound of RG to induce “ Shanghuo” by molecular docking. Our study indicated that fat digestion and absorption and cholesterol metabolism the potential mechanism of RG-induced “ Shanghuo”. An acceleration of energy expenditure in the “ Shanghuo” group was additionally verified by conducting the GC-MS method. Conclusion: The disorders in heat dissipation along with the accelerated fat metabolism and overactive energy expenditure might contribute to RG-induced “ Shanghuo”.