An optimized herbal medicine containing Scutellaria baicalensis, Alisma canaliculatum, and Atractylodes macrocephala Koidz attenuates hyperlipidemia via regulating AMPK/NLRP3 inflammasome pathway 9190

Description An optimized herbal medicine, HTB, which comprises Scutellaria baicalensis, Alisma canaliculatum, and Atractylodes macrocephala Koidz, has been frequently utilized in traditional medicine due to its anti-inflammatory and antioxidant properties. However, its antihyperlipidemic activity has not been thoroughly validated. In this study, mice were induced with acute or chronic hyperlipidemia through intraperitoneal injection of poloxamer 407 (P407) or a high-fat diet (HFD). Compared to the P407 group, HTB treatment significantly reduced elevated plasma and hepatic triglyceride and cholesterol levels. In HFD-induced mice, HTB treatment significantly mitigated weight gain, lipid profiles, glucose tolerance, and skeletal muscle functions while reducing the inflammatory response. Biochemical analyses demonstrated that HTB activated hepatic AMP-activated protein kinase (AMPK), and downregulated the expression of nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome-related proteins including caspase-1, IL-1β, and GSDMD. Proteomic analysis also revealed that HTB enhanced the expression of proteins linked to mitochondrial L-carnitine and fatty acid oxidation. These results suggest that HTB alleviates hyperlipidemia in P407- or high-fat diet-induced obese mice by modulation of the AMPK signaling pathway and the NLRP3 inflammasome. Therefore, HTB may serve as a novel lipid-lowering agent for the prevention and treatment of hyperlipidemia-related disorders. Funding Sources Korea Institute of Oriental Medicine: KSN2022230, National Research Foundation of Korea(NRF) Grant: NRF-2021R1I1A2040301.