Anti-inflammatory effects of <i>Hericium erinaceus</i> hot water extract via the JAK1/STAT3 pathway in LPS-stimulated RAW 264.7 macrophages

Several individual bioactive compounds isolated from Hericium erinaceus exhibit various physiological and biochemical activities, including neuroprotective, neurotrophic, gastrointestinal protective, immunoregulatory, and anti-inflammatory effects. However, the specific anti-inflammatory effects of H. erinaceus extracts, which can vary significantly depending on the extraction solvent, require further investigation. In this study, we aimed to investigate the anti-inflammatory effects of H. erinaceus hot water extract (HWE). Therefore, we evaluated nitric oxide (NO) production, the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the expression and release of pro- and anti-inflammatory cytokines, and changes in inflammation-related signaling pathways in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. HWE effectively suppressed NO production and iNOS expression; however, COX-2 expression exhibited a biphasic response, increasing at 1.25 mg/ml and decreasing at 2.5 mg/ml. Additionally, HWE reduced the expression and release of the proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and increased the expression and release of the anti-inflammatory cytokine IL-10. Furthermore, HWE attenuated the phosphorylation of IKK-α/β and NF-κB p65 and ameliorated LPS-induced inflammation by inhibiting the phosphorylation of JAK1 and STAT3. These findings suggest that HWE may serve as a valuable source for anti-inflammatory agents or health functional food ingredients. [BMB Reports 2025; 58(12): 494-500].