Sweroside

Sweroside is an iridoid glycoside that targets multiple targets, including the Keap1/Nrf2 axis, NLRP3 inflammasome, SIRT1, NF-κB, AMPK/mTOR pathway, and caspase family. Sweroside promotes Nrf2 nuclear translocation by competitively binding to Keap1. Sweroside also inhibits oxidative stress and NLRP3-mediated pyroptosis by activating Nrf2, inhibits NF-κB inflammatory pathway by activating SIRT1, and promotes autophagy and induces caspase-dependent apoptosis via the AMPK/mTOR pathway. Sweroside has antioxidant, anti-inflammatory, anti-apoptotic, and lipid metabolism regulating activities, and can be used in the research of myocardial ischemia-reperfusion injury, leukemia, acute lung injury, non-alcoholic fatty liver disease, and other fields^[1][2][3][4]. In Vitro:Sweroside (10-100 μM; pretreatment for 24 h followed by hypoxia/reoxygenation) enhances cell viability and reduced CK-MB and LDH release in H9c2 cells^[1].
Sweroside (50 μM; 24 h+hypoxia/reoxygenation treatment) reduces ROS and MDA levels, increases SOD and GSH-Px activities, upregulates HO-1 expression, reduces caspase-1 activity and IL-1β levels, and downregulates NLRP3, ASC, cleaved caspase-1 and IL-1β expression in H9c2 cells^[1].
Sweroside (50 μM; 24 h+hypoxia/reoxygenation treatment) inhibits Keap1 expression in H9c2 cells and promotes Nrf2 nuclear translocation^[1].
Sweroside (5-320 μM; 24-48 h) reduces cell viability in leukemia cell lines (K562, U937, HL-60, etc.) and has low toxicity to normal cells^[2].
Sweroside (20-80 μM; 24 h) induces cell cycle arrest at the S and G2/M phases in HL-60 cells, downregulates Cyclin D1, CDK4, CDC2, upregulates p53, p21, and induces apoptosis, activates caspase-3, -9 and PARP, upregulates Bax, and downregulates Bcl-2^[2].
Sweroside reduces LPS-induced inflammation in RAW264.7 cells by activating SIRT1 to mediate NF-κB and FOXO1 pathways^[3].
Sweroside (0.1-10 μg/mL; 24 h) reduces lipid accumulation and activates autophagy (upregulation of LC3B-II and downregulation of P62) in palmitic acid-treated primary mouse hepatocytes, acting through the AMPK/mTOR pathway^[4].
In Vivo:Sweroside (25-100 mg/kg; intraperitoneal injection; daily; 5 days) reduces myocardial infarction size and improved left ventricular function (LVDP, ±dp/dt) in an isolated heart ischemia-reperfusion model in Wistar rats^[1].
Sweroside (25-100 mg/kg; intraperitoneal injection; daily; 28 days) inhibits tumor growth, prolonged survival, and induces tumor cell apoptosis in a mouse HL-60 xenograft tumor model^[2].
Sweroside (15-60 mg/kg; intraperitoneal injection before LPS treatment; single dose) reduces lung wet-to-dry ratio and MPO activity, reduces inflammatory cells and cytokines, activates SIRT1, and inhibits NF-κB in an LPS-induced mouse acute lung injury model^[3].
EX-527 (HY-15452) (60 mg/kg Sweroside+10 mg/kg EX-527; intraperitoneal injection before LPS treatment; single dose) can antagonize the in vivo effects of sweroside in the acute lung injury model induced by LPS in mice^[3].
Sweroside (120 mg/kg/day; daily; 3 months) reduces hepatic lipid accumulation, activates AMPK/mTOR-mediated autophagy, and improves metabolic indicators in the high-fat diet-induced non-alcoholic fatty liver disease model in C57BL/6J mice^[4].
In a high-fat diet-induced non-alcoholic fatty liver disease model in C57BL/6J mice, 3-Methyladenine (HY-19312) (120 mg/kg/day Sweroside for 3 months+30 mg/kg 3-Methyladenine (3-MA) ??3 times a week for 2 weeks; administered for the last 2 weeks) reverses the improvement of hepatic lipid accumulation induced by sweroside^[4].