Acanthoic acid

Acanthoic acid (NP1302) is an orally active pimarane-type diterpenoid. Acanthoic acid is isolated from the root bark of Araliaceae family plant Eleutherococcus senticosus (Siberian ginseng). Acanthoic acid activates LXR and FXR. Acanthoic acid activates the AMPK-LKB1, SIRT1, and p38 MAPK signaling pathways and increases the phosphorylation level of ACC. Acanthoic acid downregulates the expression of SREBP-1, CYP2E1, HIF-1α, and PPARγ, and upregulates the expression of PPARα. Acanthoic acid induces Apoptosis by activating Caspase-3, promoting PARP cleavage, and downregulating Bcl-xL. Acanthoic acid exhibits antioxidant, anti-fibrotic, and hepatoprotective effects. It reduces lipid accumulation and lipogenesis. Acanthoic acid is used in studies on non-alcoholic fatty liver disease, alcoholic liver disease, acute promyelocytic leukemia, and Acetaminophen-induced hepatotoxicity^[1][2][3][4]. In Vitro:Acanthoic acid (5 μM; 3 days) modulates FXR, LXRα, LXRβ, and SREBP-1 protein levels in PA-stimulated AML-12 hepatocytes, consistent with activation of FXR/LXR signaling and downregulation of SREBP-1^[1].
Acanthoic acid (5 μM; 3 days) modulates FXR, LXRα, LXRβ, SREBP-1, and SREBP-1 target gene mRNA levels in PA-stimulated AML-12 hepatocytes, consistent with activation of FXR/LXR signaling and downregulation of lipogenic gene expression^[1].
Acanthoic acid (5 μM; 3 days) increases FXR fluorescence intensity in PA-stimulated AML-12 hepatocytes, consistent with activation of FXR signaling^[1].
Acanthoic acid (5 μM; 3 days) increases LXRβ fluorescence intensity in PA-stimulated AML-12 hepatocytes, consistent with activation of LXR signaling^[1].
In EtOH/LPS-stimulated AML-12 mouse hepatocytes, acanthoic acid (5-20 µM; 2 h pretreatment + 48 h co-treatment) reduces lipid deposition and inflammatory cytokine production while activating the Sirt1/LKB1/AMPK/ACC and LXRs signaling pathways^[2].
Acanthoic acid (50-200 μM; 0-24 h) inhibits HL-60 human promyelocytic leukaemia cell proliferation in a dose- and time-dependent manner, with 86% growth reduction at 150 μM after 24 h^[3].
Acanthoic acid (150 μM; 3 h) activates ERK and p38 MAPK phosphorylation in HL-60 human promyelocytic leukaemia cells after 3 h of treatment at 150 μM^[3]. In Vivo:Acanthoic acid (20-40 mg/kg; p.o.; daily; 12 weeks) ameliorates hepatic steatosis and fibrosis in high-fat diet-induced NAFLD mice through activating the FXR-LXR-mediated AMPK-SIRT1 axis^[1].
Acanthoic acid (20-40 mg/kg; p.o.; once daily; 14 days) attenuates acute alcohol-induced liver lipid deposition and inflammation in mice by activating the LKB1/Sirt1/AMPK/ACC and LXR pathways^[2].
Acanthoic acid (50-100 mg/kg; p.o.; once daily; 3 consecutive days) dose-dependently attenuates Acetaminophen (HY-66005)-induced hepatic injury in mice, with 100 mg/kg oral treatment restoring hepatic antioxidant enzyme activities and reducing serum transaminase levels, lipid peroxidation, proinflammatory cytokine levels, and apoptotic/hypoxia marker expression^[4].
Acanthoic acid (50-100 mg/kg; p.o.; once daily; 3 consecutive days) dose-dependently increases 24 h survival rate in mice challenged with a lethal dose of Acetaminophen, reaching 74% survival at 100 mg/kg oral pretreatment^[4].