Rotundic acid

Rotundic acid is an orally effective triterpenoid with a K_d value of 51.3 µM for PTP1B. Rotundic acid downregulates the AKT/mTOR pro-survival pathway and modulates the MAPK pathway. Rotundic acid induces cell cycle S-phase arrest, DNA damage and apoptosis; it inhibits migration, invasion, angiogenesis and proliferation of cancer cells. Rotundic acid improves leptin sensitivity, regulates gut microbiota and reduces cellular senescence. Rotundic acid can be used in research related to hepatocellular carcinoma, obesity, aging, acute lung injury and type 2 diabetes^[1][2][3][4]. In Vitro:Rotundic acid (10-30 μM) dose-dependently inhibits the migration of HUVEC cells^[1].
Rotundic acid (0-1000 μM) is a non-competitive inhibitor of human PTP1B, whose optimal inhibitory effect depends on the C-terminus of this protein. The IC₅₀ values against PTP1B_1-298, PTP1B_1-321 and PTP1B_1-393 are 2 mM, 481.8 μM and 443.7 μM, respectively^[2].
Rotundic acid (3.125-100 μM; 48 h) significantly extends the replicative lifespan of BY4741 yeast cells, with a maximum extension of up to 135% at the concentration of 12.5 μM^[2].
Rotundic acid (5-20 μM; 24 h) reduces cellular senescence levels in senescent WI-38 human embryonic lung fibroblasts, as evidenced by a decrease in SA-β-gal-positive cells; it also promotes cell proliferation at a concentration of 12.5 μM^[2].
Rotundic acid (15-60 μM; 24 h) shows no cytotoxicity against RAW264.7 mouse macrophages, and its concentration can reach up to 60 μM after 24 h of incubation^[3].
Rotundic acid (15-60 μM; 1 h pretreatment) dose-dependently reduces nitrite production in LPS (HY-D1056)-stimulated RAW264.7 murine macrophages^[3].
Rotundic acid (15-60 μM; 1 h pretreatment) inhibits LPS-induced release of TNF-α and IL-6 in RAW264.7 mouse macrophages^[3].
Rotundic acid (15-60 μM; 1 h pretreatment) regulates multiple inflammatory signaling pathways in LPS-stimulated RAW264.7 murine macrophages, including inhibiting the activation of NF-κB, MAPK and PI3K/Akt/mTOR, upregulating the Keap-1/Nrf2/HO-1 signaling pathway and reducing the expression of TLR4^[3].
Rotundic acid (15-60 μM; 1 h pretreatment) reduces LPS-induced NO release, ROS production and intracellular Ca²⁺ levels in RAW264.7 murine macrophages^[3].
Rotundic acid exhibits significant cytotoxic activity against Daoy, Hep-2 and MCF-7 human tumor cell lines^[4]. In Vivo:Rotundic acid (50 mg/kg; i.p.; once every 2 days; for 60 consecutive days) achieves a 75.6% tumor growth inhibition rate in a Balb/c nude mouse model with human hepatocellular carcinoma HepG2 cell xenografts. It also reduces tumor weight, inhibits proliferation and angiogenesis, induces cell apoptosis, and causes no significant body weight loss^[1].
Rotundic acid (40 mg/kg; i.p.; 1 week per month for 6 consecutive months) extends the average lifespan of naturally aged male C57BL/6J mice by 16.2% and improves their aging-related functional indicators^[2].
Rotundic acid (40 mg/kg; i.p.; once daily; for 14 consecutive days) reduces the body weight of high-fat diet-induced obese mice by up to 26.3% and decreases their food intake in a dose-dependent manner^[2].
Rotundic acid (i.p.; 40 mg/kg; once daily for 14 consecutive days) reduces body weight by 25.1% in high-fat diet-induced obese mice with an average body weight of approximately 58 g, while also decreasing their food intake, reducing adipose tissue weight, and downregulating plasma leptin levels^[2].
Rotundic acid (40 mg/kg; i.p.; once daily for 14 consecutive days) exerts no effect on body weight, food intake, or adipose tissue mass in normal lean male C57BL/6N mice^[2].
Rotundic acid (40 mg/kg; i.p.; once daily for 14 consecutive days) improves glucose homeostasis and insulin sensitivity in high-fat diet-induced obese mice^[2].
Rotundic acid (20-40 mg/kg; i.p.) reduces xylene-induced ear swelling in mice by more than 80% and ameliorates associated pathological tissue damage^[3].
Rotundic acid (20-40 mg/kg; i.p.) increases the 144-hour survival rate of LPS-induced endotoxic shock mice to 30%^[3].
Rotundic acid (10-40 mg/kg; i.p.) reduces LPS-induced levels of inflammatory markers, ameliorates pulmonary function impairment, and alleviates lung pathological damage in a mouse model of acute lung injury^[3].
Rotundic acid (40 mg/kg; oral gavage; daily; 8 weeks) improves glucose and lipid metabolism, reduces blood pressure, protects against cardiovascular, hepatic and renal damage, alleviates oxidative stress and inflammatory responses, and restores gut microbiota dysbiosis induced by a high-fat diet combined with low-dose streptozotocin in type 2 diabetic rats^[4].