Alisol B

Alisol B is a triterpene with diverse biological activities. Alisol B binds human soluble epoxide hydrolase (sEH) with a K_i of 5.97 μM and reduces sEH activity. Alisol B inhibits RANKL-induced JNK phosphorylation, NFATc1 and c-Fos expression, osteoclast formation, mature osteoclast pit-forming and actin ring activity, and SERCA pump activity. Alisol B induces calcium mobilization, CaMKK-AMPK-mTOR pathway activation, autophagic flux, autophagosome formation, G₁ phase cell cycle arrest, endoplasmic reticulum stress, unfolded protein responses, and cancer cell apoptosis. Alisol B can be used for the research of hypercalcemia, osteoporosis, rheumatoid arthritis, periodontitis, acute kidney injury, and breast cancer^[1][2][3]. In Vitro:Alisol B (0.5-5 μM; 6 days) dose-dependently inhibits 1α,25(OH)₂D₃-induced osteoclast formation in co-cultures of mouse bone marrow cells and primary calvarial osteoblasts, with complete inhibition at 5 μM^[1].
Alisol B (0.5-5 μM; 10 min) inhibits RANKL-induced JNK phosphorylation in mouse BMMs, and suppresses RANKL-induced activation of NFATc1 and expression of c-Fos, key transcription factors for osteoclastogenesis^[1].
Alisol B (1, 5 μM; 48 h) suppresses the pit-forming activity and disrupts actin ring formation of mature mouse osteoclasts on dentin slices^[1].
Alisol B (20 μM; 1 h pre-incubation, 24 h co-incubation with Cisplatin (HY-17394)) attenuates cisplatin-induced apoptosis, inflammation, and oxidative stress in HK-2 renal proximal tubule cells via a GSK3β-dependent pathway^[2].
Alisol B potently inhibits SERCA1A activity in rabbit skeletal muscle sarcoplasmic reticulum membranes with an IC₅₀ of 27 μM, and inhibits SERCA2B activity in porcine brain microsomes with an IC₅₀ of 53 μM^[3].
Alisol B (30 μM; 16-24 h) induces autophagosome formation in MCF-7 cells, as shown by increased GFP-LC3 puncta formation^[3].
Alisol B (48 h) induces cytotoxicity across a panel of cancer cell lines with IC₅₀ values ranging from 20.6 μmol/L (HepG2) to 48.7 μM (MDA-MB-231) at 48 h post-treatment^[3].
Alisol B (30 μM; 8-48 h) induces time-dependent G₁ phase cell cycle arrest in MCF-7 cells, with 93.1% of cells in G₁ phase after 48 h of treatment^[3].
Alisol B (30 μM; 4-24 h) activates the CaMKK-AMPK-mTOR pathway in MCF-7 cells, as shown by increased AMPKα phosphorylation and reduced p70S6 kinase phosphorylation over time^[3].
Alisol B (30 μM; 16 h) induces autophagy and cytotoxicity in MCF-7 cells in an intracellular calcium- and CaMKK-dependent manner^[3].
Alisol B (30 μM; 8-24 h) activates the UPR in MCF-7 cells through the PERK and ATF6 signaling pathways, but does not activate the IRE1 pathway^[3].
Alisol B (30 μM; 24-48 h) induces late apoptotic cell death in MCF-7 cells, as shown by increased Annexin V⁺7AAD⁺ cells and PARP cleavage after 48 h of treatment^[3]. In Vivo:Alisol B (100 μM; i.p.; daily; 5 days) potently suppresses 2MD-induced hypercalcemia and bone resorption in C57BL/6J mice by reducing osteoclast numbers and serum TRAP5b levels, without altering serum RANKL concentrations^[1].
Alisol B (15-60 mg/kg; p.o.; daily; 7 days) dose-dependently protects against Cisplatin-induced acute kidney injury in male C57BL/6 wild-type mice by inhibiting sEH activity, and attenuating renal apoptosis, inflammation, and oxidative stress via GSK3β-mediated p53, NF-κB, and Nrf2 signaling pathways^[2].