Micheliolide

Micheliolide is a sesquiterpene lactone and derivative of parthenolide that has been found in M. champaca and has diverse biological activities.^1,2,3,4 It is an irreversible activator of the pyruvate kinase M2 isoform (PKM2; EC₅₀ = 6 nM) that decreases viability of HL-60 cells when used at concentrations ranging from 5 to 20 ?M.¹ Micheliolide (5-10 ?M) reduces M. tuberculosis-induced secretion of IL-1β and TNF-α, expression of Cox2, and production of nitric oxide (NO) in RAW 264.7 cells.² It also inhibits M. tuberculosis-induced NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in RAW 264.7 cells. Micheliolide (30 mg/kg) decreases the severity of collagen-induced arthritis (CIA) in a mouse model of rheumatoid arthritis.³ It also increases hepatic protein levels of PPARγ and reduces hepatic inflammation and steatosis in db/db mice.⁴

1.Li, J., Li, S., Guo, J., et al.Natural product micheliolide (MCL) irreversibly activates pyruvate kinase M2 and suppresses leukemiaJ. Med. Chem.61(9)4155-4164(2018) 2.Zhang, Q., Jiang, X., He, W., et al.MCL plays an anti-inflammatory role in Mycobacterium tuberculosis-induced immune response by inhibiting NF-κB and NLRP3 inflammasome activationMediators Inflamm.2432904(2017) 3.Xu, H., Wang, J., Wang, C., et al.Therapeutic effects of micheliolide on a murine model of rheumatoid arthritisMol. Med. Rep.11(1)489-493(2015) 4.Zhong, J., Gong, W., Chen, J., et al.Micheliolide alleviates hepatic steatosis in db/db mice by inhibiting inflammation and promoting autophagy via PPAR-γ-mediated NF-кB and AMPK/mTOR signalingInt. Immunopharmacol.59197-208(2018)