Kirenol

Kirenol is a diterpenoid compound, an orally active apoptosis inducer and signaling pathway regulator, with a K_d value of 5.47 μM against the target CK2. Kirenol promotes the cleavage of Bid into tBid, regulates the protein levels/phosphorylation of Bax, Bcl-2, p53 and p21, and induces caspase-independent apoptosis, S-phase cell cycle arrest, ROS accumulation and cytotoxicity in cancer cells. Kirenol activates the CK2/AKT and AMPK-mTOR-ULK1 pathways, inhibits the signaling of NF-κB, TGF-β/Smads and NLRP3 inflammasome, and regulates the GSK3β, BMP and Wnt/β-catenin pathways. Kirenol induces autophagy, mitophagy and osteoblast differentiation, promotes mitochondrial fusion, and exerts antioxidant, anti-inflammatory, antifibrotic, renoprotective, cardioprotective, neuroprotective and analgesic effects. Kirenol is applicable to research related to chronic myeloid leukemia, ischemic stroke, diabetic nephropathy, heart failure, acute lung injury and osteoporosis^{[1][2][3][4][5][6][7]}. In Vitro:Kirenol (10-40 μg/mL; 24-72 h) potently inhibits proliferation of human chronic myeloid leukemia K562 cells in a time- and dose-dependent manner, with IC₅₀ values of 53.05 μg/mL (24 h), 18.19 μg/mL (48 h), and 15.08 μg/mL (72 h)^[1].
Kirenol (10-40 μg/mL; 24 h) induces dose-dependent apoptosis in human chronic myeloid leukemia K562 cells, with apoptosis rates ranging from 8.29% to 51.85%^[1].
Kirenol (40 μg/mL; 12-48 h) induces time-dependent loss of mitochondrial membrane potential in human chronic myeloid leukemia K562 cells over 12, 24, and 48 h^[1].
Kirenol (40 μg/mL; 12-48 h) induces time-dependent accumulation of ROS in human chronic myeloid leukemia K562 cells over 12, 24, and 48 h^[1].
Kirenol (40 μg/mL; 12-48 h) modulates Bcl-2 family protein expression in human chronic myeloid leukemia K562 cells, reducing Bcl-2 levels and increasing Bax and tBid levels over 12, 24, and 48 h, and upregulating phosphorylation of p53 (Ser 6 and Ser 37) and p21 protein expression^[1].
Kirenol (10-40 μg/mL; 48 h) induces dose-dependent S-phase cell cycle arrest in human chronic myeloid leukemia K562 cells^[1].
Kirenol (1.25-5% Kirenol-containing serum; 24 h (prior to TBHP treatment)) exerts anti-apoptotic and antioxidant effects in TBHP-injured HT22 cells by modulating apoptotic proteins, reducing ROS, and restoring antioxidant/oxidative stress marker balance^[2].
Kirenol (1.25-5% Kirenol-containing serum; 24 h (prior to TBHP treatment)) preserves mitochondrial function and promotes Opa1-mediated mitochondrial fusion in TBHP-injured HT22 cells, reversing fragmentation, increasing ATP production, restoring MMP, and upregulating Opa1 expression^[2].
Kirenol (10-80 μM pre-incubated 30 min then co-treated with 30 mM glucose for 24 h; 20 μM pre-incubated 30 min then co-treated with 10 ng/mL TGF-β1 for 24 h) inhibits activation of the TGF-β/Smads pathway and reduces extracellular matrix protein accumulation in primary mouse mesangial cells^[3].
Kirenol (20 μM; 3 h pre-incubation prior to 24 h Ang II stimulation) suppresses Ang II-induced NLRP3 inflammasome activation and mitochondrial ROS production in mouse bone marrow-derived macrophages by enhancing mitophagy, as these effects are reversed by mitophagy inhibition^[4].
Kirenol (50-200 μg/mL; 24 h post-LPS challenge) dose-dependently inhibits TNF-α mRNA expression in LPS-challenged A549 cells^[6].
Kirenol (50-200 μg/mL; 24 h post-LPS challenge) dose-dependently enhances autophagy in LPS-challenged A549 cells, as shown by increased LC3-II and decreased p62 protein levels^[6].
Kirenol (200 μg/mL; 24 h post-LPS challenge) activates the AMPK-mTOR-ULK1 pathway in LPS-challenged A549 cells, as shown by increased p-AMPK and p-ULK1, and decreased p-mTOR protein levels^[6].
Kirenol (10-40 μM; 3 days) dose-dependently upregulates the mRNA expression of key osteoblast differentiation markers (ALP, ColA1, OPN) in MC3T3-E1 cells, with significant increases of 67.8%, 40.0%, and 67.7% respectively at 40 μM after 3 days of treatment^[7].
Kirenol (10-40 μM; 3 days) dose-dependently activates the BMP signaling pathway in MC3T3-E1 cells after 3 days of treatment at 10, 20, and 40 μM by upregulating the mRNA expression of BMP2, Runx2, and Osx^[7]. In Vivo:Kirenol (1.25-5 mg/kg; i.p.; daily; 7 days) exerts dose-dependent neuroprotective effects in MCAO/R rats, reducing cerebral infarct volume by up to ~55% at 5 mg/kg, improving neurological function, mitigating oxidative stress, and promoting Opa1-mediated mitochondrial fusion via activation of the CK2/AKT pathway^[2].
Kirenol (2 mg/kg; p.o.; daily; 3 months) alleviates diabetic nephropathy in male C57BL/6J mice by reducing phosphorylation of Smad2/3 (0.64-fold) and NF-κB (0.43-fold), restoring IκBα levels, decreasing ECM accumulation and inflammatory cytokine expression, and improving renal structural and functional markers^[3].
Kirenol (50 mg/kg; i.p.; daily; starting 1 day pre-surgery until study end) exerts cardioprotective effects in pressure overload-induced heart failure by improving cardiac function, reducing hypertrophy and fibrosis, suppressing inflammatory responses, and enhancing macrophage mitophagy, with these benefits abrogated by mitophagy inhibition^[4].
Kirenol (0.1-0.5% (w/w); topical; single application of 0.3 g cream) dose-dependently inhibits carrageenan-induced acute paw edema and reduces local pro-inflammatory cytokine (IL-1β, TNF-α) levels^[5].
Kirenol (100 mg/kg; i.p.; daily; 7 days) significantly reduces LPS-induced acute lung injury in Balb/c mice by enhancing autophagy and inhibiting inflammation, as evidenced by reduced inflammatory cytokine levels, improved lung histopathology, and decreased lung edema and leukocyte infiltration^[6].