Benzoylaconine

Benzoylaconine (Benzoylaconitine) is an orally active monoester alkaloid found in the traditional Chinese medicine Aconitum carmichaelii. Benzoylaconine is an ACE2 agonist (EC₅₀: 1.5 μM) with antihypertensive and anti-heart failure effects. Benzoylaconine inhibits TLR-induced MAPK and NF-κB pathways to exert anti-inflammatory effects. Benzoylaconine upregulates the protein levels of P-gp, MRP2, and has anti-tumor effects^{[1][2][3][4][5][6]}. In Vitro:Benzoylaconine (25-100 μM, pretreatment for 1 h, then 36 h) has the effect of reducing angiotensin II-induced cardiomyocyte hypertrophy and fibrosis in cardiomyocytes and cardiac fibroblasts^[1].
Benzoylaconine (50 μM, pretreatment for 1 h, then 0.5, 36 h) cannot alleviate myocardial inflammation and injury by targeting ACE2 in ACE2 knockdown cardiomyocytes^[1].
Benzoylaconine (1-100 μM, 1 h) exerts anti-inflammatory effects in RAW264.7 macrophages by inhibiting TLR-induced MAPK and NF-κB pathways^[2].
Benzoylaconine (1-100 μM, pretreatment for 1 h, then 24 h) significantly reduces the levels of IL-1β, TNF-α, and IL-6 cytokine proinflammatory cytokines in LPS-induced RAW264.7 macrophages^[2].
Benzoylaconine (1-100 μM, pretreatment for 1 h, then 24 h) dose-dependently reduces the expression of COX-2 and iNOS in LPS-induced RAW264.7 macrophages^[2].
Benzoylaconine (27-75 μM, 2 days) dose-dependently promotes mitochondrial mass and thus mitochondrial biogenesis in HepG2 cells^[3].
Benzoylaconine has an agonistic effect on ACE2 activity (EC₅₀: 1.5 μM) and a significant inhibitory effect on ACE (EC₅₀: 0.32 μM)^[5].
Benzoylaconine (25-100 μM, 6 days) upregulates the protein levels of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) in Caco-2 and LS174T cells^[6].
In Vivo:Benzoylaconine (3-30 mg/kg, p.o., 4 weeks) effectively improves cardiac dysfunction, reduces cardiomyocyte hypertrophy and cardiac tissue fibrosis in the thoracic aortic constriction (TAC) mouse model by targeting ACE2^[1].
Benzoylaconine (10 mg/kg, i.p., once a day for seven consecutive days) increases the oxygen consumption of mice, induces mitochondrial biogenesis and activated the AMPK-PGC1ɑ pathway in mice, exerting an anti-heart failure effect^[3].
Benzoylaconine (20 mg/kg, i.v. or i.g., once a day for five consecutive days) significantly inhibits the swelling of the mouse ear and sole in the mouse ear swelling test (MEST) and the mouse foot swelling test, indicating that it has an anti-inflammatory effect^[4].
Benzoylaconine (3-30 mg/kg, p.o., once a day for 14 consecutive days) can reduce heart rate and vasodilation in the SHR mouse model, and exert antihypertensive effects by reversing smooth muscle remodeling^[5].
Benzoylaconine (0.6 mg/kg, p.o., once a day for 14 consecutive days) significantly induces the expression and efflux activity of MRP2, BCRP, and P-gp in the jejunum, ileum, and colon of FVB mice in the FVB mouse model^[6].