Monocrotaline

• CAT Number: R013037
• CAS Number: 315-22-0
• Molecular Formula: C16H23NO6
• Molecular Weight: 325.36
• Purity: ≥95%
• Synonyms: (1R,4R,5R,6R,16R)-5,6-dihydroxy-4,5,6-trimethyl-2,8-dioxa-13-azatricyclo[8.5.1.013,16]hexadec-10-ene-3,7-dione
• InChI: InChI=1S/C16H23NO6/c1-9-13(18)23-11-5-7-17-6-4-10(12(11)17)8-22-14(19)16(3,21)15(9,2)20/h4,9,11-12,20-21H,5-8H2,1-3H3/t9-,11+,12+,15+,16-/m0/s1
• InChIKey: QVCMHGGNRFRMAD-XFGHUUIASA-N
• SMILES: CC1C(=O)OC2CCN3C2C(=CC3)COC(=O)C(C1(C)O)(C)O

Monocrotaline is an 11-membered macrocyclic pyrrolizidine alkaloid. Monocrotaline inhibits OCT-1 and OCT-2 with IC50s of 36.8 µM and 1.8 mM, respectively. Monocrotaline has antitumor activity and is cytotoxic to hepatocellular carcinoma cells. Monocrotaline is used to induce a model of pulmonary hypertension in rodents. [2][6][8].
Monocrotaline a natural ligand exhibits dose-dependent cytotoxicity with potent antineoplastic activity. The in vitro cytotoxicity of monocrotaline is proved at IC50 24.966 µg/mL and genotoxicity at 2 X IC50 against HepG2 cells[2].
Monocrotaline can be used in animal modeling to construct a rat model of hypertension.
MCT causes a pulmonary vascular syndrome in rats characterized by proliferative pulmonary vasculitis, pulmonary hypertension (PH), and cor pulmonale[3].
Among preclinical models of pulmonary arterial hypertension (PAH), monocrotaline animal model offers the advantage of mimic several key aspects of human PAH, including vascular remodeling, proliferation of smooth muscle cells, endothelial dysfunction, upregulation of inflammatory cytokines, and right ventricle failure, requiring a single drug injection[4].
Changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis are observed with the injection of monocrotaline[5].
Monocrotaline (60 mg/kg; i.p.; single dose), significantly increases pulmonary artery pressure and promotes pulmonary artery structural remodeling and right ventricular hypertrophy in rats. Followed by Astragaloside (ASIV) (10 and 30 mg/kg/day for 21 days), ASIV blocks pulmonary arterial hypertension by improving inflammation and pulmonary artery remodeling[7].
Monocrotaline (60 mg/kg; i.p.; single dose) causes Pulmonary arterial hypertension (PAH) in rat models in 3-4 weeks[7].
Monocrotaline (60 mg/kg; i.p. Single dose), 7 days after surgery, exhibits dose-dependent cytotoxicity and shows potent antitumor activity in a rat model of left pneumonectomy [9].
NOTE: Monocrotaline is dissolved in 1 N HCl, diluted in sterile saline and adjusted to pH 7.4 with 1 N NaOH[7].

Reference

[1]. Gomez-Arroyo JG, et al. The monocrotaline model of pulmonary hypertension in perspective. Am J Physiol Lung Cell Mol Physiol. 2012 Feb 15;302(4):L363-9.
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[2]. Kusuma SS, et al. Antineoplastic activity of monocrotaline against hepatocellular carcinoma. Anticancer Agents Med Chem. 2014;14(9):1237-48.
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[3]. Wilson DW, et, al. Mechanisms and pathology of monocrotaline pulmonary toxicity. Crit Rev Toxicol. 1992;22(5-6):307-25.
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[4]. Nogueira-Ferreira R, et al. Exploring the monocrotaline animal model for the study of pulmonary arterial hypertension: A network approach. Pulm Pharmacol Ther. 2015 Dec;35:8-16.
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[5]. Rafikova O,et al. Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed RatLung. PLoS One. 2016 Mar 3;11(3):e0150480.
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[6]. Wu XH, et al. Experimental animal models of pulmonary hypertension: Development and challenges. Animal Model Exp Med. 2022 Sep; 5(3):207-216.
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[7]. Jin H, et al. Astragaloside IV blocks monocrotaline‑induced pulmonary arterial hypertension by improving inflammation and pulmonary artery remodeling. Int J Mol Med. 2021 Feb;47(2):595-606.
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[8]. Chen JY, et al. An in vitro study on interaction of anisodine and monocrotaline with organic cation transporters of the SLC22 and SLC47 families. Chin J Nat Med. 2019 Jul;17(7):490-497.
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[9]. Zhao J, et al. Effects of paclitaxel intervention on pulmonary vascular remodeling in rats with pulmonary hypertension. Exp Ther Med. 2019 Feb;17(2):1163-1170.
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