Drug Res (Stuttg) 2023; 73(08): 441-447
DOI: 10.1055/a-2142-5774
Original Article

GC-MS analysis and in silico docking of constituents of Cinnamomum malabatrum against CYP450 17α and CYP450 19 (Aromatase)- Key targets for hyperandrogenism

V. Soumya
1   Department of Pharmaceutical chemistry, Faculty of pharmacy, Sri Ramachandra Institute of Higher Education and Research, SRMC(DU) Porur, Chennai, India
S. Deepa
1   Department of Pharmaceutical chemistry, Faculty of pharmacy, Sri Ramachandra Institute of Higher Education and Research, SRMC(DU) Porur, Chennai, India
Knolin.K. Thachil
2   Department of Pharmaceutical chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bangalore, India
J. Saravanan
3   Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, India.
R. Hariprasad
4   Department of Pharmaceutics, PSG College of Pharmacy, Peelamedu, Coimbatore, India.
› Author Affiliations


Poly cystic ovary syndrome (PCOS) is considered as one of the common hormonal disorders affecting 6–20% of women in their reproductive age with characteristic features include anovulatory infertility, hyperandrogenism, cystic follicles and insulin resistance. The gene CYP play an important role in pathophysiology of hyperandrogenism associated with PCOS. An elevated androgens are reported in PCOS condition due to overexpression of the enzyme CYP450 17 α. As well as diminished levels of aromatase (CYP450 19) were observed in several hyperandrogenic PCOS patients. The powdered leafy material of Cinnamomum malabatrum was subjected to Soxhlet extraction. The plant extract was subjected to Gas chromatography-MS analysis (GC-MS), and the chromatogram obtained revealed the presence of active chemical constituents like 1(10),9(11)-B-Homolanistadiene for the first time and other potential compounds. Hypothesis has raised to interpret the efficiency of phytoconstituents of Cinnamomum malabatrum on these enzyme targets and which may be a novel drug candidate for the treatment and maintenance of hyperandrogenism associated with PCOS. Thus, the results obtained from the in-silico study of Cinnamomum malabatrum leaf extract using computational approaches indicate that the phytoconstituents have good affinities for the selected two key targets. ADME and PASS studies has been performed for active phytoconstituents homolanistadiene, β-sitosterol, cycloartenol and a pyrazole derivative, and results revealed the Lipinski drug-likeness and pharmacological potential. In conclusion, this work throws a new insight into the possibility of the active phytoconstituents on binding the two active CYP45017 α and CYP45019 aromatase enzymes which facilitates development of novel compounds for hyperandrogenism associated with PCOS.

Publication History

Received: 25 June 2023

Accepted: 24 July 2023

Article published online:
17 August 2023

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  • References

  • 1 Norman RJ, Dewailly D, Legro RS. et al. Polycystic ovary syndrome. The Lancet 2007; 370: 685-697
  • 2 ESHRE TR, ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertility and sterility 2004; 81: 19-25
  • 3 Azziz R, Carmina E, Dewailly D. et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertility and sterility 2009; 91: 456-488
  • 4 Soumya V, Muzib YI, Venkatesh P. et al. GC-MS analysis of Cocus nucifera flower extract and its effects on heterogeneous symptoms of polycystic ovarian disease in female Wistar rats. Chinese journal of natural medicines 2014; 12: 677-684
  • 5 Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocrine reviews 2012; 33: 981-1030
  • 6 Nestler JE. Insulin resistance and the polycystic ovary syndrome: recent advances. Current opinion in endocrinology, diabetes and obesity 2000; 7: 345-349
  • 7 Nisenblat V, Norman RJ. Androgens and polycystic ovary syndrome. Current Opinion in Endocrinology, Diabetes and Obesity 2009; 16: 224-231
  • 8 Reddy KR, Deepika ML, Supriya K. et al. CYP11A1 microsatellite (tttta) n polymorphism in PCOS women from South India. Journal of assisted reproduction and genetics 2014; 31: 857-863
  • 9 Nelson VL, Qin KN, Rosenfield RL. et al. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism 2001; 86: 5925-5933
  • 10 Akhtar M, Wright JN, Lee-Robichaud P. A review of mechanistic studies on aromatase (CYP19) and 17α-hydroxylase-17, 20-lyase (CYP17). The. Journal of steroid biochemistry and molecular biology 2011; 125: 2-12
  • 11 Garg D, Merhi Z. Relationship between advanced glycation end products and steroidogenesis in PCOS. Reproductive Biology and Endocrinology 2016; 14: 1-3
  • 12 Ashraf S, Nabi M, Rashid F, et al. Hyperandrogenism in polycystic ovarian syndrome and role of CYP gene variants: a review. Egyptian Journal of Medical Human Genetics. 2019;20:1-0.
  • 13 Leela NK, Vipin TM, Shafeekh KM. et al. Chemical composition of essential oils from aerial parts of Cinnamomum malabatrum (Burman f.) Bercht & Presl. Flavour and fragrance journal 2009; 24: 13-16
  • 14 Anderson RA, Roussel AM. Cinnamon, glucose and insulin sensitivity. Nutraceuticals, glycemic health and type 2008; 2: 127-40.
  • 15 Panickar K, Cao H, Qin B. et al. Molecular targets and health benefits of cinnamon. InMolecular Targets and Therapeutic Uses of Spices: Modern Uses for Ancient Medicine 2009; 87-115
  • 16 Ziegenfuss TN, Hofheins JE, Mendel RW. et al. Effects of a water-soluble cinnamon extract on body composition and features of the metabolic syndrome in pre-diabetic men and women. Journal of the International Society of Sports Nutrition 2006; 3: 45
  • 17 Lu J, Zhang K, Nam S. et al. Novel angiogenesis inhibitory activity in cinnamon extract blocks VEGFR2 kinase and downstream signaling. Carcinogenesis. 2010; 31: 481-488
  • 18 Roussel AM, Hininger I, Benaraba R. et al. Antioxidant effects of a cinnamon extract in people with impaired fasting glucose that are overweight or obese. Journal of the American College of Nutrition 2009; 28: 16-21
  • 19 Wang JG, Anderson RA, Graham GM. et al. The effect of cinnamon extract on insulin resistance parameters in polycystic ovary syndrome: a pilot study. Fertility and sterility 2007; 88: 240-243
  • 20 Duke JA. Database of Biologically Active Phytochemicals & Their Activity. CRC Press; 2020
  • 21 Swiss ADME. Available online: http://www.swissadme.ch/index.php
  • 22 Duffy FJ, Devocelle M, Shields DC. Computational approaches to developing short cyclic peptide modulators of protein–protein interactions. In Computational Peptidology. 2015: 241-271 Humana Press; New York, NY:
  • 23 Daina A, Michielin O, Zoete V. iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. Journal of chemical information and modeling 2014; 54: 3284-3301