Drug Res (Stuttg) 2022; 72(04): 189-196
DOI: 10.1055/a-1735-2887
Original Article

Decipher the inhibitory potential of phytocompounds from Leptadenia reticulata on dopamine D2 receptor to enhance prolactin secretion

Roshan Kumar Sharma
1   KLE Academy of Higher Education and Research, Dr. Prabhakar Kore Basic Science Research Center, Belagavi, India
Sunil S Jalalpure
2   KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi, India
Mahendra Kumar Chouhan
1   KLE Academy of Higher Education and Research, Dr. Prabhakar Kore Basic Science Research Center, Belagavi, India
3   Department of Pharmacology, Maharishi Arvind Institute of Pharmacy (MAIP), Jaipur, India
Sanjay Deshpande
4   Department of Biotechnology, KLE Technological University, Hubballi, India
Rabinarayan Acharya
5   Department of Dravyaguna, Institute for Post Graduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar, India
1   KLE Academy of Higher Education and Research, Dr. Prabhakar Kore Basic Science Research Center, Belagavi, India
6   Department of Microbiology, Belagavi Institute of Medical Sciences, Belagavi, India
› Author Affiliations
Funding The study was funded by Department of Biotechnology, Govt. of India (Grant Number: BT/PR26908/TRM/120/177/2017)


Dopamine is secreted by the hypothalamus, which inhibits the proliferation and effectiveness of lactotroph cells that release prolactin via dopamine D2 receptor (D2R). D2R activation inhibits lactotroph cell prolactin synthesis and regulates prolactin gene expression. Although, commercial medications are available for hypogalactia and agalactia, various plant sources significantly alleviate these problems. Leptadenia reticulata (Jivanti) is one of the important medicinal plants often consumed by nursing mothers to improve breast milk production. However, mechanism and chemical constituents involved in the inhibition of D2R by Jivanti is unclear. Therefore, in this study the phytocompounds reported from Jivanti were used for in-silico analysis to predict D2R inhibitory potential. The binding affinity value of campesterol and β-sitosterol (− 10.1 and −10.0 kcal/mol) with D2R has high revealed by molecular docking and stable interaction reveled by molecular dynamics simulation. Thus, these lead compounds could exert more D2R inhibitory activity resulting into prolactin release, which may lead to an increase in breast milk production. Although all selected compounds had fine permeation, non-toxic, and non-carcinogenic characteristics predicted by ADMET, campesterol had good solubility, absorption characteristics compared to other. Therefore, Jivanti, which is traditionally known medicinal plant, could be explored as a medication candidate to boost breast milk production.

Publication History

Received: 10 October 2021

Accepted: 27 December 2021

Article published online:
17 February 2022

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  • References

  • 1 Uchenna O. Problems encountered by breastfeeding mothers in their practice of exclusive breast feeding in tertiary hospitals in Enugu State, South-east Nigeria. Int J Nutr Metab 2012; 4: 107-113
  • 2 Morniroli D, Consales A, Crippa BL. et al. The antiviral properties of human milk: A multitude of defence tools from mother nature. Nutrients 2021; 13: 694
  • 3 Witkowska-Zimny M, Kaminska-El-Hassan E. Cells of human breast milk. Cell Mol Biol Lett 2017; 22: 1-1
  • 4 Brown A, Arnott B. Breastfeeding duration and early parenting behaviour: the importance of an infant-led, responsive style. PloS One 2014; 9: e83893
  • 5 Cohen JM, Hutcheon JA, Julien SG. et al. Insufficient milk supply and breast cancer risk: a systematic review. PloS One 2009; 4: e8237
  • 6 Gatti L. Maternal perceptions of insufficient milk supply in breastfeeding. J Nurs Scholarsh 2008; 40: 355-363
  • 7 Fitzgerald P, Dinan TG. Prolactin and dopamine: what is the connection? A review article. J Psychopharmacol 2008; 22: 12-19
  • 8 Gregerson KA. Mechanisms of dopamine action on the lactotroph. In Prolactin 2001; 45-61
  • 9 Radl DB, Ferraris J, Boti V. et al. Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor. PloS One 2011; 6: e18097
  • 10 Gonzalez-Iglesias AE, Murano T, Li S. et al. Dopamine inhibits basal prolactin release in pituitary lactotrophs through pertussis toxin-sensitive and -insensitive signaling pathways. Endocrinology 2008; 149: 1470-1479
  • 11 Gragnoli C, Reeves GM, Reazer J. et al. Dopamine-prolactin pathway potentially contributes to the schizophrenia and type 2 diabetes comorbidity. Transl Psychiatry 2016; 6: e785
  • 12 Ni Y, Chen Q, Cai J. et al. Three lactation-related hormones: Regulation of hypothalamus-pituitary axis and function on lactation. Mol and Cell Endocrinol 2021; 520: 111084
  • 13 Wahyuningsih D, Hidayat ST, Khafidhoh N. et al. Effect of Musa Balbisiana Colla Extract on Breast Milk Production In Breastfeeding Mothers. Belitung Nursing Journal 2017; 3: 174-182 DOI: 10.33546/bnj.103.
  • 14 Dutta S, Bisai S, Subramaniam P. Uses of Oxalis corniculata Linn as enhancer of breast milk by Kota tribe of Nilgiri hills, Tamil Nadu, India. J Med Plants 2019; 7: 114-116
  • 15 Mannion C, Mansell D. Breastfeeding self-efficacy and the use of prescription medication: a pilot study. ObstetGynecolInt 2012; DOI: 10.1155/2012/562704.
  • 16 Briskin DP. Medicinal plants and phytomedicines. Linking plant biochemistry and physiology to human health. Plant Physiol 2000; 124: 507-514
  • 17 Hegde S, Pai SR, Bhagwat RM. et al. Genetic and phytochemical investigations for understanding population variability of the medicinally important tree Saraca asoca to help develop conservation strategies. Phytochemistry 2018; 156: 43-54
  • 18 Hegde S, Pai SR, Bhagwat RM. et al. Population genetic and phytochemical dataset of Saraca asoca: A traditionally important medicinal tree. Data Brief 2019; 25: 104173
  • 19 Mohanty SK, Swamy MK, Sinniah UR. et al. Leptadenia reticulata (Retz.) Wight &Arn. (Jivanti): botanical, agronomical, phytochemical, pharmacological, and biotechnological aspects. Molecules 2017; 22: 1019
  • 20 Pal A, Sharma PP, Pandya TN. et al. Phyto-chemical evaluation of dried aqueous extract of Jivanti [Leptadenia reticulata (Retz.) Wt. etArn]. Ayu 2012; 33: 557
  • 21 Anjaria JV, Gupta I. Studies on lactogenic property of Leptadenia reticulata (Jivanti) and leptaden tablets in goats, sheep, cows and buffaloes. Indian Vet J 1967; 44: 967-974
  • 22 Anjaria JV, Varia MR, Janakiraman K. et al. Studies on Leptadenia reticulata: Lactogenic effects on rats. Indian J Exp Biol 1975; 13: 448-449 PMID: 1218901
  • 23 Godara P, Dulara BK, Barwer N. et al. Comparative GC-MS Analysis of Bioactive Phytochemicals from Different Plant Parts and Callus of Leptadenia reticulata Wight and Arn. Pharmacogn J 2019; 11: 129-140
  • 24 Ozalkaya E, Aslandoğdu Z, Özkoral A. et al. Effect of a galactagogue herbal tea on breast milk production and prolactin secretion by mothers of preterm babies. Niger J Clin Pract 2018; 21: 38-42
  • 25 Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. In Chemical biology 2015; 243-250
  • 26 Patil VS, Hupparage VB, Malgi AP. et al. Dual inhibition of COVID-19 spike glycoprotein and main protease 3CLpro by Withanone from Withania somnifera . Chin Herbal Med 2021; 13: 359-369
  • 27 Yaraguppi DA, Deshpande SH, Bagewadi ZK. et al. Genome Analysis of Bacillus aryabhattai to Identify Biosynthetic Gene Clusters and In Silico Methods to Elucidate its Antimicrobial Nature. Int J Pept Res Ther 2021; 27: 1331-1342
  • 28 Vetrivel U, Deshpande S, Hegde HV. et al. Phytochemical moieties from Indian traditional medicine for targeting dual hotspots on SARS-CoV-2 spike protein: an integrative in-silico approach. Front Med 2021; 8: 545
  • 29 Bakht MA, Yar MS, Abdel-Hamid SG. et al. Molecular properties prediction, synthesis and antimicrobial activity of some newer oxadiazole derivatives. EurJ Med Chem 2010; 45: 5862-5869
  • 30 Srivastava V, Yadav A, Sarkar P. Molecular docking and ADMET study of bioactive compounds of Glycyrrhiza glabra against main protease of SARS-CoV2. Mater Today Proc 2020; DOI: 10.1016/j.matpr.2020.10.055.
  • 31 Kaur N, Chaudhary J, Jain A. et al. Stigmasterol: a comprehensive review. Int J Pharm Sci Res 2011; 2: 2259
  • 32 Sibeko L, Johns T, Cordeiro LS. Traditional plant use during lactation and postpartum recovery: Infant development and maternal health roles. J Ethno pharmacol 2021; 114377 DOI: 10.1016/j.jep.2021.114377.
  • 33 Gopalakrishnan L, Doriya K, Kumar DS. Moringa oleifera: A review on nutritive importance and its medicinal application. Food Sci Hum Wellness 2016; 5: 49-56
  • 34 Mortel M, Mehta SD. Systematic review of the efficacy of herbal galactogogues. J Hum Lact 2013; 29: 154-162
  • 35 Bekoe EO, Kitcher C, Gyima NA. et al. Medicinal plants used as galactagogues. In Pharmacognosy-Medicinal Plants Dec 14. Intech Open 2018; DOI: 10.5772/intechopen.82199.
  • 36 Estiasih T, Ahmadi K. Bioactive compounds from palm fatty acid distillate and crude palm oil. In IOP Conference Series: Earth and Environmental Science Mar (Vol. 131, No. 1, p. 012016). IOP Publishing; 2018
  • 37 Ben-Jonathan N. Dopamine: endocrine and oncogenic functions. CRC Press; 2020. 12.
  • 38 Shastri K, Pandey GS. edited. Agnivesh, Charaka, Dridhabala, CharakaSamhita, Sutrasthana, 25/38, Chaukhambha Sanskrit Sansthan, Varanasi. 1994 P.
  • 39 Naik R, Acharya RN. A review on therapeutic potentials of “Jivanti” in Ayurveda. Anveshana Ayurveda Medical Journal. 2015 file:///C:/Users/NGSLAB~1/AppData/Local/Temp/AAMJ_442_449.pdf