Ascendancy of betle leaf in the metabolism on trophoblasts


  • Padmini Ekambaram
  • Balan Chithra



Adiponectin, CYP19A1, in-vitro hypoxia, leptin, trophoblast


Introduction and Aim: Pregnancyis a physiological state to sustain the developing fetus accompanied with high-energy demand and an increased oxygen requirement, associated with diverse metabolic and vascular changes in the maternal system. Oxygen is crucial for the proper proliferation and differentiation of trophoblast, the principal cells of the transient organ placenta. Placental hypoxia/ischemia results in the dysregulation in the physiological and metabolic activities of trophoblast. Readily available, cost-effective pharmacological herbal preparation betle leafmay be helpful in the development of novel therapeutic interventions to manage the maternal complication like hypertension and fetal growth restrictions resulting in low-birth-weight babies. This has raised the concern to ascertain the ascendancy of salivary and diastase extracts of betle leafon theexpression of leptin, adiponectin and CYP19A1 inplacental trophoblast metabolism.


Methodology: Subjecting the placental trophoblast to in vitro hypoxia may highlight the crucial role of oxygen and impact of betle leaf extracts in altering the various metabolic markers.


Results: Both the extracts modulate the levels of leptin, adiponectin and CYP19A1in regulating energy metabolism and oxidation process.


Conclusion: This study also suggests that differential expression leptin, adiponectin and CYP19A1, influences this energy imbalance in response to the stress stimuli such as the hypoxiaand its relationship with feto-placental metabolism and fetal growth. The ascendancy of betle leaf extracts on the metabolism of trophoblasts requires sufficient oxygen is inferred from the in vitro hypoxic study.

Author Biographies

Padmini Ekambaram

Principal (Former), Presidency College, Chennai

Balan Chithra

Department of Biochemistry, Bharathi Women's College (Autonomous),Affiliated to University of Madras, Chennai, Tamil Nadu, India


Redman, C.W., Sargent, I.L. Latest Advances in Understanding Preeclampsia. Science 2005; 308: 1592-1594.

Anderson, C.M., Schmella, M.J. CE: Preeclampsia Current Approaches to Nursing Management. Am J Nurs. 2017; 117(11): 30-38.

Sanjay, G., Girija, W. Preeclampsia-Eclampsia. J ObstetGynaecol India. 2014; 64(1): 4-13.

Gordon, C.D., Catherine, A.V., Priyadarsini, K., Tien-Cheng, C., Thaddeus, G.G. Trophoblast Stem Cells: Models for Investigating Trophectoderm Differentiation and Placental Development. Endocr Rev. 2009; 30(3): 228-240.

Harvey, J.K. From Trophoblast to Human Placenta. The Encyclopedia of Reproduction. 2006; 1-19.

Lei, J., Jelena, B., Ming, L., Guodong, F., Chun, P., Yan-Ling, W. Placental trophoblast cell differentiation: Physiological regulation and pathological relevance to preeclampsia. Mol Aspects Med. 2013; 34(5): 981-1023.

Ategbo, J.M.,Grissa, O., Yessoufou, A., Hichami, A., Dramane, K.L., Moutairou, K., et al., Modulation of Adipokines and Cytokines in Gestational Diabetes and Macrosomia. J Clin Endocrinol Metab. 2006; 91(10): 4137-4143.

Konstanze, M., Holger, S., Mathias, F. Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin Endocrinol. 2012; 76: 2-11.

James, J.L., Stone, P.R., Chamley, L.W. The regulation of trophoblast differentiation by oxygen in the first trimester of pregnancy. Hum Reprod Update. 2006; 12(2): 137-144.

Berkane, N., Liere, P., Oudinet, J.P., Hertig, A., Lefevre, G., Pluchino, N.,et al., From Pregnancy to Preeclampsia: A Key Role for Estrogens. Endocr Rev. 2017; 1(38-2): 123-144.

Esther, D.S., Valerie, S., Corinne, M., Antoine, T., Robert, W., Philippe, D.M., et al., Adiponectin and leptin systems in human endometrium during window of implantation. FertilSteril. 2012; 97(3): 771-778.

Chen, J., Tan, B., Karteris, E., Zervou, S., Digby, J., Hillhouse, E.W., et al., Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia. 2006; 49(6): 1292-1302.

Lihn, A.S., Richelsen, B., Pedersen, S.B., Haugaard, S.B., Rathje, G.S., Madsbad, S., et al., Increased expression of TNF-?, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels. Am J Physiol Endocrinol Metab. 2003; 285:1072-1080.

Richard, M.K.Y., Gayathri, C., Steve, K.H.T., Suraia, N., John, P.G., Rudolf, al.,Evidence for MicroRNA-Mediated Regulation of Steroidogenesis by Hypoxia. Environ Sci Technol. 2015; 49: 1138-1147.

Alejandra, P.S., Lara, J.M., Aneta, D., Pedro, P., Espana, P., Pia, P.A., et al., Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia. PLoS ONE, 2015; 10(10): 1-14.

Douglas, G.C. King, B.F. Isolation of pure villous cytotrophoblast from term human placenta using immunomagnetic microspheres. J Immunol Methods. 1989; 119: 259-268.

Wang, K., Chen, Y., Ferguson, S.D., Leach, R.E. MTA1 and MTA3 Regulate HIF1a Expression in Hypoxia-Treated Human Trophoblast Cell Line HTR8/Svneo. Med J Obstet Gynecol. 2013; 1(3): 1017. 10 pages.

Gambino, Y.P., Maymo, J.L., Perez-Perez, A., Calvo, J.C., Sanchez-Margale, V., Varone, C.L. Elsevier Trophoblast Research Award Lecture: Molecular mechanisms underlying estrogen functions in trophoblastic cells Focus on leptin expression. Placenta 33(Supp A), Trophoblast Research. 2012; 26: 63-70.

Tessier, D.R., Ferraro, Z.M., Gruslin, A. Role of leptin in pregnancy: Consequences of maternal obesity. Placenta. 2013; 34(3): 205-211.

Lea, R.G., Howe, D., Hannah, L.T., Bonneau, O., Hunter, L., Hoggard, N. Placental leptin in normal, diabetic and fetal growth-retarded pregnancies. Mol Hum Reprod. 2000; 6(8): 763-769.

Jeff, K., Murrey, D.M. Placental cytokines and preeclampsia. Frontiers in Bioscience. 2007; 12(7): 2706-2727.

Kristina, B.M., Jessica, D.M., Michael, K.M. Chapter 18 - Polyphenols and Intestinal Health. Nutrition and Functional Foods for Healthy Aging. 2017 191-210.

Marialena, K., Ariadne, M.P., Helen, M., Theodora, B., Alexandra, M., Demetrios. H., et al., Leptin and adiponectin concentrations in intrauterine growth restricted and appropriate for gestational age fetuses, neonates, and their mothers. Eur J Endocrinol. 2008; 158: 343-348.

Alexandra, G., Jocelyne, A., Sylvie, H.M., Edurne, B., Jacques, P., Michele, G.M. Hypoxia-inducible Factor 1 Transactivates the Human Leptin Gene Promoter. J Biol Chem. 2002; 277: 42953-42957.

Ming, F., Zhou, R., Cheng, W.B., Tie, W.W. Study of adiponectin expression in placenta and its correlation with preeclampsia. Zhonghua Fu Chan Ke Za Zhi. 2008; 43(2): 90-93.

Mingfang, Z., Rong, C., Weibo, S. Relationship between the expression of adiponectin in placental tissue of patients with preeclampsia and its pathogenesis. Chinese Journal of Obstetrics and Gynecology. 2008; 43(02): 90-93.

Zuleen, D.F., Mazmin, J.H., Ahmahazri, A.R., Zamri, C., Biochemical studies of Piper betle L leaf extract on obese treated animal using 1H-NMR-based metabolomic approach of blood serum samples. J Ethnopharmacol. 2007; 194: 690-697.

Bing, J., Carole, R.M. O2 Enhancement of Human Trophoblast Differentiation and hCYP19 (Aromatase) Gene Expression Are Mediated by Proteasomal Degradation of USF1 and USF2. Mol Cell Biol. 2005; 25(20): 8824-8833.

Jiang, B., Kamat, A., Mendelson, C.R. Hypoxia prevents induction of aromatase expression in human trophoblast cells in culture: potential inhibitory role of the hypoxia-inducible transcription factor Mash–2 (mammalian achaete-scute homologous protein–2). Mol Endocrinol. 2000; 14: 1661-1673.

Hertig, A., Liere, P., Chabbert-Buffet, N., Fort, J., Pianos, A., Eychenne, B., et al., Steroid profiling in preeclamptic women: evidence for aromatase deficiency. Am J Obstet Gynecol. 2010; 203(477): 1-9.




How to Cite

Ekambaram P, Chithra B. Ascendancy of betle leaf in the metabolism on trophoblasts. Biomedicine [Internet]. 2021Sep.7 [cited 2021Sep.22];41(2):358-66. Available from: