EFFICACY OF AN ACTIVE COMPOUND OF THE HERB, ASHWAGANDHA IN PREVENTION OF STRESS INDUCED HYPERGLYCEMIA
DOI:
https://doi.org/10.22159/ijpps.2018v10i10.28717Keywords:
Ashwagandha, Corticosterone, G6Pase, Gluconeogenesis, PEPCKAbstract
Objective: To find out whether an isolated compound (IC) from the ethanolic extract of roots of ashwagandha prevents stress-induced hyperglycemia by direct interference with the action of increased concentration of corticosterone on hepatocytes or by preventing hyper-secretion of corticosterone or both.
Methods: A group of rats served as controls, and those in another group were subjected to restraint (1 h) and forced swimming exercise (15 min), after a gap of 4 h daily for 4 w. The third group of rats received orally IC (5 mg/kg bw/rat) 1 h prior to exposure to stressors. After the last treatment period, a blood sample was collected and serum was separated for the estimation of corticosterone and glucose. In in vitro experiment, hepatocytes were treated with different concentrations of corticosterone (100, 200, 300, 400 and 500 ng/ml). In another set of experiment, hepatocytes were treated with different doses of IC (1, 10, 100, 1000 and 10 000 μg/ml of medium) along with corticosterone (400ng/ml). The concentration of glucose and activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined after the treatment.
Results: Stress exposure caused a significant increase in serum concentration of corticosterone and glucose whereas, administration of IC did not result in similar changes. Further, treatment of corticosterone in in vitro significantly increased the activities of PEPCK and G6Pase and concentration of glucose in a dose-dependent manner in hepatocytes. However, treatment with IC did not interfere with the corticosterone-induced an increase in the activities of PEPCK and G6Pase as well as the concentration of glucose in hepatocytes.
Conclusion: The in vivo and in vitro results put together reveal that IC does not directly interfere with the action of corticosterone on hepatocytes. However, it prevents stress-induced hyperglycemia by suppressing hyper-secretion of corticosterone.Â
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References
Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 2000;21:55-89.
Moon TH, Foster GD. Tissue carbohydrate metabolism, gluconeogenesis and hormonal and environmental influences. In: Hochachka PW, Mommsen TP. editors. Biochemistry and molecular biology of fishes. Canada. Elsevier Science; 1995. p. 65-100.
Nirupama R, Devaki M, Yajurvedi HN. Repeated acute stress induced alterations in carbohydrate metabolism in rat. J Stress Physiol Biochem 2010;6:44-55.
Nirupama R, Devaki M, Yajurvedi HN. Repeated stress exposure results in hyperglycemia for a prolonged period in rat. J Exp Zool 2010;13:537-40.
Tamashiro KL, Sakai RR, Shively CA, Karatsoreos IN, Reagan LP. Chronic stress, metabolism, and metabolic syndrome. Stress 201;14:468-74.
Burgess CS, He TT, Yan Z, Lindner J. Cytosolic phosphoenol pyruvate carboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver. Cell Metab 2007;5:313-20.
Dokken BB, Saengsirisuwan V, Kim JS, Teachy MK, Henriksen EJ. Oxidative stress-induced insulin resistance in rat skeletal muscle: role of glycogen synthase kinase-3. Am J Physiol 2008;294:615-21.
Rooney DP, Neely RD, Cullen C, Ehnis CN, Sheridan B. The effect of cortisol on glucose/glucose-6-phosphate cycle activity and insulin action. J Clin Endocrinol Metab 2008;77:1180-3.
Khasina EI, Kirillov OI. Effect of prolonged restraint on glycogen content and activities of four enzymes of carbohydrate metabolism in the liver of rats. Acta Physiol Hung 1986;67:435-9.
Franko KL, Forhead AJ, Fowden AL. Differential effects of prenatal stress and glucocorticoid administration on postnatal growth and glucose metabolism in rats. J Endocrinol 2010;204:319-29.
Nirupama R, Devaki M, Yajurvedi HN. Chronic stress and carbohydrate metabolism: Persistent changes and slow return to normalcy in male albino rats. Stress 2012;15:262-71.
Franko KL, Forhead AJ, Fowden AL. Effects of stress during pregnancy on hepatic glucogenic capacity in rat dams and their fetuses. Physiol Rep 2017;5:1-8.
Wilcox G. Insulin and insulin resistance. Clin Biochem Rev 2005;26:19-39.
Dungan K, Braithwaite SS, Preiser JC. Stress hyperglycemia. Lancet 2009;373:1798-807.
Wu L, Lu Y, Jiao Y, Liu B, Li S, Xing F, et al. Paternal psychological stress reprograms hepatic gluconeogenesis in offspring. Cell Metabol 2016;23:735-43.
Torres RC, Prevatto JP, Silva PMR, Martins MA, Carvalho VF. From type-1 diabetes HPA axis to the disease complications. J Diabetes Metab 2013. Doi:10.4172/2155-6156. S12-002.
Dar NJ, Hamid A, Ahmad M. Pharmacologic overview of Withania somnifera, the Indian Ginseng. Cell Mol Life Sci 2015;72:4445-60.
Bais A, Chandewar AV. Toxicological standardization marketed ashwagandha formulations by atomic absorption spectroscopy. Asian J Pharm Clin Res 2013;6:45-8.
Mulchand S, Seema M. Formulation of polyherbomineral matrices for treatment of osteoporosis. Asian J Pharm Clin Res 2018;11:217-23.
Panchal P, Singh K. Antimicrobial activity of withania somnifera and calotropis procera on pathogenic strains. Int J Curr Pharm Res 2015;7:76-8.
Bhattacharya SK, Muruganandam AV. Adaptogenic activity of Withania somnifera: an experimental study using rat model of chronic stress. Pharmacol Biochem Behaviour 2003;75:547-55.
Nirupama R, Devaki M, Yajurvedi HN. In vitro and in vivo studies on the hypoglycaemic potential of ashwagandha (Withania somnifera) root. Pharma Sci Monit 2014;5:48-58.
Nirupama R, Devaki M, Yajurvedi HN. A comparative study of adaptogenic effect of Withania somnifera and Mifepristone (a GR antagonist) on chronic stress-induced perturbations in glucose metabolism. Int J Pharm Res 2018;10:1-11.
Wormser U, Zakine SB, Stivelband E, Eizen O. The liver slice system: a rapid in vitro acute toxicity test for primary screening of hepatotoxic agents. Toxic In Vitro 1990;4:783-9.
Zhu A, Romero R, Petty HR. An enzymatic colorimetric assay for glucose-6-phosphate. Anal Biochem 2011;419:266-70.
Kin P, Laivenieks M, Vieille C, Zeikus JG. Effect of over expression of Actino bacillus succinogenes phosphopyruvate carboxykinase on succinate production in Escherichia coli. Appl Environ Microbiol 2004;70:1238-41.
Sahin E, Gumuslu S. Immobilization stress in rat tissues: Alterations in protein oxidation lipidperoxidation and antioxidant defence system. Comp Biochem Physiol Part C: Toxicol Pharmacol 2007;144:342-7.
Sistare FD, Haynes RC. Acute stimulation by glucocorticoids of gluconeogenesis from lactate/pyruvate in isolated hepatocytes from normal and adrenalectomized rats. J Biol Chem 1985;260:12754-60.
Perez A, Jansen-Chaparro S, Saigi I, Bernal-Lopez MR, Minambres I, Gomez-Huelgas R. Glucocorticoid-induced hyperglycemia. J Diabet 2014;6:9-20.
Surwit RS, Schneider MS. Role of stress in the etiology and treatment of diabetes mellitus. Psychosom Med 1999;55:380-93.
Pilkis SJ, el-Maghrabi MR, Claus TH. Hormonal regulation of hepatic gluconeogenesis and glycolysis. Annu Rev Biochem 1988;57:755-83.
Postic C, Dentin R, Girard J. Role of the liver in the control of carbohydrate and lipid homeostasis. Diabetes Metab 2004;30:398-408.
Schmoll D, Watkins SL, Wasner C, Walther R, Burchell A. Glucose induces glucose 6-phosphatase hydrolytic subunit gene transcription in an insulinoma cell line (INS-1). FEBS Lett 1999;443:53-6.
Croniger CM, Chakravarty K, Olswang Y, Cassuto H, Reshef L. Hanson RW. Phosphoenolpyruvate carboxykinase revisited: II. control of pepck-C gene expression. Biochem Mol Biol Educ 2002;30:353-62.
Ray PD, Foster DO, Lardy HA. Mode of action of glucocorticoids. J Biol Chem 1964;239:3396-400.
Cassuto H, Kochan K, Chakravarty K, Cohen H, Blum B, Olswang Y, et al. Glucocorticoids regulate transcription of the gene for phosphoenolpyruvate carboxykinase in the liver via an extended glucocorticoid regulatory unit. J Biol Chem 2005;280:33873-84.
Yabaluri N, Bashyam MD. Hormonal regulation of gluconeogenic gene transcription in the liver. J Biosci 2010;35:473-84.
Sampaio-Barros MM, Farias-Silva E, Grassi-Kassisse DM, Spadari-Bratfisch RC. Effect of swimming session duration and repetition on metabolic markers in rats. Stress 2003;6:127-32.
Kumar V, Murthy KNC, Bhamid S, Sudha CG, Ravishankar GA. Genetically modified hairy roots of Withania somnifera Dunal: a potent source of rejuvenating principles. Rejuvenation Res 2005;8:37-45.
Kulkarni SK, Akula KK, Dhir A. Effect of Withania somnifera dunal root extract against pentylenetetrazol seizure threshold in mice: possible involvement of GABAergic system. Indian J Exp Biol 2008;46:465-9.
Herman JP, Mueller NK, Figueiredo H. Role of GABA and glutamate circuitry in hypothalamopituitary-adrenocortical stress integration. Ann N Y Acad Sci 2004;1018:35-45.
Di S, Maxson MM, Franco A, Tasker JG. Glucocorticoids regulate glutamate and GABA synapse-specific retrograde transmission via divergent nongenomic signaling pathways. J Neurosci 2009;29:393-401.
Liu ZP, Song C, Wang M, He Y, Xu XB, Pan HQ, et al. Chronic stress impairs GABAergic control of amygdala through suppressing the tonic GABAA receptor currents. Mol Brain 2014;7:1-14.
Scaglione F, Zangara A. Valeriana officinalis and Melissa officinalis extracts normalize brain levels of GABA and glutamate altered by chronic stress. J Sleep Disord Manag 2017;3:1-7.
Kulkarni SK, Dhir A. Withania somnifera: an Indian ginseng. Progress Neuropsychopharmacol Biol Psychiatry 2008; 32:1093-105.
John J. Therapeutic potential of Withania somnifera: a report on phyto pharmacological properties. Int J Pharm Sci Rev Res 2014;5:2131-48.
Bansal P, Banerjee S. Effect of Withinia somnifera and shilajit on alcohol addiction in mice. Pharmacogn Mag 2016;12:121-8.
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