Abstract
Stress is an emerging and inevitable entity. Stress causes anxiety, depression, imbalance of homeostasis, hormone imbalance, and sleep disturbances that are closely related to the onset of metabolic syndrome. The objective of this study was to investigate effects of Ocimum sanctum extract (TZ-OSE) on anti-anxiety, anti-stress, and control of physiological changes due to sleep disturbance in a rat model with restraint stress and sleep disorder induced. After inducing the rat model with restraint stress, three behavioral tests were performed and blood cortisol concentration was determined. In Elevated plus maze test, the test substance TZ-OSE at dose of 200 mg/kg showed the best effect in increasing time that stayed on the open arms. In tail suspension test (TST) and forced swimming test (FST), TZ-OSE significantly reduced immobility duration time (IMT). TZ-OSE also decreased plasma cortisol concentration. In the model after inducing sleep disturbance, ELISA, Western blotting, and Immuno-histochemistry (IHC) were conducted. TZ-OSE treatment decreased plasma cortisol, norepinephrine, glucose, and acylated ghrelin concentrations in the rat model with sleep disorders induced. Decreases of melatonin and leptin levels in the plasma of the rat model with sleep disorders induced were increased by TZ-OSE treatment. Finally, TZ-OSE treatment decreased metabolism-related markers (p-AMPK, Glut-4, p-ACC) in stomach and muscle tissues and decreased the expression of cortisol in adrenal gland tissues. Taken together, these results suggest that TZ-OSE can decrease anxiety, depression, and stress in vivo, regulate sleep-related factors, and control energy metabolism index factors.
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Park, S. O., S. B. Kim, K. S. Lee, and P. S. Kang (2002) Reduction effect of aromatherapy on stress and insomnia. Korean J. Rural Med. 27: 17–26.
Selye, H. (1982) History of the stress concept. pp. 7–17. In: L. Goldborger and S. Breznitz (eds.). Handbook of Stress: Theoretical and Clinical Aspects. The Free Press, New York, NY, USA.
Clark, A. J., J. Flowers, L. Boots, and S. Shettar (1995) Sleep disturbance in mid-life women. J. Adv. Nurs. 22: 562–568.
Bjorvatn, B., I. M. Sagen, N. Øyane, S. Waage, A. Fetveit, S. Pallesen, and R. Ursin (2007) The association between sleep duration, body mass index and metabolic measures in the Hordaland Health Study. J. Sleep Res. 16: 66–76.
Gangwisch, J. E., D. Malaspina, B. Boden-Albala, and S. B. Heymsfield (2005) Inadequate sleep as a risk factor for obesity: analyses of the NHANES I. Sleep. 28: 1289–1296.
Gottlieb, D. J., N. M. Punjabi, A. B. Newman, H. E. Resnick, S. Redline, C. M. Baldwin, and F. J. Nieto (2005) Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch. Intern. Med. 165: 863–867.
Yaggi, H. K., A. B. Araujo, and J. B. McKinlay (2006) Sleep duration as a risk factor for the development of type 2 diabetes. Diabetes Care. 29: 657–661.
Woo, N. S. and Y. B. Seo (2013) Stress relaxation and sleep induction effect of fermented sea tangle Saccharina japonica and oyster Crassostrea gigas powder. Kor. J. Fish Aquat. Sci. 46: 702–707.
Zohar, J. and H. G. M. Westenberg (2000) Anxiety disorders: a review of tricyclic antidepressants and selective serotonin reuptake inhibitors. Acta Psychiatr. Scand Suppl. 403: 39–49.
Kindler, S., O. T. Dolberg, H. Cohen, S. Hirschmann, and M. Kotler (1997) The treatment of comorbid premature ejaculation and panic disorder with fluoxetine. Clin. Neuropharmacol. 20: 466–471.
Vaswani, M., F. K. Linda, and S. Ramesh (2003) Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog. Neuropsychopharmacol. Biol. Psychiatry. 27: 85–102.
Glass, J., K. L. Lanctôt, N. Herrmann, B. A. Sproule, and U. E. Busto (2005) Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 331: 1169.
Gunja, N. (2013) The clinical and forensic toxicology of Z-drugs J. Med. Toxicol. 9: 155–162.
Leach, M. J. and A. T. Page (2015) Herbal medicine for insomnia: A systematic review and meta-analysis Sleep Med. Rev. 24: 1–12.
Bremness, L. (1988) The Complete Book of Herbs: A Practical Guide to Growing and Using Herbs. 1st ed., pp. 238–242. Viking Studio Book, New York, NY, USA.
Choi, Y. J. (2000) Herb Life. 1st ed., pp. 177–204. Yega Publishering Co., Seoul, Korea.
Saxena, R. C., R. Singh, P. Kumar, M. P. S. Negi, V. S. Saxena, P. Geetharani, J. J. Allan, and K. Venkateshwarlu (2012) Efficacy of an extract of Ocimum tenuiflorum (OciBest) in the management of general stress: A double-blind, placebo-controlled study. Evid. Based Complement Alternat. Med. 2012: 894509.
Narendhirakannan, R. T., S. Subramanian, and M. Kandaswamy (2006) Biochemical evaluation of antidiabetogenic properties of some commonly used Indian plants on streptozotocin-induced diabetes in experimental rats. Clin. Exp. Pharmacol. Physiol. 33: 1150–1157.
Vats, V., J. K. Grover, and S. S. Rathi (2002) Evaluation of anti-hyperglycemic and hypoglycemic effect of Trigonella foenum-graecum Linn, Ocimum sanctum Linn and Pterocarpus marsupium Linn in normal and alloxanized diabetic rats. J. Ethnopharmacol. 79: 95–100.
Prasad, M. V. and F. Khanum (2012) Antifatigue activity of ethanolic extract of Ocimum sanctum in rats. Res. J. Med. Plant. 6: 37–46.
Yanpallewar, S. U., S. Rai, M. Kumar, and S. B. Acharya (2004) Evaluation of antioxidant and neuroprotective effect of Ocimum sanctum on transient cerebral ischemia and long-term cerebral hypoperfusion. Pharmacol. Biochem. Behav. 79: 155–164.
Mediratta, P. K., K. K. Sharma, and S. Singh (2002) Evaluation of immunomodulatory potential of Ocimum sanctum seed oil and its possible mechanism of action. J. Ethnopharmacol. 80: 15–20.
Singh, S., H. M. Rehan, and D. K. Majumdar (2001) Effect of Ocimum sanctum fixed oil on blood pressure, blood clotting time and pentobarbitone-induced sleeping time. J. Ethnopharmacol. 78: 139–143.
Sen, P., P. C. Maiti, S. Puri, A. Ray, N. A. Audulov, and A. V. Valdman (1992) Mechanism of anti-stress activity of Ocimum sanctum Linn, eugenol and Tinospora malabarica in experimental animals. Indian J. Exp. Biol. 30: 592–596.
Gupta, P., D. K. Yadav, K. B. Siripurapu, G. Palit, and R. Maurya (2007) Constituents of Ocimum sanctum with antistress activity. J. Nat. Prod. 70: 1410–1416.
Kumar, R. S., M. S. Rao, S. Nayak, and N. N. Sareesh (2007) Effect of Ocimum sanctum (Linn) extract on restraint stress induced behavioral deficits in male wistar rats. Pharmacologyonline. 3: 394–404.
Park, S. Y., J. J. Walker, N. W. Johnson, Z. Zhao, S. L. Lightman, and F. Spiga (2013) Constant light disrupts the circadian rhythm of steroidogenic proteins in the rat adrenal gland. Mol. Cell Endocrinol. 371: 114–123.
Lister, R. G. (1987) The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology. 92: 180–185.
Tabassum, I., Z. N. Siddiqui, and S. J. Rizvi (2010) Effects of Ocimum sanctum and Camellia sinensis on stress-induced anxiety and depression in male albino Rattus norvegicus. Indian J. Pharmacol. 42: 283–288.
Steru, L., R. Chermat, B. Thierry, and P. Simon (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology. 85: 367–370.
Porsolt, R. D., M. Le Pichon, and M. L. Jalfre (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature. 266: 730–732.
Bathala, L. R., C. V. Rao, S. M. Manjunath, S. Vinuta, and R. Vemulapalli (2012) Efficacy of Ocimum sanctum for relieving stress: a preclinical study. J. Contemp. Dent. Pract. 13: 782–786.
De Kloet, E. R., M. Joëls, and F. Holsboer (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci. 6: 463–475.
Wesensten, N. J., T. J. Balkin, and G. Belenky (1999) Does sleep fragmentation impact recuperation? A review and reanalysis. J. Sleep Res. 8: 237–245.
Prinz, P. N., S. L. Bailey, and D. L. Woods (2000) Sleep impairments in healthy seniors: roles of stress, cortisol, and interleukin-1 beta. Chronobiol Iint. 17: 391–404.
Vgontzas, A. N., E. O. Bixler, H. M. Lin, P. Prolo, G. Mastorakos, A. Vela-Bueno, A. Kales, and G. P. Chrousos (2001) Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J. Clin. Endocrinol. Metab. 86: 3787–3794.
Wurtman, R. J., J. Axelrod, and L. S. Phillips (1963) Melatonin Synthesis in the pineal gland: control by light. Science. 142: 1071–1073.
Ganguly, S., S. L. Coon, and D. C. Klein (2002) Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation. Cell Tissue Res. 309: 127–137.
Korf, W., C. Schomerus, and J. H. Stehle (1998) The pineal organ, its hormone melatonin, and the photoneuroendocrine system. Adv. Anat. Embryol. Cell Biol. 146: 1–100.
Zhdanova, I. V., R. J. Wurtman, M. M. Regan, J. A. Taylor, J. P. Shi, and O. U. Leclair (2001) Melatonin treatment for age-related insomnia. J. Clin. Endocrinol. Metab. 86: 4727–4730.
Spiegel, K., R. Leproult, and E. Van Cauter (1999) Impact of sleep debt on metabolic and endocrine function. Lancet. 354: 1435–1439.
Leproult, R., G. Copinschi, O. Buxton, and E. Van Cauter (1997) Sleep loss results in an elevation of cortisol levels the next evening. Sleep. 20: 865–870.
Chaput, J. P., J. P. Després, C. Bouchard, and A. Tremblay (2007) Short sleep duration is associated with reduced leptin levels and increased adiposity: results from the Quebec family study. Obesity. 15: 253–261.
Spiegel, K., E. Tasali, P. Penev, and E. Van Cauter (2004) Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann. Int. Med. 141: 846–850.
Taheri, S., L. Lin, D. Austin, T. Young, and E. Mignot (2004) Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med. 1: e62.
Hardie, D. G. (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat. Rev. Mol. Cell Biol. 8: 774–785.
Woods, A., D. Azzout-Marniche, M. Foretz, S. C. Stein, P. Lemarchand, P. Ferré, F. Foufelle, and D. Carling (2000) Characterization of the role of AMP-activated protein kinase in the regulation of glucose-activated gene expression using constitutively active and dominant negative forms of the kinase. Mol. Cell Biol. 20: 6704–6711.
Foretz, M., D. Carling, C. Guichard, P. Ferré, and F. Foufelle (1998) AMP-activated protein kinase inhibits the glucose-activated expression of fatty acid synthase gene in rat hepatocytes. J. Biol. Chem. 273: 14767–14771.
Koistinen, H. A., D. Galuska, A. V. Chibalin, J. Yang, J. R. Zierath, G. D. Holman, and H. Wallberg-Henriksson (2003) 5-amino-imidazole carboxamide riboside increases glucose transport and cell-surface GLUT4 content in skeletal muscle from subjects with type 2 diabetes. Diabetes. 52: 1066–1072.
Chen, W. W., R. R. He, Y. F. Li, S. B. Li, B. Tsoi, and H. Kurihara (2011) Pharmacological studies on the anxiolytic effect of standardized Schisandra lignans extract on restraint-stressed mice. Phytomedicine. 18: 1144–1147.
Voorhees, J. L., A. J. Tarr, E. S. Wohleb, J. P. Godbout, X. Mo, J. F. Sheridan, T. D. Eubank, and C. B. Marsh (2013) Prolonged restraint stress increases IL-6, reduces IL-10, and causes persistent depressive-like behavior that is reversed by recombinant IL-10. PLoS One. 8: e58488.
Bonnet, M. H. and D. L. Arand (2000) Activity, arousal, and the MSLT in patients with insomnia. Sleep. 23: 205–212.
Anothaisintawee, T., S. Reutrakul, E. Van Cauter, and A. Thakkinstian (2016) Sleep disturbances compared to traditional risk factors for diabetes development: systematic review and meta-analysis. Sleep Med. Rev. 30: 11–24.
Morselli, L. L., A. Guyon, and K. Spiegel (2012) Sleep and metabolic function. Pflugers Arch. 463: 139–160.
Fisslthaler, B. and I. Fleming (2009) Activation and signaling by the AMP-activated protein kinase in endothelial cells. Circ. Res. 105: 114–127.
He, Y., Y. Li, T. Zhao, Y. Wang, and C. Sun (2013) Ursolic acid inhibits adipogenesis in 3T3-L1 adipocytes through LKB1/ AMPK pathway. PLoS One. 8: e70135.
Mitsuhashi, K., T. Senmaru, T. Fukuda, M. Yamazaki, K. Shinomiya, M. Ueno, S. Kinoshita, J. Kitawaki, M. Katsuyama, M. Tsujikawa, H. Obayashi, N. Nakamura, and M. Fukui (2016) Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes. Endocrine. 51: 174–184.
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This work was supported by the Technology development Program(S2449517) funded by the Ministry of SMEs and Startups (MSS, Korea).
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Disclosure statement We declare no conflicts of interest associated with this manuscript. Animal experiments were approved by the Ethics Committee for Animal Experimentation, Hannam University, Daejeon, Korea (approval number: HNU 2017-6) and no informed consent was required for this study.
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Jo, K.J., Nam, G.H., Park, Y.S. et al. Evaluation of Stress-related Behavioral and Biological Activity of Ocimum sanctum Extract in Rats. Biotechnol Bioproc E 25, 170–180 (2020). https://doi.org/10.1007/s12257-019-0365-2
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DOI: https://doi.org/10.1007/s12257-019-0365-2