Raw and Wine Processed Schisandra chinensis Regulate NREM-Sleep and Alleviate Cardiovascular Dysfunction Associated with Insomnia by Modulating HPA Axis

Abstract

Clinical studies have shown that insomnia and anxiety are usually accompanied by cardiovascular dysfunction. In traditional Chinese medicine, Schisandra chinensis (SC) and wine processed Schisandra chinensis (WSC) are mainly used for the treatment of dysphoria, palpitation and insomnia. However, little attention was paid to its mechanism. In this study, we monitored the effect of SC and WSC on the nervous system and cardiovascular system of free-moving rats in the real-time. Our results show that SC and WSC can alleviate cardiovascular dysfunction while promoting sleep, and we further explored their potential mechanisms. HPLC-QTOF-MS was used for the quality control of chemical components in SC and WSC. Data sciences international (DSI) physiological telemetry system was applied to collect the electroencephalogram (EEG), electrocardiogram (ECG) and other parameters of free-moving rats to understand the effects of long-term intake of SC and WSC on rats. The content of Cortisol (CORT), neurotransmitters and amino acids in rat pituitary and hypothalamus were analyzed by UPLC-MS to determine the activity of HPA axis. The expression of melatonin receptor MT1 was analyzed by immunofluorescence technique. Our results suggested that SC and WSC may play the role of promoting sleep by increasing the expression level of melatonin receptor MT1 in hypothalamus, and modulate the activity of HPA axis by regulating the levels of the related neurotransmitters and amino acid, so as to improve the abnormal cardiovascular system of rats. This study may provide theoretical support for explicating the advantages of SC and other phytomedicines in the treatment of insomnia.

Key words

insomnia - cardiovascular system - HPA axis - neurotransmitters - Schisandra chinensis - Schisandraceae

Publikationsverlauf

Eingereicht: 21. September 2021

Angenommen nach Revision: 15. Dezember 2021

Accepted Manuscript online:
15. Dezember 2021

Artikel online veröffentlicht:
28. Februar 2022

• References

• 1 Riemann D, Nissen C, Palagini L, Otte A, Perlis ML, Spiegelhalder K. The neurobiology, investigation, and treatment of chronic insomnia. Lancet Neurol 2015; 14: 547-558
• 2 Lande RG, Gragnani C. Nonpharmacologic approaches to the management of insomnia. J Am Osteopath Assoc 2010; 110: 695-701
• 3 Taylor DJ, Mallory LJ, Lichstein KL, Durrence HH, Riedel BW, Bush AJ. Comorbidity of chronic insomnia with medical problems. Sleep 2007; 30: 213-218
• 4 Wilt TJ, MacDonald R, Brasure M, Olson CM, Carlyle M, Fuchs E, Khawaja IS, Diem S, Koffel E, Ouellette J, Butler M, Kane RL. Pharmacologic treatment of insomnia disorder: An evidence report for a clinical practice guideline by the American college of physicians. Ann Intern Med 2016; 165: 103-112
• 5 Wang Y, Fan X, Qu H, Gao X, Cheng Y. Strategies and techniques for multi-component drug design from medicinal herbs and traditional Chinese medicine. Curr Top Med Chem 2012; 12: 1356-1362
• 6 Yang Y, Wu C. Traditional Chinese medicine in ameliorating diabetic kidney disease via modulating gut microbiota. Integr Med Nephrol Androl 2021; 8: 8
• 7 Wheatley D. Medicinal plants for insomnia: A review of their pharmacology, efficacy and tolerability. J Psychopharmacol 2005; 19: 414-421
• 8 Meerlo P, Sgoifo A, Suchecki D. Restricted and disrupted sleep: Effects on autonomic function, neuroendocrine stress systems and stress responsivity. Sleep Med Rev 2008; 12: 197-210
• 9 Burford NG, Webster NA, Cruz-Topete D. Hypothalamic-pituitary-adrenal axis modulation of glucocorticoids in the cardiovascular system. Int J Mol Sci 2017; 18: 2150
• 10 Taylor KS, Murai H, Millar PJ, Haruki N, Kimmerly DS, Morris BL, Tomlinson G, Bradley TD, Floras JS. Arousal from sleep and sympathetic excitation during wakefulness. Hypertension 2016; 68: 1467-1474
• 11 Castro-Diehl C, Diez Roux AV, Redline S, Seeman T, Shrager SE, Shea S. Association of sleep duration and quality with alterations in the hypothalamic-pituitary adrenocortical axis: The Multi-Ethnic Study of Atherosclerosis (MESA). J Clin Endocrinol Metab 2015; 100: 3149-3158
• 12 Hsu CY, Chen YT, Chen MH, Huang CC, Chiang CH, Huang PH, Chen JW, Chen TJ, Lin SJ, Leu HB, Chan WL. The association between insomnia and increased future cardiovascular events: A nationwide population-based study. Psychosom Med 2015; 77: 743-751
• 13 Catena C, Colussi G, Nait F, Pezzutto F, Martinis F, Sechi LA. Early renal failure as a cardiovascular disease: Focus on lipoprotein(a) and prothrombotic state. World J Nephrol 2015; 4: 374-378
• 14 Ryou M, Stylopoulos N, Baffy G. Nonalcoholic fatty liver disease and portal hypertension. Explor Med 2020; 1: 149-169
• 15 Javaheri S, Redline S. Insomnia and risk of cardiovascular disease. Chest 2017; 152: 435-444
• 16 Szopa A, Ekiert R, Ekiert H. Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: A review on the bioactive components, pharmacological properties, analytical and biotechnological studies. Phytochem Rev 2017; 16: 195-218
• 17 Sowndhararajan K, Deepa P, Kim M, Park SJ, Kim S. An overview of neuroprotective and cognitive enhancement properties of lignans from Schisandra chinensis. Biomed Pharmacother 2018; 97: 958-968
• 18 Panossian A, Wikman G. Pharmacology of Schisandra chinensis Bail.: An overview of Russian research and uses in medicine. J Ethnopharmacol 2008; 118: 183-212
• 19 Song Y, Shan B, Zeng S, Zhang J, Jin C, Liao Z, Wang T, Zeng Q, He H, Wei F, Ai Z, Su D. Raw and wine processed Schisandra chinensis attenuate anxiety like behavior via modulating gut microbiota and lipid metabolism pathway. J Ethnopharmacol 2021; 266: 113426
• 20 Wei B, Li Q, Fan R, Su D, Chen X, Jia Y, Bi K. Determination of monoamine and amino acid neurotransmitters and their metabolites in rat brain samples by UFLC-MS/MS for the study of the sedative-hypnotic effects observed during treatment with S. chinensis. J Pharm Biomed Anal 2014; 88: 416-422
• 21 Stamper CE, Hassell jr. JE, Kapitz AJ, Renner KJ, Orchinik M, Lowry CA. Activation of 5-HT1A receptors in the rat dorsomedial hypothalamus inhibits stress-induced activation of the hypothalamic-pituitary-adrenal axis. Stress 2017; 20: 223-230
• 22 Lux-Lantos VA, Bianchi MS, Catalano PN, Libertun C. GABA(B) receptors in neuroendocrine regulation. Cell Mol Neurobiol 2008; 28: 803-817
• 23 Balkan B, Pogun S. Nicotinic cholinergic system in the hypothalamus modulates the activity of the hypothalamic neuropeptides during the stress response. Curr Neuropharmacol 2018; 16: 371-387
• 24 Meeker RB, Greenwood RS, Hayward JN. Glutamate receptors in the rat hypothalamus and pituitary. Endocrinology 1994; 134: 621-629
• 25 Ferone D, Gatto F, Arvigo M, Resmini E, Boschetti M, Teti C, Esposito D, Minuto F. The clinical-molecular interface of somatostatin, dopamine and their receptors in pituitary pathophysiology. J Mol Endocrinol 2009; 42: 361-370
• 26 Kjaer A, Knigge U, Plotsky PM, Bach FW, Warberg J. Histamine H1 and H2 receptor activation stimulates ACTH and beta-endorphin secretion by increasing corticotropin-releasing hormone in the hypophyseal portal blood. Neuroendocrinology 1992; 56: 851-855
• 27 Holty JE, Guilleminault C. REM-related bradyarrhythmia syndrome. Sleep Med Rev 2011; 15: 143-151
• 28 Pothineni NV, Shirazi LF, Mehta JL. Gender differences in autonomic control of the cardiovascular system. Curr Pharm Des 2016; 22: 3829-3834
• 29 Trinder J, Kleiman J, Carrington M, Smith S, Breen S, Tan N, Kim Y. Autonomic activity during human sleep as a function of time and sleep stage. J Sleep Res 2001; 10: 253-264
• 30 Kuo TB, Shaw FZ, Lai CJ, Yang CC. Asymmetry in sympathetic and vagal activities during sleep-wake transitions. Sleep 2008; 31: 311-320
• 31 Scholz UJ, Bianchi AM, Cerutti S, Kubicki S. Vegetative background of sleep: spectral analysis of the heart rate variability. Physiol Behav 1997; 62: 1037-1043
• 32 Bertisch SM, Pollock BD, Mittleman MA, Buysse DJ, Bazzano LA, Gottlieb DJ, Redline S. Insomnia with objective short sleep duration and risk of incident cardiovascular disease and all-cause mortality: Sleep Heart Health Study. Sleep 2018; 41: zsy047
• 33 Rodenbeck A, Hajak G. Neuroendocrine dysregulation in primary insomnia. Rev Neurol (Paris) 2001; 157: 57-61
• 34 Minkel J, Moreta M, Muto J, Htaik O, Jones C, Basner M, Dinges D. Sleep deprivation potentiates HPA axis stress reactivity in healthy adults. Health Psychol 2014; 33: 1430-1434
• 35 Walker BR. Glucocorticoids and cardiovascular disease. Eur J Endocrinol 2007; 157: 545-559
• 36 Ivy JR, Jones NK, Costello HM, Mansley MK, Peltz TS, Flatman PW, Bailey MA. Glucocorticoid receptor activation stimulates the sodium-chloride cotransporter and influences the diurnal rhythm of its phosphorylation. Am J Physiol Renal Physiol 2019; 1 (317) F1536-F1548
• 37 Calogero AE, Bagdy G, Szemeredi K, Tartaglia ME, Gold PW, Chrousos GP. Mechanisms of serotonin receptor agonist-induced activation of the hypothalamic-pituitary-adrenal axis in the rat. Endocrinology 1990; 126: 1888-1894
• 38 Calogero AE, Gallucci WT, Bernardini R, Saoutis C, Gold PW, Chrousos GP. Effect of cholinergic agonists and antagonists on rat hypothalamic corticotropin-releasing hormone secretion in vitro. Neuroendocrinology 1988; 47: 303-308
• 39 Herman JP, Mueller NK, Figueiredo H. Role of GABA and glutamate circuitry in hypothalamo-pituitary-adrenocortical stress integration. Ann N Y Acad Sci 2004; 1018: 35-45
• 40 Belda X, Armario A. Dopamine D1 and D2 dopamine receptors regulate immobilization stress-induced activation of the hypothalamus-pituitary-adrenal axis. Psychopharmacology (Berl) 2009; 206: 355-365
• 41 Khazipov R, Zaynutdinova D, Ogievetsky E, Valeeva G, Mitrukhina O, Manent JB, Represa A. Atlas of the postnatal rat brain in stereotaxic coordinates. Front Neuroanat 2015; 9: 161