Adaptogens were initially defined as substances that enhance the “state of nonspecific resistance” in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. Studies on animals and isolated neuronal cells have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. In addition, a number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly in tolerance to mental exhaustion and enhanced attention. Indeed, recent pharmacological studies of a number of adaptogens have provided a rationale for these effects also at the molecular level. It was discovered that the stress—protective activity of adaptogens was associated with regulation of homeostasis via several mechanisms of action, which was linked with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of stress response, such as molecular chaperons (e.g., HSP70), stress-activated c-Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription factor DAF-16, cortisol and nitric oxide.
References
[1]
Drake, K.V. On the pharmacology of Schizandra chinensis. Farmakol. Toksikol.？1942, 5, 32–36.
[2]
Astanin, Yu. P.; Mikhelson, M.Ya.; Egolinskij, Ya.A. The study of phenamine and some other stimulants effect on sport running. Farmakol. Toksikol.？1943, 6, 60–65.
[3]
Varlakov, M.N. On the stimulating effect of Schizandra chinensis. Pharmacia？1944, 6, 31–34.
[4]
Yefimov, V.V.; Vlasova, L.N. The effect of Schizandra-stimulant on nervous-muscular excitability in man. Biul. Eksp. Biol. Med.？1945, 19, 29–30.
[5]
Zhestyanikov, V.D. Some data on the effect of the Far East Schizandra on the CNS. ？1945, 3, 24–29.
[6]
Karo, V.I. The ergographic study of Schizandra stimulating effect. ？1945, 3, 30–33.
[7]
Kokhanova, A.N.; Peresypkina, N.V.; Balagurovskaya, E.N.; Kotel’nikova, K.M.; Grigorieva, I.T. The effect of Schizandra on muscular fatigue in man. Nechaev, S.K., Ed.; Ministry of Health of Russian Federation, Khabarovsk Medical Institute: Khabarovsk, USSR, 1950; pp. 85–89.
Lazarev, N.V. General and specific in action of pharmacological agents. Farmacol.Toxicol.？1958, 21, 81–86.
[12]
Lazarev, N.V.; Ljublina, E.I.; Rozin, M.A. State of nonspecific resistance. Patol. Fiziol. Experim. Terapia？1959, 3, 16–21.
[13]
Selye, H. Stress; Acta Medical Publisher: Montreal, Canada, 1950.
[14]
Brekhman, I.I; Dardymov, I.V. New substances of plant origin which increase nonspecific resistance. Ann. Rev. Pharmacol.？1968, 8, 419–430.
[15]
Meerson, F. Adaptation, Stress and Prophylax; . (russ.).
[16]
Eleutherococc (Bibliographic index) 1958-1981, 1st ed.; Brekhman, I.I., Ed.; USSR Academy of Sciences, Far East Scientific Center, Institute of Marine Biolofy: Vladivostok, USSR, 1982; pp. 1–14.
[17]
Wiegant, F.A.; Surinova, S.; Ytsma, E.; Langelaar–Makkinje, M.; Wikman, G.; Post, J.A. Plant adaptogens increase lifespan and stress resistance in C. elegans. Biogerontology？2009, 10, 27–42, doi:10.1007/s10522-008-9151-9. 18536978
[18]
Wiegant, F.A.C.; Limandjaja, G.; de Poot, S.A.H.; Bayda, L.A.; Vorontsova, O.N.; Zenina, T.A.; Langelaar Makkinje, M.; Post, J.A.; Wikman, G. Plant adaptogens activate cellular adaptive mechanisms by causing mild damage. In Adaptation Biology and Medicine: Health Potentials; Lukyanova, L., Takeda, N., Singal, P.K., Eds.; NarosaPublishers: NewDelhi, India, 2008; Volume 5, pp. 319–332.
[19]
Jafari, M.; Felgner, J.S.; Bussel, I.I.; Hutchili, T.; Khodayari, B.; Rose, M.R.; Vince-Cruz, C.; Mueller, L.D. Rhodiola: a promising anti-aging Chinese herb. Rejuvenation Res.？2007, 10, 587–602, doi:10.1089/rej.2007.0560. 17990971
[20]
Schriner, S.E.; Avanesian, A.; Liu, Y.; Luesch, H.; Jafari, M. Protection of human cultured cells against oxidative stress by Rhodiola rosea without activation of antioxidant defenses. Free Radic. Biol. Med.？2009, 47, 577–584, doi:10.1016/j.freeradbiomed.2009.05.025.
[21]
Panossian, A.; Hambartsumyan, M.; Hovanissian, A.; Gabrielyan, E.; Wikman, G. The Adaptogens Rhodiola and Schizandra Modify the Response to Immobilization Stress in Rabbits by Suppressing the Increase of Phosphorylated Stress–activated Protein Kinase, Nitric Oxide and Cortisol. Drug Targets Insights？2007, 1, 39–54.
[22]
Panossian, A.; Wikman, G.; Kaur, P.; Asea, A. Adaptogens exert a stress protective effect by modulation of expression of molecular chaperons. Phytomedicine？2009, 16, 617–622, doi:10.1016/j.phymed.2008.12.003.
[23]
Panossian, A.; Wikman, G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Current Clin.Pharmacol.？2009, 4, 198–219, doi:10.2174/157488409789375311.
[24]
Panossian, A.; Wikman, G. Evidence-based efficacy of adaptogens in fatigue and molecular mechanisms relared to their stress-protective activity. In International Evidence–Based Complementary Medicine Conference, Armidale, Australia, 13-15 March; Bonn, K., Ed.; University of New England: Armidale, Australia, 2009; p. 10.
[25]
European Medicines Agency. Committee on Medicinal Products EMEA/HMPC/104613/2005. Available online: http://www.emea.europa.eu/pdfs/human/hmpc/10461305en.pdf/ , accessed on 3 January 2010.
[26]
Panossian, A.; Wikman, G. Pharmacology of Schisandra chinensis Bail.: An overview of Russian research and uses in medicine. J. Ethnopharmacol.？2008, 118, 183–212, doi:10.1016/j.jep.2008.04.020. 18515024
[27]
Dardimov, I.V. Ginseng, Eleutherococcus. On the Mechanism of Biological Activity; Nauka: Moscow, USSR, 1976; pp. 1–189.
[28]
Saratikov, A.S.; Krasnov, E.A. Rhodiola rosea (Golden root), 4th ed. ed.; Tomsk State University Publishing House: Tomsk, USSR, 2004; pp. 1–286.
[29]
Lebedev, A.A. Schizandra; Tashkent: “Meditsina” Publishing House of the Uzbekistani SSR: Tashkent, USSR, 1971; pp. 1–98.
Farnsworth, N.; Kinghorn, A.D.; Soejarto, D.D.; Waller, D.P. Siberian Ginseng (Eleutherococcus senticosus): Current status as an adaptogen. In Economic and Medicinal Plant Research; Wagner, H., Hikino, H., Farnsworth, N.R., Eds.; Academic Press: London, UK, 1985; Volume 1, pp. 156–209.
[32]
Brekhman, I.I. Eleutherococcus; Nauka: Leningrad, USSR, 1968; pp. 1–168.
[33]
Brown, R.P.; Gerbarg, P.L.; Graham, B. The Rhodiola revolution; Rodale Inc.: New York, USA, 2004; pp. 1–260.
[34]
Winston, D.; Maimes, S. Adaptogens. Herbs for strength, stamina and stress relief; Healing Arts Press: Rochester, Vermont, USA, 2007; pp. 1–324.
[35]
Kurkin, V.A.; Zapesochnaya, G.G. Chemical composition and pharmacological properties of Rhodiola rosea L. Khim.Farm. Zurnal？1986, 20, 1231–1244.
[36]
Khanum, F.; Bawa, A.S.; Singh, B. Rhodiola rosea: A versatile adaptogen. Compr. Rev. Food Sci. Food Safety？2005, 4, 55–62, doi:10.1111/j.1541-4337.2005.tb00073.x.
[37]
Kelly, G.S. Rhodiola rosea: a possible plant adaptogen. Altern. Med. Rev.？2001, 6, 293–302.
[38]
Zapesochnaya, G.G.; Kurkin, V.A.; Boyko, V.P.; Kolkhir, V.K. Phenylpropanoids–promising biologically active compounds of medicinal plants. Khim.Farm. Zh.？1995, 29, 47–50.
[39]
Aksenova, R.A.; Zotova, M.I.; Nekhoda, M.F.; Cherdintsev, S.G. Comparative characteristics of the stimulating and adaptogenic effects of Rhodiola rosea preparations. In Stimulants of the central nervous system; Saratikov, A.S., Ed.; Tomsk University Press: Tomsk, USSR, 1968; Volume 2, pp. 3–12.
[40]
Panossian, A.; Nikoyan, N.; Ohanyan, N.; Hovhannisyan, A.; Abrahamyan, H.; Gabrielyan, E.; Wikman, G. Comparative study of Rhodiola preparations on behavioral despair of rats. Phytomedicine？2008, 15, 84–91, doi:10.1016/j.phymed.2007.10.003. 18054474
[41]
Barnaulov, O.D.; Limarenko, A.Y.; Kurkin, V.A.; Zapesochnaya, G.G.; Shchavlinskij, A.N. A comparative evaluation of the biological activity of compounds isolated from species of Rhodiola. Khim.Pharm. Zh.？1986, 23, 1107–1112.
[42]
Sokolov, S.Y.; Boyko, V.P.; Kurkin, V.A.; Zapesochnaya, G.G.; Rvantsova, N.V.; Grinenko, H.A. A comparative study of the stimulant property of certain phenylpropanoids. Khim. Pharm. Zh.？1990, 24, 66–68.
[43]
Sokolov, S.Y.; Ivashin, V.M.; Zapesochnaya, G.G.; Kurkin, V.A.; Shavlinskiy, A.N. Study of neurotropic activity of new substances isolated from Rhodiola rosea. Khim. Pharm. Zh.？1985, 19, 1367–1371.
[44]
Ovodov, Y.S.; Ovodova, R.G.; Solovyova, T.F.; Elyakov, G.B.; Kochetkov, N.K. Glycosides of Eleutherococcus senticosus. I. Isolation and some properties of Eleutherosides B and E. Khim. Prir. Soedin.？1965, 1, 3–7.
[45]
Ovodov, Y.S.; Frolova, G.M.; Nefedova, M.Y.; Elyakov, G.B. Glycosides of Eleutherococcus senticosus. II. Structure of Eleutherosides A, B1, C and D. Khim. Prir. Soedin.？1965, 1, 63–64.
[46]
Elyakov, G.B.; Ovodov, Y.S. The glycosides of Araliaceae. Khim. Prir. Soedin.？1972, 6, 697–709.
[47]
Norr, H. Phytochemical and pharmacological Investigations of the Adaptogens: Eleutherococcus senticosus, Ocimum sanctum, Codonopsis pilosula, Rhodiola rosea and Rhodiola crenulata. Ph.D. Dissertation, Faculty of Chemistry and Pharmacy, Ludwig–Maximillians University, Munich, Germany, 1993.
[48]
Wagner, H. Immunostimulants and adaptogens from plants. In Phytochemistry of Medicinal Plants; Amason, J.T., Ed.; Plenum Press: New York, NY, USA, 1995; pp. 1–18.
[49]
Balandin, D.A. Schizandrin—a new stimulant from Schizandra fruits. In Materials for the Study of Stimulants and Tonics from Ginseng and Schizandra Roots; Lazarev, N.V., Ed.; Far East Branch of USSR Academy of Science: Vladivostok, USSR, 1951; pp. 45–50.
[50]
Lebedev, A.A. Some materials on the pharmacology of schizandrin. In Materials for the Study of Stimulants and Tonics from Ginseng and Schizandra Roots; Lazarev, N.V., Ed.; Far East Branch of USSR Academy of Science: Vladivostok, USSR, 1951; pp. 109–117.
[51]
Lebedev, A.A. Schizandrine –a New Stimulant from Schizandra Chinensis Fruits—Summary of Thesis for a Candidate’s degree in Medicine, Tashkent State Mrdical University, Tashkent, USSR,, 1967.
[52]
Kochetkov, N.K.; Khorlin, A.Y.; Chizhov, O.S.; Sheichenko, V.I. Chemical investigation of Schizandra Chinensis. Communication 2. Structure of Schizandrin. Izv. Akad. Nauk. Ser. Khim.？1962, 5, 850–856.
[53]
Kochetkov, N.K.; Khorlin, A.Y.; Chizhov, O.S.; Sheichenko, V.I. Schizandrin, a lignan of unusual structure. Tetrahedron Lett.？1961, 31, 730–734.
[54]
Kim, S.R.; Lee, M.K.; Koo, K.A.; Kim, S.H.; Sung, S.H.; Lee, N.G.; Markelonis, G.J.; Oh, T.H.; Yang, J.H.; Kim, Y.C. Dibenzocyclooctadiene lignans from Schisandra chinensis protect primary cultures of rat cortical cells from glutamate-induced toxicity. J. Neurosci. Res.？2004, 76, 397–405, doi:10.1002/jnr.20089.
[55]
Wang, B.; Wang, X.M. Schisandrin B protects rat cortical neurons against Abeta1-42-induced neurotoxicity. Pharmazie？2009, 64, 450–454. 19694182
[56]
Ko, K.M.; Chen, N.; Leung, H.Y.; Leong, E.P.; Poon, M.K.; Chiu, P.Y. Long-term schisandrin B treatment mitigates age-related impairments in mitochondrial antioxidant status and functional ability in various tissues, and improves the survival of aging C57BL/6J mice. Biofactors？2008, 34, 331–342, doi:10.1002/biof.5520340408.
[57]
Liu, X.N.; Zhang, C.Y.; Jin, X.D.; Li, Y.Z.; Zheng, X.Z.; Li, L. Inhibitory effect of schisandrin B on gastric cancer cells in vitro. World J. Gastroenterol.？2007, 13, 6506–6511, doi:10.3748/wjg.13.6506. 18161920
[58]
Chiu, P.Y.; Leung, H.Y.; Poon, M.K.; Mak, D.H.; Ko, K.M. (–)Schisandrin B is more potent than its enantiomer in enhancing cellular glutathione and heat shock protein production as well as protecting against oxidant injury in H9c2 cardiomyocytes. Mol. Cell. Biochem.？2006, 289, 185–191, doi:10.1007/s11010-006-9163-1.
[59]
Chen, N.; Chiu, P.Y.; Ko, K.M. Schisandrin B enhances cerebral mitochondrial antioxidant status and structural integrity, and protects against cerebral ischemia/reperfusion injury in rats. Biol. Pharm. Bull.？2008, 31, 1387–1391, doi:10.1248/bpb.31.1387.
[60]
Pao, T.T.; Hsu, K.F.; Liu, K.T.; Chang, L.G.; Chuang, C.H.; Sung, C.Y. Protective action of schizandrin B on hepatic injury in mice. Chin Med J (Engl).？1977, 3, 173–179. 410602
[61]
Panossian, A.; Gabrielian, E.; Wagner, H. On the mechanism of action of plant adaptogens with particular references on cucuirbitacin R diglucoside. Phytomedicine？1999, 6, 147–155, doi:10.1016/S0944-7113(99)80002-6.
[62]
Panossian, A.; Gabrielian, E.; Wagner, H. Plant adaptogens II: Bryonia as an adaptogen. Phytomedicine？1997, 4, 83–97.
[63]
Wang, L.C.; Lee, T.F. Effect of ginseng saponins on cold tolerance in young and elderly rats. Planta Med.？2000, 66, 144–147, doi:10.1055/s-2000-11122.
[64]
Hiai, S.; Yokoyama, H.; Oura, H.; Yano, S. Stimulation of pituitary-adrenocortical system by ginseng saponin. Endocrinol. Jpn.？1979, 26, 661–665, doi:10.1507/endocrj1954.26.661.
[65]
Hiai, S.; Yokoyama, H.; Oura, H. Features of ginseng saponin-induced corticosterone secretion. Endocrinol. Jpn.？1979, 26, 737–740, doi:10.1507/endocrj1954.26.737. 396151
[66]
Kim, D.H.; Jung, J.S.; Suh, H.W.; Huh, S.O.; Min, S.K.; Son, B.K.; Park, J.H.; Kim, N.D.; Kim, Y.H.; Song, D.K. Inhibition of stress-induced plasma corticosterone levels by ginsenosides in mice: involvement of nitric oxide. Neuroreport？1998, 9, 2261–2264, doi:10.1097/00001756-199807130-00021.
[67]
Kim, D.H.; Moon, Y.S.; Jung, J.S.; Min, S.K.; Son, B.K.; Suh, H.W.; Song, D.K. Effects of ginseng saponin administered intraperitoneally on the hypothalamo-pituitary-adrenal axis in mice. Neurosci. Lett.？2003, 343, 62–66, doi:10.1016/S0304-3940(03)00300-8.
[68]
Kim, D.H.; Jung, J.S.; Moon, Y.S.; Sung, J.H.; Suh, H.W.; Kim, Y.H.; Song, D.K. Inhibition of intracerebroventricular injection stress-induced plasma corticosterone levels by intracerebroventricularly administered compound K, a ginseng saponin metabolite, in mice. Biol. Pharm. Bull.？2003, 26, 1035–1038, doi:10.1248/bpb.26.1035. 12843635
[69]
Ghosal, S.; Lal, J.; Srivatava, R.; Battacharya, R.; Upadhyay, S.N.; Jaiswal, A.K.; Chattopadhyay, U. Anti-stress activity of sitoindosides IX and X, New C-27-glycowithanolides from Withania somnifera. Phytother. Res.？1989, 3, 201–209, doi:10.1002/ptr.2650030510.
Baek, N.I.; Han, J.T.; Ahn, E.M.; Park, J.K.; Cho, S.W.; Jeon, S.G.; Jang, J.S.; Kim, Choong, K.; Choi, S.Y. Isolation of anticonvulsant compounds from the fruits of Schizandra chinensis Baili. Agric. Chem. Biotechnol.？2000, 43, 72–77.
[72]
Munck, A.; Guyre, P.M.; Holbrook, N.J. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr. Rev.？1984, 5, 25–44, doi:10.1210/edrv-5-1-25.
[73]
Fink, G. Encyclopedia of Stress; Academic Press: New York, NY, USA, 2000; Volumes 1–3.
[74]
Chrousos, G.P.; Gold, P.W. The concept of stress system disorders: Overview of behavioral and physical homeostasis. JAMA？1992, 267, 1244–1252, doi:10.1001/jama.1992.03480090092034.
[75]
Van Diermen, D.; Marston, A.; Bravo, J.; Reist, M.; Carrupt, P.A.; Hostettmann, K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J. Ethnopharmacol.？2009, 122, 397–401, doi:10.1016/j.jep.2009.01.007. 19168123
[76]
Saratikov, A.S.; Krasnov, E.A.; Chnikina, L.A.; Duvidson, L.M.; Sotova, M.I.; Marina, T.F.; Nechoda, M.F.; Axenova, R.A.; Tscherdinzeff, S.G. Rhodiolosid, a new glycoside from Rhodiola rosea and its pharmacological properties. Pharmazie？1968, 23, 392–395.
[77]
Panossian, A.; Wagner, H. Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytother. Res.？2005, 19, 819–838, doi:10.1002/ptr.1751.
[78]
Panossian, A.; Wikman, G. Effect of adaptogens on the central nervous system. Arq. Bras. Fitomed. Cient.？2005, 2, 108–130.
[79]
Cao, L.L.; Du, G.H.; Wang, M.W. Effect of salidroside on mitochondria injury induced by sodium azide. Yao Xue Xue Bao？2005, 40, 700–704.
[80]
Cao, L.L.; Du, G.H.; Wang, M.W. Effect of salidroside on cell damage induced by glutamate and intracellular free calcium in PC12 cells. J. Asian Nat.Prod. Res.？2006, 8, 159–165, doi:10.1080/1028602042000325645.
[81]
Chen, X.; Liu, J.; Gu, X.; Ding, F. Salidroside attenuates glutamate-induced apoptotic cell death in primary cultured hippocampal neurons of rats. Brain Res.？2008, 1238, 189–198, doi:10.1016/j.brainres.2008.07.051.
[82]
Cai, L.; Wang, H.; Li, Q.; Qian, Y.; Yao, W. Salidroside inhibits H2O2-induced apoptosis in PC12 cells by preventing cytochrome c release and inactivating of caspase cascade. Acta Biochim. Biophys. Sin. (Shanghai)？2008, 40, 796–802, doi:10.1093/abbs/40.9.796. 18776992
[83]
Zhang, W.S.; Zhu, L.Q.; Niu, F.L.; Deng, R.C.; Ma, C.X. Protective effects of salidroside on injury induced by hypoxia/hypoglycemia in cultured neurons. Zhongguo Zhong Yao Za Zhi？2004, 29, 459–462.
[84]
Zhang, L.; Yu, H.; Sun, Y.; Lin, X.; Chen, B.; Tan, C.; Cao, G.; Wang, Z. Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells. Eur. J. Pharmacol.？2007, 564, 18–25, doi:10.1016/j.ejphar.2007.01.089.
[85]
Jang, S.I.; Pae, H.O.; Choi, B.M.; Oh, G.S.; Jeong, S.; Lee, H.J.; Kim, H.Y.; Kang, K.J.; Yun, Y.G.; Kim, Y.C.; Chung, H.T., 2003. Salidroside from Rhodiola sachalinensis protects neuronal PC12 cells against cytotoxicity induced by amyloid-beta. Immunopharmacol. Immunotoxicol.？2003, 25, 295–304, doi:10.1081/IPH-120024498.
[86]
Li, H.B.; Ge, Y.K.; Zheng, X.X.; Zhang, L. Salidroside stimulated glucose uptake in skeletal muscle cells by activating AMP-activated protein kinase. Eur.J. Pharmacol.？2008, 588, 165–169, doi:10.1016/j.ejphar.2008.04.036.
[87]
Ma, L.; Cai, D.L.; Li, H.X.; Tong, B.D.; Wang, Y.; Pei, S.P. Protective effects of salidroside on oxidative damage in fatigue mice. Zhong Xi Yi Jie He Xue Bao？2009, 7, 237–241.
[88]
Zou, Y.Q.; Cai, Z.Y.; Mao, Y.F.; Li, J.B.; Deng, X.M. Effects of salidroside-pretreatment on neuroethology of rats after global cerebral ischemia-reperfusion. Zhong Xi Yi Jie He Xue Bao？2009, 7, 130–134, doi:10.3736/jcim20090207.
[89]
Yu, S.; Liu, M.; Gu, X.; Ding, F. Neuroprotective effects of salidroside in the PC12 cell model exposed to hypoglycemia and serum limitation. Cell. Mol. Neurobiol.？2008, 28, 1067–1078, doi:10.1007/s10571-008-9284-z.
[90]
Samuel, S.M.; Thirunavukkarasu, M.; Penumathsa, S.V.; Paul, D.; Maulik, N. Akt/FOXO3a/SIRT1-mediated cardioprotection by n-tyrosol against ischemic stress in rat in vivo model of myocardial infarction: switching gears toward survival and longevity. J Agric. Food Chem.？2008, 56, 9692–9698, doi:10.1021/jf802050h.
[91]
Owasoyo, J.O.; Neri, D.F.; Lamberth, J.G. Tyrosine and its potential use as a countermeasure to performance decrement in military sustained operations. Aviat. Space Environ. Med.？1992, 63, 364–369.
[92]
Kelly, G.S. Nutritional and botanical investigations to assist with the adaptation to stress. Altern. Med. Rev.？1999, 4, 249–265.
[93]
Ko, K.M.; Lam, B.Y. Schisandrin B protects against tert-butylhydroperoxide induced cerebral toxicity by enhancing glutathione antioxidant status in mouse brain. Mol.Cell. Biochem.？2002, 238, 181–186, doi:10.1023/A:1019907316129.
[94]
Xue, J.Y.; Liu, G.T.; Wei, H.L.; Pan, Y. Antioxidant activity of two dibenzocyclooctene lignans on the aged and ischemic brain in rats. Free Radic. Biol. Med.？1992, 12, 127–135, doi:10.1016/0891-5849(92)90006-3.
[95]
Chiu, P.Y.; Tang, M.H.; Mak, D.H.; Poon, M.K.; Ko, K.M. Hepatoprotective mechanism of schisandrin B: role of mitochondrial glutathione antioxidant status and heat shock proteins. Free Radic. Biol. Med.？2003, 35, 368–380, doi:10.1016/S0891-5849(03)00274-0.
[96]
Chiu, P.Y.; Mak, D.H.; Poon, M.K.; Ko, K.M. Role of cytochrome P-450 in schisandrin B-induced antioxidant and heat shock responses in mouse liver. Life Sci.？2005, 77, 2887–2895.
[97]
Chiu, P.Y.; Leung, H.Y.; Poon, M.K.; Ko, K.M. Chronic schisandrin B treatment improves mitochondrial antioxidant status and tissue heat shock protein production in various tissues of young adult and middle-aged rats. Biogerontology？2006, 7, 199–210, doi:10.1007/s10522-006-9017-y.
[98]
Chiu, P.Y.; Ko, K.M. Schisandrin B protects myocardial ischemia-reperfusion injury partly by inducing Hsp25 and Hsp70 expression in rats. Mol. Cell. Biochem.？2004, 266, 139–144, doi:10.1023/B:MCBI.0000049151.79238.30.
[99]
Ip, S.P.; Che, C.T.; Kong, Y.C.; Ko, K.M. Effects of schisandrin B pretreatment on tumor necrosis factor-alpha induced apoptosis and Hsp70 expression in mouse liver. Cell Stress Chaperones？2001, 6, 44–48, doi:10.1379/1466-1268(2001)006<0044:EOSBPO>2.0.CO;2. 11525242
[100]
Ko, K.M.; Chiu, PY. Structural determinants of schisandrin B which enhance mitochondrial functional ability and glutathione status as well as heat shock protein expression in rat hearts and H9c2 cells. Mol. Cell. Biochem.？2005, 276, 227–234.
[101]
Tang, M.H.; Chiu, P.Y.; Ko, K.M. Hepatoprotective action of schisandrin B against carbon tetrachloride toxicity was mediated by both enhancement of mitochondrial glutathione status and induction of heat shock proteins in mice. Biofactors？2003, 19, 33–42, doi:10.1002/biof.5520190105.
[102]
Chiu, P.Y.; Leung, H.Y.; Ko, K.M. Schisandrin B Enhances Renal Mitochondrial Antioxidant Status, Functional and Structural Integrity, and Protects against Gentamicin-Induced Nephrotoxicity in Rats. Biol. Pharm. Bull.？2008, 31, 602–605, doi:10.1248/bpb.31.602.
[103]
Chiu, P.Y.; Leung, H.Y.; Poon, M.K.; Lee, S.S.; Ko, K.M. Schisandrin B induced antioxidant response is partly mediated by cytochrome P-4502E1 catalyzed reaction in mouse liver. Mol. Cell. Biochem.？2006, 293, 87–92, doi:10.1007/s11010-006-2957-3.
[104]
Lee, I.S.; Jung, K.Y.; Oh, S.R.; Park, S.H.; Ahn, K.S.; Lee, H.K. Structure-activity relationships of lignans from Schisandra chinensis as platelet activating factor antagonists. Biol. Pharm.Bull.？1999, 22, 265–267, doi:10.1248/bpb.22.265.
[105]
Mak, D.H.; Ip, S.P.; Li, P.C.; Poon, M.K.; Ko, K.M. Effects of Schisandrin B and alpha-tocopherol on lipid peroxidation, in vitro and in vivo. Mol. Cell. Biochem.？1996, 16, 161–165.
[106]
Mak, DH; Ko, KM. Alterations in susceptibility to carbon tetrachloride toxicity and hepatic antioxidant/detoxification system in streptozotocin-induced short-term diabetic rats: effects of insulin and Schisandrin B treatment. Mol. Cell. Biochem.？1997, 175, 225–232, doi:10.1023/A:1006883919687. 9350055
[107]
Lu, H.; Liu, G.T. Effect of dibenzo[a,c]cyclooctene lignans isolated from Fructus schizandrae on lipid peroxidation and anti-oxidative enzyme activity. Chem.Biol. Interact.？1991, 78, 77–84, doi:10.1016/0009-2797(91)90104-F.
[108]
Zhao, B.L.; Li, X.J.; Liu, G.T.; Jia, W.Y.; Xin, W.J. Scavenging effect of schizandrins on active oxygen radicals. Cell Biol Int Rep.？1990, 14, 99–109.
[109]
Li, X.J.; Zhao, B.L.; Liu, G.T.; Xin, W.J. Scavenging effects on active oxygen radicals by schizandrins with different structures and configurations. Free Radic. Biol. Med.？1990, 9, 99–104.
[110]
Chiu, P.Y.; Ko, KM. Time-dependent enhancement in mitochondrial glutathione status and ATP generation capacity by schisandrin B treatment decreases the susceptibility of rat hearts to ischemia-reperfusion injury. Biofactors？2003, 19, 43–51, doi:10.1002/biof.5520190106.
[111]
Pan, S.Y.; Han, Y.F.; Carlier, P.R.; Pang, Y.P.; Mak, D.H.; Lam, B.Y.; Ko, K.M. Schisandrin B protects against tacrine-and bis(7)-tacrine-induced hepatotoxicity and enhances cognitive function in mice. Planta Med.？2002, 68, 217–220, doi:10.1055/s-2002-23145.
[112]
Panossian, A.; Wikman, G. Plant adaptogens: historical overview and perspectives. In 3rd International Symposium on Natural Drugs. Proceedings, Naples, Italy, 2–4 October 2003; Borelli, F., Capasso, F., Milic, N., Russo, A., Eds.; Grafidea S.r.l.: Milano, Italy, 2003; pp. 205–209.
[113]
Panossian, A. Adaptogens: Tonic herbs for fatigue and stress. Alt.Comp.Therap.？2003, 9, 327–332, doi:10.1089/107628003322658610.
[114]
Chernykh, S.I.; Lukhtanov, V.A.; Simonenko, N.P. Adaptation to damage in the silkworm Bombyx mori L. (Lepidoptera bombycidae). III. Adaptogens and larval resistance to stress-induced activation of latent viral infection. Entomologicheskoye Obozrenye？1985, 2, 267–272.
[115]
Boon-Niermeijer, E.K.; van den Berg, A.; Wikman, G.; Wiegant, F.A.C. Phytoadaptogens protect against environmental stress-induced death of embryos from the freshwater snail Lymnea stragnalis. Phytomedicine？2000, 7, 389–400, doi:10.1016/S0944-7113(00)80060-4. 11081990
[116]
Kunimoto, S.; Murofushi, W.; Kai, H.; Ishida, Y.; Uchiyama, A.; Kobayashi, T.; Kobayashi, S.; Murofushi, H.; Murakami-Murofushi, K. Steryl glucoside is a lipid mediator in stress-responsive signal transduction. Cell Struct. Funct.？2002, 27, 157–162, doi:10.1247/csf.27.157.
[117]
Lishmanov, Yu.B.; Krylatov, A.V.; Maslov, L.N.; Nariznaya, N.V.; Zamotinkii, A.V. Effect of Rhodiola rosea on the level of inducible Hsp-70 in miocard in stress. Bull. Exp. Biol. Med.？1996, 121, 256–258, doi:10.1007/BF02446762.
[118]
Prodius, P.A.; Manukhina, E.B.; Bulanov, A.E.; Wikman, G.; Malyshev, I.I. Adaptogen ADAPT modulates synthesis of inducible stress protein HSP 70 and increases organism resistance to heat shock. Biull. Eksp. Biol. Med.？1997, 123, 629–633.
[119]
Panossian, A.; Wikman, G.; Andreeva, L.; Boykova, A.; Nikiforova, D.; Timonina, N. Adaptogens exert a stress protective effect by modulation of expression of molecular chaperons. Planta Med.？2008, 74, 1018.
Jung, C.H.; Jung, H.; Shin, Y.C.; Shin, Y.C.; Park, J.H.; Jun, C.Y.; Kim, H.M.; Yim, H.S.; Shin, M.G.; Bae, H.S.; Kim, S.H.; Ko, S.G. Eleutherococcus senticosus extract attenuates LPS-induced iNOS expression through the inhibition of Akt and JNK pathways in murine macrophage. J. Ethnopharmacol.？2007, 113, 183–187, doi:10.1016/j.jep.2007.05.023.
[122]
Olsson, E.M.G.; von Schéele, B.; Panossian, A.G. A randomized double-blind placebo controlled parallell group study of SHR-5 extract of Rhodiola rosea roots as treatment for patients with stress related fatigue. Planta Med.？2009, 75, 105–112, doi:10.1055/s-0028-1088346.
[123]
Filaretov, A.A.; Bogdanova, T.S.; Mitiushov, M.I.; Podvigina, T.T.; Srailova, G.T. Effect of adaptogens on the activity of the pituitary-adrenocortical system in rats. Biull. Eksp. Biol. Med.？1986, 101, 573–574.
[124]
Kimura, Y.; Sumiyoshi, M. Effects of various Eleutherococcus senticosus cortex on swimming time, natural killer activity and corticosterone level in forced swimming stressed mice. J. Ethnopharmacol.？2004, 95, 447–453, doi:10.1016/j.jep.2004.08.027.
[125]
Lishmanov, Iu.B.; Trifonova, Zh.V.; Tsibin, A.N.; Maslova, L.V.; Dement'eva, L.A. Plasma beta-endorphin and stress hormones in stress and adaptation. Biull. Eksp. Biol. Med.？1987, 103, 422–424.
[126]
Maslov, L.N.; Lishmanov, Iu.B.; Naumova, A.V.; Lasukova, T.V. Do endogenous ligands of peripheral mu-and delta-opiate receptors mediate anti-arrhythmic and cardioprotective effects of Rhodiola rosea extract? Biull. Eksp. Biol. Med.？1997, 124, 151–153. 9410196
[127]
Ma？meskulova, L.A.; Maslov, L.N.; Lishmanov, Iu.B.; Krasnov, E.A. The participation of the mu-, delta-, and kappa–opioid receptors in the realization of the anti-arrhythmia effect of Rhodiola rosea. Eksp. Klin. Farmakol.？1997, 60, 38–39.
[128]
Panossian, A.; Oganessian, A.; Ambartsumian, M.; Gabrielian, E.; Wagner, H.; Wikman, G. Effects of heavy physical exercise and adaptogens on nitric oxide content in human saliva. Phytomedicine？1999, 6, 17–26, doi:10.1016/S0944-7113(99)80030-0.
[129]
Park, E.K.; Shin, Y.W.; Lee, H.U.; Kim, S.S.; Lee, Y.C.; Lee, B.Y.; Kim, D.H. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW264.7 cells induced by lipopolysaccharide. Biol. Pharm. Bull.？2005, 28, 652–666, doi:10.1248/bpb.28.652. 15802804
[130]
Park, Y.C.; Lee, C.H.; Kang, H.S.; Kim, K.W.; Chung, H.T.; Kim, H.D. Ginsenoside-Rh1 and Rh2 inhibit the induction of nitric oxide synthesis in murine peritoneal macrophages. Biochem. Mol.Biol. Int.？1996, 40, 751–757.
[131]
Abidov, M.; Crendal, F.; Grachev, S.; Seifulla, R.; Ziegenfuss, T. Effect of extracts from Rhodiola rosea and Rhodiola crenulata (Crassulaceae) roots on ATP content in mitochondria of skeletal muscles. Bull. Exp. Biol. Med.？2003, 136, 585–587, doi:10.1023/B:BEBM.0000020211.24779.15.
Panossian, A.; Wikman, G.; Wagner, H. Plant adaptogens III: Earlier and more recent aspects and concepts on their modes of action. Phytomedicine？1999, 6, 287–300.
[134]
Darbinyan, V.; Aslanyan, G.; Amroyan, E.; Gabrielyan, E.; Malmstr？m, C.; Panossian, A. Clinical trial of Rhodiola rosea L. extract SHR–5 in the treatment of mild to moderate depression. Nord. J. Psychiatry？2007, 61, 2343–2348.
[135]
Bocharov, E.V.; Kucherianu, V.G.; Bocharova, O.A.; Karpova, R.V. Neuroprotective features of phytoadaptogens. Vestn. Ross. Akad. Med. Nauk？2008, 4, 47–50.
[136]
Fulder, S. The drug that builds Russians. New Scientist？1980, 21, 83–84.
[137]
Barenboim, G.M.; Kozlova, N.B. Application of Eleutherococcus extract for increasing of biological resistance of humans under influence of different environmental noxious factors. In Eleutherococc. Strategy of Use and New Data of Fundamental Investigations; Barenboim, G.M., Ed.; MedExport, Vneshtorgizdat: Moscow, USSR, 1985; pp. 7–20.
[138]
Sarris, J. Herbal medicines in the treatment of psychiatric disorders: A systematic review. Phytother. Res.？2007, 21, 703–716, doi:10.1002/ptr.2187.
[139]
Bucci, L.R. Selected herbals and human exercise performance. Am. J. Clin. Nutr.？2000, 72, 624S–636S.
[140]
Walker, T.B.; Robergs, R.A. Does Rhodiola rosea possess ergogenic properties? Int. J. Sport Nutr. Exerc. Metab.？2006, 16, 305–315.
[141]
Bu, Y.; Jin, Z.H.; Park, S.Y.; Baek, S.; Rho, S.; Ha, N.; Park, S.K.; Kim, H.; Sun, Y.K. Siberian ginseng reduces infarct volume in transient focal cerebral ischaemia in Sprague-Dawley rats. Phytother. Res.？2005, 19, 167–169, doi:10.1002/ptr.1649. 15852490
[142]
Hartz, A.J.; Bentler, S.; Noyes, R.; Hoehns, J.; Logemann, C.; Sinift, S.; Butani, Y.; Wang, W.; Brake, K.; Ernst, M.; Kautzman, H. Randomized controlled trial of Siberian Ginseng for chronic fatigue. Psychol. Med.？2004, 34, 51–61, doi:10.1017/S0033291703008791.
[143]
Darbinyan, V.; Kteyan, A.; Panossian, A.; Gabrielian, E.; Wikman, G.; Wagner, H. Rhodiola rosea in stress induced fatigue -a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine？2000, 7, 365–371, doi:10.1016/S0944-7113(00)80055-0.
[144]
Spasov, A.A.; Wikman, G.K.; Mandrikov, V.B.; Mironova, I.A.; Neumoin, V.V. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR–5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine？2000, 7, 85–89, doi:10.1016/S0944-7113(00)80078-1.
[145]
Shevtsov, V.A.; Zholus, B.I.; Shervarly, V.I.; Vol’skij, V.B.; Korovin, Y.P.; Khristich, M.P.; Roslyakova, N.A.; Wikman, G. A randomized trial of two different doses of a SHR–5 Rhodiola roseaextract versus placebo and control of capacity for mental work. Phytomedicine？2003, 10, 95–105, doi:10.1078/094471103321659780.
[146]
Narimanian, M.; Badalyan, M.; Panosyan, V.; Gabrielyan, E.; Panossian, A.; Wikman, G.; Wagner, H. Impact of Chisan？ (ADAPT-232) on the quality-of-life and its efficacy as an adjuvant in the treatment of acute non-specific pneumonia. Phytomedicine？2005, 12, 723–772, doi:10.1016/j.phymed.2004.11.004. 16323290
[147]
Bogatova, R.I.; Malozemov, V.V. Experimental Research on the Estimation of Influence of Single Dose of Phytoadaptogens on Short-Term Memory. Report on ADAPT 232; Institute of Medical and Biological Problems (IMBP): Moscow, Russia, 1994; pp. 1–151.
[148]
Bogatova, R.I.; Shlyakova, L.V.; Salnitsky, V.P.; Wikman, G. Evaluation of the effect of single administration of a phytoadaptogen on human subject work ability during long isolation. Aerospace Environ. Med.？1997, 31, 51–54.
[149]
Berdyshev, V.V. Some aspects of single doses of adaptogens (Eleutherococcus and Schizandra). In Valeology: Diagnosis, Means and Practice in Health Care, International Collection of Scientific Papers; Breikhman, I.I., Ed.; Far East Branch of the Academy of Science of the Russian Federation, Dalnauka: Vladivostok, 1995; pp. 105–117.
[150]
Kaliko, I.M.; Tarasova, A.A. Effect of Leuzea and Golden Root extracts on dynamic peculiarities of the highest neural performance. In Stimulants of the Central Nervous System; Saratikov, A.S., Ed.; Tomsk University Publishing Press: Tomsk, USSR, 1966; pp. 115–120.
[151]
Spasov, A.A.; Mandrikov, V.B.; Mironova, I.A. The effect of the preparation rhodosin on the psychophysiological and physical adaptation of students to an academic load. Eksp. Klin. Farmakol.？2000, 63, 76–78.
[152]
Roslyakova, N.A.; Bogatova, R.I.; Verishvili, M.O.; Wikman, G. The effect of single dose of Rodelim phytoadaptogen on the performance of operators under intensive activity. In Abstract Book of Scientific Conference Biologically Active Food Supplements and Natural Medicines in Prophylaxis, Treatment and Rehabilitation, Moscow, Russia, 27–28 January 2000; pp. 157–160.
[153]
Zotova, M.I. The effect of Rhodiola rosea extract on mental working activity in man. Biochemists and Pharmacologists of Western Siberia: Tomsk, USSR, 1965; pp. 298–299.
[154]
Komar, V.V.; Kit, S.M.; Sitschuk, L.V.; Sitschuk, V.M. The effect of Carpatian Rhodiola rosea on human mental activity. Farm. Zh.？1981, 4, 62–64.
[155]
Marina, T.F.; Mikhaleva, L.K.; Suslov, N.I. Comparative effects of para-tyrosol and Rhodiola extract on the central nervous system. In Proceedings of a Joint Plenary Session of Pathophysiologists and Pharmacologists of Siberia and the Far East on Mechanisms of the Development of Pathological Processes, Kemerovo, USSR, 1994; pp. 66–68.
[156]
Strokina, T.I. The changes in higher nervous activity in neurotic patients under treatment with Eleutherococcus. In Lekastvennie Sredstva Dalnego Vostoka; Brekhman, I.I, Ed.; USSR Academy of Science, Far East Science Center., Primorye Publishing Press: Vladivostok, USSR, 1967; Volume 7, pp. 201–111.
[157]
Medvedev, M.A. Effect of Ginseng and Eleutherococcus on working parameters of radio-telegraph operators. In Materials of Studies of Ginseng and other Medicinal Plants of Far East. Issue 5; Brekhman, I.I., Belikov, I.F., Kurentsova, G.E., Eds.; Primorye Publishing Press: Vladivostok, USSR, 1963; pp. 237–239.
[158]
Winther, K.; Ranlov, C.; Rein, E.; Mehlsen, J. Russian root (Siberian Ginseng) improves cognitive factions in middle-aged people, whereas Ginkgo biloba seems effective only in the elderly. J. Neurol. Sci.？1997, 150, 90.
[159]
Gubchenko, P.P.; Fruentov, N.K. A comparative study of stimulating effect of adaptogenic agents prepared from some far-eastern plants. In New Data on Eleutherococcus and Other Adaptogens; Bulanov, A.E., Dardimov, I.V., Li, S.E., Eds.; USSR Academy of Science, Far East Science Center, Institue of Marin Biology: Vladivostok, USSR, 1986; pp. 18–25.
[160]
Gubchenko, P.P.; Fruentov, N.K. A comparative study of effectiveness of Eleutherococcus and other plant adaptogens as agents for enhancing the working capacity of the flying personnel. 1984; Brekhman, I.I., Dardimov, I.V., Li, S.E., Dobryakova, A.I., Eds.; Far East Centre of Academy of Science of the USSR: Vladivostok, USSR, 1986; pp. 171–178.
[161]
Grigorenko, G.F.; Berdishev, V.V. The use of tonic drinks and drugs increasing working capacity of sailors during night shifts. In Abstract Book of the Scientific Practical Conference on Medical and Social Aspects of the “Man-Ocean” Problem, Vladivostok, USSR, 29–30 September 1988; pp. 29–30.
[162]
Kochmareva, L.I. The effect of Schizandra chinensis and Ginseng on processes of concentration. In Materials for the Study of Ginseng and Schizandra; Belikov, I.F., Brekhman, I.I., Bykov, V.T., Lazarev, N.V., Serebryannik, B.E., Sorokhtin, G.N., Eds.; Far East Branch of USSR Academy of Science: Leningrad, USSR, 1958; pp. 12–17.
[163]
Galant, I.B. Curative effect of Schizandra chinensis and Ginseng on asthenia and asthenodepressive syndromes. In Materials for the Study of Ginseng and Schizandra; Belikov, I.F., Brekhman, I.I., Bykov, V.T., Lazarev, N.V., Serebryannik, B.E., Sorokhtin, G.N., Eds.; Far East Branch of USSR Academy of Science: Leningrad, USSR, 1958; pp. 198–208.
[164]
Leman, M.F. Treatment of reactive and asthenic states of exogenous etiology using the Far East Schizandra. J. Neuropathol.Psychiatry？1952, 52, 67–70.
[165]
Rossijskij, D.M. Schizandra chinensis and the use of its preparations in practical medicine. Vrachebn. Delo？1952, 10, 939–940.
[166]
Rossijskij, D.M. New tonics and stimulants produced from local medicinal herbs. Clin. Med.？1952, 30, 66–69.
[167]
Zakharova, P.M. Experience of using Schizandra chinensis in psychiatric practise. In Problems of Social and Clinical Psychiatry; Krasnushkin, E.K., Ed.; Moscow District Neuropsychiatric Clinic: Moscow, USSR, 1948; Volume 9, pp. 271–278.
[168]
Herbert, J.; Goodyer, I.M.; Grossman, A.B.; Hastings, M.H.; de Kloet, E.R.; Lightman, S.L.; Lupien, S.J.; Roozendaal, B.; Seckl, J.R. Do corticosteroids damage the brain? J. Neuroendocrinol.？2006, 18, 393–411, doi:10.1111/j.1365-2826.2006.01429.x. 16684130
[169]
Rezvyy, G.; Oiesvold, T.; Parniakov, A.; Olstad, R. A comparative study of diagnostic practice in psychiatry in Northern Norway and Northwest Russia. Soc. Psychiatry. Psychiatr. Epidemiol.？2005, 40, 316–323, doi:10.1007/s00127-005-0894-1.
[170]
Keith, S.J.; Regier, D.A. U.S. and Soviet perspectives on the diagnosis of schizophrenia and associated dangerousness. Schizophr. Bull.？1989, 15, 515–517, doi:10.1093/schbul/15.4.515.
[171]
Miller, M.A. The theory and practice of psychiatry in the Soviet Union. Psychiatry？1985, 48, 13–24.
[172]
Smulevich, A.B. Sluggish schizophrenia in the modern classification of mental illness. Schizoph. Bull.？1989, 15, 533–539, doi:10.1093/schbul/15.4.533.
[173]
Pharmacopoeia article PA 42-2163-96. In Extractum Rhodiolae fluidum; National Pharmacopoeia Committee, The Russian Federation Ministry of Health and Medical Industry: Moscow, USSR, 1996.
[174]
Rhizome and roots of Rhodiola rosea, Pharmacopoeia paper 75. In National Pharmacopoeia of the USSR, 11th ed. ed.; The USSR Ministry of Health, Meditsina: Moscow, USSR, 1990; Volume 2, pp. 317–319.
[175]
Krasik, E.D.; Morozova, E.S.; Petrova, K.P.; Ragulina, G.A.; Shemetova, L.A.; Shuvaev, V.P. Therapy of asthenic conditions: clinical perspectives of application of Rhodiola rosea extract (golden root). In Proceedings modern problems in psycho–pharmacology, Kemerovo, Siberian Branch of Russian Academy of Sciences, Kemerovo, USSR; Avrutskiy, G.Y., Ed.; 1970; pp. 298–300.
[176]
Krasik, E.D.; Petrova, K.P.; Rogulina, G.A. About the adaptogenic and stimulating effect of Rhodiola rosea extract. Sverdlovsk, USSR, May 1970; pp. 215–217.
[177]
Saratikov, A.S.; Marina, T.F.; Kaliko, I.M. The stimulating effect of Rhodiola rosea on the higher brain structures. Vestn. Sibirsk. Otd. USSR Acad. Sci.？1965, 8, 120–125.
[178]
Mikhailova, M.N. Clinical and experimental substantiation of asthenic conditions therapy using Rhodiola Rosea extract. In Current problems of psychiatry; Goldsberg, E.D., Ed.; Tomsk State University Press: Tomsk, USSR, 1983; pp. 126–127.
[179]
Brichenko, V.S.; Kupriyanova, I.E.; Skorokhodova, T.F. The use of herbal adaptogens together with tricyclic antidepressants in patients with psychogenic depressions. In Modern problems of pharmacology and search for new medicines; Goldsberg, E.D., Ed.; Tomsk State University Press: Tomsk, USSR, 1986; Volume 2, pp. 58–60.
[180]
Zakharov, A.A. On the problem of Schizandra tincture effect on the higher nervous activity in cases of asthenia of different origin. In Proceedings of Omsk Medical Institute; The Ministry of Health of RSFSR: Omsk, USSR, 1956; Volume 20, pp. 93–94.
[181]
Farutina, M.V. Clinical investigation of tonic effects of pantocrine, and Ginseng and Schizandra tinctures. In Materials for the study of stimulants and tonics from Ginseng root and Schizandra; Lazarev, N.V., Komarov’s, V.L., Eds.; Far East Branch of USSR Academy of Science: Vladivostok, USSR, 1951; Volume 1, pp. 131–136.
[182]
Galant, I.B.; Kuznetsova, A.I.; Suvorina, N.A.; Shikhova, S.S.; Gutschina, I.S. The experience in using Schizandra chinensis in psychiatric practice. In Clinical development and therapy of mental diseases and organisation of psychoneurological assistance–Abstract book; Ministry of Health of USSR: Moscow, USSR, 1957; pp. 112–113.
[183]
Jadad, A.R.; Moore, R.A.; Carroll, D.; Jenkinson, C.; Reynolds, D.J.; Gavaghan, D.J.; McQuay, H.J. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control. Clin.Trials？1996, 17, 1–12.
[184]
Romas, R.S. About the effect of Schizandra chinensis on higher brain structures of schizophrenia patients and chronic alcoholics. PhD Thesis, Faculty of Medicine, Pirogov’s Medical Institute, Vinnitsa, USSR, 1967.
[185]
Romas, R.S. Effect of Schizandra chinensis on reactivity of patients to some drugs. Vopr. Psykhonevrol.？1962, 30, 435–440.
[186]
Romas, R.S. The effect of Schizandra chinensis on patients with different forms of mental diseases. Voprosy Klin Nevrapat Psykhiatriii？1958, 211–216.
[187]
Lastovetskij, V.V.; Romas, R.S. Special features in the interaction of signal systems under the influence of Schizandra chinensis. Zh. Vyssh. Nerv. Deiat. Im. I. P. Pavlova？1963, 13, 604–609.
[188]
Sudakov, V.N.; Savinykh, A.B.; Agapov, Yu.K. The role of adaptogens in the psychoprophylaxis of patients with borderline states of exogenous–organic genesis. In Modern problems of Pharmacology and Search for New Medicines; Goldsberg, E.D., Ed.; Tomsk State University Press: Tomsk, USSR, 1986; pp. 61–64.
[189]
Staritsina, O.N. The experience of using Schizandra preparations against depressive states in psychiatry. Zdravookhr. Kazakhstana (Alma–Ata)？1946, 6/7, 42–44.
[190]
Sivertsev, I.I. Schizandra chinensis effect on the heart and its use in psychiatry. Farmakol. Toxikol.？1946, 9, 10–12.
[191]
Sivertsev, I.I. About the effect of Schizandra chinensis on the heart and its use in psychiatric practice. Izvetiya Akad. Nauk Kazakhskoy SSR Biol. Ser. (Alma-Ata)？1950, 91, 33–36.
[192]
Romas, R.S. Specific features of Schizandra chinensis effect on schizophrenia patients. In Materials of Science Conference of Ternopol State Medical Institute, Ternopol, USSR, 26-28 January,1960; 1960; pp. 50–51.
[193]
Metscheryakova, E.I.; Mikhailiva, N.M.; Abrameitsev, V.D. A study of Rhodiola rosea extract effcect using the MMPI method. In Problems of Rehabilitation of Patients with Nervous and Mental Diseases; Tomsk University Press: Tomsk, USSR, 1975; pp. 180–182.
