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Neuropsychopharmacology of a therapeutically used Andrographis paniculata extract: a preclinical study

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Abstract

Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) also called as Kalmegh, or “King of Bitters”. In Ayurveda, Andrographis paniculata is classified as a Rasayana herb. More than 50 % of the poly-herbal formulations commercialized in India for treatment of liver function disorders contain Andrographis paniculata. Pilot study and general neuropharmacological screening were conducted with analytically standardized Andrographis paniculata extract (AP), to evaluate its therapeutic potential for mental health problems. A battery of rodent behavioral models developed in our laboratory was used for characterizing brain function modulating activities. Daily oral administrations of even very high doses (800 mg/kg) of the extract were well tolerated by laboratory rodents without any apparent behavioral alterations. A single oral dose of the extract (AP 25 to 800 mg/kg) was inactive in mice stress-induced hyperthermia, and apomorphine induced cage-climbing tests in rats. However, dose and duration of treatment dependent efficacy of the extract after its daily doses up to 200 mg/kg/day for 10 days was observed in both the tests. Moreover, dose dependent effects of the extract in suppressing locomotion, potentiating pentobarbital sleep, and antagonizing pentylenetetrazole or maximal electroshock triggered seizures were also apparent after its 10 daily doses up to 200 mg/kg/day. Anxiolytics and antidepressants-like activity of AP treatment was also apparent in rats after 10 daily doses. Therefore, prolonged daily oral intake of Andrographis paniculata extract gradually suppresses central sensitivity to acute stressful stimuli, and eventually down regulates central dopaminergic receptors. Benzodiazepines like anxiolytic and seizure suppressing activities of the extract can be expected after its daily intake.

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References

  • Ahuja N, Cole AJ (2009) Hyperthermia syndromes in psychiatry. Adv Psychiatr Treat 15:181–191

    Article  Google Scholar 

  • Balasubramani SP, Venkatasubramanian P, Kukkupuni SK, Patwardhan B (2011) Plant-based Rasayana drugs from Ayurveda. Chin J Integr Med 17:88–94

    Article  PubMed  Google Scholar 

  • Chandrasekaran CV, Gupta A, Agarwal A (2010) Effect of an extract of Andrographis paniculata leaves on inflammatory and allergic mediators in vitro. J Ethnopharmacol 129:203–207

    Article  CAS  PubMed  Google Scholar 

  • Chandrasekaran CV, Thiyagarajan P, Deepak HB, Agarwal A (2011) In vitro modulation of LPS/calcimycin induced inflammatory and allergic mediators by pure compounds of Andrographis paniculata (King of bitter) extract. Int Immunopharmacol 11:79–84

    Article  CAS  PubMed  Google Scholar 

  • Chandrasekaran CV, Thiyagarajan P, Sundarajan K, Goudar KS, Deepak M, Murali B, Allan JJ, Agarwal A (2009) Evaluation of the genotoxic potential and acute oral toxicity of standardized extract of Andrographis paniculata (KalmCold). Food Chem Toxicol 47:1892–1902

    Article  CAS  PubMed  Google Scholar 

  • Chao WW, Lin BF (2010) Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian). Chin Med 5:17

    Article  PubMed Central  PubMed  Google Scholar 

  • Chatterjee SS, Kumar V (2012) Holistic psychopharmacology and promiscuous plants and principles of Ayurveda. Am J Plant Sci 3:1015–1021

    Article  Google Scholar 

  • Coughenor LL, McLean JR, Parker RB (1977) A new device for the rapid measurement of impaired motor function in mice. Pharmacol Biochem Behav 6:351–353

    Article  Google Scholar 

  • Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–56

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Govindarajan R, Vijayakumar M, Pushpangadan P (2005) Antioxidant approach to disease management and the role of ‘Rasayana’ harbs of Ayurveda. J Ethnopharmacol 99:165–178

    Article  CAS  PubMed  Google Scholar 

  • Henniger MS, Ohl F, Holter SM, Weissenbacher P, Toschi N, Lorscher P, Wigger A, Spanagel R, Landgraf R (2000) Unconditioned anxiety and social behaviour in two rat lines selectively bred for high and low anxiety-related behaviour. Behav Brain Res 111(1–2):153–163

    Article  CAS  PubMed  Google Scholar 

  • Jarukamjorn K, Nemoto N (2008) Pharmacological aspects of Andrographis paniculata on health and its major diterpenoid constituent Andrographolide. J Health Sci 54:370–381

    Article  CAS  Google Scholar 

  • Jurek B, Slattery DA, Maloumby R, Hillerer K, Koszinowski S, Neumann ID, van den Burg EH (2012) Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats. PLoS One 7(5):e37060

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kumar A, Dora J, Singh A, Tripathi R (2012) A review on King of Bitter (Kalmegh). Int J Res Pharm Chem 2:116–124

    Google Scholar 

  • Kumar V, Singh PN, Bhattacharya SK (2003) Neuropsychopharmacological studies on Indian Hypericum perforatum Linn. In: Ernst E (ed) Medicinal and aromatic plants-industrial profile, volume: Genus Hypericum. Taylor & Francis, New York, pp 179–226

    Google Scholar 

  • Lattoo SK, Khan S, Dhar AK, Choudhary DK, Gupta KK, Sharma PR (2006) Genetics and mechanism of induced male sterility in Andrographis paniculata (Burm. f.) Nees and its significance. Curr Sci 91:515–519

    Google Scholar 

  • Mandal SC, Dhara A, Maiti BC (2001) Studies on psychopharmacological activity of Andrographis paniculata extract. Phytother Res 15:253–256

    Article  CAS  PubMed  Google Scholar 

  • Maxwell DM, Brecht KM, Doctor BP, Wolfe AD (1993) Comparison of antidote protection against soman by pyridostigmine, HI-6 and acetylcholinesterase. J Pharmacol Exp Ther 264:1085–1089

    CAS  PubMed  Google Scholar 

  • Nakamura K (2011) Central circuits for body temperature regulation and fever. Am J Physiol Regul Integr Comp Physiol 301:R1207–R1228

    Article  CAS  PubMed  Google Scholar 

  • Ojima K, Matsumoto K, Tohda M, Watanabe H (1995) Hyperactivity of central noradrenergic and CRF systems is involved in social isolation-induced decrease in pentobarbital sleep. Brain Res 684:87–94

    Article  CAS  PubMed  Google Scholar 

  • Pellow S, File SE (1986) Anxioytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: A novel test of anxiety in the rat. Pharmacol Biochem Behav 24(3):525–529

    Article  CAS  PubMed  Google Scholar 

  • Pertwee RG (1972) The ring test: a quantitative method for assessing the ‘catalaptic’ effect of cannabis in mice. Br J Pharmacol 46:753–763

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Protais P, Costentin J, Schwartz JC (1976) Climbing behavior induced by apomorphine in mice: a simple test for the study of dopamine receptors in striatum. Psychopharmacology (Berl) 50:1–6

    Article  CAS  Google Scholar 

  • Ramanathan M, Khanna VK, Seth PK, Jaisawal AK, Bhattacharya SK (1999) Central neurotransmitter receptor binding and behaviour during streptozotocin-induced diabetes mellitus in rats. Biog Amine 15:355–365

    CAS  Google Scholar 

  • Rudzik AD, Hester JB, Tang AN, Stray RN, Friss W (1973) In: Garrattini S, Mussinii E, Randall LO (eds) The Benzodiazeplines. Raven, New York, pp 285–297

    Google Scholar 

  • Saxena RC, Singh R, Kumar P, Yadav SC, Negi MP, Saxena VS, Joshua AJ, Vijayabalaji V, Goudar KS, Venkateshwarlu K, Amit A (2010) A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmColdTM) in patients with uncomplicated upper respiratory tract infection. Phytomedicine 17:178–185

    Article  CAS  PubMed  Google Scholar 

  • Smith AP (2012a) Effects of common cold on mood, psychomotor performance, the encoding of new information, speed of working memory and semantic processing. Brain Behav Immun 26:1072–1076

    Article  PubMed  Google Scholar 

  • Smith AP (2012b) Twenty-five years of research on the behavioural malaise associated with influenza and the common cold. Psychoneuroendocrinology. doi:10.1016/j.psyneuen.2012.09.002

    Google Scholar 

  • Subramanian R, Aswami MZ, Sadikum A (2012) A bitter plant with a sweet future? A comprehensive review of an oriental medicinal plant: Andrographis paniculata. Phytochem Rev 11:39–75

    Article  CAS  Google Scholar 

  • Valdiani A, Kadir MA, Tan SG, Talei D, Abdullah MP, Nikzad S (2012) Nain-e Havandi Andrographis paniculata present yesterday, absent today: a plenary review on underutilized herb of Iran’s pharmaceutical plants. Mol Biol Rep 39:5409–5424

    Article  CAS  PubMed  Google Scholar 

  • Williamson EM (2002) Major herbs of Ayurveda. Churchill Livingstone, New York

    Google Scholar 

  • Willner P (1984) The validity of animal models of depression. Psychopharmacol (Berl) 83(1):1–16

    CAS  Google Scholar 

  • Winston D, Maimes S (2007) Adaptogens: Herbs for strength, stamina, and stress relief. Healing Art Press, Vermont

    Google Scholar 

  • Yunus MB (2008) Central sensitivity syndromes: a new paradigm and group nosology for fibromyalgia and overlapping conditions, and the related issue of disease versus illness. Semin Arthritis Rheum 37:339–352

    Article  PubMed  Google Scholar 

  • Zethof TJ, Van der Heyden JA, Tolboom JT, Olivier B (1994) Stress-induced hyperthermia in mice: a methodological study. Physiol Behav 55:109–115

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Ajit Kumar Thakur graciously acknowledged the Department of Science and Technology, Govt. of India, New Delhi for awarding INSPIRE Fellowship (IF110595). Authors would like to acknowledge Natural Remedies Pvt. Ltd., Bangalore for providing complementary sample of standardized extract of Andrographis paniculata.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Neuropharmacology Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221 005, India

    Ajit Kumar Thakur & Vikas Kumar

  2. Stettiner Straße 1, Karlsruhe, Germany

    Shyam Sunder Chatterjee

  3. Pharmacology Research Laboratories, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany

    Shyam Sunder Chatterjee

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  1. Ajit Kumar Thakur
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  2. Shyam Sunder Chatterjee
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  3. Vikas Kumar
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Correspondence to Vikas Kumar.

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Thakur, A.K., Chatterjee, S.S. & Kumar, V. Neuropsychopharmacology of a therapeutically used Andrographis paniculata extract: a preclinical study. Orient Pharm Exp Med 14, 181–191 (2014). https://doi.org/10.1007/s13596-013-0140-4

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  • DOI: https://doi.org/10.1007/s13596-013-0140-4

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