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Journal of Ayurveda and Integrative Medicine Journal of Ayurveda and Integrative Medicine
 
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LETTER TO THE EDITOR
Year : 2011  |  Volume : 2  |  Issue : 2  |  Page : 49-50  

Reverse pharmacology of Ayurvedic drugs includes mechanisms of molecular actions


Ayurveda Physician & Research Associate, Kasturba Health Society - Medical Research Centre, India

Date of Web Publication29-Jun-2011

Correspondence Address:
Namyata Pathak
Ayurveda Physician & Research Associate, Kasturba Health Society - Medical Research Centre
India
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DOI: 10.4103/0975-9476.82512

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How to cite this article:
Pathak N. Reverse pharmacology of Ayurvedic drugs includes mechanisms of molecular actions. J Ayurveda Integr Med 2011;2:49-50

How to cite this URL:
Pathak N. Reverse pharmacology of Ayurvedic drugs includes mechanisms of molecular actions. J Ayurveda Integr Med [serial online] 2011 [cited 2014 Sep 19];2:49-50. Available from: http://www.jaim.in/text.asp?2011/2/2/49/82512

Sir,

In his article "Beyond reverse pharmacology: Mechanism based screening of Ayurvedic drugs," Dr. R. D. Lele, the eminent teacher of modern medicine and scholar of Ayurveda, urges us to include advances in biomedical sciences for screening of Ayurvedic drugs. [1],[2] However, as he has not cited any of the original articles and references on Reverse Pharmacology (RP), [3],[4],[5],[6],[7] it seems that the experimental stage of RP has been overlooked. Here, an attempt is made to correct the impression that molecular screening of Ayurvedic drugs is beyond RP, and indicate which aspects of Ayurveda may truly lie beyond the current state of RP.

Lele cites quite a long list of available receptors and transporters including specific radiolabeled ligands. In view of his being a leader of nuclear medicine, any initiatives in the direction of using labeled ligands or candidate drug molecules are welcome suggestions. But the list does not provide any hints as to how Ayurvedic drugs in their complex form can be subjected to such blind screening. Even with significantly large numbers of molecules synthesized by combinatorial chemistry and with high-throughput screening, this path to drug discovery has not been very productive. That is why major pharmaceutical companies have relatively dry drug pipelines, raising the urgent need for new approaches. [8] Patwardhan and Mashelkar emphasize this point, while advocating RP for traditional medicine inspired drug discovery. [4] However, for drug discovery through RP and other approaches, it would be desirable to create a database of receptor binding sites of important phytoconstituents of Ayurvedic origin. This exercise, being a relevant part of drug discovery, is clearly not a stand-alone means to that end. We should not forget that several New Chemical Entities and biotech products binding receptors in vitro have failed in clinical trials due to the impact of kinetic-dynamic factors in vivo.

The author describes molecular biology and molecular medicine as 21 st century paradigms. However, the leaders in molecular medicine themselves are rapidly adopting systems biology, and more integrative approaches. [9],[10] Under these circumstances, an organized RP path would be a productive new paradigm for drug discovery, with its initial robust clinical observations, and objective markers during its experiential stage. For example, in a recent study with Nyctanthes arbor-tristis in patients with malaria, the parasite cure was confirmed by the disappearance of the parasitic DNA with polymerase chain reaction; the marked clinical improvement within 48 hours was accompanied by a significant drop in Tumor Necrosis Factor-α. The exploratory studies included screening of the plant extract against sensitive and resistant strains of Plasmodium falciparum in vitro.[11],[12] This exemplifies that the advances in markers can be made use of at each stage of RP. Currently, efforts are to isolate the active molecule, which would eventually facilitate mechanistic studies in molecular parasitology, during the RP experimental stage.

Dr. Lele has cited Rauwolfia serpentina, in particular reserpine, as a unique molecule illustrating diverse activities on vesicular mono-amine transport. But the loss of opportunity in research on biogenic amines was a gap of 20 years between the discovery of Rauwolfia serpentina as an antihypertensive, and the isolation of reserpine. [13],[14] During these two decades, when management of hypertension did not have many alternatives, thousands of patients died of complications. The side effects of R. serpentina observed by Sen and Bose, viz.,  Parkinsonism More Details, depression, and galactorrhea, were the fore-runners of major drug discoveries--levodopa, tricyclic antidepressants, and bromocriptine. These discoveries could have been expedited if an organized RP path had been available. We now have an opportunity to study other documented field observations with similar scientific rigor. Some lessons to further develop and expedite the process are as follows: 1. To understand and give importance to robust findings in observational therapeutics; 2. To carefully choose in vitro and in vivo models relevant to the clinical endpoints, or even to evolve novel models as needed; 3. To evolve a collaborative R and D network for quality, safety, and efficacy of whole plants and/or their extracts and/or their active principles depending on use. These research approaches have been depicted as a figure for clarity. [6]

As an eminent leader and teacher of modern medicine, the author has rightly emphasized that advances in phytopharmacology need to be utilized in Ayurvedic drug research. But there is also a need to emphasize an understanding of Ayurvedic epistemology and the principles of Dravyaguna vigyan, while embarking on modern drug research. [14] Such an approach is not easy, and would involve innovative thinking beyond the current state of RP. As Systems Biology is becoming central to understanding the complexity of human clinical phenomena, early attempts at modeling Systems Ayurveda would enhance the incorporation of the basic nature of Ayurvedic drug actions. [5],[15] As an example, [Table 1] lists a tentative correlation between clinical usage, guna-karma, and mechanisms.
Table 1: Correlation between guna-karma and mechanistic targets of Ayurvedic drugs

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RP relies on known and serendipitous clinical phenomena resulting from simple or complex Ayurvedic interventions. The endeavor to study well-documented findings would provide not only understanding in terms of identified molecular mechanisms, but will hopefully open up new domains of knowledge in Life Sciences. Unfortunately, RP is a new transdiscipline and has only one Advanced Centre of Research established by the Indian Council of Medical Research. [16] The new training programs for Vaidya--Scientists as well as for RP are planned with an eye to orient therapeutic research to Ayurvedic epistemology and the ontology of RP. [17],[18]

 
   References Top

1.Lele RD. Beyond reverse pharmacology: Mechanism-based screening of Ayurvedic drugs. J-AIM 2011;1:257-65.  Back to cited text no. 1
    
2.Lele RD. Ayurveda and Modern medicine. 2 nd Ed. Mumbai: Bhartiya Vidya Bhavan; 2001.  Back to cited text no. 2
    
3.Vaidya AB. Reverse pharmacological correlates of ayurvedic drug actions. Indian J Pharmacol 2006;38:311-5.  Back to cited text no. 3
  Medknow Journal  
4.Patwardhan B, Mashelkar RA. Traditional medicine inspired approaches to drug discovery: Can Ayurveda show the way forward? Drug Discov Today 2009;14:804-10.  Back to cited text no. 4
[PUBMED]  [FULLTEXT]  
5.Patwardhan B, Vaidya AD, Chorghade M, Joshi SP. Reverse Pharmacology and systems approach for Drug Discovery. Current Bioactive Compounds 2008;4:201-12.  Back to cited text no. 5
    
6.Vaidya AB, Devasagyam TP. Current status of herbal drugs in India: An overview J Clin Biochem Nutr 2007;41:1-11.  Back to cited text no. 6
    
7.Patwardhan B, Vaidya AD, Chorghade M. Ayurveda and natural products drug discovery. Curr Sci 2004;86:789-99.  Back to cited text no. 7
    
8.Bristol N. NIH proposes new drug development centre. World Report. Lancet 2011;377:705-6.  Back to cited text no. 8
[PUBMED]    
9.Kitano H. Computational systems biology. Nature 2002;420:206-10.  Back to cited text no. 9
[PUBMED]  [FULLTEXT]  
10.Butcher EC, Berg EL, Kunkel EJ. Systems biology in drug discovery. Nat Biotechnol 2004;22:1253-9.  Back to cited text no. 10
[PUBMED]  [FULLTEXT]  
11.Karnik SR, Tathed PS, Antarkar DS, Godse CS, Vaidya RA, Vaidya AB. Antimalarial activity and clinical safety of traditionally used Nyctanthes arbor-tristis. Linn Indian J Tradit Knowl 2008;7:330-4.  Back to cited text no. 11
    
12.Godse CS. An exploration and putative interventional effects of Nyctanthes arbor-tristis (Parijat) in malaria- clinical, metabolic parasitic and immune changes, Ph.D. Thesis, University of Mumbai, Mumbai; 2003.  Back to cited text no. 12
    
13.Sen G, Bose KC. Rauwolfia serpentina, a new Indian drug for insanity and high blood pressure Indian Med Wld 1931;2:194.  Back to cited text no. 13
    
14.Vaidya AB. Reverse Pharmacology - A paradigm shift for new drug discovery based on Ayurvedic epistemology. Ayurveda in Transition 2010. Kottakal: Arya Vaidya Sala; p. 27-38.  Back to cited text no. 14
    
15.Tillu G, Gangadharan GG, Vaidya AB, Patwardhan B. Systems Ayurveda. Conceptual foundation and framework. I-AIM: Bengaluru; 2010.  Back to cited text no. 15
    
16.Proceedings. ICMR Symposium on Reverse Pharmacology. Mumbai: Kasturba Health Society; 2008.  Back to cited text no. 16
    
17.Patwardhan B, Joglekar V, Pathak NY, Vaidya AB. Vaidya-Scientists: Catalysing Ayurveda Renaissance. Curr Sci 2011;100:476-84.  Back to cited text no. 17
    
18.News and comments. J-AIM 2011;2:96-7  Back to cited text no. 18
    



 
 
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  [Table 1]


This article has been cited by
1 Reverse pharmacology for antimalarial plants goes global
Godse, C. and Nabar, N. and Raut, A. and Joshi, J.
Journal of Ayurveda and Integrative Medicine. 2011; 2(4): 163-164
[Pubmed]



 

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