Different Approaches in Pharmacological Research

International Journal of Exclusive Global Research - Vol 3 Issue 3 March
Different approaches in Pharmacological Research

Dr.K. S. Manjunatha
Department of Pharmaceutical Chemistry, Kuvempu University, Post Graduate Centre, Kadur-
577548, Karnataka, India.
Introduction
In recent global health politics, the increasing number of diseases that are difficult to control
or treat using only mono-therapy approach has drawn the concerns of worldwide scientists.
The availability of current drugs in the market is apparently insufficient to handle the
unceasingly increase of diseases in this era. Therefore, scientists have started to search for
alternatives instead of solely defending typical reductionism approach of Western medicine. In
fact, there is a promising alternative avenue that has been practiced widely in human
population since ancient time, and that is the traditional Chinese medicine (TCM). Although
many diseases are not described in TCM term, but the physicians who practice TCM in China
attempt to treat these diseases using TCM principles have proved to be clinically effective [1].
Based on the fundamental concept of TCM, an individual is considered as “healthy” only when
all the five elements (fire, wood, metal, water and earth) and the Yin, which refers to “negative”
and Yang which represents “positive” are in balance [2]. An individual will be sick once there
is imbalance in Yin-Yang and the five elements in the body, while different kinds of
syndromes would occur according to the types of disease adhered to the body. Typically, a
disease can cause different types of syndromes that eventually cause different types of
symptoms in the human body. According to the principles of TCM, all human diseases will be
treated according to the syndromes observed, and TCM prescriptions are the most frequently
used method to treat different kinds of diseases via oral administration. According to the Shen
Nong’s herbal classic, the TCM prescription is formulated according to the capability of TCM
herbs to counter different syndromes caused by diseases which includes at least four different
roles played by TCM herbs which are sovereign, minister, assistant and envoy drugs [3].
Thus, rather than explaining varied kinds of diseases the human race faces today, this
present review looks at specifically the globally concerning multi-syndromic disease, the
hypertension. It is frequently being reported as having poor controllability using existing
antihypertensive drugs in current market via mono-therapy approach as well as these drugs’
association with undesired adverse effects would also be a topic of discussion in this
review and elaborated based on the principles of TCM along with scientific evidences.
This could be one of the most persuading examples to prove the feasibility of TCM in treating
diseases based on its principles as well as the formulation of combination of herbs using the
new scientific-based orthogonal stimulus-response compatibility approach.
Hypertension in the View of TCM
Hypertension is a well-known “silent killer” and a symptomatic disease that can cause various
concomitant diseases after years of adherence in human body. According to the
evolution of antihypertensive drugs, the classes of the antihypertensive drugs that are
preferred to be used clinically often changes from time-to-time, and combination drugs
therapy is more often used than single drug therapy in majority of hypertension patients in
order to achieve the targeted blood pressure range [4,5]. However, the chronic adverse effects
caused by the antihypertensive drugs in patients’ bodies that are being reported frequently
have drawn the concerns of worldwide scientists. For this reason, researchers have started to
employ the principles of TCM in the antihypertensive drugs researches in recent years.
According to the principles of TCM, hypertension is a multi- syndromic disease which
can cause three major syndromes. The first syndrome is the “fire” syndrome that could be
further divided into 4 types such as heart, stomach, intestine and liver fire. Secondly, there
are “phlegm-fluid retention” syndrome, and “deficiency” syndrome that could occur in kidney
and spleen [1,6]. There are some common symptoms caused by the hypertension including
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dizziness, headache, neck stiffness, and fatigue. According to literatures, one of the most
frequently used approach to formulate a TCM prescription is the orthogonal stimulus-
response compatibility group studies.
For instances, there was a TCM prescription (known as BPAid) successfully formulated by
combining four TCM herbs 25 such as Uncaria rhynchophylla, Pueraria thomsonii,
Panax notoginseng, and Alisma orientale which were selected according to their ability to
counter three major syndromes caused by hypertension, with the use of orthogonal
stimulus-response L(55) formulation, the resulting vasodilatory effects of the 50% ethanolic
crude extract of these combined TCM herbs at ratio of 5.32:2.44:9.24:1 was better than
those exerted by any of its single drug [7,8]. Besides, there was another article which
showed promising vasodilatory effects exerted by the 50% ethanolic crude extract of five
combined TCM herbs (known as Banxia Baizhu Tianma Tang) such as Glycyrrhiza uralensis
Fisch., Gastrodia elata Bl., Atractylodes macrocephala Koidz, Poria cocos (Schw.)
Wolf, and Citri reticulatae Blanco at ratio 2.71:1.14:1:5.57:7.14 formulated by using
similar approach, the orthogonal stimulus-response L (66) formulation (Tan et al., 2017b).
The antihypertensive effects of both of these TCM prescriptions were further tested in
vivo by orally administrating spontaneous hypertensive rats (SHRs) for 28-days
consecutively, and the resulting systolic (SBP), diastolic (DBP), and mean arterial
pressure (MAP) were significantly decreased, whilst there has no adverse effect shown in the
biochemical and hematological tests on the SHRs blood [9,10]. These proved the reliability and
safeness of the use of combined TCM herbs in treating disease, the hypertension in particular.
There was another example regarding the antihypertensive drugs research, the authors
combined the vasoactive compounds such as gastrodin, baicalin, tetramethylpyrazine, and
puerarin, and the best ratio for the combination of these four vasoactive compounds was
determined by using the orthogonal stimulus-response compatibility studies with L(55)
formula,
25
and the best combination ratio was found at 5.33:1:2.67:5.33 [11]. In fact,
the crude extracts of TCM herb are more preferable to be used in pharmacological
research of antihypertensive drugs due to its holistic effect in the signalling mechanism
pathways employed for exerting the vasodilatory effect as well as being cost-effective from
industrial viewpoint compared to the use of fractionated or pure vasoactive compounds [12-
14].
Conclusion
In fact, TCM was dominant before the rise of western medicine, but the limited scientific
support and evidences regarding their therapeutic effects in human have repressed its
development. However, in recent years, the increasing number of scientists that has
started to apply TCM principles as well as the combination of TCM herbs has gradually
returned to its fame that it deserved. Furthermore, the examples shown above proved
the feasibility of TCM principles at least in the case of treating hypertension, whereby
formulating the TCM prescription using the orthogonal stimulus- response compatibility
approach and the use of crude extract could provide better therapeutic effect over single
compound via its holistic mechanisms of actions. This could be the trend for future
pharmaceutical research and may as well solve the greatest problem in human history, curing
diseases that were previously impossible to cure and without adverse effects.
References
1. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J.Global burden
of hypertension: analysis of worldwide data. Lancet. 2005; 365: 217-223.
2. Wong KH, Li GQ, Li KM, Razmovski-Naumovski V, Chan K. Kudzu root: traditional
uses and potential medicinal benefits in diabetes and cardiovascular diseases. J.
Ethnopharmacol. 2011; 134: 584-607.
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3. Theisinger C, Even E, Schell J. Reading of the Divine Farmer's Classic of Materia Medica:
Shen Nong Ben Cao Jing Du. Chinese Medicine Database. 2016.
4. Düsing R. Optimizing blood pressure control through the use of fixed combinations.
Vascular health and risk management. 2010; 6: 321.
5. RahmanARA. Clinical practice guidelines on management of hypertension, in:
Hypertension, M.S.o., Malaysia, M.o.H., Malaysia, A.o.M.o. (Eds.), 4 th ed, Malaysia. 2013; 75.
6. Qian Ys, Zhang Wz, Zhou Hf. Relationship of blood pressure variability and TCM
constitution classification in essential hypertension patients. Chinese Journal of Integrated
Traditional and Western Medicine. 2003;
23: 88-90.
7. Loh YC, Tan CS, Ch'ng YS, Ahmad M, Asmawi MZ, Yam M. Vasodilatory Effects of
Combined Traditional Chinese Medicinal Herbs in Optimized Ratio. J. Med. Food. 2017b; 20:
265-278.
8. Loh YC, Tan CS, Ch'ng YS, Ahmad M, Ng CH, Yam MF. Overview of Signaling Mechanism
Pathways Employed by BPAid in Vasodilatory Activity. J. Med. Food. 2017c; 20: 1201-
1223.
9. Tan CS, Loh YC, Ng CH, Ch'ng YS, Asmawi MZ, Ahmad M, et al. Anti- hypertensive and
vasodilatory effects of amended Banxia Baizhu Tianma Tang. Biomed. Pharmacother. 2017b;
97: 985-994.
10. Xu JY, Zhang YQ, Bian XH, Yu T, Xu JL, Li L. Vasodilative Action of Combinations of
Hypotensive Components of Traditional Chinese Medicines on Rat Isolated Thoracic
Aorta. chinese journal of experimental traditional medical formulae. 2012; 18: 147-151.
11. Ch'ng YS, Loh YC, Tan CS, Ahmad M, Asmawi MZ, Wan Omar WM, et al. Vasorelaxant
properties of Vernonia amygdalina ethanol extract and its possible mechanism. Pharm. Biol.
2017; 55: 2083-2094.
12. Loh YC. New Approaches for Hypertension Treatment. International Journal of
Complementary and Alternative Medicine.2017;18
13. Loh YC, Ch'ng YS, Tan CS, Ahmad M, Asmawi MZ, Yam MF. Mechanisms of Action of
Uncaria rhynchophylla Ethanolic Extract for Its Vasodilatory Effects. J. Med. Food. 2017a; 20:
895-911.
14. Tan CS, Ch'ng YS, Loh YC, Zaini Asmawi M, Ahmad M, Yam MF.Vasorelaxation
effect of Glycyrrhizae uralensis through the endothelium- dependent Pathway. J.
Ethnopharmacol. 2017a; 199: 149-160.
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International Journal of Exclusive Global Research - Vol 3 Issue 3 March

Different approaches in Pharmacological Research

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