INTRODUCTION:

Hypertension defined as high Blood Pressure is a long term medical condition in which the blood pressure in the arteries is persistently raised¹, and hence chronic elevation of blood pressure systolic ≥140mmHg and/ or diastolic ≥90 mmHg is defined as hypertension². It has been named the “silent killer,” as it is asymptomatic and the major contributor or risk factor to cardiovascular morbidity and mortality³. Cardiovascular disease is major cause of mortality in current scenario⁴. Hypertension is responsible for around 16.5% of annual deaths worldwide (WHO, 2013), and is indeed the main cause of morbidity and mortality associated with CVDs⁵.

By 2030, the annual death toll is estimated to reach 23.5 million people (WHO, 2013).Data from 1950 to 2014 showed that the overall prevalence of hypertension in India is 29.8% (95% CI 26-7-33.0)⁶. Hypertension prevalence studies from mid-1990s to the present in urban and rural populations show an increasing trend, with a greater increase in urban (33.8%) than rural (27.6%) populations^6.7. In developed countries, hypertension is the more common in rural populations than in urban⁸. Meta – analysis of Indian prevalence studies has shown that there has been a significant increase in Hypertension in both urban and rural areas⁹.

A cross-sectional study was undertaken among a sample of 406 individuals (45-60 years) selected by the standard 30 cluster systematic random sampling technique to find out prevalence of hypertension and its associated risk factors in a rural area of Tamil Nadu. The overall prevalence of hypertension was 33% and higher among sedentary type (41%)¹⁰. It is important to note that May 17th of every year has been designated World Hypertension Day by the International Society of Hypertension (ISH), and the theme for 2013 World Health Day (7th April) was Hypertension, and hence a focus of considerable attention¹¹. One of the global targets for non communicable diseases is to reduce the prevalence of hypertension by 25% by 2025 (baseline 2010)¹².

Types of Hypertension:

Hypertension is mainly of two types: Primary or essential hypertension (90-95%) has no specific cause which may contribute to increase in blood pressure. Primary hypertensions have no single identifiable cause but associated with a number of factors¹³.

Secondary hypertension(5-10%) is caused by underlying diseases like renal damage, pheochromocytoma, muscular disorders etc. that affect the kidneys, arteries, heart or endocrine system¹⁴ . The prevalence of Essential hypertension is increasing day by day¹⁵

Signs and Symptom:

Most of the patients remain asymptomatic¹⁶. Some of the symptoms that people may experience are Headache, fatigue, dizziness, nausea, blurred vision, shortness of breath.

Risk Factors:

The risks associated with a given blood pressure are depend upon age, gender (males >females),ethnic origin (blacks > whites), diet, family history, blood cholesterol, diabetes mellitus, and pre existing vascular diseases. Important environmental factors include a high salt intake, smoking, heavy consumption of alcohol, lack of exercise and obesity¹⁶. Hypertension is the most important modifiable risk factor for both ischemic and hemorrhagic stroke¹⁷.

Complications:

Among other complications, hypertension can cause serious damage to the heart. Excessive pressure can harden arteries, decreasing the flow of blood and oxygen to the heart. This elevated pressure and reduced blood flow can cause chest pain, also called angina. Heart attack, which occurs when the blood supply to the heart is blocked and heart muscle cells die from lack of oxygen. The longer the blood flow is blocked, the greater the damage to the heart. Hypertension can also burst or block arteries that supply blood and oxygen to the brain, causing a stroke⁹. Other than coronary heart disease and stroke, its complications include heart failure, peripheral vascular disease, renal impairment, retinal haemorrhage and visual impairement¹⁸.

Need for Herbal Medicine:

Many drugs, ranging from diuretics (Indapamide, Furosemide, Amiloride), sympathoplegic agents (clonidine, reserpine), renin inhibitor (Aliskiren), angiotensin converting enzymes (ACE) inhibitors (Enalapril, Captopril, Quinapril), angiotensin receptors blockers (ARBs—Losartan, Irbesartan, Olmesartan), calcium channel blockers (Nifedipine, Verapamil, Diltiazem), α-adrenergic blockers (Prazosin, Doxazosin), β-adrenergic blockers (Nebivolol, Atenolol) to vasodilators (Minoxidil, sodium nitroprusside), are used to manage blood pressure levels in hypertensive patients^19,20. But these drugs have some side effects like diuretics may cause muscle cramps, dizziness, extreme tiredness, dehydration, blurred vision, abnormal heart rate, skin rash, and others. Side effect caused by ACE inhibitors are cough, skin rash, vomiting, kidney failure, fever, sore throat, diarrhea, and others. Side effects come with the use of calcium channel blockers are fatigue, headache, diarrhea, constipation, skin rash, edema, and others. So, scientific studies suggest different lifestyle changes and use of appropriate herbal medicine in the treatment of hypertension²¹.

Significance of Herbal Medicine:

The use of herbal medicine as a treatment modality has significantly increased over the last decade ²². This is due to several factors, principal of which is that herbal medicine is a cheaper alternative with fewer undesired side effects^20,22,23. The usage of complementary alternative medicine in developing countries is becoming even more pronounced (WHO, 2008). Evidently, the rationale for the use of herbal and plant remedies is definitely not surprising, considering the fact that they contain thousands of bioactive components that have known therapeutic applications²⁴. Remarkably, reserpine which depletes adrenergic neurotransmitters) still remains an effective treatment for hypertension²⁵. Importance of plants and herbs, per se, in the medical field must not be overlooked as they have been used throughout human history¹¹.

Siddha Medicine:

Traditional medicines are based on utilization of natural products which are of great importance. Many forms of medicines have been used by civilizations since decades and are still very much in practice. Traditional forms of medicines like – Ayurveda, Unani, traditional Chinese medicine (TCM), Kampo, Traditional Korean Medicine (TKM) have given beneficial results and are valuable for the human benefits²⁶. The Siddha system of medicine is one of the oldest traditional systems of medicine, which has been originated from India for treating various diseases including chronic conditions^27.

The unique of Siddha system is its continuous service to humanity for more than five thousand years in combating diseases and in maintaining its physical, mental, moral health²⁸. This system aims at getting to the root of the problem with its holistic approach and not just offering symptomatic relief. There is a great deal of scientific evidence to suggest that the use of carefully chosen herbal remedies and dietary supplements can help to lower blood pressure, as well as to improve the overall functioning of heart, arteries, and overall, this may explain the increasing interest in panning out the beneficial health effects of various plants and herbs in different diseases including hypertension¹¹. Quality assessment of herbal formulations is of paramount importance in order to justify their acceptability in modern system of medicine. The majority of complementary and traditional medicine therapy like Siddha medicine has not been rigorously tested in the way conventional western medicines have been. So in order to take the Siddha system of medicine in to the global lime light this review had been done as a basic attempt²⁹.

Polyherbal Formulation Veppampoo Mathirai:

In this review, we focus to provide a summary of Veppampoo mathirai, a polyherbal Siddha tablet formulation that had been used for the treatment of blood pressure³⁰. As per Siddha concept, Hypertension - “Kurudhiazhal Noi” is caused by deranged pitham humor which was vitiated by aberrant Ratha thathu and it is diagnosed by abnormal pitha naadi. Veppampoo mathirai contains a total of 15 herbal ingredients. The formulation was quoted in Siddha classical text Noigaluku Siddha Parigaaram, part I, written by Dr.M.Shanmugavelu, indicated for regulating Blood pressure and obesity³⁰ Hence, this review tries to elucidate the chemical constituents, antihypertensive property and other related pharmacological activities exhibited by each individual ingredient of the formulation, that had so far been scientifically studied and reported, which can specifically mitigate anti-inflammatory causes in arterial hypertension.

Table 1: chemical constituents, antihypertensive and other related pharmacological activities of veppampoo mathirai

Botanical name

Tamil name/ Common name

Family

Part used

Chemical Constituents

Antihypertensive

and other related pharmacological activities

References

Azadirachta indica

Vembu/Neem

Meliaceae

Flowers

Azadirachtin, Nimbin, Flavanoids, Coumarin, Tannin, Nimbinin, Nimbididinin, Nimbidic acid

Antihypertensive, Anti inflammatory, Immunostimulant, Anti oxidant,

31,32

Phyllanthus amarus

Keezha nelli/ Carry me seed

Euphorbiaceae

Whole plant

Securinine, Dihydrosecurinine, Melatonin, Phyllanthin, Amasterol A & B, Phenazine

Antihypertensive, Anti inflammatory, Anti oxidant,

33,34,35

Solanum trilobatum

Thuthuvalai/Climbing brinjal

Solanaceae

Whole plant

Saponin, Tannin, Terpenoids, Anthraquinone, Sobatum, Beta Solamarine, Solasodine, Solaine, Glycol, Disogenin

Antihypertensive, Anti oxidant, Anti inflammatory, Immunomodulator

36,37

Eclipta prostate

Karisalai/ False daisy

Asteraceae

Whole plant

Beta amyrin, Stigmosterol, Luteolin-7-O-glucoside, L-terthienyl, Methanol, Wedelolactone

Antihypertensive, Hypolipidemic, Anti oxidant, Anti inflammatory, Immunomodulator,

38,39,40

Zingiber officinale

Inji/Dried ginger

Zingiberaceae

Rhizome

Terpenes, Phenolic compounds, Gingerol 6-paradol

Antihypertensive, Antihypercholestrimic, Antiinflammatory, Antioxidant

41,42,43,44

Piper nigrum

Milagu/ Black pepper

Piperaceae

seed

Piperine, Ascorbic acid, Beta Carotene, Lauric acid, Palmatic acid

Antihypertrensive, Anti inflammatory, Antioxidant

45.46,47,48

Piper longum

Thippili/ Indian long pepper

Piperaceae

Fruit

Methanol, Ethylacetate, Phenolic acid, Flavanoids

Antihypertrensive, Antihyperlipidemic, Antioxidant

49,50,51

Terminalia chebula

Kadukai/Chebulic Myrobalan

Combretaceae

Outer skin part

Arjunglucoside1, Arjungenin, Chebulosides 1 & 2, Chebulin, Ellagic acid, Chebulinic acid, Gallic acid, Ethyl galate, Punigalagin, Terflavin A, Terchebin, Luteolin, Tannic acid

Antihypertensive, Antioxidant, Antiinflammatory

52,53,54

Terminalia bellerica

Thandrikai/Belleric Myrobalan

Combretaceae

Outer skin part

Hexahydroxydiphenic acid, Methyl ester, Gallic acid, Ellagic acid, Ethyl gallate, Galloyl glucose, Mannitol, Chebulagic acid

Antihypertensive

55,56

Emblica officinalis

Nellikkai/ Gooseberry

Phyllanthaceae

Dried fruit

Kaempferol-3-O-a-L, Rhamnopyranoside, Punicafolin, Phyllanemblinin A, Ellagic acid, Gallic acid

Antihypertensive, Hypolipidemic, Antioxidant,

Anti inflammatory

57,58,59

Eugenia caryophyllata

Kirambu/Clove

Myrtaceae

Flower bud

Eugenol, Beta caryophyllene, Vanillin, Crategolic acid, Kaempferol, Rhamnetin, Eugenitin, Eugenin, Gallic acid, Biflorin, Myricetin, Campesterol, Stigma sterol, Oleanolic acid, Bicornin

Antihypertensive, Antithrombotic, Antioxidant, Antiinflammatory

60,61,62

Cinnamom zeylanicum

Lavangapattai/Cinnamon

Lauraceae

Bark

Cinnamaldehyde, Linalool, Eugenol

Antihypertensive, Antiinflammatory, Antioxidant

63,64,65

Elatteria cardamomum

Elam/Cardamom

Zingiberaceae

seed

Flavanoids, Methanol

Antihypertensive, Antiinflammatory, Antioxidant,

66,67,68,69

Coeus vettiveroides

Vettiver/ Cuscus grass

Poaceae

root

Sesquiterpenes(3-4%), Sesquiterpenols(18-25%), Sesquiterpenones(7-8%), Zizanal, Vetivone

Antioxidant, Diuretic.

70,71,72

Citrus lemon

Elumichai/Lemon

Rutaceae

juice

Diosmin, Hesperidin, Limocitrin, D-Limonene, Beta-Pinene, Gamma-terpinene

Antihypertensive, Antiinflammatory, Antioxidant

73,74

As per Table 1, Almost all the ingredients of veppampoo mathirai exhibits Antihypertensive activity while the main ingredient Azadirachta indica as a crude extract possesses vasodilator effect, mediated through Ca⁺⁺channel blockade and NO dependant atropine sensitive pathways along with cardiac depressant activity which possibly explain its blood pressure lowering effect in animal models³². In a pilot study involved with mild hypertensive subjects Eclipta leaf powder showed diuretic, hypotensive, and hypocholesterolemic effects which helps in alleviating oxidative stress induced complications of Hypertension⁷⁵. Most of the ingredients possesses anti inflammatory, anti oxidant properties which can help in reducing inflammatory changes in arteries and prevent damage to cells by scavenging free radicals thus helps in reducing blood pressure.

CONCLUSION:

Many herbal formulations are found to be effective in the management of hypertension. But, unfortunately their efficacy were not scientifically proven and validated which is a need of the hour to the scientific community. In this regard, as a basic effort, this review gives the proven scientific properties related to anti hypertensive effect of the individual ingredients of the veppampoo mathirai Siddha formulation that had been given for the treatment of hypertension. Added to this, it is necessary that further research studies are required to explore extensively the formulation to prove its efficacy.

ACKNOWLEDGEMENT:

The authors acknowledge Government Siddha Medical College, Arumbakkam, Chennai-106, and The Tamil Nadu Dr. MGR Medical university, Guindy, Chennai-32.

CONFLICT OF INTEREST:

The authors declare there is no conflict of interest.

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Received on 10.02.2021 Modified on 13.04.2021

Research J. Pharm.and Tech 2022; 15(3):1365-1370.

DOI: 10.52711/0974-360X.2022.00228