Medicinal Importance of “Khamira Abresham Hakim Arshad Wala” an Unani

medicine in various diseases Mohammad Naime1*, Ajmal Ahmad2, Jamal Akhtar3, Mohd Tariq1, Fasih Ahmad1, Mohd Nafees

Khan1, Najmus Saher1, Maqbool Ahmad Khan1 1Central Research Institute of Unani Medicine, Central Council for Research in Unani Medicine, Ministry of AYUSH, Government of India, Lucknow-226026, U.P., India 2Department of Ophthalmology, College of Medicine, King Saud University, Riyadh-11411, Saudi Arabia 3Central Council for Research in Unani Medicine, Ministry of AYUSH, Government of India, New Delhi-110058, India

*Corresponding author: Email: naimtyagi@gmail.com

Abstract

Khamira Abresham Hakim Arshad Wala (KAHAW), a potentiated Unani medicine, participates in the function of vital organs of the body and contributes in clearance of free radicals load by increasing the antioxidant enzymes levels. The word ‘Khamira’ in the Unani system of medicine was first introduced by the Hakeem of the Mughal period. It is a squashy preparation prepared by adding herbal drugs to the base (Qiwam) which contains sugar or honey. KAHAW is used in prevention of ischemic heart diseases and several neurodegenerative disorders. Moreover, KAHAW maintains blood pressure and blood flow, strengthens the brain and liver during the period of convalescence, and mitigates side effects of measles, chicken pox and small pox. KAHAW contributes a pivotal role in healthcare despite of the great advances observed in modern medicines in recent decades. This review article has been discussed the medicinal importance of KAHAW shows antioxidant and anti-inflammatory property associated with reduced myocardial infarction and significant neuroprotective against cognative impairements and neurodegeneration and also illuminate traditionally used for the treatment of various ailments.

Keywords: khamira, free radicals, antioxidant, neuroprotective, myocardial infarction.

Introduction

The term Unani or Yunani is the Arabic word for Ionian, or: Greek means Perso-Arabic system of traditional medicine as carry out by Mughal in India. Later Unani medicine was commonly practiced in South Asia and modern day Central Asia. Since ancient times people use Unani medicines to cure chronic diseases which was extracted from natural resources like plants, animals and minerals. The origins of Unani medicine are found in the teachings of the ancient Greek physicians Hippocrates and Galen1. Unani system of medicine practiced today in India, Srilanka, Bangladesh, Iran (Persian medicine), Pakistan (Eastern medicine) and eastern part of China (Uighur medicine). The word ‘khamira’ was coined by the Indians Hakims during Mughal period which indicates fermented confection. Khamira is a semi-solid material prepared by a mixture of both herbal ingredients and animal ingredients to a base (Qiwam) made up of sugar or sugar with honey. It also contains ingredients Abresham (Bombax mori cocoon) and was first discovered by Hakim Arshad Wala and hence names Khamira Abresham Hakim Arshad Wala2, and its formulation as shown in Table 1. In addition, Khamira Abresham Hakim Arshad Wala (KAHAW) is also synthesize from different natural resources such as cardamom, Indian bay leaf, citron and saffron, presence of these natural substances in KAHAW helps to restore age-related global decline and protect the brain from the deleterious effects of reactive oxygen species (ROS). It is based on the ancient practice of simple laws of the nature and showed beneficial effect in bradycardia and cardiac weakness and also regularizes the cardiac beat and rate with well known antioxidant property. Mostly, it is a tonic for heart brain, liver and stomach, exhibit beneficial effects on various ailments for example arrhythmia, palpitation, stroke, neurobehavioural impairements, liver toxicity, asthma and cardiac debility and stimulates all majors organs of the body to function properly3,4,5, and also protects natural heat of the body. Many evidences revealed that KAHAW is the one of the most popular Unani medicine exhibit profound impact on the treatment of various human diseases, including cardiovascular diseases6, arrhythmia3, atherosclerosis5, cerebral ischemia7, and cognitive impairment8. It is a very effective herbal tonic for senile debility associated with improvement in chronic illness.

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Table 1. Composition of Khamira Abresham Hakim Arshadwala. 8,37

________________________________________________________________________________________________________________

Common names ______________________ S.No. Ingredients scientific names English Unani Source Quantities (g) ________________________________________________________________________________________________________________

1. Bombax Mori L Silk cocoon Abresham Animal 505 2. Corallium rubrum L. Coral Marjan Animal 06 3. Moschus moschiferous L. Musk Mushk Animal 05 4. Apis mellifera L. Honey Shahed Animal 250 5. Mytilus margaritiferus L. Pearl Marwareed Animal 09 6. Physeter catodon L. Ambergris Ambar Animal 06 7. Aquilaria agallocha Roxb. Eaglewood Ood Gharqi Plant 04 8. Nardostachys jatamansi D.C Indian spikenard Sumbul-Teeb Plant 05 9. Citrus medica L. Citron Turanj Plant 05 10. Syzygium aromaticum L. Clove Qaranfal Plant 05 11. Elettaria cardamomum L. Cardamom Elaichi Khurd Plant 05 12. Santalum album Sandal Sandal sufed Plant 06 13. Cinnamomum tamala Bay leaf Sazaj Hindi Plant 05 14. Punica granatum L Pomegranate Anar Plant 140 ml 15. Cydonia oblonga Mill. Quince Bihi Plant 140 ml 16. Malus pumila P. Apple Seb Plant 140 ml 17. Crocus sativus L. Saffron Zafran Plant 05 18. Pistacia lentiscus L. Mastich Mastagi Plant 05 19. Pandanus tectoriuss Screwpine Keora Plant 96 ml 20. Sacchararum officinarum L. Powder sugar Shakar Plant 750 21. Hydrated silica Jade Yashab Mineral 09 22. Aluminium oxide Ruby Yaqoot Mineral 09

________________________________________________________________________________________________________________________________________________________ Words italicized are in Urdu/Persian.

Khamira Abresham Hakim Arshad Wala is Neuroprotective

Neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and Huntington diseases are characterized by their progressive loss of defined groups of neurons in brain9. However, the cause of neurodegenerative diseases is still elusive but various factors, including oxidative stress has been implicated in neurodegenerative disorders. Oxidative stress occur due to imbalance between free radicals and antioxidant defense system results in decreased tissue antioxidants status leads to Alzheimer’s and Parkinson’s disease, atherosclerosis, heart failure, aging, cancer, diabetes mellitus and several other diseases10,11. Free radicals altered the function of lipids, protein and DNA resulting irreversible neuronal dysfunction12 is illustrated in Fig. 1. Earlier reports have provided substantial evidence that free radicals contribute to the pathogenesis of cognitive impairments associated with other neurodegenerative disorders such as Parkinson’s, and Huntington diseases13. Unani traditional medicine contains medicinal and therapeutic values like antioxidant property might provide neuroprotective therapy14,7. KAHAW is a Unani traditional medicine which is an herbal extract manifest antioxidant properties which decrements the oxygen radical generation and protects from cognitive impairments8. ICV injection of STZ in a sub diabetogenic dose generates ROS in animal models leads to perturbations of brain glucose and energy metabolism leads to cognitive deficit and elicits decreased choline acetyltransferase activity in the hippocampus15,16. Increased oxidative damge and cellular energy deficit leads to increased lipid peroxidation (LPO) and decreased gluthathione (GSH) levels in rat brain following ICV-STZ injection which causes impaired cognative function17,18. It has been already reported that STZ impaired glial and neuron cells in animal models of diabetes19. Neurons affected in cognative impairment and neurodegeneration exhibit decreased GSH and GSH dependent antioxidant enzymes such as gluthathione peroxidise (GPx), gluthathione reductase (GR), gluthathione - s- tranferase ( GST), catalase and superoxide dismutase(SOD) in STZ treated group in turn these impairement was improved by KAHAW8. In addition, KAHAW also cure others various diseases of heart, brain, melancholia etc3. Scientists have worked on herbal formulations/ or plant extract and decoded the antioxidant property of KAHAW that it might contribute to the decrease in the deterioration of cognitive function and neurobehavioral activities14,20-22. Moreover, KAHAW modulate oxidative stress by scavenging free radicals and rejuvenate neuronal loss in the infarct area by providing nutrients to damaged tissue. Oral supplementation of KAHAW treatment protects against ROS and reverses cognitive impairment associated neurodegenerative diseases as shown in Fig. 2. Hence, Unani medicine shows protective effect and mitigates free radicals generation and might have important implications for future treatment as a neuroprotective therapies in human diseases23.

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Figure 1. Imbalance between reactive pxygen species (ROS) and antioxidant enzymes (AOE) in the development of disease.

Khamira Abresham Hakim Arshad Wala is Cardioprotective

Cardiovascular diseases (CVD) are the major cause of illness and death worldwide especially in developed countries. The pathophysiology of CVD is necrosis of the myocardium leads to myocardial infarction (MI)24. MI occurs due to inadequate coronary blood perfusion to the cardiac muscles to meet the metabolic demands of the heart25. The ROS and antioxidant enzymes homeostatic balance in the cardiac muscles is altered resulting free radicals generation which play a major detrimental role in MI. ROS production leads to increased LPO and reduction of antioxidant enzymes such as SOD, CAT and GSH occur in myocardial damage during MI26. Suppression of free radical generation and/or augmented endogenous antioxidant enzymes could provide a novel strategy to prevent cardiac failure in a rat model of MI27. Isoproterenol (ISO) induced myocardial infarction in rats generates significant amount of free redicals capitalizing on antioxidative defense system leads to severe myocardial injury28-30 as shown in Fig. 1. ISO induced severe myocardial injuries associated with cardiac dysfunctions resulting elevated LPO and decreased cellular reduced GSH and anti-peroxidative enzymes, including GPX, GR and GST28,31-33. Finally ISO-treated rats and human MI seems to be similar pathophysiological and morphological changes involved in cardiac development and pathophysiology34,35. Many experimental data reaveled that Unani medicine have potent medicinal and therapeutic values like antioxidant extracted from natural resources like plants, animals and minerals. The unique properties of these herbal extract is very useful for treating a various diseases including cardiovascular diseases6. KAHAW clearly improved cardiac function in a rat myocardial infarction model by inhibiting production of ROS and boosting antioxidant levels and also been used in several others chronic diseases pathological conditions like arrhythmia3, atherosclerosis5, cerebral ischemia7 and cognitive impairment8. For instance, oral administration of KAHAW mitigates ISO-induced myocardial necrosis and oxidative stress2 as shown in Fig. 2. In addition, KAHAW attenuates dyslipidemia, hepatic steatosis and associated hypertension by decreasing oxidative stress, TNF-α and normalizing NO production36.

Khamira Abresham Hakim Arshad Wala is Nephroprotective

KAHAW contains 22 ingredients prepared from plant, animal, and mineral sources used against cardiotoxicity and nephrotoxicity8,2,37. These ingredients are enriched with high antioxidant activity for instance, Syzygium aromaticus38, Crocus sativus39, Nardostachys jatamansi40,41, Pistacia lentiscus42, Punica granatum43,44, and Bombyx mori cocoon45,37. In 2003, a WHO on traditional and complementary and alternative medicine over 80% of the world population is used to provide health coverage to support their proper use. Several approaches to targeting nephrotoxicity by KAHAW are ongoing in clinical studies. For instance, doxorubicin (DRX) is robust anti-tumor antibiotic but it causes both cardiotoxixity and nephrotoxicity which have been already examine in a variety of animal models46,47. Indeed, DRX metabolic breakdown leads to generate free radicals and these free radicals react with nucleic acids, protein and lipids causes’ cell death47. Therefore, administration of DRX in combination with KAHAW exhibits protective effects against DRX induced nephrotoxicity. DRX treated

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animal group show upregulation of LPO, blood urea nitrogen (BUN) and serum creatinine while combination of DRX with KAHAW treated animals groups brings LPO, BUN and serum creatinine near normal levels37. Moreover, pre-treatment with KAHAW improved depletion of antioxidant enzymes against DXR-induced toxicity. Numerous studies based on herbal extract products enriched in antioxidant activity have been tested against DXR-induced toxicity such as Phyllanthus urinaria48, Phyllanthus emblica49, and Craneberry50 and found that these have protective effect against DXR-induced toxicity.

Figure 2. KAHAW is strong ROS scavenger and augment AOE levels in the development of several diseases.

Conclusion & future perspective

KAHAW is a safe Unani medicine used against various ailments by maintaining homeostasis between oxidative damages and antioxidant enzymes8. Furthermore, oxidative stress leads to inflammation and are associated with a variety of chronic pathological complications for instance; arthritis, asthma, mental, cardiac, digestive disorders, urinary infections, and sexual diseases. Inflammation triggers the inflammatory cascades leads to the activation of proinflammatory cytokine such as interleukin 1βeta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) play a major role in the pathological conditions51. Remarkably, the anti-inflammatory role of KAHAW against proinflammatory cytokine such as IL-1β, IL-6, and TNF-α in various ailment remains to be elucidated. Even for the long-term effects of the KAHAW in multiple diseases is still to explore. Similarly, it is unclear whether anti-inflammatory effect of KAHAW inhibits IL-1β, IL-6, and TNF-α which are important cytokines that mediates proinflammatory processes. The fact that oxidative stress and inflammation play an important role in the pathophysiology of various ailments and the treatment with KAHAW might be a new therapeutic approach to counteract different diseases such as neurodegeneration, myocardial infarction and nephrotoxicity. The remarkable impact is that KAHAW is considered to be associated with its antioxidant and anti-inflammatory property exhibits exuberant neuroprotective potential, improved neurological deficits, combated oxidative load, mitigates deleterious effect of cytokines and increases antioxidant enzyme levels.

Acknowledgement

The authors are highly thankful to Director General, CCRUM for guidance and encouragement.

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