MOLECULAR DOCKING STUDIES OF SIDDHA HERBAL FORMULATION KUPPAIMENI CHOORNAM ON HUMAN HISTAMINE RECEPTOR (3RZE)

Background: Molecular docking has tremendous applications in the field of Siddha medicine especially herbal formulations were the interactions of the lead molecules of the formulation with that of receptors can be elucidated at the molecular level and furthermore to reach an assumption of its fundamental biochemical processes to which the formulation is targeting. Kuppaimeni Choornam (KC) is a simple herbal formulation used in Siddha medicine for urticaria and other skin allergies. As far as skin allergy is concerned Amino acids such as Asparagine (ASN), Tryptophan (Trp), Aspartate (Asp), Tyrosine (Tyr), Serine (Ser), Isoleucine (Ile), Lysine (Lys), Threonine (Thr), Phenylalanine (Phe) are the main core residues involved in mediating Human histamine receptor (3RZE). Binding of lead compounds with this core residue may inhibit the enzyme activity. Aim & Objectives: Molecular docking studies of Siddha herbal formulation KC and to screen the lead component interaction on the Human Histamine Receptor (3RZE). Methodology: Docking calculations were carried out using Auto Dock 4. Gasteiger partial charges were added to the ligand atoms. Docking simulations were performed using the Lamarckian genetic algorithm (LGA) and the Solis & Wets local search method. Initial position, orientation, and torsions of the ligand molecules were set randomly. All rotatable torsions were released during docking. Results and Conclusion: The compounds present in KC like beta-sitosterol, apigenin, luteolin, cuminaldehyde, kaempferol, and triacetonamine showed maximum interactions with 3RZE when compared to that of the standard cetirizine. Hence, these compounds of test drug possess promising Human histamine 1 receptor (3RZE) inhibition activity. For prospective pharmacological validation of Kuppaimeni Choornam, the docking studies were an important step for its scientific justification

Safety and Efficacy of a Siddha Sastric Formulation Linga Chendhuram at its Human indented therapeutic dosage in the management of Suram (Pyrexia)

Fever (Pyrexia) is a symptom of elevation in body temperature associated in various disease conditions particularly in infectious and autoimmune diseases. Because of the hypothalamic thermoregulatory control normal body temperature is maintained instead of maintaining environmental temperature due to the the excessive heat production derived from metabolic activity in liver and the muscle with heat dissipation from the lungs and skin. In Siddha literature, fever is considered as a disease under the terminology -Suram. Sage Theran denotes Suram is caused by an accumulation of aggravated Seetham in the alimentary tract which makes increase in body temperature. Suram is manifested as increased body temperature above its normal range, burning sensation in eyes, pain in the body, nausea and vomiting. For treating pyrexia, numerous medications were illustrated in the Siddha literatures. Among them, the herbometallic Sastric formulation “Linga Chendhuram (LC)” has been practiced frequently for treating fever, arthritis and venereal diseases. LC has been chosen for the study to prove as a safe and efficacious state of the drug in the management of fever in both animal model and human subjects. LC was prepared in Gunapadam laboratory of National Institute of Siddha, Chennai as per the method cited in the “1940 drug and cosmetic act” authenticated literature “Siddha Vaithiya Thirattu”. LC was analyzed for both qualitative and quantitative estimations. Preliminary physical parameters such as total ash, moisture content and extractive values were analyzed. The crystalline nature of LC and main contents were analyzed using X ray diffraction study. The content of lead and cadmium were analyzed using Atomic Absorption Spectroscopic study. The concentration of elements in oxide form was analyzed through Wavelength dispersive X-Ray Fluorescence. The concentration of trace and heavy metals were analyzed using Inductively Coupled Plasma – Optical Emission Spectrometer. From the result of above studies, we inferred that LC was feasible to conduct the study on animal model and human subjects. Mercuric and Sulphur trioxides were found as major constituents in LC. To evaluate the safety of LC, Wistar albino rats were used for performing acute and 28 days repeated oral toxicity studies following OECD guidelines. 2000 mg/kg of LC was tested on six rats and observed nil mortality and morbidity. Median lethal dose was estimated as more than 2000 mg/kg for the test drug. The sub-acute toxicity was observed on Wistar rats by giving LC at three dose levels (18, 90 & 180 mg/kg) for 28 days along with its vehicle (Diluted honey). The test drug dose was fixed from the human conversion dose (195 mg/day) to rat. No mortality and abnormal clinical signs were observed during 28 days. All test dose treated animals gave comparable body weight and organ weight gain with that of control. Haematological, biochemical parameters and urinalysis were within the normal limit. No significant abnormality was detected in gross necropsy study on organs and in H&E sliced organs. The efficacy of LC at the dose of 18, 90 and 180 mg/kg was evaluated on BALB/C mice and Wistar rats. In the evaluation of analgesic activity by hot pate method, the pain reaction time was prolonged in test groups on 60 min post treatment when compared with control. Acetic acid induced writhing test was performed on mice and observed LC has significant analgesic activity by inhibiting the incidence of writhing as compared to control. LC at high dose 180 mg/kg has better central and peripheral analgesic activity. In the model of Carrageenan induced acute inflammation of paw, significant reduction in paw volume was observed in all the test groups when compared to positive control group. The percentage of inhibition of maximum oedema inhibition was high in LC group treated at 180 mg/kg and observed that the inflammatorty action achieved by LC in dose dependent manner. Cotton pellet granuloma method was performed on rat and observed LC has significant anti-inflammatory activity by reducing the granuloma formation. LC at three dosage levels was studied for antipyretic activity in rats using Brewer‟s yeast- induced pyrexia models. LC at all tested dose levels produced a significant dose dependent inhibition of temperature elevation compared with the normal rat. After 2 h treatment, LC significantly decreased yeast induced pyrexia in rats. These results indicate that LC has potent antipyretic activity which and pharmacologically justifies its use in the management of fever. The safety and efficacy of LC to humans was determined by giving LC at its therapeutic dose 65 mg/dose suspended with vehicle honey for three times daily for the duration of 5 days to the clinical subjects was done on human. The study was designed as non- randomized open labeled without control single centric study. The age group between 20 to 60 years and both gender of 75 patients were recruited after analyzing the inclusion and exclusion criteria. The patients were recruited having temperature between 100 to 103°F. Among 75, 70 patients (36 male and 34 female) completed the study of 5 days treatment. The temperature was measured by digital thermometer every 30 min for first 4 h and three hours once for further period. The intensity of pain was observed using Visual Analogue Scale (VAS) three hours once during the course of treatment. 28 patients show better reduction of elevated body temperature with in 120 min after treatment and 20 patients showed better reduction of elevated body temperature with in 240 min after treatment. CONCLUSION: 1. LC has long shelf life period and free from toxins. 2. Median lethal dose for LC was calculated as more than 2000 mg/kg body weight. 3. No observed effect level (NOEL) of LC administered by us to Wistar Rats through oral route over a period of 28 days was found to be 180 mg/kg body weight for both male and female rats. 4. LC at 18, 90 & 180 mg/kg demonstrated anti pyretic, analgesic and anti-inflammatory properties in animal model. 5. The clinical study proved that LC at its intended human therapeutic dosage 65 mg/kg along with honey is a safe and efficacious drug in treating Suram (Pyrexia)

ACUTE AND SUB ACUTE TOXICITY STUDIES OF A SIDDHA SASTRIC FORMULATION LINGA CHENDHURAM IN WISTAR RATS

Linga Chendhuram (LC) is a herbo-mineral formulation cited in Siddha literature Siddha Vaithiya Thirattu comprises of purified Lingam (Cinnabar) processed in herbal juice – Citrullus colocynthis and used in the management of various types of fever, arthritis and anaemia at 65 mg/dose. Acute and Sub-acute oral toxicity of Linga Chendhuram was carried out in Wistar rats under OECD guidelines 423 and 407. In acute study, LC was administered at 2000mg/kg orally and animals were observed for toxic signs for 14 days. In sub-acute toxicity study, test groups were treated with LC at 18, 90 and 180 mg/kg/day along with 2 ml of diluted honey and control group with distilled water 2 ml/day for 28 days daily. LC at 2000mg/kg produced no treatment related toxic signs or mortality during the study. Haematological and biochemical parameters were analyzed using auto analyzer with standard kits and one way ANOVA followed by Dunnett test was performed for significant analyses. Gross necropsy and histopathology studies using H&E stain were done on major organs. LD50 was found more than 2 g/kg. No-Observed-Adverse-Effect level of LC was seen at 180 mg/kg in 28 days of treatment. No abnormal findings were noted in high dose group organs. Administration of LC at its human therapeutic dose of 195 mg/kg in rat (180 mg/kg) is safe

VALIDATION OF SIDDHA PATHOLOGICAL CONCEPTS OF SIRAKAMBAVATHAM AND ITS PARALLEL ANALYSIS WITH CEREBRO VASCULAR ACCIDENTS (STROKE)

The Siddha system of medicine is widely practiced in South India and consists of an enormous classical literature that emphasize on pathological basis of disease. Contrary to conventional pathological basis of diseases, the Siddha pathology is solely based on the humoral makeup of individuals and rests on the conceptual framework formed by 96 Thathuvams (philosophies). These concepts connect the physical and inert energies of human body facilitating its existence at subtle and gross levels. Sirakkambavatham is one among the 80 Vatha diseases mentioned in the Siddha literature Yugivaithiyasinthaamani. The present literature survey has been conducted to provide an updated integrative framework of information about the pathological concepts of Sirakkambavatham from Siddha literature and its parallel analysis with Cerebrovascular accidents (Stroke).Validating the traditional text in the limelight of modern literature unveils the traditional wisdom of ancient saints of South India and provides a better approach for disease diagnosis, prevention and its management

AN OBSERVATIONAL STUDY TO VALIDATE THE SYMPTOMATOLOGY AND TO EVOLVE THE DIAGNOSTIC METHODOLOGY OF SIRAKKAMBA VATHAM THROUGH SIDDHA DIAGNOSTIC TOOLS

Sirakamba vatham is a clinical entity described by Sage Yugi in his treatise Yugi Vaithiya Chinthamani- 800, as one among the 80 types of Vatha diseases described in Siddha system of medicine. The study was aimed at in depth analysis of the clinical features mentioned under Sirakamba vatham of Siddha literature and to evolve standard Siddha diagnostic methods for management for Sirakamba vatham. This study was an observational, single center study with the sample size of 26, divided into Group I (control group) having normal individuals and group II (cases with Sirakkamba vatham). At the end of the study, it was concluded, that the symptoms of Sirakkamba vatham closely resembled the symptoms of Cerebro Vascular Accident especially of posterior circulation stroke

NEERKURI BY SAGE THERAIYAR - A REVIEW ON SIDDHA WAY OF URINE EXAMINATION IN THE LIGHT OF CONTEMPORARY CLINICAL METHODS

The Siddha system is said to have emerged in antiquity, from the highly evolved consciousness of the Siddhars. The clarified intellect and heightened intuition of Sage Theraiyar, resulting from Yogic powers, enabled to expound to the world the signs of a disease in the Urine of a person in his treatise “Theraiyar Neerkuri Vaithyam†a book that details urine examination findings for diagnostic and prognostic purposes. The present paper deals with scientific validation of Neerkuri (urine examination), an important diagnostic tool in Siddha system of medicine. The methodology of diagnosis in Siddha system is based on eight fold examination of pulse, tactile perception, tongue, color and complexion, speech, eyes, stools and urine. Of all these parameters, Urine examination has gained paramount importance next to pulse examination. This paper parallels analyses the signs of urine examination between a few quotes from Sage Theraiyar text and modern text. This is an attempt to understand the Siddha system of diagnosing pathological conditions which are a non-invasive, highly cost effective procedure which can be used for both diagnostic and prognostic purposes

A REVIEW ON HYPO HIDROTIC EFFECT OF SIDDHA FORMULATION - KUNGUMAPOO MATHIRAI

Hyperhidrosis is a condition present with excess sweating of palms on the hands, soles of the feet, forehead and axillae. This is socially embarrassing. There are few herbs to treat hyperhidrosis in Siddha system of medicine. The drug Kungumapoo Mathirai is being used in Siddha system of medicine for many years to treat hyperhidrosis. The ingredients used in the preparation of Kungumapoo Mathirai are Crocus sativus, Zingiberofficinale, Piper nigrum, Piper cubeba, Costus speciosus, Carum capticum, Piper longum, Syzygium aromaticu, Elettaria cardomom, Korosanai (Oxbile), Vengaram (Sodium biborate), Lingam (Red sulphide of mercury), Sambrani poo (Dry powder of Styrax benzoin). This article reviews the hypo hydration effect of the drug Kungumapoo Mathirai and its ingredients. This review will help to get much information on hypohydrosis effect of the chemical constituents of the drug. The antioxidant properties of the ingredients which is acting as hypo hydrating agent and their mechanism in controlling the nervous excitement by reducing the action potential in detail. The use of herbal drugs is becoming more popular due to the adverse effects of synthetic Anticholenergics and Antispasmodic drugs which are used to treat hyperhidrosis worldwide. Excellence of Siddha, formulated each and every medicines on the basis of Thiridhosa theory and five elemental theory, which are the basic principles of Siddha medicine. The basic theory of Siddha formulation Kungumapoo Mathirai is also explained here

EFFICACY OF CHUNDAI VATRAL CHOORNAM A SIDDHA POLY HERBAL FORMULATION IN TREATING TENSION TYPE OF HEADACHE (TTH) -A CASE REPORT

Siddha system is an ancient system of medicine which is popularly practised around south India particularly in Tamilnadu. Siddhars were considered as the pioneer of Siddha system, this system of medicine mainly encompasses for a healthy life for human beings. Among the broad spectrum of treatment aspects in Siddha system Siddhars classify the forms of internal medicines into 32 types which are all unique by its preparations. Choornam is one of the forms of internal medicine which can be used as single as well as poly herbal formulations. In this case report a poly-herbal formulation in Siddha system was used to treat tension type of headache (TTH). A 30 years old male patient visited out-patient department of Ayothidoss Pandither Hospital in National Institute of Siddha, Chennai. Patient reported with the complaints of episodic and chronic headache which is band like around the head, the intensity becomes mild to moderate, pain increased during working hours for past 2 years. Patient advised to follow the internal medicine Chundai vatral choornam it relives the TTH immediately when he got those symptoms.       &nbsp

A REVIEW ON SIDDHA EXTERNAL THERAPY - NASIYAM (NASAL INSTILLATION)

Siddha system of medicine, one of the ancient, traditional Indian systems of medicine has unique diagnostic methods, therapeutics and treatment procedures. It has a vast range of external modalities of treatment for health management. This external management is classified into 32 types. They include minor surgical procedures and treatment procedures. These therapies are used both as mainstream and supportive therapies - both curative and prophylactic. Most of the therapies are aimed to maintain the equilibrium of the three humours (Vatham, Pitham, Kabam). Among them Nasiyam (Nasal instillation) is one of the external therapies which is a non-invasive procedure. Nasiyam is the process by which the drug is administered through nostrils. This is the treatment procedure to balance the Thirithodam in its normal level. This paper documents the efficacy of Nasiyam, methods of application, shelf life, effect of Nasiyam in treating various diseases, the list of single drug and compound drug formulations that can be used as Nasiyam, Indications and contraindications are discussed in detail. Nasiyam therapy is used to treat the diseases of vitiated Kabam such as migraine, sinusitis, bronchial asthma, nasal polyp etc

ANTI ARTHRITIC ACTIVITY OF HERBO MINERAL SIDDHA PREPARATION ARUMUGA CHENDURAM AGAINST TYPE II COLLAGEN INDUCED ARTHRITIS IN EXPERIMENTAL RATS

Siddha system of medicine is the eternal science of life. It is a system that has its extensive bonding with Dravidian culture, language and beliefs. The system of medicine mostly prevailed and prospered in the regions of Dravidian cultures by the great Siddhars. It’s unique as one only than other AYUSH traditional systems of medicine across India with its distinctive abundant usage of medicinal plants, metals, minerals and animal products. Siddhars used the steps of Alchemy to prepare various medicines from metallic and mineral origin for attainment elixir and various rare diseases. Siddha medicine is classified into 32 types of internal and external medicine each. Among the 32 types of internal medicine Chendhuram is a medicine shelf life of 75 years usually from herbo-mineral combinations. Arumuga Chendhuram (ARC) is a herbo-mineral formulation cited in Siddha literature ‘Siddha Vaithiya Thirattu’. ARC was orally administered at higher dose 2gm/kg to the Wistar Albino rats in acute toxicity study and during 28 days of repeated (sub acute) toxicity study, at daily doses of 12, 24 & 48mg/kg of body weight to the Wistar Albino rats. Type II collagen arthritis is another model for developing autoimmune arthritis. The immune pathogenesis mediated by T cell and B cell response to collagen. By this model, nearly 100% arthritis can be achieved. In our study, ARC after 42 days treatment reduced the arthritic swelling significantly and degree of inflammation evident to act against auto immune disorder