|Year : 2021 | Volume
| Issue : 1 | Page : 2-8
Antipyretic activity of mrityunjaya rasa prepared by various compounds of mercury in experimental animals
Manoj Kumar Dash1, Namrata Joshi2, Madhuri Vindhyaraj1, Saroj M Parhate1
1 Department of Rasashastra and B.K, Government Ayurveda College, Raipur, Chhattisgarh, India
2 Department of Rasashastra, Faculty of Ayurveda, IMS, BHU, Varanasi, Uttar Pradesh, India
|Date of Submission||17-Sep-2020|
|Date of Decision||24-Sep-2020|
|Date of Acceptance||29-Sep-2020|
|Date of Web Publication||26-Mar-2021|
Manoj Kumar Dash
Department of Rasashastra and B.K, Government Ayurveda College, Raipur, Chhattisgarh
Source of Support: None, Conflict of Interest: None
Introduction: Mrityunjaya Rasa(MR) is a herbomineral Ayurvedic anti-pyretic formulation containing Shuddha Hingula (Purified Cinnabar), Shuddha Gandhaka (Purified Sulphur), Shuddha Tankana (Purified Borax), Shuddha Vatsanabh (Purified Aconite) Pippali (Piper lonum) and Maricha (Piper nigrum). Objective: The present pharmacological study was undertaken to study the comparative antipyretic activity of different samples of Mrityunjaya Rasa with slight variations in ingredients; Mrityunjaya Rasa 'A' (Hingula based), Mrityunjaya Rasa 'B' (Kajjali based), Mrityunjaya Rasa 'C' (Rasasindura based), Mrityunjaya Rasa 'D' (without metallic content). Material and Method: Pyrexia was induced by subcutaneous injection of 20% wt/v of Brewer's yeast in distilled water (10ml/kg) in 36 animals divided into 6 groups, each group containing 6 animals. Basal rectal temperature was measured before the injection of yeast, and the rise in rectal temperature was recorded after 18 hrs of yeast injection. Group 'A' treated as normal control while group 'B' as standard control (treated with Paracetamol) Group C, D, E, F were drug tested groups. Results: The data generated during all stages of study showed that all samples of Mrityunjaya Rasa (22.5 mg/kg per day) exert highly significant (P<0.001) decrease in temperature after ½ hour and 1 hr of administration except Mrityunjaya Rasa D which was non-significant after 1 hr. Mrityunjaya Rasa 'C' (Rasasindura based), was found to be significant (P<0.05) even after 3 hrs in comparison to standard drug (Paracetamol). Conclusion: The results of present study show the importance of mercury in intensifying the therapeutic efficacy of a formulation. Further, result obtained in Mrityunjaya Rasa containing Rasasindura group explains the importance of concept of gandhakaj jarana in rasashastra.
Keywords: Brewer's yeast, Hingula, Kajjali, Mrityunjaya Rasa, paracetamol, pyrexia, Rasasindura
|How to cite this article:|
Dash MK, Joshi N, Vindhyaraj M, Parhate SM. Antipyretic activity of mrityunjaya rasa prepared by various compounds of mercury in experimental animals. J Ayurveda 2021;15:2-8
|How to cite this URL:|
Dash MK, Joshi N, Vindhyaraj M, Parhate SM. Antipyretic activity of mrityunjaya rasa prepared by various compounds of mercury in experimental animals. J Ayurveda [serial online] 2021 [cited 2021 Apr 13];15:2-8. Available from: http://www.journayu.in/text.asp?2021/15/1/2/311911
| Introduction|| |
All ancient scholars were of the same opinion that the condition producing agony in the body is Jwara (Pyrexia). According to Ayurveda, it not only the agony produced in the body but also in the Manas as well as sense organs comes under definition of Jwara, i.e., “Deha-Indriya-Manah-Santap.” Indulgence in Mithya-aahara vihara (Improper food habit and life style) aggravates dosha, individually or in combinations, spread through Rasa dhatu and dislodge the Jatharagni (digestive fire) present in its own position i.e. amashya (stomach). It results in obstruction of body channels (srotasa) by imbalanced dosha causing further rise of body temperature, spreads all over the body with aggravation produces Jwara (Pyrexia). Fever is an elevation of body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamic set point. The body temperature refers to the temperature of the viscera and tissues of the body. It is kept within the normal level by maintaining a balance between heat gain and heat loss. In spite of the fact that numerous modern solutions, for example, paracetamol, aspirin, and nimesulide have been utilized to treat fever, however, different reactions such as dyspepsia, ulceration and hemorrhage in gastrointestinal tract, rashes, epigastric distress, heartburn, and pruritus made the researchers to think for a natural, safe, and effective antipyretic medicine.
In the present study, Mrityunjaya Rasa (MR), one of the antipyretic Ayurvedic formulations mentioned in Ayurvedic Formulary of India, is taken as a trial drug. It is considered as one among the best formulations used by physicians in their practice in terms of its availability in the market and also use of formulation in different kinds of Jwara. It consists of Shuddha Hingula (purified cinnabar), Shuddha Gandhaka (purified sulfur), Shuddha Tankana (purified borax), Shuddha Vatsanabha (purified aconite), and other herbal drugs such as Pippali (Piper longum) and Maricha (Piper nigrum). Parada is one of the chief Ingredient of MR in the form of Hingula and in Ayurveda, for making Parada (mercury) ingestible, it is treated with several pharmaceutical processes such as Shodhana (general and specific purification), Samskara (different processing), and Marana (incineration) to convert it into a therapeutically suitable form, used in small dose in several formulations, with specific Anupana (adjuvant) as per the requirement of the disease. For the preparation of MR, some pharmaceutical companies are using Shodhita Hingula, while some other pharmaceutical companies prepare it using either Kajjali or Rasasindura keeping other ingredients same as there is nearly no availability of native cinnabar, and we are getting only synthetic cinnabar or chemically prepared cinnabar. Moreover, Hingulottha Parada is considered best as it is devoid of Saptkanchuki Doshas and fit for all purpose. In all the Rasa preparations, the use of Parada (Hingula, Kajjali, and Rasasindura) is considered for two purposes, namely, activation of herbs or preservation of herbs. Owing to the above-stated facts in the present study, Hingula, Hingulottha Parada prepared Kajjali, and Rasasindura are being used in the trial as an ingredient for mercury in preparation of the trial drug, i.e., MR. Moreover, as in the present era, people are afraid of consuming metallic preparations, so one more group of MR was also taken under trial, which was devoid of metal/mineral constituents of the formulation.
| Materials and Methods|| |
Materials for pharmaceutical study
Raw drugs required for preparation, i.e., Ashuddha Hingula (unpurified cinnabar), Ashuddha Gandhaka (unpurified sulfur), Ashuddha Tankana (unpurified borax), Ashuddha Vatsanabha (unpurified aconite), Pippali (Piper longum), and Maricha (Piper nigrum) were collected from the local market and got authenticated in respective Department of Rasa Shastra and Dravyaguna of College. Adraka (Zingiber officinalis) used for levigation was purchased from the local market of Raipur. Extraction of mercury from cinnabar (Hingulottha Parada Nirmana) [Figure 1], preparation of Kajjali, Rasasindura, and preparation four samples of MR [Figure 2],[Figure 3],[Figure 4] were done in the Department of Rasashastra and Bhaishajya Kalpana of Institute.
|Figure 1: Pharmaceutical extraction of mercury for cinnabar (Hingulottha Parada Nirmana)|
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Four different samples of MR were prepared with a slight variation in ingredients. MR A was prepared with Shuddha Hingula, Shuddha Gandhaka, Shuddha Vatsanabha, Shuddha Tankana, Pippali, and Maricha with levigation of Adraka Swarasa. MR B was prepared with Kajjali, Shuddha Vatsanabha, Shuddha Tankana, Pippali, and Maricha with the trituration of Adraka Swarasa. MR C was prepared with Rasasindura, Shuddha Vatsanabha, Shuddha Tankana, Pippali, and Maricha with the trituration of Adraka Swarasa. MR D was prepared with only herbal ingredients of MR formulation, i.e., Vatsanabha, Pippali, and Maricha, with trituration of Adraka Swarasa.
A total of 36 Wistar rats of both sexes weighing between 150 and 250 g were taken. The animals are randomly selected, marked with Picric acid H (mark on head), B (mark on back), T (mark on tail), HT (mark on head and tail), HB (mark on head and back), and BT (mark on tail and back) for individual identification, and kept in their cages for at least 5 days before dosing to allow for acclimatization to the laboratory conditions.
The experiments were carried out after obtaining permission from the institutional animal ethics committee.
Approval of institutional ethical committee
The experiments were carried out after obtaining permission from the institutional animal ethics committee (approval number-IBIR/IAEC/206/VI/02).
The dose for the present experimental study was calculated by anticipating the human dose to animal dose based on the body surface area ratio using the table of Paget and Barnes. Accordingly, in the same way, human therapeutic dose of MR (125–250 mg/day) converted to rat dose as 22.5 mg/kg in a day. The dose of MR samples was fixed on the basis of the human therapeutic dose mentioned in the classics [Table 1].
Pyrexia was induced by subcutaneous injection of 20% w/v of Brewer's yeast (10 ml/kg) in distilled water. Basal rectal temperature was measured before the injection of yeast by inserting a digital thermometer to a depth of 2 cm into the rectum. The rise in rectal temperature was recorded 18 h after yeast injection [Figure 5].
Administration of doses
Calculated dose had been administered orally with the help of oral fiddling needle after inducing pyrexia.
All the values were expressed as mean ± standard error of the mean. The data were analyzed by unpaired test. A level of P < 0.05 was considered statically significant and <0.001 was considered highly significant. The level of significance was noted and interpreted accordingly in each group.
| Discussion|| |
In the present study, all groups showed a consistent and significant rise in rectal temperature after 18 h of administration of Brewer's yeast. An average mean increase in rectal temperature was 2.37°C. Brewer's yeast is a fungus containing lypo-polysaccharides which is a cell wall component of Gram-negative bacteria. It binds with microphages, releasing cytokinase, IL-1 etc., into the blood circulation, leading to antibody and antigen reaction. It reduces blood–brain barrier and releases arachidonic acid mediated by the enzyme phospholipase, prostaglandin E-2 synthesis, and cyclooxygenase. Finally, the synthesis and release of PGE-2 into anterior hypothalamus, resulting in pyrexia. Summarized data obtained from the statistical calculation antipyretic study shows the significance level of each group as shown in [Table 2] and [Table 3].
In the vehicle control group, rise in temperature was significant; however, the reduction in temperature was not significant.
In this group, paracetamol (PCM) was given. This group showed a significant decrease in rectal temperature after 30 min, 1 h, and 2 h and less decrease in temperature after 3 h. It may be due to paracetamol inhibits COX-1 and COX-2 through metabolism by the peroxidase function of these isoenzymes. This results in inhibition of phenoxyl radical from a critical tyrosine residue essential for the cyclooxygenase activity of COX-1 and COX-2 and prostaglandin synthesis.
The data obtained in reducing pyrexia in Group C indicate that the MR at the dose of 22.50 mg/kg decreases the rectal temperature significantly in early stages of dose administration (after 30 min and 1 h), but nonsignificant reduction was observed thereafter. This may be due to principle ingredients Hingula and Vatsanabha that reduce Jwara., Other ingredients such as Pippali, Maricha, and Adraka Swarasa are added to the formulation to enhance the antipyretic effect of the principle ingredient. Ingredients such as Gandhaka and Tankana included in the formulation for their agonistic effect on principle ingredient.
In Group D, Kajjali was included as a main ingredient, and Kajjali by its Yogawahi property (as a catalyst) increases the antipyretic property of other ingredients present in the formulation. Here also highly significant reduction was seen in the first ½ h and 1 h, but later on reduction was although observed but was not found statistically significant.
The data obtained in Group E were highly significant in reducing rectal temperature in early stage of dose administration (after 30 min and 1 h). Even after 2 h of drug administration, significant reduction was observed, which was maintained up to 3 h. The possible factor may be that it contains Rasasindura which is having properties like more particle size distribution and more absorption in body cells. The colloidal particles of Rasasindura get attached to the human intestine and provide a larger surface area, thereby increasing the absorption of other ingredients present in MR. In short, it acts as a carrier for the other ingredients present in MR. Rasasindura and Vatsanabha have diuretic property which may produce sufficient amount of urine leads to a reduction of temperature.
The Group F which contains only the active purified herbs without any metals/minerals also showed highly significant results in reducing the rectal temperature in early stages of dose administration, but in later stage, no such effect was observed. Nowadays, many modifications in the classical formulation are introduced for the sake of dispensability and marketability. Ideally, the effect of the active purified herbs in MR was reducing rectal temperature significantly in the initial phase, i.e., after 30 min of administration, but it was statistically nonsignificant afterward. As the shelf life of herbal powder is far less than a Rasaushadhi and sustained relief was also not seen for a long duration, use of this combination without metal/mineral components needs further research. Furthermore, this might be the reason for ancient seers to include Parada and other mineral components in the formulation for getting the desired effect.
A question always strikes the mind, whether treating Jwara needs an antipyretic effect or Amapachana effect? From author point of view treating Jwara, it needs both antipyertic and Amapachana effect, as fever is a marker for sickness in many infectious and inflammatory disorders. According to the classical view, the beginning of fever is induced by provocative ingestion of Apathya Ahara Vihara (unwholesome food and lifestyle), resulting in expelling or inhibition of Kayagni (digestive fire) from its original place forming toxic substance Ama (undigested toxic substance), by which it increases the body heat with their own heat blocking the channels spreading all over the body with aggravation producing Jwara. Fever is induced by endogenous pyrogen from inflammatory cells (cytokines mainly IL-1 and IL-6 denote necrosis factors and others). The endogenous pyrogen increases the set point of the hypothalamic center through the action of prostaglandin E-2, produced by cyclooxygenase is regarded as principal mediator for fever.
Jwara is vitiated Tridosa Janya Vyadhi (diseases due to Tridosha), in which vitiated Amashayagat Agni (digestive fire in stomach and intestine) spreads all over the body and blocks the channels. Hence, treatment principle of Jwara suggest drugs which suppress the vitiated Vatadidoshas, possess Deepana (appetizer)-Pachana (digestant) action, resulting in improvement of Agni and thereby Shamana of Ama dosha (biotoxin) should be used. MR contains Deepana (appetizer), Pachana (digestant) Dravyas such as Hingula, Gandhaka, Tankana, Pippali, Maricha, and Ardraka. Katu (pungent taste) and Madhura Rasa (sweet taste) having Ushana Virya (hot potency) dominating formulations are given in Jwara because Katu Rasa (pungent) is Kapha Shamaka, Agni deepana, and Shroto Vivarana. Katu Rasa (Pungent) and Ushnavirya (hot potency) dravyas of Mritujaya rasa include Hingula, Rasa sindoora, Tankana, Pippali, and Adraka expels the vitiated Doshas from the Srotasa. Madhura Rasa (Sweet taste) is Vata-Pitta Shamaka (calms Vata-Pitta) and Trishna Prashmana (controlling thirst). MR also contains Madhura Rasa (sweet taste) ingredients such as Gandhaka and Vatsanabha that nourishes Soumyadhatu (mild tissue elements) and Trushna (thirst). Ushana Virya is Vata-Kaphahara (alleviate Vata and Kapha) and having systemic effects such as Deepana (appetizer), Pachana (digestant), and Swedana (to sweat). Hingula,, Gandhaka, Rasa Sindoora, Tankana, Maricha, and Vatsanabha are Ushnaveerya (Hot potency) Dravyas present in the formulation that diminishes the Doshas, improves Agni (Digestive Fire) and blocking of Srotasa by Ama. Phytoconstituents present in the herbal drugs contains glycosides that may be related to Madhura Rasa (sweet taste) while volatile oils and bitter alkaloids may be related to Katu Rasa (pungent taste) and Ushnaveerya (Hot potency). An effective antipyretic agent might interrupt aggregation pyrooxygenesis at any state that connects peripheral information or it may depress central pyrogenic signals or it may affect both. Hence, by their Amapachana activity, Ayurvedic drug induces antipyretic effect.
| Conclusion|| |
All drug-tested groups showed highly significant result at an interval of ½ h after dose administration, and only MR C showed a significant result to reduce rectal temperature up to 3 h, which was not seen in other groups, as onset of therapeutic action and duration of therapeutic action of Ayurvedic formulation are believed to be more.
The results of the present study shows the importance of mercury for intensifying the therapeutic efficacy of a formulation as encouraging results were obtained in groups treated with Hingula; Kajjali, or Rasasidura, with best results obtained in Rasasindura containing group. It is self-explaining about the importance of the concept of Gandhaka Jarana in Parada.
Limitation of the study
In the present study, pyrexia was induced by Brewer's yeast, which induces fever after 9–18 h of administration. Hence, it is very much important to develop a model which may increase the temperature within the interval of 4–5 h after administration to test the classical Ayurvedic formulations used as an antipyretic agent.
The whole study is preliminary in nature and needs a broad outline of research in the future with more scientific criteria.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]