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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 4  |  Issue : 1  |  Page : 52-57

Antihyperlipidemic activity of Hridayarnava Rasa (an Ayurvedic herbo-metalo-mineral formulation) in Charles Foster albino rats


1 Central Ayurveda Research Institute for Drug Development, Kolkata, West Bengal, India
2 Pharmacology Laboratory, IPGT and RA, Gujarat Ayurved University, Jamnagar, Gujarat, India
3 Department of Rasashastra and Bhaishajya Kalpana, AIIA, New Delhi, India

Date of Submission15-Dec-2017
Date of Acceptance16-Mar-2018
Date of Web Publication25-May-2018

Correspondence Address:
Swapnil Y Chaudhari
Central Ayurveda Research Institute for Drug Development, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrsm.jcrsm_68_17

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  Abstract 


Background: Hyperlipidemia is modifiable risk factor for cardiovascular diseases, and its prevalence is alarmingly increased in India. Although many treatment modalities are effectively used in the conventional system, they have certain limitations and adverse effects. Ayurvedic metallic and herbo-mineral formulations are safely practiced in Indian subcontinent without any noticeable side effects. Hridayarnava Rasa is one such Ayurvedic herbo-metalo-mineral formulation containing Tamra Bhasma (incinerated copper) as an integral component that is being successfully prescribed in the management of lipid disorders.
Materials and Methods: Tamra Bhasma is prepared with different Amritikarana methods which are said to eliminate all the blemishes from the end product and increases its therapeutic efficacy. The antihyperlipidemic activity of Hridayarnava Rasa prepared from Tamra Bhasma processed in Panchamrita (HRTBP) was carried out in Charles Foster albino rats having hyperlipidemia induced by high-fat diet. The parameters including body weight, organ weight, serum lipid profile, and histopathology of liver, heart, kidney, and aorta were studied.
Results and Coclusion: Results revealed that HRTBP attenuated increased lipid profile and pathological changes in heart, liver, and kidney induced by administration of hyperlipidemic diet. Hridayarnava Rasa has shown mild antihyperlipidemic activity in experimental animals.
Background: Hyperlipidemia is modifiable risk factor for cardiovascular diseases, and its prevalence is alarmingly increased in India. Although many treatment modalities are effectively used in the conventional system, they have certain limitations and adverse effects. Ayurvedic metallic and herbo-mineral formulations are safely practiced in Indian subcontinent without any noticeable side effects. Hridayarnava Rasa is one such Ayurvedic herbo-metalo-mineral formulation containing Tamra Bhasma (incinerated copper) as an integral component that is being successfully prescribed in the management of lipid disorders.
Materials and Methods: Tamra Bhasma is prepared with different Amritikarana methods which are said to eliminate all the blemishes from the end product and increases its therapeutic efficacy. The antihyperlipidemic activity of Hridayarnava Rasa prepared from Tamra Bhasma processed in Panchamrita (HRTBP) was carried out in Charles Foster albino rats having hyperlipidemia induced by high-fat diet. The parameters including body weight, organ weight, serum lipid profile, and histopathology of liver, heart, kidney, and aorta were studied.
Results and Coclusion: Results revealed that HRTBP attenuated increased lipid profile and pathological changes in heart, liver, and kidney induced by administration of hyperlipidemic diet. Hridayarnava Rasa has shown mild antihyperlipidemic activity in experimental animals.

Keywords: Amritikarana, Ayurveda, Hridayarnava Rasa, Hyperlipidemia, Rasashastra


How to cite this article:
Chaudhari SY, Nariya MB, Ruknuddin G, Prajapati PK, Hazra J. Antihyperlipidemic activity of Hridayarnava Rasa (an Ayurvedic herbo-metalo-mineral formulation) in Charles Foster albino rats. J Curr Res Sci Med 2018;4:52-7

How to cite this URL:
Chaudhari SY, Nariya MB, Ruknuddin G, Prajapati PK, Hazra J. Antihyperlipidemic activity of Hridayarnava Rasa (an Ayurvedic herbo-metalo-mineral formulation) in Charles Foster albino rats. J Curr Res Sci Med [serial online] 2018 [cited 2018 Jul 19];4:52-7. Available from: http://www.jcrsmed.org/text.asp?2018/4/1/52/233204




  Introduction Top


Cardiovascular diseases are estimated to account for 26% of mortality caused due to noncommunicable diseases in India.[1] Raised lipid levels are well documented as a major predictive risk factors for cardiovascular diseases and atherosclerosis.[2],[3] About 79% of the general adult population has abnormalities in at least one of the lipid parameters with no urban-rural difference observed in India.[4] Statins and fibrates are the most promising drugs used as hypolipidemic agents. Their clinical efficacy on hyperlipidemia is also widely reported.[5],[6] However, the use of these synthetic drugs has certain adverse effects. Although statins are well tolerated by patients, they cause hepatopathy, renal failure, increased risk of diabetes, and rhabdomyolysis in rare cases.[7],[8] Considering the wide magnitude of lipid disorders in Indian subcontinent and absence of promising therapy with safety in conventional systems; suffering population is turning toward certain other alternatives for safe and effective remedies. Ayurveda, an ancient medical system of Indian subcontinent with its armamentarium exclusively deals with therapeutic use of herbals, metals, minerals after application of certain pharmaceutical procedures in a comprehensive way. These herbo-mineral formulations are safely practiced since ages without any noticeable adverse effects. Hridayarnava Rasa, one such herbo-metalo-mineral compound formulation containing Tamra Bhasma (incinerated copper) as an integral component is indicated in the treatment of abnormal lipid levels. Previous studies reported safety of both Tamra Bhasma and Hridayarnava Rasa in experimental animals up to genotoxic level.[9],[10],[11],[12] Lipids and cholesterol are directly related to cardiac diseases. Tamra (copper) is reported as Medopaha (destroyer of fats/lipids), Lekhana (scraps excessive fat), and Sthoulyahara (anti-obesity) in Ayurvedic treatises.[13],[14],[15] A special role of copper in lipid metabolism and its deficiency raises blood cholesterol. Diet high in copper has a beneficial effect on blood cholesterol.[16] These references directly indicate the impact of copper as a lipid-lowering agent. The antihyperlipidemic activity of Tamra Bhasma is also well reported.[17],[18] However, studies on a formulation with Tamra Bhasma as a component are not available. Considering this, the study is aimed to evaluate antihyperlipidemic activity of Hridayarnava Rasa in Charles Foster albino rats.


  Methodology Top


Test drugs

Tamra Bhasma preparation

Tamra Bhasma was prepared by following standard guidelines as prescribed in Ayurvedic classics. Copper scraps with 99.89% pure copper were procured from local industrial area, Jamnagar, India. It was subjected to general and specific processing procedures followed by incineration by mixing with Shuddha Gandhaka (processed sulfur), Kajjali (black sulfide of mercury), and juice of Citrus jambhiri Lush.[19] In Amritikarana, it was mixed with half part processed sulfur and Panchamrita. It was subjected to heat treatment and the Amritikarana procedure was repeated for two more times.[20]

Preparation of Hridayarnava Rasa

Hridayarnava Rasa was prepared by triturating equal proportions of Kajjali (black sulfide of mercury) and Tamra Bhasma with the decoction of Triphala (three myrobalans) and juice of Solanum nigrum Linn. It was labeled as Hridayarnava Rasa prepared from Tamra Bhasma processed in Panchamrita (HRTBP).[21]

Animals

Charles Foster adult albino rats (200 ± 20 g) of either sex were procured and housed in animal house attached to the Pharmacology Laboratory, IPGT and RA, Gujarat Ayurved University, Jamnagar and were exposed to natural day and night cycles with ideal laboratory conditions in terms of ambient temperature (23°C ± 2°C) and humidity (50%–60%). Animals were fed ad libitum with Amrut brand rat pellet feed supplied by Pranav Agro Industries and tap water. The experiment was carried out after obtaining permission from the Institutional Animal Ethics Committee/17/2015/02 and ethical norms approved by Committee for the Purpose of Control and Supervision of Experiments on Animals guidelines.

Dose fixation

The therapeutic clinical dose of Hridayarnava Rasa is 125 mg twice a day (250 mg/day).[22] The suitable dose for rats was calculated by referring to the table of Paget and Barnes and was found to be 22.5 mg/kg body weight of rat.[23] The test drug was administered orally along with honey (1 ml/kg) as an adjuvant with the help of gastric catheter sleeved to syringe.

Acute toxicity study

Young, healthy, nulliparous, nonpregnant Charles Foster albino female rats were selected and acclimatized for 7 days before the experiment. HRTBP along with honey as an adjuvant was orally administered at limit dose of 2000 mg/kg to overnight fasted rats by following the Organization for Economic Cooperation and Development 425 guidelines.[24] The rats were observed closely for behavioral changes, signs, and symptoms of toxicity and mortality, if any continuously for the first 6 h and thereafter periodically up to 14 days.

Antihyperlipidemic activity

Charles Foster albino rats were randomly grouped into four, each consisting of six rats comprising three males and three females. Group I was served as normal control (NC) that only received regular rat diet and water. Group II received hyperlipidemic diet and served as cholesterol control (CC). Group III received hyperlipidemic diet and honey, while Group IV received hyperlipidemic diet and HRTBP at a dose of 22.5 mg/kg. Test drug was administered at morning hours and hyperlipidemic diet was administered at evening hours for 20 consecutive days. Hyperlipidemic diet consists of hydrogenated vegetable oil (Vanaspati Ghee-Raag brand, Batch No. 46AO VAO5E07, Adani Wilmar Ltd., Gujarat) and well-pulverized cholesterol extra pure powder (Batch No. 7245739, Sisco Research Laboratories, Taloja, Maharashtra, India) made into 20% suspension in coconut oil (Parachute coconut oil, Batch No. HQ210, Goa). The suspension was administered at the dose of 0.5 ml/100 g rat. On the 21st day, after overnight fasting, the animals were weighed and blood was collected from retro-orbital plexus under light ether anesthesia.[21] Blood serum was assessed for total cholesterol, high-density lipoprotein-cholesterol, triglyceride, very low-density lipoprotein (VLDL)-cholesterol, and LDL-cholesterol by an autoanalyzer (Fully automated Biochemical Random Access Analyzer, BS-200, Lilac Medicare Pvt. Ltd., Mumbai, Maharashtra, India).[25],[26],[27] Then, the rats were sacrificed with an overdose of diethyl ether anesthesia and the abdomen was opened through midline incision to record the autopsy changes followed by dissecting out the important organs such as the liver, kidney, heart, and aorta. After noting signs of gross lesions and ponderal changes of major organs; all were transferred to 10% phosphate-buffered formalin solution for fixation and later on subjected to dehydrating, wax embedding, sectioning, and staining with hematoxylin and eosin for histological evaluation. The slides were viewed under trinocular research Carl-Zeiss's microscope at various magnifications to note down the changes in the microscopic features of the tissues.

Statistical analysis

Results of the study were expressed as mean ± standard error of mean for six rats per experimental group. Data were analyzed using both paired, unpaired student's t-test and one-way analysis of variance to compare the mean values of quantitative variables among the groups followed by Holm–Sidak test for unpaired data using Sigma stat 3.5 software to determine significant difference between groups at P < 0.05.


  Results Top


Acute toxicity study

The results showed that HRTBP along with adjuvant did not affect any behavioral changes and other parameters during entire experimental period of 14 days. It did not show any signs and symptoms of toxicity and mortality when given orally at a dose of 2000 mg/kg.

Anti-hyperlipidemic study

Behavioral changes were not observed in treated groups during the antihyperlipidemic study in comparison to control group. No mortality was observed in CC, vehicle control (VC), and Hridayarnava Rasa groups. Weight gain was observed in NC rats during antihyperlipidemic study. Significant weight gain was observed in HRTBP-treated group, but percentage change in weight pattern did not differ significantly from the changes observed in CC and VC groups [Table 1]. Relative weight of heart, liver, and kidney was measured to assess effect of HRTBP on organ weight. Administration of hyperlipidemic diet did not alter weight of heart and liver to significant extent except significant decrease was observed in relative weight of kidney in CC group when compared with NC group [Table 2].
Table 1: Effect of Hridayarnava Rasa on body weight

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Table 2: Effect of Hridayarnava Rasa on relative organ weight

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Administration of hyperlipidemic diet resulted in increase in serum levels of cholesterol, triglycerides, LDL, and VLDL in CC group on comparison to NC group.

HRTBP showed attenuation of total cholesterol, triglycerides, and VLDL levels in hyperlipidemic rats when compared with diet-induced hyperlipidemic control at 21st day [Table 3]. The histopathological study evaluated normal cytoarchitecture in the liver, kidney, heart, and aorta in NC group [Figure 1]a, [Figure 1]e and [Figure 2]a, [Figure 2]e. Hyperlipidemic diet produced mild-to-moderate pathological changes in these organs such as rupture of endothelium and recruitment of cells in aorta, fatty changes in heart, sinusoidal inflammation and fatty changes with cell migration in liver and fatty changes, and cell infiltration in kidney. Some sections of aorta in CC group showed increase in adventitia [Figure 1]b, [Figure 1]f and [Figure 2]b, [Figure 2]f. These pathological changes were also observed to lesser magnitude in VC group [Figure 1]c, [Figure 1]g and [Figure 2]c, [Figure 2]g. HRTBP-treated group showed almost normal cytoarchitecture in heart, liver, and kidney except mild erosion of endothelium in the aorta [Figure 1]d, [Figure 1]h and [Figure 2]d, [Figure 2]h.
Table 3: Effect of Hridayarnava Rasa on biochemical parameters

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Figure 1: Photomicrographs of sections of the liver and kidney. Photomicrographs of the liver tissues taken at ×400. (a) Normal cytoarchitecture in control group. (b) Sinusoidal inflammation, fatty changes, and cell migration in cholesterol control. (c) Mild fatty changes and cell migration in sinusoidal in vehicle control group. (d) Almost normal cytoarchitecture in Hridayarnava Rasa prepared from Tamra Bhasma processed in Panchamrita group. Photomicrographs of kidney tissues taken at ×400. (e) Normal cytoarchitecture in control group. (f) Fatty changes and cell infiltration in cholesterol control. (g) Fatty changes and cell infiltration in vehicle control group. (h) Almost normal cytoarchitecture in Hridayarnava Rasa prepared from Tamra Bhasma processed in Panchamrita group

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Figure 2: Photomicrographs of sections of heart and aorta. Photomicrographs of the heart tissues taken at ×400. (a) Normal cytoarchitecture in control group. (b) Moderate fatty changes and cell recruitment in cholesterol control. (c) Almost normal cytoarchitecture in vehicle control group. (d) Almost normal cytoarchitecture in Hridayarnava Rasa prepared from Tamra Bhasma processed in Panchamrita group. Photomicrographs of the aorta tissues taken at ×400 magnification. (e) Normal cytoarchitecture in Control group. (f) Rupture of endothelium and recruitment of cells, increase in adventitia in cholesterol control. (g) Mild erosion of endothelium and loss of adventitia in vehicle control group. (h) Mild erosion of endothelium in Hridayarnava Rasa prepared from Tamra Bhasma processed in Panchamrita group

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  Discussion Top


Atherosclerosis is characterized by the accumulation of lipid in the arterial wall resulting in narrowing of the vessel lumen becoming major cause of coronary artery diseases (CAD).[28] Lipid metabolism disorders have strong linkage in the development and progression of CAD and become risk factors in the manifestation of atherosclerosis.[29],[30] Diet-induced hyperlipidemia in animal model are considered to be useful in evaluating antihyperlipidemic activity. Administration of hyperlipidemic diet led to significant increase in body weight of CC group albino rats when compared to NC rats. Serum cholesterol levels increase by accelerating the biosynthesis of saturated fats in the diet when taken in excess, whereas diet containing polyunsaturated fatty acids lowers the cholesterol level.[31],[32] Administration of hyperlipidemic diet leads to significant decrease in relative weight of kidney when compared to NC group. HRTBP is administered with honey as an adjuvant.[22] HRTBP significantly attenuated hyperlipidemic diet-induced weight gain when compared with CC group. It indicates antagonizing effect of test drug against hyperlipidemic diet-induced changes in the body weight. Administration of hyperlipidemic diet resulted in increase in the serum levels of cholesterol, triglycerides, LDL, and VLDL. Increased serum levels of cholesterol, triglycerides, and VLDL levels were attenuated in the animals treated with HRTBP, but the results were found to be statistically insignificant. The observed antihyperlipidemic activity of HRTBP is further evidenced through the histopathological study of liver, heart, kidney, and aorta. Organs from HRTBP-treated group showed significant attenuation effect on hyperlipidemic diet-induced pathological changes showing their normal architecture presentation. The above antihyperlipidemic profile revealed that HRTBP not only reverses hyperlipidemic diet-induced abnormal lipid levels and pathological changes in the liver, heart, and kidney but also showed normal cytoarchitecture in rats. Thus, it is inferred that drug is devoid of any serious toxic effects by histopathological observations.

Vehicle honey is reported to possess antihyperlipidemic and antioxidant activities.[33],[34] Vehicle-treated group also showed pathological changes to some extent in histopathological studies, which shows that the activity shown by the HRTBP can be attributed to the drug and also can be considered as the synergistic effect of drug with honey. VLDL transports endogenous triglycerides. Reduction in triglyceride level is consistent with reduction in VLDL (similar percentage reduction of both markers in either group), suggesting probably transport of endogenous triglycerides by VLDL to peripheral tissues may be one among antihyperlipidemic mechanisms of HRTBP.[35]

Copper deficiency and overload have multiple and significant effects on systemic and cellular lipid metabolism. Studies have proven that copper misbalance is an emerging factor in hyperlipidemia and they revealed association of copper deficiency and lipid metabolism.[36],[37],[38] Some of the cardiac pathology caused by copper deficiency could be linked to the lysyl oxidase deficiency, which is a copper-dependent enzyme involved in the cross-linking of collagen and elastin.[39]Tamra Bhasma, rich source of copper, is an integral component in Hridayarnava Rasa possesses antihyperlipidemic, antioxidant, lipid peroxidation, and free-radical scavenging activities.[40],[41] The other ingredients of Hridayarnava Rasa like three myrobalans and Solanum nigrum Linn. possess different pharmacological actions that are anticipated to play a key role in antihyperlipidemic activity of Hridayarnava Rasa. The observed antihyperlipidemic activity of Hridayarnava Rasa may be due to its one of above mentioned pharmacological actions.

HRTBP has shown mild antihyperlipidemic activity at therapeutic dose levels as it reverted increasedlipid levels and pathological changes induced in heart, liver, and kidney due to hyperlipidemic diet. Acute toxicity demonstrated that Hridayarnava Rasa at a dose of 2000 mg/kg orally did not produce any observable toxic effects and mortality suggesting LD50 value may be higher than 2000 mg/kg by oral route and can be categorized as substances with low health hazard potential. Hridayarnava Rasa can be safely used at therapeutic dose level in the management of lipid disorders with specific adjuvant.

Financial support and sponsorship

This study was financially supported by Institute for Postgraduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar 361008.

Conflicts of interest

There are no conflicts of interest.



 
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