Evaluation of anti-obesity activity of Lantana camara var Linn on butter induced Hyperlipidemia in Rats

Rohit Gundamaraju¹*, Diana Vivian Atigari¹, Mrs. D. S. Helen Sheeba¹, Dr. Ramesh C.²

¹Department of Pharmacology, Malla Reddy Institute of Pharmaceutical Sciences, Maisammaguda, Dhulapally (Post via Hakimpet), Secunderabad (500014) AP, India.

²GSN Pharmaceuticals Pvt. Ltd., Rajeev Gandhi Nagar, Kukatpally, Hyderabad (500072), AP, India.

ABSTRACT:

The hypolipidemic activity of Lantana camara was studied on high fat diet induced models of hyperlipedemia in rats. Hyper lipidemia condition established by butter was evidenced by enhancement in levels of cholesterol, tri-glycerides, LDL, VLDL. Methanolic extract showed significant hypolipidemic effect by lowering of serum levels of serum cholesterol, TG, LDL, VLDL and increased dl level. Ethanobotanical knowledge of medicinal plants is some of the most prominent source of new drugs and has shown potential results for treatment of obesity. Prelimnary phytochemical analysis revealed thye presence of phyto constituents such as steroids, flavinoids, alkaloids.

KEYWORDS: High fat diet, Lantana camara, obesity.

INTRODUCTION:

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduce the life expectancy. Obesity is the mother of all diseases and thus increases the likelihood of various diseases, particularly heart diseases, type 2 diabetics, osteoarthritis.

Hyperlipidemia contributes significantly in the manifestation and development of atherosclerosis and coronary heart diseases (CHD). Atherosclerosis, are the most common cause of mortality and morbidity worldwide. Although several factors, such as diet high in saturated fats and cholesterol, age, family history, hypertension and life style play a significant role in causing heart failure.¹

Lantana camara is basically a weed in which there are about 650 varieties in over 60 countries. L. camara is a low erect or subcondent, vigorous shrub with stout recurved prickles and strong odour of black current. L. camara has several uses and in some areas as firewood. Several studies have been conducted on this plant, and the plant is reported to have activities like anti-microbial, anti-bacterial, anti-diabetic, insecticidal activity.

The high levels of cholesterol is mainly responsible for onset of chronic heart diseases. A 20% reduction in blood cholesterol can decrease about 31 % of chronic heart disease. The lipid lowering drugs such as fibrates, statins, have many adverse effects. Thus, there is a considerable interest in development of lipid lowering drugs from natural products as they are found to have less adverse effects.²

MATERIALS AND METHODS:

Collection of plant materials: Lantana camara whole plants materials were collected from Tirupathi. The plant authentication was done by Department of Botany, Sri Venkateshwara University, Tirupathi Dist. Chittoor, Andhra Pradesh, and the voucher was preserved.

Preparation of the extract: Leaves of Lantana camara were shade dried at room temperature for 2-3 days. These dried leaves were then powdered in a mixture. The extraction process was done in a Soxhlet extractor. The fine powder (100 grams) was suspended in (200 ml) of methanol for 24 hours at room temperature. After extraction, the solvent was evaporated by rotary evaporator and the residue was dried.

Experimental animals: Healthy adult albino rats of Wister strain weighing 150-200g were used in the present study. The experiment was performed after the granting of the institutional animal ethical committee approval. The animals were properly housed under natural photo periodic conditions and atmospheric conditions along with access to food and water ad labitum throughout the study.

Preliminary Phytochemical analysis: The methanol extract of Lantana camara was subjected to preliminary phytochemical analysis to assess the presence of various phytoconstituents; it revealed the presence of flavonoids, alkaloids and glycosides. ³ Healthy young male albino rats (150-200 gm) were used from animal house of GSN Pharma Pvt. Ltd. The groups of rats were kept separately individual stainless steel hoppers. The test animals should be characterized by strain, source, sex, weight and age. The animals were kept individually for feeding in conventional laboratory diets with an unlimited supply of drinking water.

Obesity inducer: In this experiment butter was mainly used as the inducer of obesity in animal procured from Hyderabad. 400mg of butter/kg b. wt dissolved in 10ml of buffered saline was used for the induction.

Experimental design: Group 1 was considered as control group which received only the vehicle (0. 5% sodium carboxy methyl cellulose; Group 2 was considered as the high fat diet group which received the butter. Group 3 was considered as 1st test group and received the test extract that is methanolic extract of 250mg/kg weight per oral along with butter. Group 4 was considered as 2nd test group and received the test extract that is methanolic extract of 500mg/kg weight per oral along with butter. Group 5 was considered as standard group which received the standard drug atorvostatin (10mg/kg) along with butter.

Sample collection: At the end of 21st day blood was collected from the retro orbital plexus after overnight fasting and then was centrifuged and the serum was obtained and was estimated for the total cholesterol, LDL, VLDL, HDL.

Statistical Analysis: Results were presented as mean± SD. The significance of difference among the groups were assessed using one way analysis of variance (ANOVA) followed by Dunken’s Multiple Reliance test using SPSS software. P_0. 05 was considered significant.

RESULTS:

The preliminary phyto chemical screening revealed the presence of phytochemical constituents such as glycosides, alkaloids, flavanoids, steroids, tanins in the methanolic extract of Lantana camara.

Sr. No.

Test

Constituents of Lantana camara

Alkaloids

Carbohydrates

Saponins

Tanins

Terpenoids

Flavinoids

Glycosides

+indicates presence and – indicates absence

DISCUSSION:

Obesity is the major and health problem in India and developing countries, which leads to important risk factors like arthrosclerosis, stroke etc. Obesity increases the likelihood of other diseases. Obesity evokes the damages in various tissue, which in turn, deregulates the cellular functions leading to damage to various pathological conditions.

Obesity is a leading preventable cause of death worldwide, with increasing prevalence in adults and children, and authorities view it as one of the most serious public health problems of the 21st century. Obesity is stigmatized in much of the modern world (particularly in the Western world), though it was widely perceived as a symbol of wealth and fertility at other times in history, and still is in some parts of the world.⁴

The present studies were performed to assess the hypolipidemic activity and to prove its claim in folklore practice against various disorders. Probucol, a hypolipidemic drug is a potent lipophilic antioxidant and the ability to inhibit atherosclerosis has been attributed to its antioxidant properties. Probucol lowers the level of cholesterol in the bloodstream by increasing the rate of LDL catabolism. Additionally, probucol may inhibit cholesterol synthesis and delay cholesterol absorption. Probucol is a powerful antioxidant, which inhibits the oxidation of cholesterol in LDLs, this slows the formation of foam cells, which contribute to atherosclerotic plaques. Similarly, flavonoids present in the plant Lantana camara may be responsible for its hypolipidemic action and as already reported significant antioxidant activity of chloroform extract further confirms its significant hypolipidemic activity.

Table : Effect of Lantana camara on biochemical parameters

S. No Groups	Total Cholesterol (mg/dl)	Triglyceride(mg/dl)	HDL(mg/dl)	LDL(mg/dl)	VLDL(mg/dl)
1 Group I
(Control)	158± 1.58	114.0±51.58	60.0 ±1.58	88± .42	24 ±1.47
2 Group II
(Butter Induced)	242.40±40.48	370.0± 1.58	39.0 ±1.59	163±1.69	74.16±1.58
3 Group III
(Plant extract 250mg)	**202.90±1.58	***185.0± 1.58	***42± 1.58	**106±1.78	**35.0±1.58
4 Group IV
(Plant extract 500mg)	***180.0+ 1.48	***168.50+ 1.58	***40+1.58	***110+1.68	***36.0+1.58
5 Group V
(Standard Lovastatin)	***159.20± 1.92	***164.52±1.58	***36.58±1.31	***122± .59	***39 ±1.53

Values are expressed as mean ± SEM. Levels of significance- Group II compared with Group I, III and IV. **p_0.01 and ***p_0.001.

In the above tabular column, the total cholesterol level is at normal levels in the control group, where as it is drastically enhanced in the group II where the animals were induced with butter. The butter was responsible for the increased levels of total cholesterol. In the group III, there is decrease in the levels of cholesterol, and more significant decrease in the levels of cholesterol in the group IV. The group V containing the standard shows much more decrease in the levels of total cholesterol. Triglycerides were at normal levels in the control group, and increased in the group II. Decrease in levels of triglycerides was found in the group III where it was induced by the test drug (250mg). Significant decrease in the levels of triglycerides was found in the group IV where higher doses of test drug has been induced (500mg). Standard drug has shown more significant decrease in the levels of triglycerides. and so are the cases with LDL and VLDL. But in the case of HDL, the levels of HDL in the group II is less than that of control group as it’s the phenomenon of vice versa.

High cholesterol is also referred to as hypercholesterolemia. Cholesterol is a fatty substance that is important part of the outer lining of cells in the body of animals. Cholesterol is also found in the blood circulation of humans. It is also a precursor for the synthesis of steroid hormones. High levels of cholesterol can increase the risk of heart disease.

Cholesterol is synthesized in all animal tissue. It’s important relates to its role in the stabilization of membrane structures because of its rigid planar structure. It also as a precursor for the synthesis of steroid hormones. Increased amount of cholesterol leads to cardiovascular disease particularly coronary heart disease (CHD). ⁵

The plasma cholesterol was reduced remarkably on treating with the HFD rats with methanolic extract of Lantana camara var Linn. Reduction of 1% of cholesterol reduces 2-3% risk of coronary heart disease.⁶

Triglycerides are a type of fat in the bloodstream and fat tissue. Triglyceride (triacylglycerol, TAG or triacylglyceride) is an ester composed of a glycerol bound to three fatty acids. It is the main constituent of vegetable oil and animal fats.⁷

Most of the fats digested by humans are triglycerides. Triglycerides are formed from a single molecule of glycerol, combined with three molecules of fatty acid. The glycerol molecule has three hydroxyl (OH-) groups. Each fatty acid has a carboxyl group (COOH-). In triglycerides, the hydroxyl groups of the glycerol join the carboxyl groups of the fatty acid to form ester bonds.

The enzyme pancreatic lipase acts at the ester bond, hydrolysing the bond and "releasing" the fatty acid. In triglyceride form, lipids cannot be absorbed by the duodenum. Fatty acids, monoglycerides (one glycerol, one fatty acid) and some diglycerides are absorbed by the duodenum, once the triglycerides have been broken down.

Chain lengths of the fatty acids in naturally occurring triglycerides can be of varying lengths, but 16, 18 and 20 carbons are the most common. Natural fatty acids found in plants and animals are typically composed only of even numbers of carbon atoms due to the way they are bio-synthesized from acetyl CoA. Bacteria, however, possess the ability to synthesize odd- and branched-chain fatty acids. Consequently, ruminant animal fat contains odd numbered fatty acids, such as 15, due to the action of bacteria in the rumen.

Most natural fats contain a complex mixture of individual triglycerides. Because of this, they melt over a broad range of temperatures. Cocoa butter is unusual in that it is composed of only a few triglycerides, one of which contains palmitic, oleic, and stearic acids, in order of concentration.

HDL is short for high-density lipoprotein. Each bit of HDL cholesterol is a microscopic blob that consists of a rim of lipoprotein surrounding a cholesterol center. The HDL cholesterol particle is dense compared to other types of cholesterol particles, so it's called high-density.⁸

LDL is a risk factor and plays a role at several steps of artherosclerosis. An LDL particle is a microscopic blob consisting of an outer rim of lipoprotein surrounding a cholesterol center. LDL is called low-density lipoprotein because LDL particles tend to be less dense than other kinds of cholesterol particles. Increasing evidence has revealed that the concentration and size of the LDL particles more powerfully relates to the degree of atherosclerosis progression than the concentration of cholesterol contained within all the LDL particles.⁹

VLDL (very low density lipoprotein) transports cholesterol and triglycerides within the body. It is made in the liver in response to a high-carbohydrate meal. Conditions known to increase levels include diabetes, obesity, and acute hepatitis. It is thought to play a role in atherosclerosis as well. Lifestyle changes and medications are often successful in reducing levels in the blood. These particles are smaller than chylomicrons.

VLDL production is directly related to the body fat. ¹⁰ Severe elevations in the VLDL cholesterol lead to hypercholesterolemia Triglycerides are mainly stored in the adipose tissue. The plasma lipo proteins are major sources of fatty acids to synthesis triacylglycerols. The excess of fat diet increased the TG level which is one of the major causes of damage to the arteries¹¹ and also leads to conditions like artherosclerosis.

CONCLUSION:

In congruence with these results, it may be confirmed that due to the presence of phytoconstituents such as flavanoids, glycosides and alkaloids in the methanolic extract, it could be responsible for the observed significant anti-obesic activity. This activity initially was assessed with the ethano-pharmacological survey, but finally confirmed with the above activity. So the present study proves that the methanolic extract of Lantana camara exhibited a significant Anti-obesic activity.

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Received on 23.08.2012

Modified on 28.08.2012

Accepted on 04.09.2012

Research J. Pharmacology and Pharmacodynamics. 4(5): September –October, 2012, 315-318