hypolipidemic activity of nathaichoori chooranam (nc) (siddha drug) on high fat diet induced...
Upload: international-journal-of-pharmacy-research-and-science-ijprsonline
Post on 07-May-2015
164 views
DESCRIPTION
Abstract: Hyperlipidemia is a major risk factor in the initiation and progression of atherosclerotic lesions, conditions such as coronary heart disease, ischemic cerebrovascular disease and peripheral vascular disease. This leads to high mortality and morbidity rate in developed countries. This is mainly due to altered lipoprotein metabolism. Standard treatments for Hyperlipidemia & dyslipidemia with statins and with the other available agents have adverse effects. Thus, there is more need for development of newer pharmacological agents which are more efficient in lowering LDL Cholesterol and Triglycerides. The hypolipidemic activity of Nathaichoori Chooranam was studied on high fat diet induced hyperlipidemic rats. Hyperlipidemia in experimental rats was evidenced by an enhancement in the levels of Cholesterols, Triglycerides, LDL and VLDL. The trial drug showed significant hypolipidemic effect by lowering the serum levels of biochemical parameters, such as significant reduction in the level of serum Cholesterol, TGL, LDL, VLDL and increase in HDL level which was similar to the standard drug atorvastatin. So, it is concluded that the Nathaichoori chooranam can be used in the treatment of Hyperlipidemia and Obesity.TRANSCRIPT
Int. J. Pharm. Res. Sci., 2014, 02(1), 104-109. www.ijprsonline.com ISSN: 2348 –0882==============================================================================
104
Hypolipidemic activity of Nathaichoori Chooranam (NC) (Siddha drug) on High fat diet InducedHyperlipidemic Rats.
K Kanakavalli1,*, S Thillaivanan2, P Parthiban3
1. Prof &. H.O.D, U.G. Pothu Maruthuvam Dept, GSMC, Chennai.2. Asst. Medical Officer (Siddha), GPHC, Jamunamarathur.3. Prof & H.O.D, P.G. Pothu Maruthuvam Dept, GSMC, Chennai.
Corresponding Author Mail.id: drkkanakavalli@gmail.com.------------------------------------------------------------------------------------------------------------------------------
Abstract:Hyperlipidemia is a major risk factor in theinitiation and progression of atherosclerotic lesions,conditions such as coronary heart disease, ischemiccerebrovascular disease and peripheral vasculardisease. This leads to high mortality and morbidityrate in developed countries. This is mainly due toaltered lipoprotein metabolism. Standard treatmentsfor Hyperlipidemia & dyslipidemia with statins andwith the other available agents have adverse effects.Thus, there is more need for development of newerpharmacological agents which are more efficient inlowering LDL Cholesterol and Triglycerides. Thehypolipidemic activity of Nathaichoori Chooranam(NC) was studied on high fat diet inducedhyperlipidemic rats. Hyperlipidemia in experimentalrats was evidenced by an enhancement in the levelsof Cholesterols, Triglycerides, LDL and VLDL.The trial drug showed significant hypolipidemiceffect by lowering the serum levels of biochemicalparameters, such as significant reduction in the levelof serum Cholesterol, TGL, LDL, VLDL andincrease in HDL level which was similar to thestandard drug atorvastatin. So, it is concluded thatthe Nathaichoori chooranam can be used in thetreatment of Hyperlipidemia and Obesity.
KEYWORDS: Spermacocce hispida, atorvastatin,Rubiaceae, Lipid lowering agent, Siddha medicine,Atherosclerosis, Obesity.Introduction:
Hyperlipidemia contributes significantly in themanifestation and development of atherosclerosisand coronary heart diseases (CHD).Atherosclerosis is the most common cause ofmortality and morbidity worldwide. Althoughseveral factors, such as diet high in saturated fatsand cholesterol, age, family history, hypertensionand life style play a significant role in causing heartfailure [1]. The high levels of cholesterolparticularly TC, TG and LDL cholesterol is mainlyresponsible for the onset of CHDs. A 20%reduction of blood cholesterol level can decreaseabout 31% of CHD incidence, and 33% of itsmortality rate. The known lipid lowering drugs,such as fibrates, statins and bile acid sequestrantshave many side effects in patients [2]. Thus, thereis a considerable interest on development oflipid lowering drugs from natural products in therecent years.Spermacocce hispida Linn (Family-Rubiaceae)(Tamil Name- Nathaichoori, Kuzhimeettan) hasbeen extensively used in siddha system of medicinefor various ailments like stomach disorders,Diabetes, Skin diseases, Bronchial asthma etc. Theflowers have been used to boils, eruptions, tumors,swelling etc. The whole plant is used for medicinalproperties; it is widely distributed in the WesternGhats of Kerala and in Tamilnadu [3]. The seeds ofthe plants are used as coolant, demulcent, and givenfor diarrhea and dysentery. Seeds have been
Int. J. Pharm. Res. Sci., 2014, 02(1), 104-109. www.ijprsonline.com ISSN: 2348 –0882==============================================================================
104
Hypolipidemic activity of Nathaichoori Chooranam (NC) (Siddha drug) on High fat diet InducedHyperlipidemic Rats.
K Kanakavalli1,*, S Thillaivanan2, P Parthiban3
1. Prof &. H.O.D, U.G. Pothu Maruthuvam Dept, GSMC, Chennai.2. Asst. Medical Officer (Siddha), GPHC, Jamunamarathur.3. Prof & H.O.D, P.G. Pothu Maruthuvam Dept, GSMC, Chennai.
Corresponding Author Mail.id: drkkanakavalli@gmail.com.------------------------------------------------------------------------------------------------------------------------------
Abstract:Hyperlipidemia is a major risk factor in theinitiation and progression of atherosclerotic lesions,conditions such as coronary heart disease, ischemiccerebrovascular disease and peripheral vasculardisease. This leads to high mortality and morbidityrate in developed countries. This is mainly due toaltered lipoprotein metabolism. Standard treatmentsfor Hyperlipidemia & dyslipidemia with statins andwith the other available agents have adverse effects.Thus, there is more need for development of newerpharmacological agents which are more efficient inlowering LDL Cholesterol and Triglycerides. Thehypolipidemic activity of Nathaichoori Chooranam(NC) was studied on high fat diet inducedhyperlipidemic rats. Hyperlipidemia in experimentalrats was evidenced by an enhancement in the levelsof Cholesterols, Triglycerides, LDL and VLDL.The trial drug showed significant hypolipidemiceffect by lowering the serum levels of biochemicalparameters, such as significant reduction in the levelof serum Cholesterol, TGL, LDL, VLDL andincrease in HDL level which was similar to thestandard drug atorvastatin. So, it is concluded thatthe Nathaichoori chooranam can be used in thetreatment of Hyperlipidemia and Obesity.
KEYWORDS: Spermacocce hispida, atorvastatin,Rubiaceae, Lipid lowering agent, Siddha medicine,Atherosclerosis, Obesity.Introduction:
Hyperlipidemia contributes significantly in themanifestation and development of atherosclerosisand coronary heart diseases (CHD).Atherosclerosis is the most common cause ofmortality and morbidity worldwide. Althoughseveral factors, such as diet high in saturated fatsand cholesterol, age, family history, hypertensionand life style play a significant role in causing heartfailure [1]. The high levels of cholesterolparticularly TC, TG and LDL cholesterol is mainlyresponsible for the onset of CHDs. A 20%reduction of blood cholesterol level can decreaseabout 31% of CHD incidence, and 33% of itsmortality rate. The known lipid lowering drugs,such as fibrates, statins and bile acid sequestrantshave many side effects in patients [2]. Thus, thereis a considerable interest on development oflipid lowering drugs from natural products in therecent years.Spermacocce hispida Linn (Family-Rubiaceae)(Tamil Name- Nathaichoori, Kuzhimeettan) hasbeen extensively used in siddha system of medicinefor various ailments like stomach disorders,Diabetes, Skin diseases, Bronchial asthma etc. Theflowers have been used to boils, eruptions, tumors,swelling etc. The whole plant is used for medicinalproperties; it is widely distributed in the WesternGhats of Kerala and in Tamilnadu [3]. The seeds ofthe plants are used as coolant, demulcent, and givenfor diarrhea and dysentery. Seeds have been
Int. J. Pharm. Res. Sci., 2014, 02(1), 104-109. www.ijprsonline.com ISSN: 2348 –0882==============================================================================
104
Hypolipidemic activity of Nathaichoori Chooranam (NC) (Siddha drug) on High fat diet InducedHyperlipidemic Rats.
K Kanakavalli1,*, S Thillaivanan2, P Parthiban3
1. Prof &. H.O.D, U.G. Pothu Maruthuvam Dept, GSMC, Chennai.2. Asst. Medical Officer (Siddha), GPHC, Jamunamarathur.3. Prof & H.O.D, P.G. Pothu Maruthuvam Dept, GSMC, Chennai.
Corresponding Author Mail.id: drkkanakavalli@gmail.com.------------------------------------------------------------------------------------------------------------------------------
Abstract:Hyperlipidemia is a major risk factor in theinitiation and progression of atherosclerotic lesions,conditions such as coronary heart disease, ischemiccerebrovascular disease and peripheral vasculardisease. This leads to high mortality and morbidityrate in developed countries. This is mainly due toaltered lipoprotein metabolism. Standard treatmentsfor Hyperlipidemia & dyslipidemia with statins andwith the other available agents have adverse effects.Thus, there is more need for development of newerpharmacological agents which are more efficient inlowering LDL Cholesterol and Triglycerides. Thehypolipidemic activity of Nathaichoori Chooranam(NC) was studied on high fat diet inducedhyperlipidemic rats. Hyperlipidemia in experimentalrats was evidenced by an enhancement in the levelsof Cholesterols, Triglycerides, LDL and VLDL.The trial drug showed significant hypolipidemiceffect by lowering the serum levels of biochemicalparameters, such as significant reduction in the levelof serum Cholesterol, TGL, LDL, VLDL andincrease in HDL level which was similar to thestandard drug atorvastatin. So, it is concluded thatthe Nathaichoori chooranam can be used in thetreatment of Hyperlipidemia and Obesity.
KEYWORDS: Spermacocce hispida, atorvastatin,Rubiaceae, Lipid lowering agent, Siddha medicine,Atherosclerosis, Obesity.Introduction:
Hyperlipidemia contributes significantly in themanifestation and development of atherosclerosisand coronary heart diseases (CHD).Atherosclerosis is the most common cause ofmortality and morbidity worldwide. Althoughseveral factors, such as diet high in saturated fatsand cholesterol, age, family history, hypertensionand life style play a significant role in causing heartfailure [1]. The high levels of cholesterolparticularly TC, TG and LDL cholesterol is mainlyresponsible for the onset of CHDs. A 20%reduction of blood cholesterol level can decreaseabout 31% of CHD incidence, and 33% of itsmortality rate. The known lipid lowering drugs,such as fibrates, statins and bile acid sequestrantshave many side effects in patients [2]. Thus, thereis a considerable interest on development oflipid lowering drugs from natural products in therecent years.Spermacocce hispida Linn (Family-Rubiaceae)(Tamil Name- Nathaichoori, Kuzhimeettan) hasbeen extensively used in siddha system of medicinefor various ailments like stomach disorders,Diabetes, Skin diseases, Bronchial asthma etc. Theflowers have been used to boils, eruptions, tumors,swelling etc. The whole plant is used for medicinalproperties; it is widely distributed in the WesternGhats of Kerala and in Tamilnadu [3]. The seeds ofthe plants are used as coolant, demulcent, and givenfor diarrhea and dysentery. Seeds have been
Int. J. Pharm. Res. Sci., 2014, 02(1), 104-109. www.ijprsonline.com ISSN: 2348 –0882==============================================================================
105
recommended as a substitute for coffee. Seeds arecrushed into paste and taken orally to treat stomachproblems [4]. All the parts of the plant have anethno medicinal importance. As Spermacoccehispida (Nathaichoori), plant species have beentraditionally claimed for the treatment ofAthithoolarogam (Obesity). Hence, in the presentstudy, an attempt has been made to screen theSiddha drug that is Nathaichoori Chooranam, forthe hypolipidemic activity to prove its claim infolklore practice.
MATERIALS AND METHODS:SOP of the drug ‘Nathaichoori Chooranam’:The seeds of Nathaichoori (Spermacocce hispida)were collected and dried. Then the dried seeds werefried, powdered and mixed well.AimAim of the study is to evaluate the safety andefficacy of the siddha drug ‘Nathaichoorichooranam’ (NC).Chemicals
Analytical grade chemicals used for these studieswere obtained from s.d. fine chemicals Ltd,Mumbai.AnimalsAdult albino wistar rats of either sex weighingaround 125-180 gms were used. The animals weremaintained at normal room temperature with ahumidity of 55+ 5%. All the animals were fed withpellet diet obtained from Poultry Research Station,Nandanam, Chennai –35 and tap water ad libitumthroughout the experimental period. The animalswere acclimatized to the laboratory conditionsbefore experimental procedures were started. Thehealth, normal behavior and reproductive status ofthe animals were assessed and only healthy animals
were selected for the experiment. The experimentalprotocol for the drug Nathaichoori chooranam (NC)(AJ/IAEC/10/) (AJ/IAEC/10/12) were approved bythe CPCSEA/IAEC of Mohamed sathak A.J collegeof pharmacy, Sholinganallur, Chennai.Drug stock solutionThe test drug used for the study was suspended eachtime with 1% (w/v) solution of sodium carboxymethyl cellulose before administration.Hyperlipidemic inducer:Butter was used as the hyperlipidemic inducer inanimal procured from Chennai. 400mg of butter/Kgb.w. dissolved in 10ml of buffered saline was usedfor the induction of hyperlipidemic rats.Acute Oral Toxicity Study (LD50 Determination)For acute oral toxicity study OECD guidelines 423was followed. It is a stepwise procedure with threeanimals of a single sex per step. Depending on themortality and/or morbidity of the animals a fewsteps may be necessary to judge the toxicity of thetest substance. This procedure has advantage overother methods because of minimal usage of animalswhile allowing for acceptable data.The method uses defined doses (5, 50, 300,2000mg/kg body weight) and the results allow asubstance to be ranked and classified according tothe globally harmonized system. The starting doseof Nathaichoori chooranam was 2000mg/kgbodyweight p.o. The dose was administered to therats which were fasted overnight with water adlibitum and observed for signs of toxicity. The samedose was once again tried with another three ratsand were observed for 72 hours for symptoms likechange in skin color, salivation, diarrhea, sleep,tremors, convulsions and also respiratory,autonomic and CNS effects.
Evaluation of Hypolipidemic activity:Experimental Design:
Group I was considered as solvent control whichTableI.Groupingof Experimental Animals.
Int. J. Pharm. Res. Sci., 2014, 02(1), 104-109. www.ijprsonline.com ISSN: 2348 –0882==============================================================================
105
received normal rodent pellet diet. Group II wasconsidered as high fat diet group and received thebutter diet; Group III was considered positivecontrol group which received standard drug
Atorvastatin (10 mg/kg) .Group IV was consideredas test group I and received the trial drugNathaichoori Chooranam at the dose of 100 mg/ Kgbody weight per oral along with the high fat dietand Group V was considered as test group II whichreceived the trial drug at the dose of 200 mg/ Kgbody weight in High dose along with the high fatdiet.(Table-I).
Sample Collection:
At the end of 21st day, blood serum was withdrawnfrom the retro orbital plexus after overnight fastingfor the study of biochemical parameters. Serum wasestimated for the total cholesterol, triglycerides,LDL, VLDL and HDL cholesterol [5].Statistical Analysis:Results were presented as mean ± SD. Thesignificance of difference among the groups wereassessed using one way analysis of variance(ANOVA) followed by Dunken’s Multiple Reliancetest using SPSS software.(P< 0.05) was consideredsignificant.
RESULTS:Hypolipidemic activity:A marked increase in the level of serum cholesterol,triglycerides, LDL and VLDL were found in theanimals which received high fat diet andHDL levels were decreased. Administrations of trialdrug NC at the dose of 200 mg/kg showedsignificant reduction in the level of serumcholesterol, triglyceride, LDL, VLDL and increasein HDL level which was similar to the standardAtorvastatin, and are almost near the levels ofnormal control.A significant percentage reduction of serumcholesterol, triglyceride, LDL, VLDL andpercentage increase in HDL in test extract was alsocomparable with the standard drug. A potenthypolipidemic effect of the trial drug was evidentby a significant reduction in the level of serumcholesterol, LDL, VLDL and triglycerides in thecholesterol treated animals and also markedincrease in the HDL Cholesterol level (Table-II).
Table –II. LipidProfile Study onWistar Rats.
Sl.No. Wistar Rats Feeding P.O.
1. Group I Solvent
control
Fed with normal
rodent pellet diet.
P.O.
2. Group II Negative
control Diet
Fed with high fat
diet (HFD) and
water ad libitum
P.O.
3. Group III Positive
control
Atorvastatin
10mg/kg + P.O.
4. Group IV Low Dose
Nathaichoori
Chooranam(100
mg/kg of b.w)
Nathaichoori
Chooranam +
HFD P.O.
5. Group V High Dose
Nathaichoori
Chooranam(200
mg/kg of b.w)
Nathaichoori
Chooranam +
HFD P.O.
Int. J. Pharm. Res. Sci., 2014, 02(1), 104-109. www.ijprsonline.com ISSN: 2348 –0882==============================================================================
106
DISCUSSION:Hyperlipidemia continues to be a health majorproblem in India and other developing countries,which lead to important risk factors likeatherosclerosis, stroke etc. Hyperlipidemia evokesthe damages in various tissue, which in turn,deregulates the cellular functions leading to damageto various pathological conditions [6]. Heart diseaseis raising an epidemic scale in Indian men andwomen, vegetarians and nor-vegetarians whetherthey are living in India or abroad [7]. The WorldHealth Organization report emphasizes that the
cardio vascular diseases to be the largest cause ofdeath and disability in India by 2020 [8]. Thepresent studies were performed to assess thehypolipidemic activity and to prove its claim infolklore practice against various disorders.Probucol, a hypolipidemic drug is a potentlipophilic antioxidant and the ability to inhibitatherosclerosis has been attributed to its antioxidantproperties. Probucol lowers the level of cholesterolin the bloodstream by increasing the rate of LDLcatabolism. Additionally, probucol may inhibitcholesterol synthesis and delay cholesterolabsorption. Cholesterol is synthesized in allanimal tissue. Its important relates to its role inthe stabilization of membrane structures because ofits rigid planar structure. It is also a precursor forthe synthesis of steroid hormones. Increasedamount of cholesterol leads to cardiovasculardisease particularly coronary heart disease (CHD)[ 9].Triglycerides are mainly stored in the adiposetissue [10]. The plasma lipoproteins are majorsources of fatty acid to synthesis triacylglycerols.The excess of fat diet increased the TG levelwhich is one of the causes of hardening of arteries[11].The plasma cholesterol was reduced remarkably ontreating the HFD rats with the trial drugNathaichoori chooranam. Reduction of 1%cholesterol produces a 2% to 3% reduction incoronary heart disease risk [12]. LDL is a riskfactor and plays a main role at several paths ofatherosclerosis [13]. A decrease in oxidative stressand protection of LDL from oxidation mighttherefore be a strategy with great promise forprevention of atherosclerosis associatedcardiovascular disease (cvd) [14].VLDL is the main carrier and it is less harmfulthan TGL but still can damage the arterial lining.VLDL production is directly related to the body
Sl.
No.
Wistar
Rats
Total
Chole
strol
mg/dl
H
DL
mg
/dl
LD
L
mg
/dl
VL
DL
mg/
dl
Triglyc
erides
mg/dl
(TGL)
1. SOLV
ENT
CONT
ROL
48 22 3 18 92
2. NEGA
TIVE
CONT
ROL
65 14 15 25 114
3. POSIT
IVE
CONT
ROL
47 21 4 18 91
4. LOW
DOSE
43 20 6 18 93
5. HIGH
DOSE
35 28 2 14 73
Int. J. Pharm. Res. Sci., 2014, 02(1), 104-109. www.ijprsonline.com ISSN: 2348 –0882==============================================================================
107
fat [15].Severe elevation in the VLDL cholesterollead to hypercholesterolemia. The plasmalipoproteins are major sources of fatty acid tosynthesis triacylglycerols. The excess of fat dietincreased the TG level which is one of the causesof hardening of arteries [11].
HDL is known as the good cholesterol it hasreversed the transport function. It carriescholesterol away from the coronary categories anddrops it off at the liver [16].LDL particles are often termed as bad cholesterolbecause they have been linked to atheromaformation whereas high concentrations of HDL areoften referred to as good cholesterol, as it canremove cholesterol from cells & atheroma & hencecan offer protection [17].Conclusion:Hyperlipidemia is considered to be major riskfactor for the obesity and premature atherosclerosisand essentially the cholesterol inatherosclerotic plaque is derived from thatof circulatory cholesterol. In conclusion, it canbe said that the trial drug Nathaichoori chooranamexhibited a significant hypolipidemic effect at thedose of 200 mg/kg body weight. Efforts are inprogress to isolate and characterize the activeprinciple, which is responsible for thehypolipidemic efficacy of this valuable siddha herb.The hypolipidemic effect of the trial drug‘Nathaichoori chooranam’ (NC) in particular couldbe considered as a beneficial therapeutic value onlipid profile.References:
[1]. Blackwelder W D , The cause of complication ofDM, Indian Journal of Experimental Biology, 25(1977) 490.[2]. Chattopadhyaya R, Pathak D and Jindal DP,Indian Drugs, 33 (1996) 85-97.
[3]. Narayan DP, Kumar U, Agro‘s Dictionary ofMedicinal Plants. Agro bios Publisher, Jodhpur(2003).[4]. Chellaiah M, Muniappan A, Nagappan R et al,Medicinal plants used by traditional healers inKancheepuram district of Tamilnadu, India, Journalof Ethnobiology and Ethnomedicine, 2 (1999) 43.[5]. Sowmya A. Ananthi T, Hypolipidemic activityof Mimosa pudica Linn on Butter InducedHyperlipidemia in Rats, Asian J. Res. Pharm. Sci,1(4) (2011)123-126.[6]. Chander R , Kapoorn K and Singh C , Lipidper oxidation of hyperlipidemic rat serum inchronic ethanol and acetaldehyde administration, JBiosciences, 13 (2003) 289-274.[7]. Satish A Chandra. IJAPR, 2(5) (2011) 162 –167.[8]. Blankenhorn DH, Hodis HN, The Westernjournal of medicine, 159(2) (1993) 172–9.[9]. Aparna Berteri R, Risk of coronary artery heartdisease, Health Screen, 1 (2003) 28-29.[10]. Ahire AE and Laddha KS, Hypolipidemiceffects of Carthamus tinctorius in rats, Indian Drugs.42(8) (2005) 545-546.[11]. Xu Y, He Z and King GL, Introduction ofhyperglycemia and dyslipidemia in the pathogenesisof diabetic vascular complications, Curr Diab Rep,5(2) (2005) 91-97.[12]. Ornish D and Rosner B, The effect ofintake of dietary fat, JAMA. 49 (2005) 263-267.[13]. Witzum JL, The oxidation hypothesis ofatherosclerosis. Lancet 344(8925) (1994) 793-795.[14]. Steinberg D and Gotto AM, Preventingcoronary artery disease by lowering cholesterollevels- Fifty years from bench to bedside. JAMA,282(21) (1999) 43-50.[15]. Kesavulu M, Kemeshwara M, Rao Band Giri R, Lipid per oxidation and antioxidantenzyme status in type to diabetics with coronary
Int. J. Pharm. Res. Sci., 2014, 02(1), 104-109. www.ijprsonline.com ISSN: 2348 –0882==============================================================================
108
heart disease, Diab Res and Clin Prac., 1(53) (2001)33-39.[16]. Ginsberg H and Annapurna N A, Lipoproteinphysiology in non diabetic and diabetic status
relation to atherogenesis, J. Debetic Care, (2004)839-855.[17]. Durrington P. Dyslipidaemia, Lancet, 362(2003) 717-731.