ANTIOXIDANT AND LIPID LOWERING EFFECTS OF ELAEOCARPUS GANITRUS IN CHOLESTEROL FED RABBITS
HTML Full TextANTIOXIDANT AND LIPID LOWERING EFFECTS OF ELAEOCARPUS GANITRUS IN CHOLESTEROL FED RABBITS
Pratibha K. Jain, Priyanka Sharma and Suresh C. Joshi*
Reproductive Toxicology Unit, Center for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur - 302055, Rajasthan, India.
ABSTRACT: Elaeocarpus ganitrus Roxb. is reported to exhibit multifarious pharmacological activities. However no scientific study has been conducted to evaluate antiatherosclerotic /lipid lowering activity of E. ganitrus Roxb. The present study was designed to investigate the antihyperlipidaemic and antioxidant activity of 70% ethanolic extract of E. ganitrus seed (EGEE) in cholesterol fed hyperlipidaemic rabbits. The EGEE was administered at a dose level of 250 and 500 mg/kg/day (p.o.) for 60 days to hyperlipidaemic rabbits. Lipid profile in serum and antioxidant parameters in tissues (Liver, Heart and Aorta) were determined. The statistical analysis was carried out using one way ANOVA followed by Tukey’s multiple comparison tests. EGEE showed a decrease in the levels of serum total cholesterol, triglycerides, phospholipids, LDL, VLDL (P ≤ 0.01, ≤ 0.001) in a dose dependant manner in treated animals. HDL ratio improved profoundly as well as marked decline was noticed in atherogenic index after administration with EGEE. A considerable decrease in lipid per oxidation and a significant elevation in Glutathione, Catalase and SOD levels (P ≤ 0.01, ≤ 0.001) were observed in EGEE treated rabbits. The overall experimental results suggests that the biologically active phytoconstituents such as phytosterols, fats, alkaloids, flavonoids, carbohydrates, proteins and tannins present in the EGEE may be responsible for the significant hypolipidaemic as well as antioxidant activity, signifying the potential protective role in coronary heart disease.
Keywords: |
Atherosclerosis, Hyperlipidaemic, Phytoconstituents, Cholesterol
INTRODUCTION: In the face of unremitting advances in therapeutic interventional and surgical therapies for the treatment of atherosclerotic coronary disease the later remains the principal killer in the western and the developing world. 1 Dyslipidaemia and resultant atherosclerosis are believed to stem from the imbalance of the lipid metabolites in the affected organism.
Hyperlipidaemia (mainly increased level of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL) cholesterol along with decrease in high-density lipoprotein (HDL) cholesterol contributes significantly to the manifestation and development of atherosclerosis and coronary heart diseases (CHDs). 2
The World Health Organization report emphasizes that the cardio vascular diseases to be the leading cause of death and disability in India by 2020. It is usually established that oxidative stress is strongly related to atherogenesis. 3 An antioxidant which inhibits oxidation of LDL should be effective for suppressing atherosclerosis. 4
Elaeocarpus ganitrus Roxb. belongs to family Elaeocarpaceae is a large evergreen broad-leaved tree. In Hindi it is recognized as Rudraksha 5 is prevalent for its fascinating fruit stones and medicinal properties.
The widespread investigation of literature exposed that E. ganitrus Roxb. is an imperative basis of various pharmacologically and medicinally significant chemicals, such as indispensable triterpenes, tannins like geraniin and 3, 4, 5-trimethoxy geraniin, indolizilidine alkaloids grandisines, rudrakine and flavnoids quercitin.
Furthermore it is noted to have myriad pharmacological activities that involve anti-inflammatory, 7 analgesic, 8 hypoglycemic, 9 antidepressant, 10 antiasthmatic, 11 sedative, 8 antihypertensive, 12 antiulcerogenic, 11 anticonvulsant, 13 and antimicrobial. 14 As per our literature survey, no scientific study has been conducted to evaluate antiatherosclerotic/ cholesterol lowering activity of E. ganitrus Roxb. With this background information, the present study is undertaken to screen E. ganitrus Roxb. for its ability to decrease lipid levels as well as antioxidant activity in hyperlipidaemic rabbits.
MATERIALS AND METHODS:
Collection of plant material: Authentic seeds of E. ganitrus were obtained from Jayoti Vidyapeeth Women’s University, Jaipur and authenticated by authority of Department of Botany, University of Rajasthan, Jaipur. A voucher specimen number (RUBL21180) was submitted at University herbarium department for future reference.
Extraction of plant material: The seeds were coarsely powdered and extracted with 70% ethanol for 48 hrs, by soxhlet extraction method. Then ethanol was filtered and then separated under reduced pressure to obtain solid mass in a rotary evaporator and this was stored in a desiccator. Ethanolic extract of E. ganitrus seed contains indolizidine types of alkaloids, flavanoids, tannins, carbohydrate and proteins. 15 Some dominant phytoconstituents in ethanolic extract of E. ganitrus which possess hypolipidaemic and antioxidant activity are depicted as:
FIG. 1: CHEMICAL CONSTITUENS OF ELAEOCARPUS GANITRUS ROXB.
Animal model: New Zealand white male rabbits weighing 1.50-2.0 kg were used in the study. The animals were acclimatized for 10 days before being used for the experiments. The animals were grouped (5 rabbits in each group) and housed in polypropylene cages at constant temperature and also maintained under a standard diet (Ashirwad Industrial Ltd., Punjab) and green leafy vegetables and water ad libitum. Experimental dose was administered to rabbits orally via gavage. The experimental protocol was approved by
Institutional Animal Ethical Committee (IAEC) and was executed according to the guidelines of Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA), India.
Acute Toxicity Study: The acute toxicity of the EGEE was determined using Albino mice weighing 20-25 gm. Animals were maintained on normal diet and water prior to and during the course of experiment. Fixed dose (OECD Guideline No. 423) method of CPCSEA was adopted for the toxicity studies. EGEE was nontoxic and caused no mortality up to 5g/Kg orally in mice. Therefore, the LD50 value of EGEE is >5g/Kg of body weight.
Experimental design:
The rabbits were divided into following groups:
Group I: Control –Placebo treated for 120 days.
Group II a: Cholesterol feeding for 60 days
Group II b: Cholesterol feeding for 120 days
Group III: Cholesterol feeding for 60 days then no treatment for next 60 days (i.e. from day 61-120)
Group IV a : Cholesterol feeding for 60 days then treated with 250 mg/Kg ethanolic extract of EGEE for next 60 days.
Group IV b: Cholesterol feeding for 60 days then treated with 500mg/Kg ethanolic extract of EGEE for next 60 days.
Cholesterol feeding: 500 mg cholesterol/kg. b. wt./rabbit/day in 5ml coconut oil Animal were sacrificed after completion of treatment, blood and tissue were taken out for biological examinations.
Induction of Hyperlipidaemia: Hyperlipidaemia was induced in New Zealand white male rabbits by daily oral administration of 500 mg cholesterol/kg. b. wt. /rabbit/day in 5ml coconut oil.
Collection of blood: On the 61st day or 121st day of respective treatment blood was collected by cardiac puncture, under mild ether anaesthesia and the serum was separated by centrifugation after 30 minutes and stored at -20°C for biochemical analysis.
Biochemical analysis: The serum total cholesterol, triglycerides, phospholipids, high - density lipoprotein (HDL), low density lipoprotein (LDL) were measured in an autoanalyzer using special kits (Accurex, Biomedical Pvt. Ltd.) and very low density cholesterol was calculated by using formula VLDL: TG/5. Tissues (Liver, Heart and Aorta) were homogenized by homogenizer and analysed for antioxidant parameters i.e. Lipid Peroxidation, 16 Catalase, 17 Glutathione, 18 and Super Oxide Dismutase (SOD). 19 HDL Ratio, 20 Atherogenic Index and Deviation Percentage were calculated as:
Statistical analysis
The results were expressed as mean±S.E.M. Statistical analysis was carried out by using One way ANOVA followed by Tukey’s multiple comparison tests using Graphpad PRISM software (version 5). P values <0.05 were considered as statistically significant.
RESULTS AND DISCUSSION: Findings of the current study suggested that administration with EGEE significantly attenuated the elevated total cholesterol, triglyceride, phospholipid, lipoprotein cholesterol (HDL, LDL and VLDL) concentrations in cholesterol induced hyperlipidaemic rabbits. A marked reduction was also observed in atherogenic index and the HDL ratio improved significantly after supplementation with seed extract at a dose level of 250 and 500 mg/kg b.wt/day.
As Table 1 illustrated that rabbits fed on cholesterol (Group–IIa and IIb) showed a highly significant rise (P ≤ 0.001) in the concentration of serum total cholesterol level as compared to control. Whereas, the total cholesterol levels of groups treated with 250 and 500 mg/kg/day EGEE were significantly reduced -63.19% and -70.02% respectively when compared to group-IIb animals and a decline of only -22.65% was noticed in no treatment group. Further, IVa and IVb group animals showed significant fall ((P ≤ 0.001) in the level of total cholesterol in comparison to no treatment group rabbits.
A significant elevation in serum cholesterol level after cholesterol feeding in rabbits were probably due to the overproduction of VLDL in the liver or by delayed catabolism of VLDL or both. 21, 22 The reduction in serum cholesterol level after treatment with EGEE may be due to improved elimination of LDL from plasma by mounting LDL-receptor activity.23
The strong presence of flavonoids in extract may contribute to antihypercholesterolemic effect as they decrease the levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) and decrease in apo- B secretion in hepatocytes. 24, 25
Further as shown in Table 1, serum triglyceride level was trending upward in hyperlipidaemic groups IIa, IIb (P ≤ 0.001) when compared to control but the downward trend was observed in the treatment group (P ≤ 0.001) at various doses i.e 250 mg and 500 mg/kg.b.wt/day in comparison to hyperlipidaemic group IIb. Treatment groups showed -49.08% and -66.41% reductions in serum triglyceride level whereas no treatment group showed only -26.65% reduction when compared to hyperlipidaemic rabbits. Extract treated group further demonstrated a significant decrease (P ≤ 0.01, P ≤ 0.001) in triglyceride level when compared to group III animals.
Cholesterol feeding elevates serum triglyceride levels essentially by preventing its uptake and clearance by inhibiting catabolising enzymes like lipoprotein lipase (LPL) and lecithin cholesterol acetyl transferase (LCAT). 26 EGEE significantly suppresses the elevated blood concentration of TGs through increased expression and activity of lipoprotein lipase (LPL) and to decrease hepatic synthesis and secretion of triglycerides. 27 It could be due to inhibition of lipolysis so that fatty acid do not get converted into triglyceride. 28
Serum phospholipid concentration demonstrated an increment after 60 days and 120 days of cholesterol feeding when compared to control rabbits as depicted in Table 1. A significant decline (P ≤ 0.001) was noticed in post-treatment with EGEE (i.e. dose 250 mg/kg.b.wt./day reduction was -32.81% and 500mg/kg.b.wt/day reduction was -67.34%) whereas in no treatment group reduction was -13.39% when compared to group IIb animals.
It could be clearly observed from Table 1, that treatment with EGEE extract resulting in a marked decrease in phospholipid level as compared to the level of the no treatment hypolipidaemic animals (P ≤ 0.01 and P ≤ 0.001). The reduction in phospholipid levels in EGEE treated animals possibly due to a higher level of phospholipase that metabolized the blood phospholipids in cholesterol fed animals. 29
In the present study, there was elevation in serum LDL level in response to cholesterol feeding as compare to normal control group. (Table 1) In contrast, as depicted in Table 1 the EGEE extract produced a significant decrease (P ≤ 0.001) in the levels of LDL-cholesterol (i.e. reduction was -71.24 % in 250 mg./kg.b.wt./day and -80.73% in 500 mg./kg.b.wt./day) when compared with hyperlipid- aemic rabbits (Group IIb). LDL level was brought down to only -23.94% in no treatment group (Group III). A significant fall (P ≤ 0.001) was noticed after oral administration of EGEE at various doses (250mg and 500mg/kg.b.wt/day) when compared to no treatment hyperlipidaemic rabbits. One of the key steps in the development of atherosclerosis is oxidative modification of LDL. The LDL- cholesterol lowering could result from a reduced LDL- synthesis and/ or an increased LDL metabolism. 30
Cholesterol feeding resulted in a rise in serum VLDL-Cholesterol levels in group IIa and IIb when compared to control group. (Table 1) On the other hand, as shown in Table 1 the induction of hyperlipidaemia in rabbits followed by treatment with plant extract at both the dose level i.e. 250 and 500 mg./kg.b.wt./day caused a significant reduction (P ≤0.001) in the serum levels of VLDL-cholesterol -51.75% and -54.64% respectively whereas no treatment group brought down it only -22.72% in comparison to hyperlipidaemic rabbits (120 days). Further, a significant (P ≤ 0.001) decline in VLDL level was observed when group IVa and IVb was compared to group III animals. Oral administration of EGEE brought down the VLDL cholesterol levels markedly. The reduction might be due to an increased uptake by extrahepatic tissues as well as by increasing the fractional catabolic rate of LDL cholesterol and by increasing the liver LDL receptors activity. 31
In hyperlipidaemic rabbits, HDL cholesterol in comparison to total cholesterol was showing downward trend, whereas after treatment with EGEE it showed upward trend in dose dependent manner (Table 1). Table 1 illustrated that Cholesterol/phospholipid ratio (C/P ratio) was elevated after cholesterol feeding for 60 and 120 days respectively which was reduced after treatment with EGEE extract.
Further HDL ratio significantly improved in a dose dependent manner after administration with EGEE as indicated in Table 1. The atherogenic index (AI) which is the measure of the extent of atherosclerotic lesions based on serum lipids is determined in all five groups. An ameliorative action of plant extract on atherogenic index was observed in both EGEE extract treated groups in a dose dependant manner.
TABLE 1: EFFECT OF ETHANOLIC EXTRACT OF E. GANITRUS ON SERUM BIOCHEMISTRY IN RABBIT
Identification | Group | Total Cholesterol | Triglyceride | Phospholipid | VLDL Chol. | LDL Chol. | HDL Chol. | Chol/
Phospho Ratio |
HDL Ratio | Athero-genic Index | |||||
mg/dl | |||||||||||||||
Control
(Placebo treated) from day 1-120 |
I | 123.33
± 7.75 |
77.05
± 4.12 |
119.72 ±5.25 | 15.41
±0.825 |
60.92
±1.30 |
43.07
±1.24 |
1.03 | 53.66 | 1.98 | |||||
Atherodiet + Chol.feeding* from day 1-60 | II a
% Deviation (I) |
615.00a ±21.79
+398.66 |
346.33a ±20.25
+349.48 |
374.41a ±7.02
+212.73 |
69.26a
±4.05 +349.44 |
372.19a
±11.40 +510.94 |
138.14 a ±2.34
+220.73 |
1.64
+59.22 |
28.96
-46.03 |
3.19
+61.11 |
|||||
Atherodiet + Chol.feeding* from day 1-120 | II b
% Deviation (I) |
1041.66a ±27.82
+744.61 |
475.66a ±9.02
+517.35 |
611.00a ±8.50
+410.35 |
95.13a
±1.80 +517.32 |
644.67a ±10.33
+958.22 |
148.89 a ±3.58
+245.69 |
1.70
+65.04 |
16.67
-68.93 |
4.96
+150.50 |
|||||
Atherodiet + Chol.feeding* from day 1-60. No treatment from day 61-120 | III
% d Deviation (IIa) |
475.66b
±17.85 -22.65 |
254.00b ±8.32
-26.65 |
324.26b ±11.72
-13.39 |
50.80b
±1.66 -26.65 |
283.07b
±6.42 -23.94 |
115.36 b±5.38
-16.49 |
1.46
-10.97 |
32.01
+10.53 |
2.89
-9.40 |
|||||
Atherodiet + Chol.feeding* from day 1-60+Elaeocarpus ganitrus ethanolic extract** from day
61-120 |
IV a
% Deviation (IIa) |
226.33b,d±15.10
-63.19 |
176.33b,d±6.74
-49.08 |
253.89 b, e
±15.31 -32.18 |
35.26b,d
±1.34 -49.09 |
107.03b,d ±4.75
-71.24 |
73.40 b, d ±2.37
-46.86 |
0.89
-45.73 |
47.99
+65.71 |
1.93
-39.49 |
|||||
Atherodiet + Chol. feeding* from day
1-60 +Elaeocarpus ganitrus ethanolic extract*** from day 61-120 |
IV b
% Deviation (IIa) |
184.33b,d ±4.48
-70.02 |
116.33b,d ±4.09
-66.41 |
122.26b,d ±4.39
-67.34 |
23.26b,d
±0.81 -66.41 |
71.70 b, d ±5.73
-80.73 |
66.27b,d±3.30
-52.02 |
1.50
-8.53 |
56.13
+93.81 |
1.43
-55.17 |
|||||
*Cholesterol feeding –500mg/ kg.b.wt in 5 ml coconut oil / day Values± 5 determination
** E. ganitrus- 250 mg/ kg.b.wt. / day a- P≤ 0.001 Highly Significant Group IIa, IIb compared with Group I
*** E. ganitrus 500mg/ kg.b.wt. / day b- P≤ 0.001 Highly Significant Group III, IV a and IVb compared with
c- P≤0.01 Significant Group IIb
d- P≤ 0.001 Highly Significant Group IV a and IV b compared with
e- P≤ 0.01 Significant Group III
ns- non significant
The ratio of LDL-C to HDL-C is also a protective indicator of cardio vascular disease incidence. The cholesterol induction produced a significant increase of this marker. The administration of EGEE provides a beneficial action on rabbit lipid metabolism with regard to the reduction of AI. Again, the administration of EGEE significantly improved the HDL ratio showing the beneficial effect of this plant in preventing atherosclerosis incidence. For analyzing lipid peroxidation, MDA levels were measured in liver, heart and aorta homogenates. A significant rise (P ≤ 0.001) in MDA was observed in the hyperlipidaemic rabbits in comparison with the control. Moreover, lipid peroxidation was significantly reduced (P ≤ 0.01
and P ≤ 0.001) as depicted by the lower levels of MDA in liver, heart and aorta after oral administration of EGEE in a dose-dependent manner when compared with hyperlipidaemic rabbits (Fig. 1). This indicates that EGEE extract react with peroxyl radicals including the inhibition of lipid peroxidation chain propagation. 32
The level of GSH was lower in the animals fed with cholesterol when compared to control ones in all the three tissues. A significant elevation (P ≤ 0.001 and P ≤ 0.01) was observed in GSH content of all the three organs when treated with EGEE at the dose level of 250 and 500 mg/kg. b. wt./day (Fig. 2).
It is possible that extract might have reduced the extent of oxidative stress, leading to lesser GSH degradation or increase in the biosynthesis of GSH. 33, 34 The CAT and SOD activity appeared to be lower in the hypercholesterolaemic groups in comparison to control group in all the three organs. In contrast statistically significant elevation (P ≤ 0.01 and P ≤ 0.001) was observed in catalase (Fig. 3) as well as SOD activity (Fig.4) of liver, heart and aorta in EGEE administered rabbits.
FIG. 1: EFFECT OF ETHANOLIC EXTRACT OF E.GANITRUS ON LIPID PEROXIDATION IN RABBITS
Values ± 5 determinations
- P ≤ 0.001 Highly Significant Group IIa, IIb compared with Group I
- P ≤ 0.01 Significant
- P ≤ 0.001 Highly Significant Group III, IVa, IVb compared with Group IIb
- P≤0.01 Significant
ns- Non Significant
FIG. 2: EFFECT OF ETHANOLIC EXTRACT OF E. GANITRUS ON GLUTATHIONE ACTIVITY IN RABBITS
Values ± 5 determinations
- P ≤ 0.001 Highly Significant Group IIa, IIb compared with Group I
- P ≤ 0.01 Significant
- P ≤ 0.001 Highly Significant Group III, Iva, IVb compared with Group IIb
- P ≤ 0.01 Significant
ns- Non Significant
FIG. 3: EFFECT OF ETHANOLIC EXTRACT OF E.GANITRUS ON CATALASE ACTIVITY IN RABBITS
Values ± 5determinations
- P ≤ 0.001 Highly Significant Group IIa, IIb compared with Group I
- P ≤ 0.01 Significant
- P ≤ 0.001 Highly Significant Group III, IVa, IVb compared with Group IIb
- P ≤ 0.01 Significant
ns- Non Significant
FIG. 4: EFFECT OF ETHANOLIC EXTRACT OF E. GANITRUS ON SOD ACTIVITY IN RABBITS
Values ±5 determinations
- P ≤ 0.001 Highly Significant Group IIa, IIb compared with Group I
- P ≤ 0.01 Significant
- P ≤ 0.001 Highly Significant Group III, IVa, IVb compared with Group IIb
- P≤0.01 Significant
ns- Non Significant
EGEE treated hyperlipidaemic rabbits had considerably elevated levels of SOD and CAT, reversing the ill effects of hyperlipidaemia. It is well known that flavonoids and polyphenols are natural antioxidants but have also been reported to significantly increase SOD and CAT activities. 35, 36 Total phenolic content in E.ganitrus was detected to be 56.79±1.6 mg gallic acid equivalents/g of dry material. Total flavonoids in E. ganitrus were detected to be 18.58± 0.3 mg rutin equivalents/g of dry material. 37 These findings recommend that the antioxidant capacity of EGEE is by virtue of phenolics and flavonoid components.
Flavonoids defend alpha tocopherol and conceivably other antioxidants against oxidation. 38 Furthermore, Lee et al., 201139 suggested that quercetin as a preventive measure against cardiovascular risk.
Berberine (BBR), an alkaloid isolated from the Chinese herb huanglian, upregulates hepatic LDLR expression by extending the half-life of LDLR mRNA without affecting gene transcription. 40 It is possible that the presence of alkaloids like:
(+)- elaeocarpiline, isoelaeocarpiline,
(-)-epielaeocarpiline,
(+)-epiisoelaeocarpiline,
(+)-epialloelaeocarpiline,
(-)-alloelaeocarpiline, elaeocarpidine, pseudoepi-isoelaeocarpiline and rudrakin in EGEE 41 may possess LDLR mRNA stabilization property and stimulating effect on hepatic LDLR expression. Bharti 2013 42 revealed that kaempferol and Quercetin were found to dominate in seeds of EGEE. Quercetin supplementation altered expression profiles of several lipid metabolism-related genes in HFD control mice. 43 Further the kaempferol reduced the accumulation of visceral fat and improved hyperlipidaemia in HFD-fed obese rats by increasing lipid metabolism. 44
In accordance with these results, it may be confirmed that due to the presence of biologically active phytoconstituents such as alkaloids, flavanoids and tannins in the ethanolic extract, may demonstrates the multitarget, multicomponent features for regulating lipid metabolism. 45
In conclusion, it can be said that the ethanolic extract of Elaeocarpus ganitrus seed exhibited a significant cardioprotective as well as antioxidant activity in rabbits. To elucidate the precise mechanism of action and expression studies related to lipid metabolism of specific biological moiety, further processing of ethanolic fraction of E. ganitrus is required to establish the efficacy of the EGEE as a hypolipidaemic drug.
ACKNOWLEDGEMENTS: This study was supported by University Grant Commission, New Delhi, India.
CONFLICTS OF INTEREST: Nil
REFERENCES:
- Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics – 2012update: a report from the American Heart Association. Circulation Adv Appl Sci Res 2011; 2: 440-450.
- Harrison D, Kathy KG, Hornig B, Drexler H. Role of oxidative stress in atherosclerosis. Am J Cardiol. 2003; 91: 7A–11A.
- Harauma A, Murayama T, Ikeyama K, Sano H,Arai H, Takano R et al. Mulberry leaf powder prevents atherosclerosis in apolipoprotein E-deficient mice. Biochem Biophys Res Commun. 2007; 358:751-6.
- Niki E. Antioxidants and Atherosclerosis. Biochem Soc Trans. 2004; 32:156-159.
- Asolkar LV, Kakkar KK, Chakre OJ, editors. Second supplement to glossary of Indian medicinal plant with active principles. New Delhi: Publication and Information Directorate, CSIR; 1992.
- Khandelwal KR, editors. Practical Pharmacognosy, Preliminary phytochemical screening. Pune: Niralli Parkashan; 2004.
- Nain J, Garg K, Dhahiya S. Analgesic and anti-inflammatory activity of Elaeocarpus sphaericus leaf extract. Int J Pharm and Pharma Sci. 2012; 4:379-81.
- Katavic PL, Venables DA, Rali T, Carroll AR. Indolizidine alkaloids with delta-opioid receptor binding affinity from the leaves of Elaeocarpus fuscoides. J Nat Prod. 2007; 69: 1295-9.
- Hule AK,Shah AS, Gambhire MN, Juvekar An evaluation of the antidiabetic effects of Elaeocarpus ganitrus in experimental animals. Indian J Pharmacol. 2011; 43: 56-9.
- Dadhich A, Jasuja ND, Chandra S, Sharma G. Antidepressant effects of fruit extract of Elaeocarpus ganitrus in force swim test. Int J Pharm Sci Res. 2014; 5: 2807-12.
- Singh RK, Bhattacharya SK, Acharya SB. Studies on extracts of Elaeocarpus sphaericus fruits on in vitro rat mast cells. Phytomed. 2000; 7: 205-7.
- Sakat SS, Wankhede SS, Juvekar AR, Mali VR, Bodhankar SL. Antihypertensive effect of aqueous extract of Elaeocarpus ganitrus Seeds in renal artery occluded hypertensive rats. Int J PharmTech Res. 2009; 1:779-82.
- Dasgupta A, Agarwal SS, Basu DK. Anticonvulsant activity of the mixed fatty acids of Elaeocarpus ganitrus (Rudraksha). Indian J Physiol Pharmacol. 1984; 28: 245-6.
- Kumar G, Karthik L, Rao KVB. Phytochemical composition and in vitro antimicrobial activity of Bauhinia racemosa Lamk (Caesalpiniaceae). Int J Pharma Sci Res. 2010; 1: 51-8.
- Singh B, Chopra A, Ishar MPS, Sharma A, Raj T. Pharmacognostic and antifungal investigations of Elaeocarpus ganitrus (Rudrakasha). Indian J Pharma Sci. 2010; 72: 261-65.
- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Analyt Biochem. 1979; 95: 351-8.
- Claiborne A. Catalase activity. In: Greenwald R, editors. Handbook of methods for oxygen radical research. Boca Raton Florida: CRC Press; 1985. p. 283-4.
- Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem. 1975; 250: 5474-80.
- Das K, Samanta L, Chainy GBN. A modified spectrophotometric assay for superoxide dismutase using nitrite formation by superoxide radicals. Indian J Biochem Biophy. 2000; 37: 201-4.
- Hjermann I, Enger SC, Helgeland A, Holme I,Leren P, Trygg K. The effects of dietary changes on high density lipoprotein cholesterol. The oslo study. Am J Med. 1979; 66:105-109.
- Chapman MJ, Caslake M, Packard C, McTaggart F. New dimension of statin action on apo- B atherogenicity. Clin Cardiol. 2003; 26: I-7–I-10.
- Wehinger A, Tancevski I, Schgoer W, Eller P,Hochegger K, Morak M et al. Phospholipid transfer protein augments in THP-1-derived macrophages induced by lipolyzed hypertriglyceridemic plasma. Arterioscler Thromb Vasc Biol. 2007; 27: 908-14.
- Lin Y, Meijer GW, Vermeer MA, Trautwein EA. Soy protein enhances the cholesterol- lowering effect of plant sterol ester in cholesterol-fed hamsters. J Nutr. 2004; 134:143-8.
- Thakur N, Hayashi T, Iguchi A. HMG-CoA reductase inhibitor stabilizes rabbit atheroma by increasing basal NO and decreasing superoxidase. Am J Physiol. 2001; 281: 75-83.
- Borradaile NM, de Dreu LE, Barrett PH, Huff MW. Inhibition of hepatocyte apo-B secretion by naringenin: Enhanced rapid intracellular degradation independent of reduced microsomal cholesteryl esters. J Lipid Res. 2002; 43: 1544-54.
- Maruthappan VG, Shree KS. Blood cholesterol lowering effect of Adenanthera pavonina seed extract on atherogenic diet induced hyperlipidaemia rats. Int J Pharma Sci Res. 2010; 1: 87-94.
- Anderson JW. Whole grains protect against atherosclerotic cardiovascular disease. Proc Nutr Soc. 2003; 62: 135-42.
- Pande VV, Dubey S. Antihyperlipidemic activity of Sphaeranthus indicus on atherogenic diet induced hyperlipidemia in rats. Int J Green Pharm. 2009; 3: 159-61.
- Adaramoye OA, Nwaneri VO, Anyanwu KC, Farombi EO, Emerole GO. Possible anti-atherogenic effect of Kolaviron (a Garcinia kola seed extract) in hypercholesterolaemic rats. Clin Exp Pharmacol Physiol. 2005; 32: 40-6.
- Latha M, Pari L. Antihyperlipidaemic effect of aqueous extract of Scoparia dulcis in albino rats treated with Streptozotocin. J Herbs Spices Med Plants. 2005; 11: 59-66.
- Delsing DJM, Post SM, Groenendijk M, Solaas K, Boom H, Duyvenvoorde W et al. Rosuvastatin reduces plasma lipids by inhibiting VLDL production and enhancing hepatobiliary lipid extraction in apo E*3-Leiden mice. J Cardiovas Pharm. 2005; 45: 53-60.
- Kulisic T, Radonic A, Katalinic V, Milos M. Use of different methods for testing antioxidative activity of organo essential oil. Food Chem. 2003; 85: 633-40.
- Hashim MS, Lincy S, Remya V, Teena M, Anila L. Effect of polyphenolic compounds from Coriandrum sativum on H2O2-induced oxidative stress in human lymphocytes. Food chem. 2005; 92: 653-60.
- Prasanna GS, Purnima A. Protective effect of leaf extract of Trichilia connaroides on hypercholesterolemia induced oxidative stress. Int J Pharmacol. 2011; 7:106-12.
- Fang YZ, Yang S, Wu G. Free radicals, antioxidants and nutrition. 2002; 18: 872-9.
- Visavadiya NP, Narasimhacharya AVRL. Hypolipidemic and antioxidant activities of Asparagus racemosus in hypercholesteremic rats. Indian J Pharmacol. 2005; 37: 376-80.
- Luo XD, Basile MJ, Kennelly EJ. Polyphenolic antioxidants from the fruits of Chrysophyllum cainito (star apple). J Agric Food Chem. 2002; 50:1379-82.
- Yu SG, Thomas AM, Gapor A, Tan B,Qureshi N, Qureshi AA. Dose –response impact of various tocotrienols on serum lipid parameters in 5-week-old female chickens. Lipids. 2006; 41: 453-61.
- Lee KH, Park E, Lee HJ, Kim MO,Cha YJ, Kim JM et al. Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers. Nutr Res Pract. 2011; 5: 28-33.
- Abidi P, Zhou Y, Jiang J, Liu b. ERK-dependent regulation of hepatic LDL receptor expression by herbal medicine berberine. Arterioscler Thromb Vasc Biol. 2005; 25: 2170-6.
- Ray AB, Dutta SC, Dasgupta SR. A new alkaloid from Elaeocarpus ganitrus. Phytochem. 1979; 18:700-1.
- Bharti A. Determination of quercetin in extract of Elaeocarpus ganitrus seed by using HPTLC method. Int Res J Pharm. 2013; 4: 186-8.
- Jung CH,Cho I, Ahn J, Jeon TI, Ha TY. Quercetin reduces high-fat diet-induced fat accumulation in the liver by regulating lipid metabolism genes. Phytother Res. 2013; 27: 139-43.
- Chang CJ, Tzeng TF, Liou SS, Chang YS, Liu IM. Kaempferol regulates the lipid-profile in high-fat diet-fed rats through an increase in hepatic PPARα levels. Planta Med. 2011; 77: 1876-82.
- Wei JB, Jiao G, Hai YW, Yang C. Lipid-Regulating Effect of Traditional Chinese Medicine: Mechanisms of Actions. Evid Based Complement Alternat Med, Article ID 970635, 10 pages, 2012. doi:10.1155/2012/970635.
How to cite this article:
Jain PK, Sharma P and Joshi SC: Antioxidant and lipid lowering effects of Elaeocarpus ganitrus in cholesterol fed rabbits. Int J Pharm Sci Res 2018; 9(2): 526-34.doi: 10.13040/IJPSR.0975-8232.9(2).526-34.
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Article Information
13
526-534
580
1032
English
IJPSR
P. K. Jain, P. Sharma and S.C. Joshi*
Reproductive Toxicology Unit, Center for Advanced Studies, Department of Zoology, University of Rajasthan, Jaipur, Rajasthan, India.
s_c_joshi2003@rediffmail.com
15 May, 2017
19 July, 2017
25 July, 2017
10.13040/IJPSR.0975-8232.9(2).526-34
01 February, 2018