Vangoori Y, Dakshinamoorthi A. Effect of Myristica Fragrans Extract on Lipid Profile, Glucose, Body Weight, Liver and Renal Functions in Experimental Obese Rats. Biomed Pharmacol J 2019;12(2).
Manuscript received on :31-Jan-2019
Manuscript accepted on :23-Mar-2019
Published online on: 10-04-2019
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Effect of Myristica Fragrans Extract on Lipid Profile, Glucose, Body Weight, Liver and Renal Functions in Experimental Obese Rats

Yakaiah Vangoori1 and Anusha Dakshinamoorthi*2

1Pharmacology. Santhiram Medical College, Nandyal (AP). PhD Scholar- Sri Ramachandra Institute of Higher Education and Research (SRIHER) – Chennai, India.

2Pharmacology, Sriramachandra Institute of Higher Education and Research, Chennai, India.

Corresponding Author E-mail: drdanusha@gmail.com

Abstract:

The effect of the ethanolic extract of Myristica fragrans was evaluated on cafeteria diet induced body weight, glucose and lipid elevations in albino rats. 54 rats were taken and divided into two models (Preventive and Curative). In preventive models, after 70 days of treatment, the extract, at doses of 200 and 400mg/kg, significantly prevented the body weight, glucose and lipid levels (p < 0.001) dose dependently. In curative model, initially obesity was induced by giving high fat diet for 5 weeks, and then treatment period was 10 weeks. After 70 days, body weight, glucose, lipid levels were controlled (p < 0.01) but lesser than preventive model. The standard drug Orlistat at 5mg/kg effectively prevented the body weight, glucose and lipid levels when compared with control and test groups. With these observations and previous data, the study concludes that Myristica fragrans extract can stimulate AMP-Kinase enzyme system and can reduce glucose and lipid concentrations. This may be useful for obesity treatment.

Keywords:

Glucose; LFT; Mace; Myristica Fragrans; Obese; Orlistat; Pancreatic Lipase; RFT; Weigh Gain

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Vangoori Y, Dakshinamoorthi A. Effect of Myristica Fragrans Extract on Lipid Profile, Glucose, Body Weight, Liver and Renal Functions in Experimental Obese Rats. Biomed Pharmacol J 2019;12(2).

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Vangoori Y, Dakshinamoorthi A. Effect of Myristica Fragrans Extract on Lipid Profile, Glucose, Body Weight, Liver and Renal Functions in Experimental Obese Rats. Biomed Pharmacol J 2019;12(2). Available from: https://bit.ly/2OZGLpr

Introduction

As per previous research reports, hyperlipidemia can cause cardiovascular problems, hyperglycemia, obesity and have major role in pathogenesis of various tissues. Obesity can induce insulin resistance, there by hyperglycemia, increase in blood pressure, dyslipidemia, collectively called “metabolic syndrome”.1 Obesity, which has been termed as “New World syndrome” is now considered by world health organisation as a global problem. According to 2014-WHO report, 1.9 billion adults are overweight, of which 600 million are obese. The obesity is spreading to not only developed countries, but also all over the world 4.5 million people were died in 2013 due to overweight and obesity.2 Obesity can be treated by reducing lipid levels. Animal models are useful tools for obesity research as they readily gain weight when fed with high-fat diet. Rats fed with HFD develop hyperlipidemia. Human obesity clinical features are almost similar to animal models physiologically.3 Therefore diet induced hyperlipidemia model was selected to observe the hypolipidemic effect of Myristica fragrans extract in the present study. Plants contain different chemical compounds and can act on specific cell sites. Many new drugs have been produced from the plant source, and these find use among the most common complementary and alternative medicine systems.4 Presence of multiple-Phytochemical combinations in plant drugs may result in synergistic effect by their action on multiple molecular targets, thus offering advantages over treatments which use a single constituent.5 The development of standardized, safe and effective drugs from plant origin can provide economical alternatives for the treatment of obesity. Therefore, there is a need to develop and screen large number of plant extracts and this approach can surely be a driving force for the discovery of anti-obesity drugs from medicinal plants. Myristica fragrans is  an  aromatic  evergreen  tree  cultivated  in  South  Africa,  India,  and  other  tropical countries. It is commonly used spice. It has been prescribed in Asia for many diseases like rheumatism, muscle spasm, to decrease appetite, and Hyperlipidemia.6,7 It was found hypolipidemic effects in rabbits in some previous research reports8,9 but there are no anti-obesity studies with Myristica fragrans.  It has been reported that the spice can be toxic when ingested in large quantities (1-3 nutmegs) causing convulsions, hallucinations, and possibly death.10 Some active compounds present in Nutmeg can also alter physiological functions of hepatic and renal systems. Hence, the objectives of the current study are to investigate the hypolipidemic and Antiobesity effect of MF in high fat-fed rats and to evaluate the pharmacological activities on hepatic and renal functions.11

AIM

To evaluate the effect of ethanolic extract of Myristica fragrans on body weight, lipid profile, hepatic and renal systems in experimentally induced obese wistar albino rats.

Material and Methods

Fresh and dried Mace was purchased from wholesale grocery store for the preparation of extract. Authentication was done by Dr. Suryanarayana Moorthi, PhD, Professor of Botany. Its uses were explained by Dr. Gurunath Reddy. B.A.M.S. Nandyal, Andhra Pradesh. Dried mace was ground to a fine powder and extract was prepared by using Soxhlet apparatus with ethyl alcohol as solvent.12

Research Design

Fifty four (54) healthy albino rats (male/female) weighing between 150-160 gm were taken from central animal house, Santhiram Medical college and randomly divided into two models (preventive and treatment models). Before starting the study, Institutional Animal Ethics Committee (IAEC) permission was taken. (CPCSEA/05/3/2018). For all the rats, body weight, normal lipid profile, Glucose levels was done before starting the study.

Before Induction of Obesity-(Preventive Models)

Healthy Albino Wistar rats (30) weighing between 150- 160 g will be taken. Group-I, treated with standard pellet diet, and 2-5 groups fed with Cafeteria diet along with standard pellet diet daily up to 10 weeks.

Rats will be divided into 5 groups, each group contain 6 rats (Male/Female)

Dosing once a day.  Study period will be 10 weeks.

Grouping of Animals

GROUP 1: (Standard pellet diet-Negative control)

GROUP 2: CD –positive control

GROUP 3: CD + Orlistat 5mg/kg (Standard)

GROUP 4: CD + Test I MFE 200mg/kg

GROUP 5: CD + Test II MFE 400mg/kg.

At the end of the study period, body weight, lipid profile-TC (Total cholesterol), TG (Triglycerides), LDL (Low density lipoprotein), VLDL (Very low density lipoprotein), HDL (High density lipoprotein), liver function test-SGPT (Serum glutamic puruvic transaminases), SGOT (Serum glutamic oxaloacetic transaminase), ALP (Alkaline phosphatase) and renal function test (CREATININE, UREA, URIC ACID) was done to examine MFE preventive effects on body weight and lipid profile.

After Induction of Obesity- (Treatment Models)

24 rats will be feed cafeteria diet (CD) along with pellet diet to induce obesity (diet induced obesity) for 5 weeks from the time of weaning and included in the study and will randomly divided into  4 groups. Study period will be 10 weeks.

After induction of obesity, Group-I, considered as obese control, and group-II treated with standard drug.  Groups (III-IV) treated with MF Extract once a day for 10 weeks in boiled milk orally.

Grouping Animals

GROUP 1: Obese control

GROUP 2: Standard- Orlistat 5mg/kg

GROUP 3: MFE 200mg/kg

GROUP 4: MFE 400mg/kg.

Hyper calorie/cafeteria diet:  (It consisted of 3 variants)13

Condensed milk + bread + peanuts + pellet chow (4:1:4:1),

Chocolate + biscuits + dried coconut + pellet chow (3:2:4:1), and

Cheese + boiled potatoes + pellet chow (4:2:1).

The different variants were fed on alternate days throughout the treatment period (10 weeks).

At the end of the study period, body weight, lipid profile (TC, TG, LDL, VLDL, HDL), liver function test (SGPT.SGOT, ALP) and renal function test (CREATININE, UREA, URIC ACID) was done to examine MFE curative effects on body weight and lipid profile.

Statistical Analysis

All the data was presented as mean ± SEM. The one way ANOVA was used to analyze the data, followed by Dunnett’s test. The results were measured statistically using SPSS Statistics 20.0 (IBM software) for the analysis. The results considered significant if p values < 0.05.

Results and Discussion

At the end of 70th day, Body weight was recorded and blood was withdrawn from retro-orbital sinus from all the groups and assessed for lipid profile and compared with control group. When plasma lipid levels were analyzed, CD (Cafeteria Diet) or high fat diet caused substantial elevation in TC, TD, LDL, VLDL, and reduced the levels of HDL when compared with normal control group (Group-1). Treatment with ethanolic extract of Myristica fragrans significantly (p<0.05) and dose dependently reduced the concentrations of TC, TD, LDL, VLDL, but increased the levels of HDL when compared to CD fed obese control rats (Group-2) depicted in table 1.

Table 1: Effect of Myristica Fragrans on Lipid Profile: (n=6, Mean±SEM). Table 1: Effect of Myristica Fragrans on Lipid Profile: (n=6, Mean±SEM).

 

Click here to view figure

 

Figure 1: Effect of Myristica fragrans on lipid profile. Figure 1: Effect of Myristica fragrans on lipid profile.

 

Click here to view figure

 

MF-Extract Effect on Body Weight

at the end of 70 days, body weight was recorded in all the groups. In group-I, there was no change in body weight but in group-II, there was tremendous gain in body weight due to high fat diet. In group-III, body weight gain was well prevented due to standard drug when compared with group-IV and V. In MF extract treated groups (IV, V) body weight gain controlled dose dependently and significantly (p<0.001) less compared with obese group (II) over 70 days. Effect of Myristica extract was less in treatment models when compared with preventive models. (Tab: 2).

Table 2: Effect of Myristica fragrans on Body weight (preventive & treatment groups).

Groups Body weight

(preventive)

Body weight

(Obese+treatment)

  Day-1 Day-70 Day-1 Day-70
Group-1

(Normal control)

162.83±4.81 170.00±5.11 —– —-
Group-2

Obese(CD)

156.21±2.51 325.51±1.43 250.12±2.41* 340.34±1.22
Group-3

(CD+Orlistat)

160.35±2.63 198.13±9.64 233.31±1.22 250.31±2.11
Group-4

CD+MEF 200mg/kg

166.91±3.12 258.56±3.41 261.51±1.26 301.25±6.31
Group-5

CD+MEF 400mg/kg

158.41±5.48 210.41±1.84 271.41±3.34 280.12±2.61

 

Comparison of Lipid profile within and in-between the groups. (n=6, Mean±SEM) *p<0.05, **p<0.01, ***p<0.001 compared to Control statistically analysed by one-way ANOVA followed by Dunnett’s t-test.

Effect of MF Extract on Glucose

There was a significant (p<0.05) rise in blood sugar levels in both (preventive and treatment) obese groups in comparison with untreated control. Treatment with MFE for 70 days reduced blood glucose levels significantly (p<0.01) when compared to untreated obese group (Tab: 3)

Table 3: Effect of Myristica fragrans on Blood glucose (preventive & treatment groups).

Groups Blood Glucose

(Preventive)

Blood Glucose

(Obese+treatment)

  Day-1 Day-70 Day-1 Day-70
Group-1

Control

 

65.12±2.14

 

66.32±1.24

——- ——-
Group-2

Obese(CD)

 

61.22±1.40

 

171.41±6.22

 

146.32±4.21

 

176.36±4.52

Group-3

(Orlistat)

66.18±4.16 79.15±3.11 157.21±4.13 91.29±3.46
Group-4

CD+MEF 200mg/kg

71.16±4.32 124.16±1.18 158.11±5.35 135.51±2.54
Group-5

CD+MEF 400mg/kg

63.14±1.17 88.17±1.20 165.25±6.81 126.11±9.61

 

Comparison of Lipid profile within and in-between the groups. (n=6, Mean±SEM) *p<0.05, **p<0.01, ***p<0.001 compared to Control statistically analysed by one-way ANOVA followed by Dunnett’s t-test.

Effect of MFE on Liver Functions

High fat diet can accumulate more fat in liver and can lead to fatty liver in animals. This can increase liver enzymes SGPT and SGOT. If enzyme levels increased, that can be considered as marker of obesity, and decreased of these enzyme levels can be taken as an anti-obesity effect. (14). In the present study, there is no much effect on SGPT, SGOT levels in obese groups and treatment groups over 70 days of study period when compared with control and in between groups. (Tab: 4&5).

Table 4: Effect of Myristica fragrans on Liver function. (Preventive model).

Groups SGPT SGOT ALP
  Day-1 Day-70 Day-1 Day-70 Day-1 Day-70
Group-1

Control

27.3±1.21 35.3±6.24 40.3±2.43 44.1±6.42 91.1±0.82 110.6±2.82
Group-2

Positive control (CD)

29.6±5.26 52.2±6.41 31.1±2.24 49.2±1.23 89.3±4.72 102.6±4.24
Group-3

(Orlistat 5mg/kg)

34.6±6.81 31.6±6.26 34.4±5.31 41.6±6.52 80.6±0.29 89.6±4.54
Group-4

CD+MEF 200mg/kg

30.5±1.46 38.4±1.42 35.1±3.48 38.8±2.24 79.6±1.52 102.1±3.41
Group-5

CD+MEF 400mg/kg

31.6±6.34 34.1±4.23 35.6±4.61 41.1±4.81 91.1±6.53 121.6±4.25

 

Comparison of Lipid profile within and  in-between the groups. (n=6, Mean±SEM) *p<0.05, **p<0.01, ***p<0.001 compared to Control statistically analysed by one-way ANOVA followed by Dunnett’s t-test.

Table 5: Effect of Myristica fragrans on Liver function. (Treatment model).

 Obese groups  SGPT  SGOT  ALP
  Day-1 Day-70 Day-1 Day-70 Day-1 Day-70
Group-1

Obese control (CD)

22.3±0.69 47.1±2.26 31.4±4.26 49.5±5.61 87.1±4.11 124.9±3.24
Group-2

(Orlistat 5mg/kg)

31.1±0.14 32.2±4.21 31.9±3.51 39.1±6.54 91.3±3.52 102.3±0.51
Group-3

MEF 200mg/kg

29.2±0.22 34.4±0.11 28.3±6.14 27.1±6.41 88.4±4.43 99.4±2.26
Group-4

MEF 400mg/kg

31.1±0.28 42.2±0.49 32.4±8.51 29.9±4.26 77.3±0.81 128.1±6.41

 

Comparison of Lipid profile within and in-between the groups. (n=6, Mean±SEM) *p<0.05, **p<0.01, ***p<0.001 compared to Control statistically analysed by one-way ANOVA followed by Dunnett’s t-test.

Effect of MFE on Renal Functions

Significant rise in creatinine, urea, and uric acid were noticed in obese rat models. High fat deposition in renal system due to fat food can damage the kidneys and change the levels of urea and uric acid.15 This can be considered as an index of obesity. If these levels reduced to normal, can be considered as an anti-obesity action. Based on this concept, the concentrations of creatinine, uric acid and urea levels were measured in the normal, obese control and MFE treated groups but there were no significant changes observed in pre treatment and post treatment models. (Tab: 6 & 7).

Table 6: Effect of Myristica fragrans on renal function. (Preventive model).

Groups CREATININE UREA URIC ACID
  Day-1 Day-70 Day-1 Day-70 Day-1 Day-70
Group-1

Control

0.72±0.03 0.82±0.01 25.43±2.31 39.4±0.6 3.1±0.04 3.9±0.09
Group-2

Positive control (CD)

0.81±0.01 0.90±0.03 28.32±1.28 41.1±0.5 2.3±0.03 4.1±0.04
Group-3

(Orlistat 5mg/kg)

0.71±0.03 0.86±0.02 24.29±2.18 33.3±0.4 2.4±0.03 3.6±0.03
Group-4

CD+MEF 200mg/kg

0.66±0.08 0.79±0.05 26.52±6.28 35.1±0.2 2.7±0.04 2.8±0.05
Group-5

CD+MEF 400mg/kg

0.78±0.04 0.92±0.01 27.29±1.32 40.2±0.7 2.6±0.01 3.1±0.03

 

Comparison of Lipid profile within and in-between the groups. (n=6, Mean±SEM) *p<0.05, **p<0.01, ***p<0.001 compared to Control statistically analysed by one-way ANOVA followed by Dunnett’s t-test.

Table 7: Effect of Myristica fragrans on Renal function. (Treatment model).

Obese groups Creatinine Urea Uric Acid
  Day-1 Day-70 Day-1 Day-70 Day-1 Day-70
Group-1

Obese control (CD)

0.72±0.04 0.92±0.02 25.21±2.32 31.3±0.8 3.1±0.02 3.9±0.06
Group-2

(Orlistat 5mg/kg)

0.69±0.02 0.75±0.01 29.32±3.13 30.3±0.6 2.0±0.03 3.1±0.04
Group-3

MEF 200mg/kg

0.58±0.04 0.64±0.06 29.61±5.41 33.4±0.4 2.1±0.06 2.9±0.06
Group-4

MEF 400mg/kg

0.67±0.06 0.71±0.04 28.23±4.21 32.2±0.7 2.2±0.04 2.8±0.03

 

Comparison of Lipid profile within and in-between the groups. (n=6, Mean±SEM) *p<0.05, **p<0.01, ***p<0.001 compared to Control statistically analysed by one-way ANOVA followed by Dunnett’s t-test.

Conclusion

These results suggest that Myristica fragrans extract may have clinical value in the treatment of hyperlipidemia, and obesity. Based on the observations and previous research studies, the possible mechanism for hypolipidemic property may be due to presence of Saponins in mace extract. Saponins can inhibit the pancreatic lipase enzyme16; thereby reduce the cholesterol levels.7 Tetrahydrofuran (Lignan) is one of the active chemical compound present in the Mace, also contributes to prevent weight gain by stimulating AMPK enzyme in differentiated C2, C12 cells. Its steroidal compounds have inhibitory effect on hunger sensory mechanism in hypothalamus.6 This could be beneficial to the obese persons and to treat hypercholestremic associated complications. With 400 mg/dl as maximum dose in the present study, does not change any physiological functions of the hepatic and renal systems. Further studies are needed to establish the safety.

Acknowledgements

The author Yakaiah Vangoori expresses his gratitude to his guide, Dr. D. Anusha and the staff of Santhiram Medical College, Nandyal, Andhra Pradesh for their support and guidance throughout this research work.

Conflict of Interest

There is no conflict of interest.

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