Elsevier

Chemico-Biological Interactions

Volume 221, 25 September 2014, Pages 42-51
Chemico-Biological Interactions

Mitigating efficacy of piperine in the physiological derangements of high fat diet induced obesity in Sprague Dawley rats

https://doi.org/10.1016/j.cbi.2014.07.008Get rights and content

Highlights

  • Piperine was isolated from methanolic extract of Piper nigrum seeds.

  • We evaluated the efficacy of piperine consumption against HFD induced obesity.

  • Piperine reversed the elevated level of biochemical parameters caused by HFD.

  • Piperine supplementation to HFD-induced obese rats altered body composition.

  • Piperine is potent nutraceutical, an alternative to synthetic drugs in obese model.

Abstract

An increased risk of obesity has become a common public health concern as it is associated with hypertension, diabetes, osteoarthritis, heart diseases, liver steatosis etc. Pharmacological intervention with natural product-based drugs is considered a healthier alternative to treat obesity. This study was aimed to evaluate anti-obesity effects of piperine on high fat diet (HFD) induced obesity in rats. Piperine was isolated from methanolic extract of Piper nigrum by using column chromatography and confirmed by LC–MS analysis. Male SD rats were fed HFD initially for 15 weeks to induce obesity. After induction of obesity, piperine was supplemented in different doses (20, 30 and 40 mg/kg b.wt) through HFD for 42 days to experimental rats. HFD induced changes in body weight, body composition, fat percentage, adiposity index, blood pressure, plasma levels of glucose, insulin resistance, leptin, adiponectin, plasma and tissue lipid profiles, liver antioxidants were explained. The activities of lipase, amylase and lipid metabolic marker enzymes such as HMG-CoA reductase, carnitine palmitoyl transferase (CPT), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), lecithin-cholesterol acyl transferase (LCAT) and lipoprotein lipase (LPL) were assessed in experimental rats. Supplementation of piperine at a dose of 40 mg/kg b.wt has significantly (p < 0.05) reversed the HFD-induced alterations in experimental rats in a dose dependant manner, the maximum therapeutic effect being noted at a dose of 40 mg/kg b.wt. Our study concludes that piperine can be well considered as an effective bioactive molecule to suppress of body weight, improve insulin and leptin sensitivity, ultimately leading to regulate obesity.

Introduction

Obesity, a nutritional disorder, is defined as nonstandard or unwarranted fat accumulation and growth of adipose tissue leading to obesity [1]. Because of its rising prevalence and its association with chronic health disorders such as insulin resistance, dyslipidemia, hypertension, cardio vascular diseases, non alcoholic fatty liver and osteoarthritis, obesity has become a major health concern in developed and developing countries [2], [3], [4].

Different kinds of therapies are available to help control obesity including appetite regulation, lipid digestion and absorption, promotion of lipolysis, inhibition of adipogenesis and behavior modification [5]. Among these, diet management, physical exercise and behavior modification are indispensable to control obesity. Despite potential global market for anti-obesity drugs, presently there are a few FDA approved drugs to treat obesity. Although the currently available drugs such as orlistat, sibutramine and rimonabant have modest clinical efficacy, their use is often restricted due to associated gastrointestinal or cardiovascular or central nervous system side effects. Among these drugs orlistat, the pancreatic lipase inhibitor is clinically approved for obesity treatment [6]. Even though the occurrence of obesity continues to increase in modern society; there are no satisfactory pharmacological therapies for its treatment. Supplementation of drugs that target lipid mobilization, utilization and reduction of nutrient absorption comprises one of the most important therapeutic approaches.

Phytoconstituents have always been a commendable source of drugs and many of the currently available drugs have been derived directly or indirectly from them. These phytoconstituents remain a focus of attention in our quest for the development of novel emphasizes the need for anti-obesity drugs. According to World Health Organization (WHO) report [7], continuous exploration and screening of medicinal plants with satisfactory weight management efficiency. A growing body of facts has clearly established that medicinal plants and their constituents play a fundamental role in appetite regulation and energy homeostasis [8].

Since prehistoric age, traditional formulations derived from medicinal plants have been used for therapeutic purposes. To date, there is growing attention on therapeutic efficacy of spices including pepper because their intake appears to be connected with treatment of certain chronic diseases as reported by several researchers [9], [10]. Piper nigrum Linn commonly known as black pepper has been traditionally used to treat cholera, dyspepsia, gastric ailments, and diarrhea [3], [4], [10]. Previous studies have shown the presence of phytochemicals like piperine, piperidine and pellitorine oil in P. nigrum Linn [9], [10], [11]. Moreover, to our best knowledge, data that deliberated the anti-obesity effects of piperine on diet-induced obesity in rats that dealt with pathophysiological factors are limited. Therefore, this study was intended to investigate the mitigating efficacy of piperine on pathophysiological deragments in HFD-induced obese rats.

Section snippets

Animals

All experiments related to diet induced obesity were carried out with male SD rats. Experiments were conducted at National Center for Laboratory Animal Sciences, National Institute of Nutrition, Hyderabad, India (Regd. No. 154/1999/CPCSEA). Animals were housed individually in standard polycarbonate cages with top grill having facilities for holding pelleted diet and drinking water in polycarbonate bottles with stainless steel sipper tubes (Techniplast, Italy) at 22 ± 2 °C, with 14–16 air changes

Results

Piperine, (1-[5-(1,3-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl] piperidine) is a naturally occurring alkaloid found rich in P. nigrum, a widely used important spice across the world. The LC–MS analysis of piperine showed molecular formula C17H22NO3. The LC–MS spectrum, library search and the structure of obtained piperine shown in Fig. 1.

The changes in body weight, food and water intake in different groups of animals during the experimental period are summarized in Table 1 and Fig. 2(A–E). There

Discussion

The quest for novel and safe therapeutic molecules continues to combat different aliments. Plants and herbs serve as potential perennial source of to explore such novel bioactive factors. In the present work we reported that high fat diet induces obesity and associated pathophysiological changes in the experimental animals which are significantly reverted by the treatment with piperine in a dose dependent manner. Obesity which was marked by increased body weight, BMI, blood pressure, total fat,

Conclusions

To conclude, supplementation of piperine caused significant attenuation in the physiological changes produced by HFD in rats. This might be due to the deterrence of pathological mechanisms responsible for lipid storage and weight gain, possibly by reverting leptin and adiponectin activity and increasing energy expenditure. Together, these observations strongly suggest that piperine, a major phytoconstituent of black pepper serves as an effective therapeutic agent for the management of obesity

Conflict of Interest

The authors declare that there are no potential conflicts of interest.

Acknowledgements

Authors are thankful to Department of Bio Technology-New Delhi, India (Grant No.: BT/PR7799/PBD/17/849/2013) for providing Junior Research Fellowship and Financial Assistance to carry out this research work and also thankful to Dr Rama Rao (Indian Institute of Chemical Technology-India), Dr P Suresh (Director-NCLAS, NIN), Dr R Ravindar Naik (Technical Officer-A), National Institute of Nutrition-India, for their constant encouragement and their valuable suggestions.

References (51)

  • A.K. Sharma et al.

    Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPARγ, PPARα and e-NOS

    J. Nutr. Biochem.

    (2012)
  • A.E. Decle et al.

    AMPK mediates the initiation of kidney disease induced by a high-fat diet

    J. Am. Nephrol.

    (2011)
  • D.B.F. Carla et al.

    Diet-induced obesity in rats leads to a decrease in sperm motility

    Rep. Biol. Endocrinol.

    (2011)
  • I.J.N. Padmavathi et al.

    Prenatal and perinatal zinc restriction: effects on body composition, glucose tolerance and insulin response in rat offspring

    Exp. Physiol.

    (2009)
  • Z. Min et al.

    Differential responses of hepatic endoplasmic reticulum stress and inflammation in diet-induced obese rats with high-fat diet rich in lard oil or soybean oil

    PLoS One

    (2013)
  • D.T. Villareal et al.

    Weight loss, exercise, or both and physical function in obese older adults

    New Eng. J. Med.

    (2011)
  • WHO, 2013. Facts on obesity. http://www.who.int/features/factfiles/obesity/en/ (accessed on...
  • N. Ravirajsingh et al.

    Anti-obesity potential of Clerodendron glandulosum. Coleb leaf aqueous extract

    J. Ethanopharmocol.

    (2011)
  • A. Agbor et al.

    Piper species protect cardiac, hepatic and renal antioxidant status of atherogenic diet fed hamsters

    Food Chem.

    (2012)
  • K. Srinivasan et al.

    Reversal of glucose intolerance by pioglitazone in high-fat diet fed rats

    Exp. Clin. Pharmacol.

    (2004)
  • S.B. Masood et al.

    Black pepper and health claims: a comprehensive treatise

    Crit. Rev. Food Sci. Nutr.

    (2013)
  • V.R. Rao et al.

    Simultaneous determination of bioactive compounds in Piper nigrum L. and a species comparison study using HPLC-PDA

    Nat. Prod. Res.

    (2011)
  • S.M. Jeyakumar et al.

    Chronic dietary vitamin A supplementation regulates obesity in an obese mutant WNIN/Ob rat model

    Obesity

    (2006)
  • D.R. Matthews et al.

    Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man

    Diabetologia

    (1985)
  • S.S.S. Prasad et al.

    Carbenoxolone treatment ameliorated metabolic syndrome in WNIN/Ob obese rats, but induced severe fat loss and glucose intolerance in lean rats

    PLoS One

    (2012)
  • Cited by (73)

    • Piperine mitigates aortic vasculopathy in streptozotocin-diabetic rats via targeting TXNIP-NLRP3 signaling

      2023, Life Sciences
      Citation Excerpt :

      It has also been reported that PIP (36 mg/kg) demonstrated an antihyperglycemic effect in STZ diabetic rats by acting as peroxisome proliferator-activated receptor (PPAR)-γ agonist [26]. Moreover, PIP markedly diminished hyperglycemia in high-fat diet rats [10,13,14]. Accordingly, the hypoglycemic activity of PIP could help maintain tight control of diabetic glycemia.

    • Piperine attenuates hepatic steatosis and insulin resistance in high-fat diet-induced obesity in Sprague-Dawley rats

      2022, Nutrition Research
      Citation Excerpt :

      In a collagenase-induced rat arthritis model, oral administration of 100 mg/kg per body weight of piperine significantly enhanced the activities of antioxidant enzymes such as superoxide dismutase, glutathione, and catalase [25]. Several studies have shown that a diet supplemented with piperine significantly reduces high-fat diet (HFD)-induced increases in serum lipid concentration and inhibits the accumulation of fat in mice/rats [26–29]. In summary, piperine exhibits various biological activities and is a promising nutraceutical.

    View all citing articles on Scopus
    View full text