Mitigating efficacy of piperine in the physiological derangements of high fat diet induced obesity in Sprague Dawley rats
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)
- et al.
Antioxidant effect of herbs and spices on copper mediated oxidation of lower and very low density lipoprotein
Chin. J. Nat. Med.
(2010) - et al.
Lipid peroxidation measured as TBARS in tissue slices: characterization and comparison with homogenates and microsomes
Free Radic. Biol. Med.
(1988) Tissue sulfhydryl groups
Arch. Biochem. Biophys.
(1959)Catalase in vitro
Methods Enzymol.
(1984)- et al.
Fenofibrate prevents and reduces body weight gain and adiposity in diet induced obese rats
FEBS Lett.
(2001) - et al.
High-fat hypercaloric diet induces obesity, glucose intolerance and hyperlipidemia in normal adult male Wistar rat
Diab. Clin. Pract.
(1996) - et al.
Controlled high fat diet induces an obese syndrome in rats
J. Nutr.
(2003) - et al.
The effect of total extract of Securigera securidaca L. seeds on serum lipid profiles, antioxidant status, and vascular function in hypercholesterolemic rats
J. Ethonopharmocol.
(2009) - et al.
Perspectives of the non-statin hypolipidemic agents
Pharmacol. Ther.
(2010) - et al.
Preventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress in male wistar rats
Food Chem. Toxicol.
(2009)
Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPARγ, PPARα and e-NOS
J. Nutr. Biochem.
AMPK mediates the initiation of kidney disease induced by a high-fat diet
J. Am. Nephrol.
Diet-induced obesity in rats leads to a decrease in sperm motility
Rep. Biol. Endocrinol.
Prenatal and perinatal zinc restriction: effects on body composition, glucose tolerance and insulin response in rat offspring
Exp. Physiol.
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
Weight loss, exercise, or both and physical function in obese older adults
New Eng. J. Med.
Anti-obesity potential of Clerodendron glandulosum. Coleb leaf aqueous extract
J. Ethanopharmocol.
Piper species protect cardiac, hepatic and renal antioxidant status of atherogenic diet fed hamsters
Food Chem.
Reversal of glucose intolerance by pioglitazone in high-fat diet fed rats
Exp. Clin. Pharmacol.
Black pepper and health claims: a comprehensive treatise
Crit. Rev. Food Sci. Nutr.
Simultaneous determination of bioactive compounds in Piper nigrum L. and a species comparison study using HPLC-PDA
Nat. Prod. Res.
Chronic dietary vitamin A supplementation regulates obesity in an obese mutant WNIN/Ob rat model
Obesity
Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man
Diabetologia
Carbenoxolone treatment ameliorated metabolic syndrome in WNIN/Ob obese rats, but induced severe fat loss and glucose intolerance in lean rats
PLoS One
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2022, Nutrition ResearchCitation 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.