Abstract

Ghrelin is a stomach-derived peptide that has been identified as the only circulating hunger hormone that exerts a potent orexigenic effect via activation of its receptor, the growth hormone secretagogue receptor (GHS-R1a). Hence, the ghrelinergic system represents a promising target to treat obesity and obesity-related diseases. In this study we analysed the GHS-R1a receptor activating potential of Harpagophytum procumbens, popularly known as Devil's Claw, and its effect on food intake in vivo. H. procumbens is an important traditional medicinal plant from Southern Africa with potent anti-inflammatory and analgesic effects. This plant has been also used as an appetite modulator but most evidences are anecdotal and to our knowledge, no clear scientific studies relating to appetite modulation have been done to this date. The ghrelin receptor activation potential of an extract derived from the dried tuberous roots of H. procumbens was analysed by calcium mobilization and receptor internalization assays in human embryonic kidney cells (Hek) stably expressing the GHS-R1a receptor. Food intake was investigated in male C57BL/6 mice following intraperitoneal administration of H. procumbens root extract in ad libitum and food restricted conditions. Exposure to H. procumbens extract demonstrated a significant increased cellular calcium influx but did not induce subsequent GHS-R1a receptor internalization, which is a characteristic for full receptor activation. A significant anorexigenic effect was observed in male C57BL/6 mice following peripheral administration of H. procumbens extract. We conclude that H. procumbens root extract is a potential novel source for potent anti-obesity bioactives. These results reinforce the promising potential of natural bioactives to be developed into functional foods with weight-loss and weight maintenance benefits.

Highlights

  • Ghrelin is a 28 amino acid peptide, which is synthetized mainly in the stomach, identified as the first and only known peripheral hormone exerting an appetite-stimulating effect through activation of its receptor, the growth hormone secretagogue receptor (GHSR1a) [1]

  • We investigate the effect of a plant extract derived from the dried tuberous roots of Harpagophytum procumbens on GHSR1a receptor modulation in vitro and on food intake in vivo

  • Chemical characterization of the dried Harpagophytum procumbens root powder To allow a better understanding of the possible bioactives found in the dried H. procumbens root powder we analysed its chemical composition (Table 1)

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Summary

Introduction

Ghrelin is a 28 amino acid peptide, which is synthetized mainly in the stomach, identified as the first and only known peripheral hormone exerting an appetite-stimulating effect through activation of its receptor, the growth hormone secretagogue receptor (GHSR1a) [1]. Several studies have shown the orexigenic effects of ghrelin following central or peripheral administration [2,3,4]. This receptor is implicated in the central secretion of the growth hormone (GH) from the anterior pituitary cells [5], its role in the appetite modulation is via activation of orexigenic neurons in the hypothalamic arcuate nucleus (ARC) A dysregulated appetite signalling, including aberrant ghrelin signalling, may contribute to the development of metabolic disorders such as obesity [7]. The high rate of obesity has led to increases in complications associated with obesity, notably the Metabolic Syndrome (Reaven’s Syndrome X; the Insulin Resistance Syndrome) which includes cardiovascular risk factors such as insulin resistance (type 2 diabetes), glucose intolerance, dyslipidemia and hypertension [8]

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