The hypothalamus and its neural circuits play an important role in the regulation of feeding behavior and bodyweight gain [1]. Numerous neuropeptides produced in the hypothalamus are involved in food intake and bodyweight regulation [2] and [3]. Among neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP) have been shown to cause profound increases in feeding when administered intracerebroventricularly [4] and [5]. In contrast, the proopiomelanocortin (POMC)/cocaine and amphetamine regulated transcript (CART) neurons of the arcuate nucleus of the hypothalamus inhibit feeding [6] and [7]. These results suggest that up-regulation of anorexigenic POMC/CART neuropeptides and/or down-regulation of orexigenic NPY/AgRP neuropeptides may contribute to the control of food intake and obesity. Rutecarpine (Rut), an indolopyridoquinazolinone alkaloid, is a major component of the
MC 1568 of Evodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang. E. rutaecarpa has been used in Korea, Japan, and China as a traditional anti-inflammatory herbal medicine and has been reported to have a wide spectrum of pharmacological activities, such as quinone reductase activity induction [8], anti-inflammation [9], [10] and [11], immunosuppression [12], vasorelaxation [13] and [14], and platelet aggregation inhibition [15], [16] and [17]. Dietary supplementation with evodiamine, another alkaloid of the fruit of E. rutaecarpa, has been shown to ameliorate diet-induced obesity, partially by inhibiting adipocyte differentiation through ERK activation [18]. Evodiamine prevented obesity in UCP1-deficient mice and may trigger a UCP1-independent mechanism to prevent diet-induced obesity. Evodiamine also improved leptin resistance and insulin sensitivity in mice [18]. Considering these pharmacological activities, evodiamine should be considered as a unique
compound in this plant that inhibits obesity. However, in spite of previous reports [19], [20] and [21], pharmacological studies of the effects of rutecarpine against orexigenia and obesity have not been explored.
