Salacia root, a unique Ayurvedic medicine, meets multiple targets in diabetes and obesity

Abstract

In many traditional schools of medicine it is claimed that a balanced modulation of several targets can provide a superior therapeutic effect and decrease in side effect profile compared to a single action from a single selective ligand, especially in the treatment of certain chronic and complex diseases, such as diabetes and obesity. Diabetes and obesity have a multi-factorial basis involving both genetic and environmental risk factors. A wide array of medicinal plants and their active constituents play a role in the prevention and treatment of diabetes. Salacia roots have been used in Ayurvedic medicine for diabetes and obesity since antiquity, and have been extensively consumed in Japan, the United States and other countries as a food supplement for the prevention of obesity and diabetes. Recent pharmacological studies have demonstrated that Salacia roots modulate multiple targets: peroxisome proliferator-activated receptor-alpha-mediated lipogenic gene transcription, angiotensin II/angiotensin II type 1 receptor, alpha-glucosidase, aldose reductase and pancreatic lipase. These multi-target actions may mainly contribute to Salacia root-induced improvement of type 2 diabetes and obesity-associated hyperglycemia, dyslipidemia and related cardiovascular complications seen in humans and rodents. The results of bioassay-guided identification indicate that mangiferin, salacinol, kotalanol and kotalagenin 16-acetate are at least in part responsible for these multi-target regulatory activities of Salacia roots. The evidence suggests that this unique traditional medicine fulfills a multiple-target strategy in the prevention and treatment of diabetes and obesity. Although toxicological studies have suggested minimal adverse effects of the herbal medicine in rodents, a clinical trial is crucial to further confirm the safety of Salacia roots. In addition, further mechanistic studies are necessary in order to allow a better understanding of how use of Salacia root may interact with other therapeutic interventions.

Introduction

Human cells and tissues are composed of complex, networked systems with redundant, convergent and divergent signalling pathways. Most human diseases with a high population incidence, such as diabetes and heart disease, have a multifactorial basis that involves both genetic and environmental risk factors (Reich and Lander, 2001, Loktionov, 2003, Kaplan and Junien, 2000). In many traditional schools of medicine it is claimed that a balanced modulation of several targets can provide a superior therapeutic effect and decrease in side effect profile compared to the action of a single selective ligand, especially in the treatment of some chronic and complex diseases (Morphy et al., 2004). Effort is being devoted to finding new therapeutics aimed at multiple targets, which has become a new paradigm in drug discovery (Zhang, 2005). To hit the multiple targets implicated in complex diseases such as diabetes, two strategies are conceivable. The first attempts to employ a single compound to hit multiple targets; this can be termed as a one-compound-multiple-target strategy (Morphy et al., 2004). The other is using two or more active ingredients in one drug (Keith et al., 2005). Hence, it is of considerable interest to note that some natural products act on multiple targets to influence multiple biological activities, producing significant physiological effects, and thereby providing benefits that cannot be obtained with a single compound.

Type 2 diabetes is considered to be part of metabolic syndrome, which is a cluster of interrelated common clinical disorders, including impaired glucose tolerance, insulin resistance, dyslipidemia, hypertension, obesity, prothrombotic and proinflammatory states (Reilly and Rader, 2003, Tenenbaum et al., 2003). Hyperglycemia and dyslipidemia progress to atherogenesis, with consequent macrovascular and microvascular complications (Reilly and Rader, 2003, Tenenbaum et al., 2003). Thus people with diabetes are at an increased risk of cardiovascular, peripheral vascular and cerebrovascular diseases (Alberti and Zimmet, 1998).

A wide array of medicinal plants and their active constituents play a role in the prevention and treatment of diabetes (Bailey and Day, 1989, Ivorra et al., 1989, Marles and Farnsworth, 1995). Salacia species (Family: Celastraceae) are widely distributed in India, Sri Lanka, China and other Southeast Asian countries, and many plants from this genus (e.g. S. oblonga, S. reticulata, and S. prinoides) have been used for thousands of years in traditional medicines particularly for the treatment of diabetes and obesity; but also for gonorrhoea, rheumatism, pruritus and asthma (Chandrasena, 1935, Jayaweera, 1981, Vaidyaratnam, 1996). Several reports from studies in animals have described hypoglycemic activity of Salacia species, including S. oblonga (Augusti et al., 1995, Krishnakumar et al., 1999, Krishnakumar et al., 2000, Matsuura et al., 2004), S. reticulata (Karunanayake et al., 1984, Sirasinghe et al., 1990, Shimoda et al., 1998, Kumara et al., 2005), S. prinoides (syn. S. chinensis) (Pillai et al., 1979), and S. macrosperma (Venkateswarlu et al., 1993). Further hypoglycemic activity of herbal preparations containing Salacia species have also been reported in human studies (Kajimoto et al., 2000, Collene et al., 2005, Heacock et al., 2005, Jayawardena et al., 2005). Some toxicological studies have suggested minimal adverse effects of the herbal medicine in rodents (Wolf and Weisbrode, 2003, Flammang et al., 2006, Flammang et al., 2007, Rong et al., in press). Recently, Salacia species have been extensively consumed in Japan, the United States and other countries as a food supplement for the prevention of obesity and diabetes, as well as being the subject of broad studies for diabetes management.

This review will provide the reader with new understanding of Salacia root's properties with an emphasis on regulation of multiple molecular targets of importance in diabetes and obesity and their consequent complications.