Obesity is a health burden affecting over 2.3 billion people of all ages globally. The development and progression of obesity involve a complex pathogenesis, and several drugs have been developed to target these pathways. In recent years, dipeptidyl peptidase-4 (DPP-4) inhibitors or gliptins, such as sitagliptin, saxagliptin, and vildagliptin, have been considered as a viable obesity management option. Gliptins inhibit DPP-4, an enzyme known to deactivate the GLP-1 hormone, contributing to the development and progression of obesity and other metabolic diseases. GLP-1 is one of the important incretin hormones secreted in the L-cells of the gut for the maintenance of blood sugar homeostasis. It exhibits other pleiotropic effects through its receptors in the liver, brain, and stomach to delay gastric emptying, reduce appetite, and induce significant weight loss. In healthy individuals, GLP-1 has a half-life of \>2 minutes due to the activities of DPP-4 . Some studies have observed higher DPP-4 levels in obese individuals, further reducing the incretin effects of GLP-1. Gliptins are primarily invented to manage type 2 diabetes. However, their weight loss effects are quite significant, presenting as a potent management option for obesity.
Synthetically produced drugs are often associated with side effects and contraindications. For conditions such as obesity, patients often require unique management options due to sensitivity and the high likelihood of comorbidities. For instance, obese individuals are more vulnerable to pancreatitis and pancreatic cancer, whereas gliptins are associated with a high incidence of acute pancreatitis. Gliptins also present other side effects such as upper respiratory infections, headache, urinary tract infections, arthralgia, and in severe cases, Stevens-Johnson syndrome. Cost-wise, gliptins are considerably expensive. The current FDA-approved gliptins are intended for the management of diabetes. Prescribing them for obesity may lead to higher demand and prices as well as scarcity. Hence, there is a need for a wider range of safe, cost-effective, and potent alternatives.
Natural products continue to emerge as potential drug leads for several metabolic disease conditions due to their potency and low toxicity. DGE (Dichrostachys glomerata), a popular Cameroonian spice, and CQE (Cissus quadrangularis), an ornamental and medicinal plant growing in Africa and Asia, have shown tremendous effects on weight loss. A recent study showed that DGE induced 22.85% weight loss in 60 subjects in 12 weeks. In a double-blind placebo-controlled study involving 35 subjects, CQE reduced body fat by 12.8% in 8 weeks. The mechanism of these two extracts is not fully understood. It has been proposed that DGE and CQE are anorectic. Some studies suggested that DGE and CQE reduced food intake through increased adiponectin secretion and the AMPK pathway.
Additionally, CQE was shown to boost serotonin levels. Serotonin has received much attention in weight loss research in the past. It has been implicated for its appetite-suppressing effect on the arcuate nucleus hypothalamus, a region responsible for food intake and energy expenditure.
Up to the present, no study has investigated the effect of DGE or CQE on GLP-1 or DPP-4 levels. Hence, this study aims to evaluate the efficacy of DGE and CQE as potent alternatives to gliptins in obesity management.
