Effect of Aqueous Extracts of Cissus Quadrangularis and Dichrostachys Glomerata on GLP-1 Concentration and DPP-4 Activity in Overweight and Obese Adults

Obesity is a global health crisis affecting over 2.3 billion individuals worldwide. This prospective study aims to evaluate the comparative effects of Cissus quadrangularis (CQR-300) and Dichrostachys glomerata (Dyglomera™) extracts on obesity-related parameters, focusing on their impact on glucagon-like peptide-1 (GLP-1) levels and dipeptidyl peptidase-4 (DPP-4) enzyme activity in obese subjects. Parameters such as GLP-1 levels, DPP-4 activity, food intake, body weight, blood lipids, fasting blood glucose, and visceral fat mass will be measured at baseline and various intervals.

In our previous pre-clinical trial involving 18 adult male Wistar rats (150-200 g), randomly divided into three groups: a control group fed a normal diet, and two treatment groups receiving Dyglomera™ (400 mg/kg) or CQR-300 (300 mg/kg) alongside a normal diet, the results demonstrated that both Dyglomera™ and CQR-300 significantly increased GLP-1 levels and inhibited DPP-4 activity compared to the control group. These effects were associated with reduced food intake, body weight, and fasting blood glucose levels. Additionally, both extracts positively modified blood lipid profiles, with significant changes in HDL, LDL, and triglyceride levels. The findings suggest that Dyglomera™ and CQR-300 exert their anti-obesity effects through mechanisms involving GLP-1 enhancement and DPP-4 inhibition, offering potential therapeutic pathways for weight management and metabolic health.

This prospective study aims to provide clinical evidence supporting the use of these plant extracts in addressing obesity and its related complications.

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. Dyglomera™ (Dichrostachys glomerata), a popular Cameroonian spice, and CQR-300 (Cissus quadrangularis), an ornamental and medicinal plant growing in Africa and Asia, have shown tremendous effects on weight loss. A recent study showed that Dyglomera™ induced 22.85% weight loss in 60 subjects in 12 weeks. In a double-blind placebo-controlled study involving 35 subjects, CQR-300 reduced body fat by 12.8% in 8 weeks. The mechanism of these two extracts is not fully understood. It has been proposed that Dyglomera™ and CQR-300 are anorectic. Some studies suggested that Dyglomera™ and CQR-300 reduced food intake through increased adiponectin secretion and the AMPK pathway.

Additionally, CQR-300 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 Dyglomera™ or CQR-300 on GLP-1 or DPP-4 levels. Hence, this study aims to evaluate the efficacy of Dyglomera™ and CQR-300 as potent alternatives to gliptins in obesity management.

Eligibility Criteria:
Inclusion Criteria:

* Healthy males and non-pregnant/non-lactating females
* Participants aged 18 to 65 years old
* Participants with BMI between 25 and 30 kg/m²
* Participants willing to comply with the study protocol

Exclusion Criteria:

* Participants younger than 18 years or older than 65 years
* Participants not available for the study period
* Morbid obesity (BMI \> 34.9 kg/m²)
* Diabetes mellitus requiring daily insulin management
* Pregnancy or breastfeeding
* Active infection
* Systemic diseases, including HIV/AIDS, Active hepatitis, Clinical signs of active malignancy within the past 5 years
* Use of any medication or natural health product that might affect the parameters of interest in this study