Standardization parameters and synergism of source plant materials for the antidiabetic efficacy of the Rauvolfia-Citrus tea

Abstract

The introduction of glucagon-like peptide 1 (GLP-1)-based therapies has greatly improved the management of type 2 diabetes (T2D), as they ensure good blood glucose control and promote weight loss. Ingestion of standardized herbal remedies that promote the same endogenous metabolic processes affected by the GLP-1-based treatments could provide cheaper alternatives in low- and middle-income countries, where there is currently an increase in the incidence of T2D. The focus in this study was to determine quality control parameters and the prime factors for the Rauvolfia-Citrus tea (RC-tea), as used in Nigerian traditional medicine to treat T2D. We have previously shown that the RC-tea that is made by boiling leaves of Rauvolfia vomitoria Afzel. and fruits of Citrus aurantium L. causes normalization of blood glucose and reduction of ectopic lipid accumulation in genetic diabetic (BKS-db) mice and in humans with T2D. The standardized RC-tea was made by boiling 40 g dried R. vomitoria foliage and 200 g fresh C. aurantium fruits per litre. The resulting golden-brown extract is free of microbial contamination, has pH 5 and contains ca. 230 mg naringin (marker compound for C. aurantium) and 25 mg robinin (marker compound for R. vomitoria) per litre. In addition, the herbal extract has the characteristic HPLC-DAD fingerprint where the marker compounds, naringin and robinin have retention times of approximately 26.3 min and 26.9 min, respectively, when using the outlined column and gradient elution conditions. Comparative evaluations of the antidiabetic effects of the standardized RC-tea and boiling water-extracts made with C. aurantium fruits alone (CA), R. vomitoria foliage alone (RV) and a combination of CA and RV, (CA + RV) in BKS-db mice, indicate that components from R. vomitoria foliage drive the reductions in ectopic lipid accumulation, since CA-treated mice lacked this effect. However, the normalization of blood glucose arises from combination of components from the two source plant materials as administration of either CA or RV resulted in hypoglycaemia. Interestingly, treatment with the CA + RV mixture, generated by mixing individually produced CA and RV plant extracts, resulted in hyperglycaemia, possibly due to drug-drug interactions of the blood glucose-reducing components in either plant extract. Hence, our data show that the best antidiabetic outcome results from the traditional practice of boiling R. vomitoria foliage and C. aurantium fruits together.