The potential antidiabetic properties of purple tea [Camellia sinensis (L.) O Kuntze], purple tea ellagitannins, and urolithins

Abstract

Diabetes is one of the largest health challenges of the 21st century and is amongst the top 10 causes of death globally. Although there is no cure for type 2 diabetes (T2DM), several pharmaceutical drugs are available for treatment, however most have associated side effects. Tea (Camellia sinensis) has been consumed for centuries as traditional medicine for various diseases, including diabetes. The mechanism of action of many traditional medicines, including tea, often requires elucidation. Purple tea is a natural mutant of Camellia sinensis, grown in China and Kenya, and is rich in anthocyanins and ellagitannins (ETs). The main aim of the project is to determine the antidiabetic activity of purple teas as well as the associated ETs and metabolites.

In silico molecular docking of identified tea ETS, and urolithins to nine antidiabetic targets revealed that corilagin, strictinin, tellimagrandin I, urolithin A and urolithin B were the best antidiabetic candidates. In silico drug-target interactions generated by SwissTragetPrediction highlighted the potential antidiabetic properties of the ETs and urolithins and also indicated no associations that could lead to harmful cross-reactions.

Commercial green-purple teas were identified as ET sources, with especially high concentrations of corilagin. In addition, the concentration of the ETs in purple tea samples with different degrees of oxidation were also evaluated. Corilagin and strictinin concentrations were significantly higher in green-purple tea than in black-purple and pu’erh-purple tea variants. Furthermore, it was determined that the ellagitannins had a unique peak-to-trough UV ratio, which can be used to detect ellagitannins spectroscopically. The UV peak-to-trough ratio of the ellagitannins was below 1.5, while for catechins it was at least 2.5 Through the untargeted UPLC-qTOF-MS analysis, a total of 807 ion features were identified, of which 109 were significantly different between the purple and green tea cultivars. 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-b-D-glucose (GHG), quercitrin and kaempferol 3-(6-acetylgalactoside) were identified as purple tea discriminatory metabolites.

Commercial purple teas, containing ETs, were identified as potent α-glucosidase inhibitors with IC50 values significantly lower (p < 0.05) than green teas and acarbose. The ETs, corilagin, strictinin and tellimagrandin I were identified as potent inhibitors of α-amylase and α-glucosidase, with Ki values significantly lower (p < 0.05) than acarbose. The α-glucosidase Ki values of strictinin (0.11 ± 0.03 µM), corilagin (0.33 ± 0.13 µM) and tellimagrandin I (0.12 ± 0.01 µM) were significantly lower than the Ki value of acarbose (472 ± 35 µM). Molecular dynamic simulations revealed that the strictinin-3L4Y complex converges and stabilises much quicker than the acarbose-3L4Y complex, and strictinin formed more hydrogen bonds with 3L4Y than acarbose.

Non-cytotoxic concentrations of urolithin A and urolithin B were as effective (p > 0.05) as metformin in increasing 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose (2-NBDG) glucose uptake in adipocytes, muscle cells and hepatocytes. In addition, similar (p > 0.05) to metformin, both urolithin A and urolithin B reduced lipid accumulation in adipocytes and hepatocytes, evaluated with the Oil red O assay.

In conclusion, drinking purple teas rich in ETs, such as corilagin, strictinin and tellimagrandin I, can potentially inhibit α-glucosidase in the small intestine, before being metabolised to urolithins. The bioavailable urolithins can enhance glucose uptake in adipose, muscle cells and hepatocytes, while also decreasing lipid accumulation in adipocytes and hepatocytes. Consequently, these multifunctional compounds target starch hydrolysis, glucose uptake, and hepatic and perivascular lipid accumulation with minimal cytotoxic effects.