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

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: Here we aimed to determine whether commercial green and purple teas are a source of ellagitannins and whether green and purple teas, purple tea ellagitannins and their metabolites urolithins have antidiabetic activity. MATERIALS AND METHODS: Targeted UPLC-MS/MS was employed to quantify the ellagitannins corilagin, strictinin and tellimagrandin I, in commercial teas. The inhibitory effect of commercial green and purple teas and purple tea ellagitannins was evaluated on α-glucosidase and α-amylase. The bioavailable urolithins were then investigated for additional antidiabetic effects, by evaluating their effect on cellular glucose uptake and lipid accumulation. RESULTS: Corilagin, strictinin and tellimagrandin I (ellagitannins) were identified as potent inhibitors of α-amylase and α-glucosidase, with Ki values significantly lower (p < 0.05) than acarbose. Commercial green-purple teas were identified as ellagitannin sources, with especially high concentrations of corilagin. These commercial purple teas, containing ellagitannins, were identified as potent α-glucosidase inhibitors with IC50 values significantly lower (p < 0.05) than green teas and acarbose. Urolithin A and urolithin B were as effective (p> 0.05) as metformin in increasing 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. CONCLUSIONS: This study identified green-purple teas as an affordable widely available natural source with antidiabetic properties. Furthermore, additional antidiabetic effects of purple tea ellagitannins (corilagin, strictinin and tellimagrandin I) and urolithins were identified.

Exploring the anti-proliferative activity of Pelargonium sidoides DC with in silico target identification and network pharmacology.

Pelargonium sidoides DC (Geraniaceae) is a medicinal plant indigenous to Southern Africa that has been widely evaluated for its use in the treatment of upper respiratory tract infections. In recent studies, the anti-proliferative potential of P. sidoides was shown, and several phenolic compounds were identified as the bioactive compounds. Little, however, is known regarding their anti-proliferative protein targets. In this study, the anti-proliferative mechanisms of P. sidoides through in silico target identification and network pharmacology methodologies were evaluated. The protein targets of the 12 phenolic compounds were identified using the target identification server PharmMapper and the server for predicting Drug Repositioning and Adverse Reactions via the Chemical-Protein Interactome (DRAR-CPI). Protein-protein and protein-pathway interaction networks were subsequently constructed with Cytoscape 3.4.0 to evaluate potential mechanisms of action. A total of 142 potential human target proteins were identified with the in silico target identification servers, and 90 of these were found to be related to cancer. The protein interaction network was constructed from 86 proteins involved in 209 interactions with each other, and two protein clusters were observed. A pathway enrichment analysis identified over 80 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched with the protein targets and included several pathways specifically related to cancer as well as various signaling pathways that have been found to be dysregulated in cancer. These results indicate that the anti-proliferative activity of P. sidoides may be multifactorial and arises from the collective regulation of several interconnected cell signaling pathways.

Comparison of the antioxidant content of fruits, vegetables and teas measured as vitamin C equivalents.

Most of the health benefits of black, green and oolong teas made from Camellia sinensis are attributed to their antioxidant content. Many plants and spices have been used to make infusions that are erroneously referred to as 'teas'. The term 'rich in antioxidants' is often used to describe such infusions, often without scientific support. We have used the DPPH method to quantify the total radical scavenging capacity (RSC) of a wide range of 'teas', fruits and vegetables. The results are presented as vitamin C equivalents. These results are compared to the RSC of the recommended portions of fruits and vegetables in the food guide pyramid for a healthy and balanced diet. The EC(50) results show that there are no statistically significant differences in the RSC of black, green and oolong teas. However, the RSC of 'teas' made from other species of plants are significantly lower. Our results show that one or two cups of tea would provide a similar amount of RSC as five potions of fruits and vegetables or 400 mg vitamin C equivalents. This would be comparable to two capsules (200 mg) of vitamin C. Caution is advised in extrapolating these in vitro results to humans due to bioavailability.

Analysis of black tea theaflavins by non-aqueous capillary electrophoresis.

In this study a new capillary electrophoresis (CE) method was developed to quantify the four major theaflavins occurring in black tea. Where aqueous based CE methods showed poor selectivity and considerable band broadening, non-aqueous CE achieved baseline separation of the theaflavins within 10 min. The effects of the organic solvent composition and background electrolyte concentration on the separation selectivity and electrophoretic mobilities were investigated. Our optimized separation solution consisted of acetonitrile-methanol-acetic acid (71:25:4, v/v) and 90 mM ammonium acetate. This method was used to analyze three black tea samples.

Simultaneous analysis of tea catechins, caffeine, gallic acid, theanine and ascorbic acid by micellar electrokinetic capillary chromatography.

A micellar electrokinetic capillary chromatography (MEKC) method for the simultaneous analysis of five tea catechins, theanine, caffeine, gallic acid and ascorbic acid has been developed. The catechins are (-)-epicatechin, (+)-catechin, (-)-epigallocatechin, (-)-epicatechin gallate and (-)-epigallocatechin gallate. p-Nitrophenol serves as both reference and internal standard. All the components are separated within 13 min with a 57 cm uncoated fused-silica column. On-column detection was carried out at 200 nm. This method has been used to measure these compounds in fresh tea leaves and tea liquor. The limit of detection for all analytes ranged from 1 to 20 microg/ml.

Inhibition of PhIP mutagenicity by catechins, and by theaflavins and gallate esters.

Aqueous solutions of gallic acid, methyl gallate, catechins, theaflavins and tannic acid were tested for inhibition of the mutagenicity of PhIP in the Salmonella typhimurium TA98 assay with an S9 fraction from the liver of rats induced with alpha-naphthoflavone and phenobarbital. The IC50S were in the 80-250 microM range for the gallated catechins, theaflavins and tannic acid. No inhibition could be found with these compounds when a direct acting mutagen was used. This indicates that the anti-mutagenic properties of these phenolic compounds may be due to their inhibition of the cytochrome P-450 enzymes.

Inhibition of xanthine oxidase by catechins from tea (Camellia sinensis).

Some epidemiological studies have associated tea drinking with several health benefits, while other such studies have been inconclusive. The liver enzyme, xanthine oxidase (XO) produces uric acid and reactive oxygen species (ROS) during the catabolism of purines. Excess of the former can lead to gout and of the latter to increased oxidative stress, mutagenesis and possibly cancer. Polyphenols are antioxidants, and it has been suggested that they can reduce oxidative stress by their antioxidant properties. We report here on the inhibition of XO by five tea catechins and two flavones. The Ki values (microM) and types of inhibition were catechin (C) (Ki = 303.95, uncompetitive), epicatechin (EC) (Ki = 20.48, mixed), epigallocatechin (EGC) (Ki = 10.66, mixed), epicatechin gallate (ECg) (Ki = 2.86, mixed) and epigallocatechin gallate (EGCg) (Ki = 0.76, competitive). The Ki of EGCg was similar to that of allopurinol (Ki = 0.30, mixed), the drug of choice for inhibition of XO in gout patients. Thus, tea catechins may act at.an earlier stage than has previously been suspected, by inhibiting ROS production, rather than only neutralizing the already formed ROS. This suggests a new mechanism whereby tea drinking may prevent oxidative stress related diseases, e.g. atherosclerosis and cancer.

Inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) mutagenicity by black and green tea extracts and polyphenols.

Solutions of lyophilized preparations of standard black and green tea extracts were made and tested over a range of six concentrations as inhibitors of the mutagenicity caused by the fool mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the Salmonella typhimurium TA98 assay containing S9 fraction from rats induced with alpha-naphthoflavone and phenobarbital. Extracts of both black and green tea were equally good inhibitors of mutagenicity. Purified polyphenols were prepared from tea extracts by solvent extraction. The polyphenols of black tea were more potent inhibitors of mutagenicity than the polyphenols of green tea. These findings suggest that black tea may have similar health-promoting properties to those reported previously for green tea.

Screening of tea clones for inhibition of PhIP mutagenicity.

Standard black and green tea extracts have been known to inhibit mutagenicity caused by PhIP, in the Salmonella typhimurium TA98 assay containing S9 fraction from the liver of rats induced with alpha-naphthoflavone and phenobarbital. Breeding and selection programs for high yielding tea clones have successfully increased yields in many tea producing areas. Six clonal teas and three seedling teas were obtained from a tea producing area in Southern Africa. Standard black and green teas were used as controls. Dose-dependent inhibition of the bacterial mutagenicity elicited by two concentrations of PhIP was found in the extracts of all the teas tested. This indicates that the clonal teas have not lost their anti-mutagenic properties. Small differences were found amongst the clonal teas in their ability to inhibit mutagenicity. This indicates that it may be possible to enhance this trait in future breeding and selection programs.