| Kinkeliba (Combretum micranthum, Fam. Combretaceae) is an undomesticated shrub species of western Africa and is one of the most popular traditional bush teas of Senegal. The herbal beverage is traditionally used for weight loss, digestion, as a diuretic and mild antibiotic, and to relieve pain. The fresh leaves are used to treat malarial fever. Leaf extracts, the most biologically active plant tissue relative to stem, bark and roots, were screened for antioxidant capacity, measuring the removal of a radical by UV/VIS spectrophotometry, anti-inflammatory activity, measuring inducible nitric oxide synthase (iNOS) in RAW 264.7 macrophage cells, and glucose-lowering activity, measuring phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in an H4IIE rat hepatoma cell line. Radical oxygen scavenging activity, or antioxidant capacity, was utilized for initially directing the fractionation; highlighted subfractions and isolated compounds were subsequently tested for anti-inflammatory and glucose-lowering activities. The ethyl acetate and n-butanol fractions of the crude leaf extract were fractionated leading to the isolation and identification of a number of polyphenolic compounds. Some of these compounds, the catechins and glycosylflavones, were previously reported in kinkeliba. Other compounds, the flavans and galloylated C-glycosylflavone derivatives, are being reported for the first time in this species and family. Finally, a group of major constituents in the kinkeliba leaves were discovered to be a series of compounds with a new skeleton, a flavan-piperidine alkaloid. The four kinkeloids, as they are named here first, were isolated and structurally elucidated by 1- and 2-D NMR spectroscopy and HRMS spectrometry. The catechins and flavans were the active compounds by antioxidant capacity and epicatechin was identified as a glucose-lowering compound by PEPCK inhibition. The positive glucose-lowering activities led to an animal study that tested the activity of the crude extract and ethyl acetate and n-butanol fractions in mice fed a high-fat diet, resulting in the development of a diabetic model. After six weeks of daily treatments, the treated groups showed lowered baseline blood glucose levels as well as decreased PEPCK levels in the liver, strongly suggesting that kinkeliba constituents may be beneficial in the treatment of Type 2 diabetes. |
