Abstract

Chukrasia tabularis A.Juss. is a canopy tree widely distributed in Asia and commonly used for construction-grade timber. While the residues resulting from the timber exploration constitute the major source of waste, other parts of the plant remain underutilized. Therefore, aiming the valorisation of a major residue resulting from C. tabularis wood industry, the leaves were here investigated on their potential content in bioactive constituents, but also on their capacity to modulate mediators and enzymes engaged in metabolic disorders, particularly those involved on the development and progression of diabetes. HPLC–DAD–ESI/MSn and UPLC-ESI-QTOF-MS2 characterization of a methanol extract obtained from the leaves, allowed the identification of 25 phenolic constituents, quercetin-3-O-rhamnoside being identified as the main bioactive. The leaf extract and the major flavonoid (quercetin-3-O-rhamnoside) were investigated on their impact towards a series of targets involved in the physiopathology of diabetes. The extract displayed significant scavenging properties against nitric oxide and superoxide radicals, inhibiting also lipid peroxidation and aldose reductase activity. While no noteworthy effects were noted on pancreatic lipase and α-amylase activity, the extract strongly inhibited α-glucosidase (IC50 = 21.14 µg/mL) and proved to be ca. 5 times more effective than the benchmark drug, acarbose. Moreover, the leaf extract significantly inhibited also 5-lipoxygenase (5-LOX) (IC50 = 13.12 µg/mL). Kinetic studies on α-glucosidase and 5-LOX activity disclosed a mixed type inhibition. Furthermore, C. tabularis extract reduced LPS-induced overproduction of NO, L-citrulline and IL-6 in activated RAW 264.7 macrophages. When individually assayed, quercetin-3-O-rhamnoside significantly contributed to the antiradical properties and inhibitory effects of the extract upon the enzymatic targets, but other phenolic bioactives appear also to underlie the recorded anti-inflammatory effects. Taken together, our results demonstrate that the leaves of C. tabularis are rich in phenolic constituents with a great potential to improve metabolic disorders. The evidenced bioactivity of this industrial product might feed R&D programs for the development of new drugs that might simultaneously improve glycaemic, oxidative and inflammatory benchmarks in diabetic patients.

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