Triple high-resolution α-glucosidase/α-amylase/PTP1B inhibition profiling combined with HPLC-HRMS-SPE-NMR for identification of anti-diabetic constituents from Morus alba L.

Morus alba L. is one of the most well-known and widely distributed trees of the family Moraceae, and many parts of this plant are used for anti-diabetic purposes [1]. In the present study, the crude EtOAc extract of M. alba root bark was found to possess potent inhibition of α-glucosidase, α-amylase and protein-tyrosine phosphatase 1B (PTP1B) with IC₅₀ values of 1.70 ± 0.72, 5.16 ± 0.69 and 5.07 ± 0.68 µg/mL. The extract was subsequently investigated by triple high-resolution α-glucosidase/α-amylase/PTP1B inhibition profiling combined with HPLC-HRMS-SPE-NMR [2]. This lead to the identification of six natural Diels-Alder adducts and seven isoprenylated flavonoids as potent α-glucosidase and α-amylase inhibitors with IC₅₀ values in the range of 0.60 ± 0.09 to 27.15 ± 7.10µM (for α-glucosidase) and 1.22 ± 0.34 to 69.38 ± 8.58µM (for α-amylase) respectively. These compounds were together with two 2-arylbenzofurans found to exhibit potent PTP1B inhibition with IC₅₀ values ranging from 4.04 ± 0.38 to 21.67 ± 3.38µM as well. This is the first report of all these compounds as α-glucosidase, α-amylase and/or PTP1B inhibitors. These findings provide the scientific rationale for developing M. alba into a polypharmacological herbal remedy.

Fig. 1

Yong Zhao acknowledges the Chinese Scholarship Council for a scholarship. Arife Önder is thanked for technical assistance.

[1] Grajek K, Wawro A, Kokocha D. Int J Pharm Sci Res 2015; 6: 3110 – 3122.

[2]Wubshet SG, Tahtah Y, Heskes AM, Kongstad KT, Pateraki I, Hamberger B, Møller BM, Staerk D. J Nat Prod 2016; 79: 1063 – 1072.