Protein tyrosine phosphatase 1B inhibitors isolated from Artemisia roxburghiana

Abstract

Artemisia roxburghiana is used in traditional medicine for treating various diseases including diabetes. The present study was designed to evaluate the antidiabetic potential of active constituents by using protein tyrosine phosphatase 1B (PTP1B) as a validated target for management of diabetes. Various compounds were isolated as active principles from the crude methanolic extract of aerial parts of A. roxburghiana. All compounds were screened for PTP1B inhibitory activity. Molecular docking simulations were performed to investigate the mechanism behind PTP1B inhibition of the isolated compound and positive control, ursolic acid. Betulinic acid, betulin and taraxeryl acetate were the active PTP1B principles with IC 50 values 3.49 ± 0.02, 4.17 ± 0.03 and 87.52 ± 0.03 mM, respectively. Molecular docking studies showed significant molecular interactions of the triterpene inhibitors with Gly220, Cys215, Gly218 and Asp48 inside the active site of PTP1B. The antidiabetic activity of A. roxburghiana could be attributed due to PTP1B inhibition by its triterpene constituents, betulin, betulinic acid and taraxeryl acetate. Computational insights of this study revealed that the C-3 and C-17 positions of the compounds needs extensive optimization for the development of new lead compounds.

Ethnomedicinal Investigation of Medicinal Plants of Chakrata Region (Uttarakhand) Used in the Traditional Medicine for Diabetes by Jaunsari Tribe

“… Pati (H) Shrub (W)/aerial parts Essential oil (mainly contains β-caryophyllene, germacrene D, caryophyllene oxide and cis-β-elemenone [ 34 ] A decoction of leaves with water is used in the morning The oral administration of hydro-methanolic extracts of aerial parts (200 and 400 mg/kg) and its chloroform fraction (200 mg/kg) for 15 days showed a reduction in blood glucose level of STZ induced diabetic rats [ 35 ] Artemisia roxburghiana Wall. ex Besser Roxburgh’s Wormwood (E), Kuranja/Kinid (L) Herb (W)/aerial parts Betulin ( 4 ), betulinic acid ( 5 ), artemisinin ( 6 ) [ 36 ] The decoction of aerial parts is used either alone or in combination with the dried fruits of Zizyphus jujube (1) The methanol extract of aerial parts (100 µg/mL), betulinic acid (IC 50 3.49 µM) and betulin (IC 50 4.17 µM) showed protein tyrosine phosphatase 1B (PTP1B) enzyme inhibitory activity in vitro [ 37 ] (2) The ethanol leaves extract (1 μg/mL) showed insulin secretagogue activity at a concentration of when tested for insulin release from insulinoma cell line (INS-1 cells) [ 38 ] (3) Artemisinin showed trypsin inhibitory activity [ 36 ] Artemisia vulgaris L. Dhamanaka (S), Douna (H), Indian Wormwood/Mugwort (E) Herb (W)/whole plant Essential oil (mainly contains α-pinen, menthol, β-eudesmol and spathulenol) [ 39 ] A decoction of leaves with water is used in the morning Oral administration of ethanol leaves extract (250 and 500 mg/kg) for 16 weeks reduced the renal impairment in diabetic nephropathy rats through anti-diabetic, anti-oxidant and protective morphological changes in STZ induced diabetes rats [ 40 ] Euphorbiaceae Mallotus philippensis (Lam.) Müll.Arg.…”

“…(1) The methanol extract of aerial parts (100 µg/mL), betulinic acid (IC 50 3.49 µM) and betulin (IC 50 4.17 µM) showed protein tyrosine phosphatase 1B (PTP1B) enzyme inhibitory activity in vitro [ 37 ]…”

“…Through this mechanism, they are known to enhance insulin receptor phosphorylation and stimulate glucose uptake into cells. On the other hand, its flavonoids inhibit cAMP phosphodiesterase which is a modulator of insulin secretion [ 37 ]. G. sylvestre has been reported to interact with glyceraldehyde-3-phosphate dehydrogenase, a key enzyme in the glycolysis pathway.…”

Screening for Triterpenoid Saponins in Plants Using Hyphenated Analytical Platforms

“…Triterpenoid saponins are secondary metabolites synthesized in plant and mammalian cells. Several studies have reported on the role of triperpenoid saponins as natural defence compounds in plants [2,3,4,5], and some members of triterpenoid saponins have also been found to possess beneficial pharmacological properties [6,7,8]. The literature contains structures of several hundred saponins isolated from various sources including plants and animals.…”

Type 2 Diabetes Mellitus and Protein-Tyrosine Phosphatase 1B1

“…It contains an N-terminal catalytic domain, two proline-rich sequences and a C-terminal hydrophobic region. The active site of PTP1B is located in the P fold of 214-221 residue, in which Cys215 and Arg221 are critical to its phosphatase catalytic sites [8]. PTP1B is localized on the cytoplasmic face of the endoplasmic reticulum (ER) by means of its 35 amino acid C-terminal sequence.…”