Anti-diabetic potential of Chamaerops humilis L. aerial parts: Phenolic compounds with α-amylase and α-glucosidase inhibitory activates in-vitro, in-vivo and in-silico studies

Five compounds were isolated from the aerial parts of Chamaerops humilis L. and characterized as tricin-7rutinoside (1), tricin (2), dihydrotricin (3) diasteroisomer of tricin 4 '-O(erythro-beta-guaiacyl glyceryl) ether (salcolin A)(4a), tricin-4 '-O-(threo-beta-guaiacyl glyceryl) ether (salcolin B) (4b) and (-)-(5s, 6s)-5,6-dihydro-3,8,10trihydroxy-5-(4-hydroxy-3-methoxyphenyl)-6-hydroxymethyl-2,4-dimethoxy 7H benzo [e] xanthen-7-one (5). Their structures were elucidated by comparing their spectral data with those reported in the literature. To the best of our knowledge, compounds (3-5) were reported here for the first time from Chamaerops humilis. The methanolic extract of Chamaerops humilis (CHME) and the five isolated compounds were studied for its antidiabetic effect using in vitro alpha-glucosidase and alpha-amylase inhibitory assay that showed a significant activity. The toxicological study indicated that CHME was safe up to 5000 mg/kg bw. Two doses were selected for the in vivo study (800 and 1600 mg/kg bw) and orally administered to high fat diet/streptozotocin-induced diabetic rats for 10 consecutive days. The results revealed that the CHME improved the blood glucose levels in a dose dependent manner, the dose 1600 mg/kg showed the best results dependently along the period of the experiment. CHME and the five isolated compounds were evaluated in silico for their anti-diabetic effect. The antiinflammatory effect of CHME (1600 mg/kg bw) was proved by significant downregulation of expression for interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-1 (MMP-1) genes. In conclusion, CHME and its constituents may be a potential hypoglycemic agent working through the antiinflammatory and enzyme inhibitory pathways. The docking studies demonstrated that compounds Tricin7rutinoside and Salcolin isomers had promising binding energies of -9.10 kcal/mol and -8.70 kcal/mol, respectively, against alpha-amylase. These binding energies were superior to that of acarbose, which had a binding energy of -7.60 kcal/mol. In addition, docking analysis provided promising results for the inhibition of alpha-glucosidase by Tricin7-rutinoside and Dihydrotricin with binding affinity -7.9 kcal/mol and -7.9 kcal/mol, respectively while the binding affinity of acarbose is -6.40 kcal/mol. Overall, the methanolic extract from Chamaerops humilis exhibited good in silico of alpha-amylase and alpha-glucosidase enzyme inhibition potential. These findings suggest that these compounds may have potential as anti-diabetic agents, with further research needed to verify their efficacy and safety.