Modulatory Effect of Pyrus pyrifolia Fruit and its Phenolics on Key Enzymes against Metabolic Syndrome: Bioassay-Guided Approach, HPLC Analysis, and In Silico Study

Abstract

This study aims to isolate the active constituents of Pyrus pyrifolia Nakai fruits using a bioassay-guided fractionation approach, test their activity in vitro against key enzymes for metabolic disorders, and support it with molecular docking simulations. The antioxidant potential of the methanolic extract (ME), its polar (PF), and non-polar fractions (NPF), along with the inhibitory activity against α-glucosidase, α-amylase, lipase, angiotensin I converting enzyme (ACE), renin, inducible nitric oxide synthase (iNOS), and xanthine oxidase (XO) were assessed. The PF exhibited the highest antioxidant and enzyme inhibitory activity. Purification of PF yielded rutin, isoquercitrin, isorhamnetin-3-O-β-D-glucoside, chlorogenic acid, quercetin, and cinnamic acid. HPLC-UV analysis of the PF allowed for the quantification of 15 phenolic compounds, including the isolated compounds. Cinnamic acid was the most powerful antioxidant in all assays and potent enzyme inhibitor against the tested enzymes (α-glucosidase, α-amylase, lipase, ACE, renin, iNOS, and XO). Additionally, it showed high affinity to target α-glucosidase and ACE active sites with high docking scores (calculated total binding free energy (ΔGbind) -23.11 kcal/mol and − 20.03 kcal/mol, respectively]. A 20-ns molecular dynamics simulation using MM-GBSA analysis revealed a stable conformation and binding patterns in a stimulating environment of cinnamic acid. Interestingly, the isolated compounds’ dynamic investigations including RMSD, RMSF, and Rg demonstrated a stable ligand − protein complex to the active site of iNOS with ΔGbind ranging from − 68.85 kcal/mol to -13.47 kcal/mol. These findings support the notion that P. pyrifolia fruit is a functional food with multifactorial therapeutic agents against metabolic syndrome-associated diseases.

Revealing Edible Bird Nest as Novel Functional Foods in Combating Metabolic Syndrome: Comprehensive In Silico, In Vitro, and In Vivo Studies

“…Metabolic syndrome is closely related to the incidence of oxidative stress and several related diseases such as obesity and diabetes ( Figure 5 ) [ 28 ]. In people with metabolic syndrome, iNOS levels are found to be higher, and this correlates with the incidence of oxidative stress [ 29 ]. In addition, lowering and inhibiting ROS1 kinase, FTO protein, and lipase can reduce the incidence of metabolic syndrome in obese people, and inhibiting these receptors can also be an anti-aging approach [ 20 , 30 , 31 ].…”

Identification and molecular docking of xanthine oxidase and α‐glucosidase inhibitors in Opuntia ficus‐indica fruit

“…Many enzyme inhibitors had been identified and isolated from extracts of fruits, vegetables, and herbs. According to previous reports, polyphenols, such as quercetin, isorhamnetin, and rutin, had been isolated and identified from natural plants as XOD and α-Glu inhibitors (Li, Gong, et al, 2022;Mahdy et al, 2023). Thus, the natural products extracted from the plant can act as efficient inhibitors of XOD and α-Glu.…”