Bioassay-Guided Isolation, Metabolic Profiling, and Docking Studies of Hyaluronidase Inhibitors from Ravenala madagascariensis.

Esraa M Mohamed,Hossam M Hassan,Hani A Alhadrami,Farid A Badria,Mona H Hetta,Mohamed A Selim,Mostafa E Rateb,Asmaa M Aboulmagd,Usama Ramadan Abdelmohsen

doi:10.3390/molecules25071714

Abstract

Hyaluronidase enzyme (HAase) has a role in the dissolution or disintegration of hyaluronic acid (HA) and in maintaining the heathy state of skin. Bioassay-guided fractionation of Ravenala madagascariensis (Sonn.) organ extracts (leaf, flower, stem, and root) testing for hyaluronidase inhibition was performed followed by metabolic profiling using LC–HRMS. Additionally, a hyaluronidase docking study was achieved using Molecular Operating Environment (MOE). Results showed that the crude hydroalcoholic (70% EtOH) extract of the leaves as well as its n-butanol (n-BuOH) partition showed higher HAase activity with 64.3% inhibition. Metabolic analysis of R. madagascariensis resulted in the identification of 19 phenolic compounds ranging from different chemical classes (flavone glycosides, flavonol glycosides, and flavanol aglycones). Bioassay-guided purification of the leaf n-BuOH partition led to the isolation of seven compounds that were identified as narcissin, rutin, epiafzelechin, epicatechin, isorhamnetin 7-O-glucoside, kaempferol, and isorhamnetin-7-O-rutinoside. The docking study showed that narcissin, rutin, and quercetin 3-O-glucoside all interact with HAase through hydrogen bonding with the Asp111, Gln271, and/or Glu113 residues. Our results highlight Ravenala madagascariensis and its flavonoids as promising hyaluronidase inhibitors in natural cosmetology preparations for skin care.

Highlights

The skin is the external or exterior organ of our bodies which plays as a fence against chemical, physical, and biological pollutants [1]
Partitions of the leaves were evaluated for their Hyaluronidase enzyme (HAase) inhibition activity, where hydro-alcoholic as well as its n-BuOH extracts of R. madagascariensis showed higher inhibition
The n-BuOH was subjected to chromatographic purification, yielding seven compounds identified as narcissin, rutin, epicatechin, isorhamnetin 7-O-glucoside, isorhamnetin

Summary

Introduction

The skin is the external or exterior organ of our bodies which plays as a fence against chemical, physical, and biological pollutants [1]. Earlier studies proved that the efficient HAase’s inhibitory ability of some flavonoids, like apigenin, luteolin, quercetin, kaempferol, and rutin is due to their closely related structure [17], on the other hand the activity towards Hyal increases with the increasing the number of hydroxyl groups, especially in the 2,30 position (quercetin) and 50 (myricetin) and decreased after glycosylation or substitution of hydroxyl groups [13,14] Natural extracts such as brown seaweed (Padina pavonica) have shown an inhibitory effect on hyaluronidase and is used as an anti-aging product [18]. The n-butanol, aqueous and methanol extracts of Pleurotus citrinopileatus were found to act as hyaluronidase inhibitors by 9.7%, 10.8%, and 25.4%, at concentrations of 2.0, 1.1, and 4.1 mg/mL, respectively, the aqueous and methanolic extract of Pleurotus tuber-regium showed hyaluronidase inhibition by 22.19% and 3.94%, respectively, at 100 μg/mL while Trametes lactinea aqueous and acetonic extract inhibited hyaluronidase by 88.6%

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Results

Conclusion