Chemical characterization and in vitro immunomodulatory effects of different extracts of moss Hedwigia ciliata (Hedw.) P. Beauv. from the Vršačke Planine Mts., Serbia.

Marija R. Mandić,Uroš M. Gašić,Bojan Dj. Božić,Jen-Tsung Chen,Biljana Dj. Božić Nedeljković,Aneta D. Sabovljević,Sonja N. Duletić-Laušević,Mariana M. Oalđe,Tanja M. Lunić,Marko S. Sabovljević

doi:10.1371/journal.pone.0246810

Abstract

Bioactive compounds from natural sources are of great importance because of their potential pharmacological activity and tremendous structural diversity. In this study, the chemical composition of different moss extracts of Hedwigia ciliata P. Beauv. have been examined, as well as their antioxidant, antineurodegenerative/anti-neuroinflammatory, antidiabetic, and antiproliferative potential. The extracts were prepared by Soxhlet extractor using solvents of different polarity. Chemical characterization of the extracts revealed the presence of phenolics and flavonoid compounds, together with triterpenoids as secondary metabolites of high biological activity. Significant antioxidant properties of all the extracts were exhibited using the β-carotene assay. The highest activities were found for water:ethanol extract (with the highest inhibition rate of 96%), but also significant inhibition was measured for ethanol and ethyl acetate extracts (80% and 70%, respectively). Confirmation of biocompatibility of investigated moss extracts has been performed using normal human fibroblast cell line, MRC-5. The H. ciliata extracts exhibited significant antiproliferative activity (~ 50%) against the MDA-MB-231 (human breast adenocarcinoma cell line), which has not previously been reported elsewhere. The Griess assay confirmed the potential anti-neuroinflammatory activity of the extracts, as significant effects in reducing NO production by LPS-stimulated BV2 (normal murine microglia cell line) was observed. This data is in line with noted antineurodegenerative potential measured by the inhibition of acetylcholinesterase (with the highest inhibition rate of 60% for ethyl acetate extract) and tyrosinase (with the highest inhibition rate of 70% for ethanol extract). Additionally, the H. ciliata extracts exhibited significant antidiabetic effect mediated by α-glucosidase inhibition (with the highest inhibition rate of 80% for ethyl acetate extract). The obtained data suggest the presence of immunomodulatory effects of the moss extracts in vitro, which allows the design of new experiments aimed at detecting and characterizing bioactive compounds of the extracts and additionally elucidate detailed mechanisms of their effects.

Highlights

Numerous studies have indicated the presence of immunomodulatory molecules in various plant extracts, with some highlighting the potential use of phenolics, flavonoids, and terpenoids as immunomodulatory agents [1,2]
According to the obtained results, extracts E1 and E2 exhibited similar phenolic acid content, while the highest concentration of phenolic acids was shown to be in E3 extract, which indicated a significantly higher level of these compounds than in the other tested extracts
Further studies on the mechanism of apoptotic pathways are needed, these results suggest that antiproliferative effects of these extracts toward MDA-MB-231 cells may be caused by ROS and nitric oxide (NO) increased production

Summary

Introduction

Numerous studies have indicated the presence of immunomodulatory molecules in various plant extracts, with some highlighting the potential use of phenolics, flavonoids, and terpenoids as immunomodulatory agents [1,2]. As there is a growing demand for new active compounds and design of new drugs, mosses provide the opportunity to discover new antimicrobial and antitumor therapeutic agents [4]. Bryophytes represent a large group of plants that are widespread in almost every part of the world. They are divided into three phyla–mosses, liverworts, and hornworts. Mosses grow on various types of substrates such as soil, stones, rocks, trees, rotting trunks, roofs, in lakes and rivers [5]. Their distribution depends on abiotic factors as well as geo-historical events. There are evidences that the first species of mosses appeared 472 million years ago, making them one of the oldest land plants on the planet [5,6]

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