Assessment of the Antiangiogenic and Anti-Inflammatory Properties of a Maslinic Acid Derivative and its Potentiation using Zinc Chloride

Ioana Zinuca Pavel,Cristina Adriana Dehelean,Flavia Baderca,Andreea Cioca,Ciprian-Valentin Mihali,Corina Danciu,Stefana Avram,Iulia Pinzaru,Elena-Alina Moacă,Rene Csuk,Danina Mirela Muntean

doi:10.3390/ijms20112828

Abstract

Maslinic acid is a pentacyclic triterpene with a plethora of biological activities, including anti-inflammatory, antioxidant, antimicrobial, cardioprotective, and antitumor effects. New derivatives with improved properties and broad-spectrum activity can be obtained following structural changes of the compound. The present study was aimed to characterize a benzylamide derivative of maslinic acid—benzyl (2α, 3β) 2,3-diacetoxy-olean−12-en-28-amide (EM2)—with respect to the anti-angiogenic and anti-inflammatory effects in two in vivo experimental models. Consequently, the compound showed good tolerability and lack of irritation in the chorioallantoic membrane assay with no impairment of the normal angiogenic process during the tested stages of development. In the acute ear inflammation murine model, application of EM2 induced a mild anti-inflammatory effect that was potentiated by the association with zinc chloride (ZnCl2). A decrease in dermal thickness of mice ears was observed when EM2 and ZnCl2 were applied separately or in combination. Moreover, hyalinization of the dermis appeared only when EM2 was associated with ZnCl2, strongly suggesting the role of their combination in wound healing.

Highlights

Extensive experimental research was performed in recent years in the field of drug discovery in the effort to find natural therapeutic approaches for the management of severe conditions such as cancer.Investigating the enormous potential of the Plant Kingdom represents an attractive alternative for drug development [1]
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Other groups showed that maslinic acid could prevent inflammation by the enhancement of several cytokines interleukin (IL)-8, IL−1α, IL−1β, and interferon (IFN)-γ, though stimulating macrophage M1 response involved in anticancer defense activities [38]

Summary

Introduction

Extensive experimental research was performed in recent years in the field of drug discovery in the effort to find natural therapeutic approaches for the management of severe conditions such as cancer.Investigating the enormous potential of the Plant Kingdom represents an attractive alternative for drug development [1]. Medicinal plants as such or in the form of total/ standardized extracts or pure isolated phytochemicals, still represent today one of the main sources for the identification and development of novel active molecules [2]. Pentacyclic triterpenes represent one of the highly investigated group of phytochemicals. This class possesses various therapeutic effects, being used in numerous diseases including cancer [6,7,8]. In order to determine the safety of maslinic acid, Sanchez-Gonzalez et al evaluated the effect of the compound after acute and repeated oral administration in mice [11]. Haematological and biochemical assays revealed neither differences nor side effects as compared to the untreated mice, indicating that the compound can be considered a safe molecule [11]

Results

Discussion

Conclusion