Studies of the structure-antioxidant activity relationships and antioxidant activity mechanism of iridoid valepotriates and their degradation products.

Feifei Wang,Bin Liu,Yumei Zhang,Shouhai Wu,Yi He,Shuangcheng Ma,Zhong Dai,Luis Eduardo M Quintas

doi:10.1371/journal.pone.0189198

Abstract

Oxidative stress has been associated with diverse diseases, including obesity, cancer and neurodegeneration. In fact, Valeriana jatamansi Jones (valerian) and its extracts possess strong antioxidant activities that extend their application in clinical practice to the treatment of these illnesses, even though the underlying mechanisms are not well understood. Iridoid valepotriate, a characteristic iridoid ester in valerian with poor chemical stability, possesses considerable antioxidant components. The original compounds and their degradation products have been found to exhibit strong antioxidant activities. However, the relationship between their structure and antioxidant effects and the mechanism underlying their oxidation resistance remain unclear. A forced degradation study using three iridoid valepotriates (valtrate, acevaltrate and 1-β acevaltrate) was performed in this work, and the structures of their degradation products were estimated by TLC-MS and LC-MS. Comparison of the antioxidant activities of the iridoid valepotriates before and after forced degradation revealed that degradation reduced the activities of the iridoid valepotriates in free radical scavenging and cytotoxic and cell apoptosis tests. The results suggested that the oxirane nucleus is important for defining the antioxidant profile of iridoid valepotriate. We uncovered possible mechanisms that could explain the antioxidant activities, including the generation of two hydroxyl groups through intramolecular transfer of an H• from an oxirane ring and a reduction in ROS levels through interactions with GABAergic signalling pathways.

Highlights

The human body constantly reacts with oxygen to produce highly reactive molecules known as reactive oxygen species (ROS) or free radicals
We initially identified the structural characteristics of iridoid valepotriates [valtrate (V), acevaltrate (AV) and 1-β acevaltrate (BAV), Fig 1] and their degradation products
Based on the Heteronuclear multiple bond coherence (HMBC) data, the chemical shifts of the four ester carbonyls were assigned as δC 172.6 (C-13), 171.2 (C-16), 171.8 (C-22) and 172.2 (C-2’) for AV and δC 172.6 (C-13), 172.9 (C-16), 168.9 (C-22) and 172.3 (C-2’) for BAV; these results correspond to the data in the literature [32,33] (S1 Fig)

Summary

Introduction

The human body constantly reacts with oxygen to produce highly reactive molecules known as reactive oxygen species (ROS) or free radicals. The strong cellular oxidizing potential of excess ROS might cause oxidative damage to proteins, membranes and genes [1, 2]. Oxidative stress has been implicated as a major cause of cellular injuries in a wide variety of clinical. Studies of the structure-antioxidant relationships and mechanism of iridoid valepotriates and degradations abnormalities, in the central nervous system (CNS). In tumour cells, the generation of ROS has contributed to the development of sophisticated systems to counterbalance oxidative stress through rapid proliferation [3]. Based on this information, drugs with antioxidant activities are widely used for the treatment of cancer, anxiety neurosis, and Parkinson’s disease, among other diseases

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Results

Conclusion