Abstract

Valeriana rigida Ruiz & Pav. (V. rigida) has long been used as a herbal medicine in Peru; however, its phytochemicals and pharmacology need to be scientifically explored. In this study, we combined the offline 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH)-/ultrafiltration-high-performance liquid chromatography (HPLC) and high-speed counter-current chromatography (HSCCC)/pH-zone-refining counter-current chromatography (pH-zone-refining CCC) to screen and separate the antioxidants and aldose reductase (AR) inhibitors from the 70% MeOH extract of V. rigida, which exhibited remarkable antioxidant and AR inhibitory activities. Seven compounds were initially screened as target compounds exhibiting dual antioxidant and AR inhibitory activities using DPPH-/ultrafiltration-HPLC, which guided the subsequent pH-zone-refining CCC and HSCCC separations of these target compounds, namely 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, 5-O-caffeoylquinic acid, 3,4-O-di-caffeoylquinic acid, 3,5-O-di-caffeoylquinic acid, 4,5-O-di-caffeoylquinic acid, and 3,4,5-O-tri-caffeoylquinic acid. These compounds are identified for the first time in V. rigida and exhibited remarkable antioxidant and AR inhibitory activities. The results demonstrate that the method established in this study can be used to efficiently screen and separate the antioxidants and AR inhibitors from natural products and, particularly, the root extract of V. rigida is a new source of caffeoylquinic acids with antioxidant and AR inhibitory activities, and it can be used as a potential functional food ingredient for diabetes.

Highlights

  • Our results revealed that the 70% MeOH root extract of V. rigida possesses remarkable in vitro antioxidant and aldose reductase (AR) inhibitory activities (Table S1 and Table 1), which are mainly attributed to the presence of seven caffeoylquinic acids, 3-CQA, 4-CQA, 5-CQA, 3,4-diCQA, 3,5-diCQA, 4,5-diCQA, and 3,4,5-triCQA as demonstrated by offline DPPH-/ultrafiltrationHPLC (Figures 1 and 2) and 96-well plate assays (Tables 4 and 5)

  • The present study is the first to report that the 70% MeOH root extract of V. rigida possesses considerable in vitro antioxidant and AR inhibitory activities, and it demonstrated that the antioxidant and AR inhibitory activities of the extract were mainly attributed to the presence of seven caffeoylquinic acids 3-CQA (1), 4-CQA

  • The results indicated that the caffeoylquinic acids-rich root extract of

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Summary

Introduction

Intensive glycemic control can delay the progression of diabetic complications, which may presumably occur due to the potential “metabolic memory” caused by early hyperglycemia and inadequate glycemic control [8]. Several pathways, such as polyol pathway, advanced glycation end products/receptors, hexosamine pathway, and others, can be activated and may reach the advanced stage in hyperglycemia condition; they may produce an excess of reactive oxygen species (ROS) and lead to cellular oxidative stress, which is considered an important cause and therapeutic target of diabetic complications [4,9,10,11]. Many natural components have revealed anti-diabetic potential via inhibiting ROS/oxidative stress and AR, such as curcuminoids, resveratrol [12], quercitrin [13], quercetin [14,15], and chlorogenic acid [16,17], which highlights the importance to screen and separate potent antioxidants and AR inhibitors from natural products

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