The Anti-Oxidative and Anti-Neuroinflammatory Effects of Sargassum horneri by Heme Oxygenase-1 Induction in BV2 and HT22 Cells.

Wonmin Ko,Kyounghoon Lee,Nayeon Kim,Ginnae Ahn,Hwan Lee,Eun-Rhan Woo,Sang Rul Park,Sun Hee Cheong,Young Seok Han,Hee Geun Jo,Dong-Sung Lee

doi:10.3390/antiox10060859

Abstract

Sargassum horneri is used as a traditional medicinal agent and exhibits various pharmacological effects. In this study, we found that the 70% EtOH extract contained 34.37 ± 0.75 μg/mg fucosterol. We tested the antioxidant activities of the 70% EtOH extracts and their fractions. The CH2Cl2-soluble fraction showed the strongest DPPH and ABTS radical scavenging activities. Next, we evaluated the anti-neuroinflammatory effects of S. horneri on lipopolysaccharide (LPS)-stimulated BV2 cells. Pretreatment with the extract and fractions suppressed LPS-induced production of nitric oxide (NO) in BV2 cells. The 70% EtOH, CH2Cl2-soluble fraction, and water-soluble fraction inhibited the production of prostaglandin E2, interleukin-6, and tumor necrosis factor-α, as well as markedly blocking LPS-induced expression of inducible NO synthase and cyclooxygenase-2 via inactivation of the nuclear factor-kappa B pathway. In addition, the CH2Cl2-soluble fraction showed the most remarkable heme oxygenase (HO)-1 expression effects and increased nuclear erythroid 2-related factor translocation in the nucleus. In HT22 cells, the CH2Cl2-soluble fraction inhibited cell damage and ROS production caused by glutamate via the regulation of HO-1. Therefore, CH2Cl2-soluble fractions of S. horneri can attenuate oxidative action and neuroinflammatory responses via HO-1 induction, demonstrating their potential in the treatment of neuroinflammatory diseases.

Highlights

Oxidative stress is known to be an important cause of aging and various nervous system disorders
The dried S. horneri was extracted with 70% EtOH and partitioned sequentially with equal volumes of n-hexane, dichloromethane (CH2 Cl2 ), ethyl acetate (EtOAc), and n-butanol (n-BuOH) (Figure 1)
Because heme oxygenase (HO)-1 and nuclear factor erythroid-derived 2-related factor-2 (Nrf2) are well known to play a very important role in regulating oxidative damage and inflammation in most cell types [52,53], we investigated whether the antioxidant and anti-inflammatory effects of the CH2 Cl2 -soluble fraction were directly related to heme oxygenase-1 (HO-1) expression in experiments pretreated with HO-1 inhibitors

Summary

Introduction

Oxidative stress is known to be an important cause of aging and various nervous system disorders. It is biologically produced by oxidative imbalance. Oxidative imbalance occurs due to the formation of reactive oxygen species (ROS) and abnormalities in the antioxidant system of the body [1]. The accumulation of free radicals and ROS can cause acute and chronic diseases. The accumulation of oxidative stress and ROS is known to intensify neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease by causing the destruction and dysfunction of neuronal cells [1,2]. Chronic inflammatory diseases are a significant cause of death, and patients with inflammation-related diseases, including stroke, diabetes mellitus, and ischemic heart

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