Abstract

In order to find new natural products with anti-inflammatory activity, chemical investigation of a 3000-meter deep-sea sediment derived bacteria Bacillus subtilis B5 was carried out. A new macrolactin derivative was isolated and identified as 7,13-epoxyl-macrolactin A (1). Owing to the existence of the epoxy ring, 1 exhibited a significant inhibitory effect on the expression of inducible nitric oxide and cytokines, compared with previously isolated known macrolactins (2–5). Real-time Polymerase Chain Reaction (PCR) analysis showed that the new compound significantly inhibited the mRNA expressions of inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Reverse transcription-PCR analysis demonstrated that the new compound reduced the mRNA expression level of IL-1β in a concentration-dependent manner.

Highlights

  • The process of inflammation is the result of immune system activation which coordinates the normal defense mechanism of our body in response to microbial infection

  • Based on the above results, we further investigated the effects of 1 on IL-1β mRNA expressions in LPS-stimulated RAW 264.7 macrophages by Reverse Transcription-Polymerase Chain Reaction (PCR) analysis

  • Evaluation of its anti-inflammatory effect indicated that the new compound inhibited the expression of proinflammatory cytokines IL-1β, IL-6 and inducible nitric oxide synthase (iNOS) induced by LPS

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Summary

Introduction

The process of inflammation is the result of immune system activation which coordinates the normal defense mechanism of our body in response to microbial infection. Uncontrolled inflammation is believed to play crucial roles in the pathogenesis of various diseases, such as cardiovascular diseases [1], inflammatory bowel disease [2], cancer [3], diabetes [4], asthma [5], and Alzheimer’s disease [6]. Biochemical parameters, such as expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and 5-lipoxygenase [7,8], and levels of tumor necrosis factor-α (TNF-α), interferon γ (IFN-γ), interleukin-1 (IL-1), and interleukin-6 [9,10]. Several types of drugs are used to treat inflammatory disorders, such as biological, steroidal, and nonsteroidal anti-inflammatory drugs. They cause adverse side effects, and biological

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