Abstract

Traditional Chinese medicine (TCM), such as Huanglian-Jie-Du-Tang, a heat-clearing and detoxifying decoction is beneficial for alleviation of inflammation-related diseases. The objective of the present study is to uncover the effect and mechanism of heat-clearing, detoxifying and blood stasis removing decoction (HDBD) on the treatment of acute soft tissue injury (STI) which is characterized with excessive inflammatory cascade at the onset. Male Sprague–Dawley (SD) rats with hammer beating served as the in vivo models of acute STI. Hematoxylin–Eosin (HE) staining was used for histopathology assessment. The levels of inflammatory factors, including prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1t and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Human dermal microvascular endothelium cell line HMEC-1 and rat vascular endothelium cell line RAOEC were used to explore the mechanism in vitro. Luciferase gene reporter assay was applied to determine the relationship between miR-26b-5p and Cyclo-oxygenase 2 (COX2). The results showed that HDBD intervention significantly reduced the temperature difference between the healthy side and affected side of rats with hammer beating, together with the decreased levels of COX2, PGE2, TNF-α, IL-6 and IL-1β, and the increased level of miR-26b-5p. In mechanism, miR-26b-5p targeted COX2 and decreased its expression, leading to significant decreases in the levels of PGE2, TNF-α and IL-6 in RAOEC and HMEC-1 cells. In addition, miR-26b-5p inhibition impaired the effects of HDBD on the suppression of PGE2, TNF-α, IL-6 and IL-1β in vitro. In conclusion, the present study revealed that HDBD relieved acute STI via modulating miR-26b-5p/COX2 axis to inhibit inflammation.

Highlights

  • Acute soft tissue injury (STI) is a common exercise injury in clinic, imposing a large burden on society due to the direct healthcare costs and time lost from productive employment [1,2]

  • HDBD treatment significantly reduced the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), IL-6, Prostaglandin E2 (PGE2) and IL-1β in the muscle tissues caused by hammer beating (Figure 1B–E)

  • These results demonstrated that HDBD could assuage acute STI and inhibit the excessive inflammatory responses

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Summary

Introduction

Acute soft tissue injury (STI) is a common exercise injury in clinic, imposing a large burden on society due to the direct healthcare costs and time lost from productive employment [1,2]. Acute STI is characterized by aseptic inflammation and causes injuries in several manners, such as local edema, bruising, pain, muscle fiber fracture and petechiae [3,4]. Targeting the excessive inflammatory cascade has been considered as an effective method to improve acute STI [7,8]. Cyclo-oxygenase 2 (COX2), called as prostaglandin-endoperoxide synthase 2 (PTGS2), serves as a crucial inflammation factor as same as tumor necrosis factor-α (TNF-α), interleukin (IL)-6 (IL-6) and IL-1β [9,10]. Increased evidence has shown that COX2 inhibitors (coxibs) display a good curative effect on the improvement of acute STI [2,11,12]. Prostaglandin E2 (PGE2), an arachidonic acid metabolite, serves as an inflammatory mediator in STI [8,13,14].

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