Andrographolide relieved pathological pain generated by spared nerve injury model in mice

Huang-Chi Wang,Hsin-Sheng Tsay,Hui-Nung Shih,Yi-An Chen,Kai-Ming Chang,Dinesh Chandra Agrawal,Siendong Huang,Yi-Lo Lin,Meng-Jen Lee

doi:10.1080/13880209.2018.1426614

Abstract

Context: Andrographolide (Andro), found in large quantities in Andrographis paniculata Nees (Acanthaceae), is anti-inflammatory, especially in the central nervous system (CNS) glia.Objective: The objective of this study is to test Andro’s ability to reduce allodynia in a spared nerve injury model.Material and methods: Male 30 g BalbC mice were divided into four groups: (1) Sham-operated control (Sham-group); (2) nerve injured and treated with saline (Saline-group); (3) nerve injured and treated with Andro (Andro-group); (4) nerve injured and treated with non-steroidal anti-inflammatory drugs (NSAIDS) (NSAIDS-group). Andro or NSAIDS (diclofenac salt) were injected intraperitoneally at 5 mg/kg body weight daily. Mechanical allodynia was assessed by von Frey tests at 3, 7, and 14 d. For immunohistochemical analysis, samples were collected at 7 d.Results: The threshold for inducing allodynia increased and the response percentage reduced in the Andro-group when compared with the Saline-group, as well as when compared with NSAIDS groups throughout 3–14 d. The ratio of threshold for OP-Andro/OP-saline and for OP-Andro/OP-NSAIDS groups was 20.42 and 11.67 at 14 d, respectively. The ratio of response percentage for OP-Andro/OP-saline and for OP-Andro/OP-NSAIDS was 0.32 and 0.39 at 14 d, respectively. Interleukin-1 (IL-1) immunostaining in the spinal cord was reduced in the Andro-group. Astrocytic activities were not significantly reduced in the Andro-group compared with the Saline-group at 7 d post-operation (PO)Conclusions: Andro reduced mechanical allodynia more than NSAIDS at the same concentration, and the observed behaviour was associated with a reduction in inflammatory cytokine produced in the spinal cord.

Highlights

Andrographolide (Andro) is found in large quantity in Andrographis paniculata Nees (Acanthaceae) (Koteswara et al 2004)
It was reported that Andro was able to reduce the lipopolysaccharide (LPS)-induced pro-inflammatory factors such as inducible nitric oxide synthase, cyclooxygenase 2 (COX2), prostaglandin E2 (PGE2), and tumour necrosis factor (TNF)-a expression in microglia (Wang et al 2004)
The withdrawal thresholds of the ipsilateral hind paw in the OP-Andro group were found to be significantly increased compared with OP-saline group and OP-NSAIDs group

Summary

Introduction

Andrographolide (Andro) is found in large quantity in Andrographis paniculata Nees (Acanthaceae) (Koteswara et al 2004). Andrographis paniculata is used in traditional medicine in China and India as an antidote for snakebite and insect bites. It is used for the treatment of dyspepsia, influenza, dysentery, malaria, and respiratory infections, and as an antipyretic, detoxicant, anti-inflammatory, febrifugal, and antiphlogistic agent. We have earlier reported that Andro suppressed TNF-induced astrocytic IL-1, IL-6, and TNF (Tzeng et al 2012) As both microglia and astrocytes have been identified as targets for alleviating allodynia (Watkins and Maier 2003; Ji et al 2006; McMahon and Malcangio 2009; Gao and Ji 2010a, 2010b), our main interest in the present study was to test if Andro relieves neuropathic pain

Objectives

Methods

Results

Conclusion