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Inflammopharmacology

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01-10-2019 | Original Article

Osthole ameliorates neurogenic and inflammatory hyperalgesia by modulation of iNOS, COX-2, and inflammatory cytokines in mice

Authors: Gurjit Singh, Rajbir Bhatti, Rahul Mannan, Drishtant Singh, Anup Kesavan, Palwinder Singh

Published in: Inflammopharmacology | Issue 5/2019

Abstract

Background

Osthole is a bioactive component reported in medicinal plants such as Angelica pubescens and Cnidium monnieri, known for analgesic activity. However, the toxicity, median effective dose (ED₅₀), and dual modulation of nitric oxide and cyclooxygenase pathways along with inflammatory cytokines of osthole are yet to be determined.

Methods

The animals (mice) were assessed for general behaviour and mortality in varying doses (50, 300, and 2000 mg kg⁻¹) of osthole for acute toxicity over 14 days. The analgesic activity was investigated using acetic acid and formalin-induced hyperalgesia, and anti-inflammatory activity was explored in carrageenan-induced paw oedema. ED₅₀ of osthole was calculated using Design Expert software. Involvement of nitric oxide and cyclooxygenase pathways was investigated by agonist challenges with l-arginine and substance P, respectively. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined in spinal sections by immunohistochemical analysis. Lipopolysaccharide (LPS) challenge was used to assess in vivo effect on inflammatory cytokines (TNFα and IL-6).

Results

Acute toxicity studies revealed no behavioural abnormality or mortality on osthole treatment and unremarkable histological findings. Osthole was found to significantly decrease acetic acid and formalin-induced hyperalgesia (ED₅₀ = 5.43 mg kg⁻¹) and carrageenan-induced paw oedema with no toxicity symptoms. Osthole produced a marked decrease in iNOS and COX-2 expression as well as TNFα and IL-6. The findings corroborate to modulation of iNOS and COX-2 and inflammatory cytokines by osthole. This study provides promising insights and prospects for application of osthole in pain management.

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Title: Osthole ameliorates neurogenic and inflammatory hyperalgesia by modulation of iNOS, COX-2, and inflammatory cytokines in mice
Authors: Gurjit Singh
Rajbir Bhatti
Rahul Mannan
Drishtant Singh
Anup Kesavan
Palwinder Singh
Publication date: 01-10-2019
Publisher: Springer International Publishing
Published in: Inflammopharmacology / Issue 5/2019
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-018-0486-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Osthole ameliorates neurogenic and inflammatory hyperalgesia by modulation of iNOS, COX-2, and inflammatory cytokines in mice

Abstract

Background

Methods

Results

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

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