Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice

Abstract Background Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin...

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Main Authors: Ruqayya Afridi, Ashraf Ullah Khan, Sidra Khalid, Bushra Shal, Hina Rasheed, Muhammad Zia Ullah, Omer Shehzad, Yeong Shik Kim, Salman Khan
Format: Article
Language:English
Published: BMC 2019-09-01
Series:BMC Pharmacology and Toxicology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40360-019-0335-5
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author Ruqayya Afridi
Ashraf Ullah Khan
Sidra Khalid
Bushra Shal
Hina Rasheed
Muhammad Zia Ullah
Omer Shehzad
Yeong Shik Kim
Salman Khan
author_facet Ruqayya Afridi
Ashraf Ullah Khan
Sidra Khalid
Bushra Shal
Hina Rasheed
Muhammad Zia Ullah
Omer Shehzad
Yeong Shik Kim
Salman Khan
author_sort Ruqayya Afridi
collection DOAJ
description Abstract Background Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain. Methods The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freund’s Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes. Results Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model. Conclusion The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.
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spelling doaj.art-9c8c654683234e66845acc2bda0714b82022-12-22T00:35:48ZengBMCBMC Pharmacology and Toxicology2050-65112019-09-0120111610.1186/s40360-019-0335-5Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in miceRuqayya Afridi0Ashraf Ullah Khan1Sidra Khalid2Bushra Shal3Hina Rasheed4Muhammad Zia Ullah5Omer Shehzad6Yeong Shik Kim7Salman Khan8Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam UniversityDepartment of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam UniversityDepartment of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam UniversityDepartment of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam UniversityDepartment of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam UniversityDepartment of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam UniversityDepartment of Pharmacy, Abdul Wali Khan UniversityCollege of Pharmacy, Seoul National UniversityDepartment of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam UniversityAbstract Background Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain. Methods The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freund’s Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes. Results Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model. Conclusion The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.http://link.springer.com/article/10.1186/s40360-019-0335-5PoncirinInflammatory painCytokinesHyperalgesiaAllodynia
spellingShingle Ruqayya Afridi
Ashraf Ullah Khan
Sidra Khalid
Bushra Shal
Hina Rasheed
Muhammad Zia Ullah
Omer Shehzad
Yeong Shik Kim
Salman Khan
Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice
BMC Pharmacology and Toxicology
Poncirin
Inflammatory pain
Cytokines
Hyperalgesia
Allodynia
title Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice
title_full Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice
title_fullStr Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice
title_full_unstemmed Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice
title_short Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice
title_sort anti hyperalgesic properties of a flavanone derivative poncirin in acute and chronic inflammatory pain models in mice
topic Poncirin
Inflammatory pain
Cytokines
Hyperalgesia
Allodynia
url http://link.springer.com/article/10.1186/s40360-019-0335-5
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