Antinociceptive properties of 25-methoxy hispidol A, a triterpinoid isolated from Poncirus trifoliata (Rutaceae) through inhibition of NF-κB signalling in mice.

Abstract

The 25-methoxy hispidol A (25-MHA) is a triterpenoid, isolated from the immature fruit of Poncirus trifoliata (Rutaceae). The pretreatment with 25-MHA markedly (p < 0.001) attenuated the formalin-induced biphasic responses as well as acetic acid-induced writhing responses. The intraperitoneal administration of 25-MHA significantly attenuated the mechanical hyperalgesia (p < 0.001) and allodynia (p < 0.05). Similarly, 25-MHA also significantly attenuated (p < 0.001) complete Freund's adjuvant (CFA)-induced paw edema in mice. The 25-MHA treatment significantly attenuated the production of nuclear kappa B (NF-κB) (p65 nuclear subunit). The cytokines are the important mediators of inflammation and pain; however, treatment with 25-MHA exhibited significant inhibition (p < 0.001) on the mRNA expression levels of various inflammatory mediators. The 25-MHA administration also significantly enhanced antioxidant enzymes (p < 0.001) and inhibited the oxidative stress markers. The current study indicates that 25-MHA significantly (p < 0.001) inhibited the nitric oxide (NO) in mice plasma. Similarly, the haematoxylin and eosin (H&E) staining shows that 25-MHA administration significantly inhibited the inflammatory process in the mice paw tissue compared with the CFA-treated group. The 25-MHA treatment did not exhibited any toxicity on the liver, kidney, muscles strength, and motor co-ordination in mice. The 25-MHA was coadministered with the various drugs such as tramadol, piroxicam, and gabapentin to observe the synergistic effect.

• Authors: Ashrafullah Khan, Muhammad Zia Ullah, Ruqayya Afridi, Hina Rasheed, Sidra Khalid, Hadayat Ullah, Hussain Ali, Shakir D AlSharari, Yeong Shik Kim, Salman Khan
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 33 Issue 2 Pg. 327-341 (Feb 2019) ISSN: 1099-1573 [Electronic] England
• PMID: 30456885 (Publication Type: Journal Article)
• Copyright: © 2018 John Wiley & Sons, Ltd.

Chemical References

• 25-methoxyhispidol A
• Analgesics
• NF-kappa B
• Triterpenes
• Nitric Oxide
• Carrageenan
• Freund's Adjuvant
• Nitric Oxide Synthase Type II

Topics

• Analgesics (pharmacology, therapeutic use)
• Animals
• Carrageenan
• Down-Regulation (drug effects)
• Edema (chemically induced, drug therapy)
• Freund's Adjuvant
• Hyperalgesia (chemically induced, drug therapy, metabolism)
• Inflammation (drug therapy, metabolism)
• Male
• Mice
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Pain (chemically induced, drug therapy, metabolism)
• Poncirus (chemistry)
• Rutaceae (chemistry)
• Signal Transduction (drug effects)
• Triterpenes (pharmacology, therapeutic use)