Amna Khan1, Li Zhang2, Chang Hu Li3, Ashraf Ullah Khan1,4, Bushra Shal1, Adnan Khan1, Sajjad Ahmad5, Fakhar Ud Din6, Zia Ur Rehman7, Feng Wang8, Salman Khan9. 1. Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. 2. Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, People's Republic of China. 3. Division of Radiation Physics, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. 4. Faculty of Pharmaceutical Sciences, Abasyn University, Peshawar, KPK, Pakistan. 5. Department of Health and Biological Sciences, Abasyn University, Peshawar, 25000, Pakistan. 6. Department of Pharmacy, Faculty of Biological Sciences, Quad-i-Azam University, Islamabad, Pakistan. 7. Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan. 8. Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, People's Republic of China. wangfeng5024@126.com. 9. Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. skhan@qau.edu.pk.
Abstract
BACKGROUND: The 7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid isolated from the Tussilago farfara Linneaus (Asteraceae), was evaluated against acute Carrageenan and chronic complete Freund's adjuvant (CFA)-induced arthritis in mice. METHODS: Acute and chronic arthritis were induced by administering Carrageenan and CFA to the intraplantar surface of the mouse paw. Edema, mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia were assessed in the paw. Similarly, histological and immunohistological parameters were assessed following arthritis induced by CFA. Antioxidants, inflammatory cytokines, and oxidative stress markers were also studied in all the treated groups. RESULTS: The ECN treatment significantly attenuated edema in the paw and elevated the nocifensive threshold following induction of this inflammatory model. Furthermore, ECN treatment markedly improved the arthritis index and distress symptoms, while attenuating the CFA-induced edema in the paw. ECN treatment also improved the histological parameters in the paw tissue compared to the control. At the same time, there was a significant reduction in edema and erosion in the ECN-treated group, as measured by radiographic analysis. Using the Comet's assay, we showed that ECN treatment protected the DNA from chronic CFA-induced arthritis. Immunohistochemistry analysis showed a marked decrease in the expression level of p-JNK (phosphorylated C-Jun N-terminal kinase), NF-κB (Nuclear factor-kappa B), COX-2 (Cyclooxygenase-2), and TNF-α (Tumour necrosis factor-alpha) compared to the CFA-treated group. Biophysical analysis involving molecular docking, molecular dynamics simulations, and binding free energies of ECN were performed to explore the underlying mechanism. CONCLUSION: ECN exhibited significant anti-inflammatory and anti-arthritic activity against Carrageenan and CFA-induced models.
BACKGROUND: The 7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid isolated from the Tussilago farfara Linneaus (Asteraceae), was evaluated against acute Carrageenan and chronic complete Freund's adjuvant (CFA)-induced arthritis in mice. METHODS: Acute and chronic arthritis were induced by administering Carrageenan and CFA to the intraplantar surface of the mouse paw. Edema, mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia were assessed in the paw. Similarly, histological and immunohistological parameters were assessed following arthritis induced by CFA. Antioxidants, inflammatory cytokines, and oxidative stress markers were also studied in all the treated groups. RESULTS: The ECN treatment significantly attenuated edema in the paw and elevated the nocifensive threshold following induction of this inflammatory model. Furthermore, ECN treatment markedly improved the arthritis index and distress symptoms, while attenuating the CFA-induced edema in the paw. ECN treatment also improved the histological parameters in the paw tissue compared to the control. At the same time, there was a significant reduction in edema and erosion in the ECN-treated group, as measured by radiographic analysis. Using the Comet's assay, we showed that ECN treatment protected the DNA from chronic CFA-induced arthritis. Immunohistochemistry analysis showed a marked decrease in the expression level of p-JNK (phosphorylated C-Jun N-terminal kinase), NF-κB (Nuclear factor-kappa B), COX-2 (Cyclooxygenase-2), and TNF-α (Tumour necrosis factor-alpha) compared to the CFA-treated group. Biophysical analysis involving molecular docking, molecular dynamics simulations, and binding free energies of ECN were performed to explore the underlying mechanism. CONCLUSION: ECN exhibited significant anti-inflammatory and anti-arthritic activity against Carrageenan and CFA-induced models.
Authors: Sidra Khalid; Muhammad Z Ullah; Ashraf U Khan; Ruqayya Afridi; Hina Rasheed; Adnan Khan; Hussain Ali; Yeong S Kim; Salman Khan Journal: Front Pharmacol Date: 2018-03-20 Impact factor: 5.810