Zubair Hafiz Muhammad, Elsadek Mohamed Farouk, Asghar Sajid, Al-Numair Khalid S, Saadullah Malik, Chaudhry Shafqat Rasul, Efferth Thomas, Asif Muhammad
Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Punjab, 63100, Pakistan.
Department of Biochemistry, College of Sciences, King Saud University, Riyadh, Saudi Arabia.
Inflammopharmacology. 2025 Jan;33(1):241-256. doi: 10.1007/s10787-024-01611-y. Epub 2025 Jan 3.
Clove oil obtained from Syzygium aromaticum (L.) is traditionally employed to treat inflammation associated with rheumatism, gastric disorders, and as an analgesic. Chemo-herbal combinations are known to have potent anti-inflammatory and analgesic effects, while mitigating the drug related side effects. The purpose of this study was to evaluate anti-inflammatory, analgesic and antipyretic effects of a combination of flurbiprofen and clove oil in a micro-emulsion (FCM) form using various in vivo models. Micro-emulsion of flurbiprofen and clove oil (FCM) was prepared following reported protocols and three different dose combinations (25, 12.5 and 6.25 mg/kg) were evaluated in carrageenan and histamine-induced acute inflammation, CFA-induced arthritis, yeast-induced pyrexia, and acetic acid-induced writhing models. qPCR studies were conducted to explore the possible mechanism of action. GC-MS of clove oil was performed to explore its chemical composition. FCM 25 mg/kg treated group exhibited significantly better (p < 0.05) effects compared to clove oil (CM) and flurbiprofen (FBR) (25 mg/kg) treated groups in both acute and chronic models. Histopathological study of joints showed a reduction in infiltration of inflammatory cells, bone erosion, and tissue oedema in FCM (25 mg/kg) treated group as compared to other treatment groups. Significant up-regulation in mRNA expression of anti-inflammatory (IL-4, IL-10) and down-regulation of pro-inflammatory genes (NF-κB, IL-6, TNF-α, IL-1β and COX-2) was observed in all the FCM-treated groups but, 25 mg/kg-treated group showed comparatively better results. Gross macroscopic examination of stomach sections also showed relatively less deleterious effects of test treatments (CM and FCM) as compared with FBR treated group. Serum levels of liver enzymes (alanine aminotransferase (ALT), and alkaline phosphatase (ALP)), blood urea nitrogen (BUN) and creatinine were also found to be normal as compared to FBR and tween-water (TW) treated groups. GC-MS of clove oil revealed that it was rich in eugenol contents. This study reveals that a combination of flurbiprofen and clove oil in a micro-emulsion form could be a promising approach to enhance therapeutic actions and to mitigate synthetic drugs related side effects in clinical settings. It might implicate a synergistic action on the modulation of inflammatory genes expression. Further research is warranted to explore the full potential of this combination in treating various inflammatory conditions.
从丁香（Syzygium aromaticum (L.)）中提取的丁香油传统上用于治疗与风湿、胃部疾病相关的炎症，并用作镇痛药。已知化学草药组合具有强大的抗炎和镇痛作用，同时可减轻药物相关的副作用。本研究的目的是使用各种体内模型评估氟比洛芬和丁香油微乳剂（FCM）组合的抗炎、镇痛和解热作用。按照报道的方案制备氟比洛芬和丁香油微乳剂（FCM），并在角叉菜胶和组胺诱导的急性炎症、弗氏完全佐剂诱导的关节炎、酵母诱导的发热以及醋酸诱导的扭体模型中评估三种不同剂量组合（25、12.5和6.25 mg/kg）。进行qPCR研究以探索可能的作用机制。对丁香油进行GC-MS分析以探究其化学成分。在急性和慢性模型中，FCM 25 mg/kg治疗组与丁香油（CM）和氟比洛芬（FBR）（25 mg/kg）治疗组相比，表现出显著更好（p < 0.05）的效果。关节组织病理学研究显示，与其他治疗组相比，FCM（25 mg/kg）治疗组的炎症细胞浸润、骨侵蚀和组织水肿减少。在所有FCM治疗组中均观察到抗炎基因（IL-4、IL-10）的mRNA表达显著上调，促炎基因（NF-κB、IL-6、TNF-α、IL-1β和COX-2）的表达下调，但25 mg/kg治疗组显示出相对更好的结果。胃切片的大体宏观检查还显示，与FBR治疗组相比，试验治疗（CM和FCM）的有害影响相对较小。与FBR和吐温-水（TW）治疗组相比，血清肝酶（丙氨酸转氨酶（ALT）和碱性磷酸酶（ALP））、血尿素氮（BUN）和肌酐水平也正常。丁香油的GC-MS分析表明其富含丁香酚成分。本研究表明，氟比洛芬和丁香油的微乳剂组合可能是一种有前景的方法，可增强治疗作用并减轻临床环境中合成药物相关的副作用。它可能对炎症基因表达的调节具有协同作用。有必要进一步研究以探索该组合在治疗各种炎症性疾病中的全部潜力。
