Anjum Irfan, Mobashar Aisha, Jahan Shah, Najm Saima, Nafidi Hiba-Allah, Bin Jardan Yousef A, Bourhia Mohammed
Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore 54000, Pakistan.
Department of Immunology, University of Health Sciences Lahore, Lahore 54600, Pakistan.
Pharmaceuticals (Basel). 2023 May 30;16(6):811. doi: 10.3390/ph16060811.
Apigenin is a phytochemical obtained from Its role in interstitial cystitis is not yet known. The present study is aimed at understanding the uroprotective and spasmolytic effects of apigenin in cyclophosphamide-induced interstitial cystitis. The uroprotective role of apigenin was analyzed by qRT-PCR, macroscopic analysis, Evans blue dye leakage, histological evaluation, and molecular docking. The spasmolytic response was measured by adding cumulative concentrations of apigenin to isolated bladder tissue pre-contracted with KCl (80 mM) and carbachol (10-10) on non-incubated and pre-incubated tissues with atropine, 4DAMP, methoctramine, glibenclamide, barium chloride, nifedipine, indomethacin, and propranolol. Apigenin inhibited pro-inflammatory cytokines (IL-6, TNF-α and TGF 1-β) and oxidant enzymes (iNOS) while increasing antioxidant enzymes (SOD, CAT, and GSH) in CYP-treated groups compared to the control. Apigenin restored normal tissue of the bladder by decreasing pain, edema, and hemorrhage. Molecular docking further confirmed the antioxidant and anti-inflammatory properties of apigenin. Apigenin produced relaxation against carbachol-mediated contractions, probably via blockade of M receptors, K channels, L-type calcium channels, and prostaglandin inhibition. While the blockade of M receptors, K channels, and β-adrenergic receptors did not contribute to an apigenin-induced spasmolytic effect, apigenin presented as a possible spasmolytic and uroprotective agent with anti-inflammatory, antioxidant effects by attenuating TGF-β/iNOS-related tissue damage and bladder muscle overactivity. Thus, it is a potential agent likely to be used in treatment of interstitial cystitis.
芹菜素是一种从[具体来源未给出]中获得的植物化学物质。其在间质性膀胱炎中的作用尚不清楚。本研究旨在了解芹菜素在环磷酰胺诱导的间质性膀胱炎中的泌尿保护和解痉作用。通过qRT-PCR、宏观分析、伊文思蓝染料渗漏、组织学评估和分子对接分析了芹菜素的泌尿保护作用。通过向用氯化钾（80 mM）和卡巴胆碱（10 - 10）预收缩的离体膀胱组织中添加累积浓度的芹菜素，在未孵育和用阿托品、4DAMP、甲溴东莨菪碱、格列本脲、氯化钡、硝苯地平、吲哚美辛和普萘洛尔预孵育的组织上测量解痉反应。与对照组相比，芹菜素在环磷酰胺处理组中抑制促炎细胞因子（IL - 6、TNF - α和TGF 1 - β）和氧化酶（诱导型一氧化氮合酶），同时增加抗氧化酶（超氧化物歧化酶、过氧化氢酶和谷胱甘肽）。芹菜素通过减轻疼痛、水肿和出血，使膀胱组织恢复正常。分子对接进一步证实了芹菜素的抗氧化和抗炎特性。芹菜素对卡巴胆碱介导的收缩产生松弛作用，可能是通过阻断M受体、钾通道、L型钙通道和抑制前列腺素实现的。虽然阻断M受体、钾通道和β - 肾上腺素能受体对芹菜素诱导的解痉作用没有贡献，但芹菜素通过减轻TGF - β/诱导型一氧化氮合酶相关的组织损伤和膀胱肌肉过度活动，表现为一种可能具有抗炎、抗氧化作用的解痉和泌尿保护剂。因此，它是一种可能用于治疗间质性膀胱炎的潜在药物。
