Amanat Safa, Shal Bushra, Kyoung Seo Eun, Ali Hussain, Khan Salman
Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Faculty of Health Sciences, IQRA University, Islamabad Campus, (Chak Shahzad), Islamabad, Pakistan.
Int Immunopharmacol. 2022 May;106:108604. doi: 10.1016/j.intimp.2022.108604. Epub 2022 Feb 8.
Cystitis is a chronic bladder pain associated with frequency and nocturia. In the present study, Icariin a prenylated flavonoid extracted from Epimedium koreanum, was investigated against cyclophosphamide (CYP)-induced cystitis pain in mice model. Preliminarily in an acute model, single dose of CYP (150 mg/kg; i.p) was administered followed by Icariin (5, 25 and 50 mg/kg, i.p.). The visceral sensitivity and nociceptive behaviors were significantly ameliorated by pretreatment with Icariin (25, 50 mg/kg) that were assessed by spontaneous pain scoring, von Frey test and clinical scoring. Further, in chronic model Icariin (25 mg/kg, i.p.) was administered for 10 consecutive days prior to CYP (75 mg/kg; i.p) challenged every 3rd day for the duration of 10 days. Icariin not only had a protective effect on edema including bladder wet weight and hemorrhage but also had a potential to reduce vascular permeability, mast cells infiltration and tissue fibrosis. Evidently, Icariin prevented the neutrophilia/lymphopenia caused by CYP, and markedly improved the antioxidant enzymes level including superoxide dismutase, glutathione sulfo-transferase, catalase, glutathione level and reduced Malondialdehyde level, myeloperoxidase activity and nitric oxide, and also decreased the production of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) in bladder. Icariin markedly enhanced the Nrf-2, heme oxygenase (HO-1) and IкB-α expression, while attenuated the expression level of Keap1, TLR-4, NF-кB, i-NOS, COX-2 and TRPV1 as compared to negative group. This research illustrated the anti-inflammatory properties of Icariin and effectively improved CYP-induced cystitis pain.
膀胱炎是一种与尿频和夜尿相关的慢性膀胱疼痛。在本研究中，对从朝鲜淫羊藿中提取的一种异戊烯基黄酮——淫羊藿苷，在小鼠模型中针对环磷酰胺（CYP）诱导的膀胱炎疼痛进行了研究。在急性模型中，初步给予单次剂量的CYP（150mg/kg；腹腔注射），随后给予淫羊藿苷（5、25和50mg/kg，腹腔注射）。通过自发疼痛评分、von Frey试验和临床评分评估，淫羊藿苷（25、50mg/kg）预处理可显著改善内脏敏感性和伤害性反应行为。此外，在慢性模型中，在每3天腹腔注射CYP（75mg/kg）共10天之前，连续10天腹腔注射淫羊藿苷（25mg/kg）。淫羊藿苷不仅对包括膀胱湿重和出血在内的水肿有保护作用，还具有降低血管通透性、肥大细胞浸润和组织纤维化的潜力。显然，淫羊藿苷可预防CYP引起的中性粒细胞增多/淋巴细胞减少，并显著提高抗氧化酶水平，包括超氧化物歧化酶、谷胱甘肽硫转移酶、过氧化氢酶、谷胱甘肽水平，降低丙二醛水平、髓过氧化物酶活性和一氧化氮水平，还可减少膀胱中肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的产生。与阴性组相比，淫羊藿苷显著增强了Nrf-2、血红素加氧酶（HO-1）和IκB-α的表达，同时减弱了Keap-Ⅰ、TLR-4、NF-κB、诱导型一氧化氮合酶、环氧化酶-2和瞬时受体电位香草酸亚型1（TRPV1）的表达水平。本研究阐明了淫羊藿苷的抗炎特性，并有效改善了CYP诱导的膀胱炎疼痛。
