大托叶猪屎豆通过抑制 TNF-α 和 IL-6 对乙酸诱导的小鼠溃疡性结肠炎的保护作用。
Protective effect of Sesbania grandiflora on acetic acid induced ulcerative colitis in mice by inhibition of TNF-α and IL-6.
机构信息
Dadasaheb Balpande College of Pharmacy, Department of Pharmacology, Near Swami Samarth Dham Mandir, Manewada road, Besa, Nagpur 440034, Maharashtra, India.
Dadasaheb Balpande college of Pharmacy, Department of Pharmacognosy and Phytochemistry, Near Swami Samarth Dham Mandir, Manewada road, Besa, Nagpur 440034, Maharashtra, India.
出版信息
J Ethnopharmacol. 2018 Jun 12;219:222-232. doi: 10.1016/j.jep.2018.02.043. Epub 2018 Mar 10.
ETHNOPHARMACOLOGICAL RELEVANCE
The plant Sesbania grandiflora (Linn) belonging to the family Fabaceae is commonly known as sesbania, agathi, and katurai. The plant is accredited for alleviating a spectrum of ailments including inflammation, colitis, diarrhea, dysentery, leprosy, gout, rheumatism, jaundice, bronchitis, convulsion and anxiety. It is also used as antitumour, anthelmintic, and laxatives in Ayurveda and Siddha system of Indian traditional medicine.
AIM
To reveal protective effect of Sesbania grandiflora in acetic acid induced ulcerative colitis in mice.
MATERIALS AND METHOD
Polyphenol, flavonoid and flavanone contents of different extracts of S. grandiflora leaves were quantified and correlated with their antioxidant capacity in-vitro (DPPH assay) for identification of potential fraction. In further studies hydroalocholic extract (HASG, 100 and 200 mg/kg) was evaluated for protective effect towards acetic acid induced ulcerative colitis (UC) animals administered with 150 µl of 5% acetic acid once, intrarectally. The colonic mucosal injury was assessed by estimating disease activity index (DAI), which took into account weight loss, stool consistency and occult/gross bleeding. Macroscopic changes like colon length, spleen weights, ulcer area and ulcer index were determined. Haematological parameters like WBC count, RBC count, Hb (g/dL), HCT (%), PLT count and FFA level were determined. Biochemical analysis was carried out for asserting the levels of tissue myeloperoxidase (MPO) accumulation, SOD concentrations, reduced GSH and lipid peroxidation in UC induced and treated animals. The cardinal inflammatory biomarkers like nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin (IL-6) were determined. Histopathological investigation was carried out and scores were calculated.
RESULTS
HASG showed presence of highly polymerized polyphenols and flavonoids amongst other extracts of S. grandiflora, which is correlated to its rich antioxidant potential (IC =19.21). HPLC fingerprinting quantifies the presence of quercetin in concentration of 81.7 µg/mg of HASG. HASG (200 mg/kg) and Prednisolone (2 mg/kg) significantly reduced DAI and macroscopic scores. The haematological changes in experimental animals were restored upon treatment with HASG and Prednisolone. HASG showed potent antioxidant activity (In-vivo) by restoring the levels of SOD, GSH, MPO, MDA and NO. HASG was found to inhibit FFA levels, which may indicate inhibition of TLR4 receptor mediated inflammation. The levels of serological biomarkers like TNF-α and IL-6 were found to be suppressed. Histopathological investigation reveals decrease signs of ulceration, necrosis, cellular infiltration, hyperaemia in HASG treated animals. The results of HASG (200 mg/kg) were found to be comparable with Prednisolone (2 mg/kg) significantly.
CONCLUSION
The protective action of HASG against acetic acid induced UC is attributed to the antioxidant like action (In-vitro and In-vivo) of highly polymerized polyphenols and flavonoids especially quercetin. Also HASG was found to reduce the levels of TNF-α and IL-6, thereby suppressing their inflammatory response in UC.
植物学相关性
豆科植物Sesbania grandiflora(Linn)通常被称为 sesbania、agathi 和 katurai,它具有缓解多种疾病的作用,包括炎症、结肠炎、腹泻、痢疾、麻风病、痛风、风湿、黄疸、支气管炎、惊厥和焦虑。在印度传统医学的阿育吠陀和悉达系统中,它也被用作抗肿瘤、驱虫剂和泻药。
目的
揭示Sesbania grandiflora 对乙酸诱导的溃疡性结肠炎小鼠的保护作用。
材料和方法
定量测定 Sesbania grandiflora 叶片不同提取物中的多酚、类黄酮和黄烷酮含量,并将其与体外抗氧化能力(DPPH 测定)相关联,以鉴定潜在的有效部位。在进一步的研究中,评估水醇提物(HASG,100 和 200mg/kg)对乙酸诱导的溃疡性结肠炎(UC)动物的保护作用,向动物直肠内给予 150μl 的 5%乙酸一次。通过估计疾病活动指数(DAI)评估结肠黏膜损伤,DAI 考虑了体重减轻、粪便稠度和隐血/肉眼出血。通过测量结肠长度、脾脏重量、溃疡面积和溃疡指数来确定宏观变化。还测定了白细胞计数(WBC)、红细胞计数(RBC)、血红蛋白(g/dL)、HCT(%)、血小板计数(PLT)和游离脂肪酸(FFA)水平等血液学参数。进行生化分析以确定组织髓过氧化物酶(MPO)积累、SOD 浓度、还原型谷胱甘肽(GSH)和脂质过氧化水平在 UC 诱导和治疗动物中的变化。还测定了一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)和白细胞介素(IL-6)等主要炎症生物标志物的水平。进行了组织病理学检查并计算了评分。
结果
HASG 显示出比其他 Sesbania grandiflora 提取物具有更高聚合度的多酚和类黄酮,这与其丰富的抗氧化潜力(IC=19.21)相关。HPLC 指纹图谱定量测定 HASG 中槲皮素的含量为 81.7μg/mg。HASG(200mg/kg)和泼尼松龙(2mg/kg)可显著降低 DAI 和宏观评分。用 HASG 和泼尼松龙治疗后,实验动物的血液学变化得到恢复。HASG 在体内表现出强大的抗氧化活性,通过恢复 SOD、GSH、MPO、MDA 和 NO 的水平来实现。发现 HASG 能抑制游离脂肪酸(FFA)水平,这可能表明抑制 TLR4 受体介导的炎症。血清生物标志物如 TNF-α 和 IL-6 的水平也被发现受到抑制。组织病理学检查显示 HASG 治疗动物的溃疡、坏死、细胞浸润、充血等迹象减少。HASG(200mg/kg)的结果与泼尼松龙(2mg/kg)的结果相当显著。
结论
HASG 对乙酸诱导的 UC 的保护作用归因于高度聚合的多酚和类黄酮(尤其是槲皮素)的抗氧化作用(体外和体内)。此外,HASG 还被发现可降低 TNF-α 和 IL-6 的水平,从而抑制其在 UC 中的炎症反应。