Qazi Neelam Gul, Khan Arif-Ullah, Abbasi Sumra Wajid, Malik Imran, Naeem Komal
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Nums Department of Biological Sciences, National University of Medical Sciences Rawalpindi, Rawalpindi, Pakistan.
Front Pharmacol. 2022 Aug 16;13:936161. doi: 10.3389/fphar.2022.936161. eCollection 2022.
This present study aims to delineate crude extract (Rd.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rd.n-Hex, Rd.ETAC, and Rd.Aq), and emodin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti-, antiulcer effects, and toxicology. Plant extracts attributed dose-dependent protection against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance transverse by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, it causes a concentration-dependent relaxation of both spontaneous and K (80 mM)-induced contraction, Rd.n-Hex and verapamil were relatively potent against K-induced contractions and shifted the Ca concentration-response curves (CRCs) to the right, Rd.Cr and Rd.ETAC shifted the isoprenaline-induced inhibitory CRCs to the left, showing potentiating effect similar to papaverine. Rd.n-Hex showed anti- effect. Extracts and emodin also show an inhibitory effect against H/K-ATPase. showed a gastroprotective and antioxidant effect. Histopathological evaluation showed improvement in cellular architecture and decrease in the expression of inflammatory markers such as cyclooxygenase (COX2), tumor necrosis factor (TNF-α), and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry, ELISA, and western blot techniques. In RT-PCR, it decreases H/K-ATPase mRNA levels. was analyzed for certain safety aspects and exhibited a relative safety profile as no impairment was observed in kidneys, heart, liver, and brain further assisted by biochemical and hematological analysis. Docking studies revealed that emodin against H/K-ATPase pump and voltage gated L-type calcium channel showed E-value of -7.9 and -7.4 kcal/mol, respectively. MD simulations and molecular mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area MMPBSA/GBSA findings are consistent with the and docking results. In conclusion, extracts and its phytoconstituent could be considered a potent antioxidant and anti-inflammatory drug candidates that possess anti-diarrheal, anti-secretary, antispasmodic, anti- and anti-ulcer potential. Toxicity studies were done according to OECD standards 425. It belongs to group 5 (LD50 > 2000 mg/kg), which suggests that it is in the lower toxicity class.
本研究旨在阐明粗提物（Rd.Cr）、正己烷、乙酸乙酯、水相组分（Rd.n-Hex、Rd.ETAC和Rd.Aq）以及大黄素的止泻、抗分泌、解痉、胃肠道转运时间、抗[此处原文缺失相关内容]、抗溃疡作用及毒理学特性。植物提取物对蓖麻油诱导的腹泻具有剂量依赖性保护作用，并能剂量依赖性地抑制小鼠肠道液体分泌。在大鼠胃肠道转运模型中，它们缩短了木炭横向移动的距离。在兔空肠制备物中，其可引起自发性收缩和K（80 mM）诱导收缩的浓度依赖性舒张，Rd.n-Hex和维拉帕米对K诱导的收缩作用相对较强，并使钙浓度-反应曲线（CRC）右移，Rd.Cr和Rd.ETAC使异丙肾上腺素诱导的抑制性CRC左移，显示出与罂粟碱相似的增强作用。Rd.n-Hex显示出抗[此处原文缺失相关内容]作用。提取物和大黄素对H/K-ATP酶也有抑制作用。[此处原文缺失相关内容]显示出胃保护和抗氧化作用。组织病理学评估显示细胞结构改善，炎症标志物如环氧化酶（COX2）、肿瘤坏死因子（TNF-α）和磷酸化核因子κB（p-NFƙB）的表达降低，通过免疫组织化学、酶联免疫吸附测定和蛋白质印迹技术得以验证。在逆转录聚合酶链反应中，其降低了H/K-ATP酶mRNA水平。[此处原文缺失相关内容]进行了某些安全性方面的分析，并且呈现出相对安全的概况，因为通过生化和血液学分析未观察到对肾脏、心脏、肝脏和大脑的损害。对接研究表明，大黄素作用于H/K-ATP酶泵和电压门控L型钙通道时，E值分别为-7.9和-7.4 kcal/mol。分子动力学模拟以及分子力学泊松玻尔兹曼表面积和分子力学广义玻恩表面积MMPBSA/GBSA的研究结果与[此处原文缺失相关内容]和对接结果一致。总之，[此处原文缺失相关内容]提取物及其植物成分可被视为具有强大抗氧化和抗炎作用的药物候选物，具有止泻、抗分泌、解痉、抗[此处原文缺失相关内容]和抗溃疡的潜力。毒性研究按照经合组织标准425进行。它属于第5组（半数致死量>2000 mg/kg），这表明它处于低毒性类别。
