Rehman Najeeb Ur, Ansari Mohd Nazam, Ahmad Wasim, Ahamad Syed Rizwan
Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Department of Pharmacy, Mohammed Al-Mana College for Medical Sciences, Dammam 34222, Saudi Arabia.
Plants (Basel). 2022 Apr 27;11(9):1183. doi: 10.3390/plants11091183.
The present study attempted to evaluate and rationalize the medicinal use of the methanolic extract of the fruits of () in the treatment of hyperactive gut disorders. The in vivo, castor oil-induced diarrhea model in mice was followed to test its antidiarrheal effect. To test the antispasmodic effect and to explore its pharmacodynamic details, isolated small intestines (ileum) obtained from rats were selected to provide physiological conditions for the ex vivo assays. In the in vivo assays, the orally administered extract of protected mice from diarrheal drops with resultant percent inhibitions of 40% and 80% at the respective doses of 200 mg/kg and 400 mg/kg, while the highest protection (100%) was observed with a positive control drug, loperamide, at 10 mg/kg. In the ileum, produced an antispasmodic effect in a concentration-dependent manner by inhibiting the carbachol (CCh; 1 µM) and high K (80 mM)-evoked spasms with resultant EC values of 1.44 mg/mL (1.08-1.78) and 1.27 mg/mL (0.98-1.66), respectively. Papaverine, a known phosphodiesterase enzyme (PDE) inhibitor and blocker of Ca channels (CCB), also inhibited both CCh and high K induced contractions at comparable EC values of 8.72 µM (7.92-9.24) and 8.14 µM (7.62-8.84), respectively. Contrary to the extract and papaverine, verapamil showed distinctly higher potency in regard to inhibiting high K, compared to CCh-evoked spasms that had EC values of 0.16 µM (0.13-0.261) and 2.54 µM (2.28-2.92), respectively. The inhibitory effects of on PDE were further confirmed when the pre-incubated extract shifted the isoprenaline-mediated relaxation curves (CRCs) towards the left, similar to papaverine, whereas the CCB-like effect was confirmed when the pre-incubated tissues with caused deflection in the Ca CRCs towards the right, constructed in Ca free medium with suppression of the maximum response. Thus, this study provides detailed, mechanistic support for the medicinal use of in the treatment of hyperactive gut disorders.
本研究旨在评估并合理化（）果实甲醇提取物在治疗肠道功能亢进紊乱方面的药用价值。采用小鼠蓖麻油诱导腹泻的体内模型来测试其止泻效果。为测试其解痉作用并探究其药效学细节，选用从大鼠获取的离体小肠（回肠）为离体实验提供生理条件。在体内实验中，口服给予该提取物可保护小鼠免受腹泻影响，在200毫克/千克和400毫克/千克的相应剂量下，腹泻抑制率分别为40%和80%，而阳性对照药物洛哌丁胺在10毫克/千克时观察到最高保护率（100%）。在回肠中，（提取物名称未给出，推测为前文提到的果实甲醇提取物）通过抑制卡巴胆碱（CCh；1微摩尔）和高钾（80毫摩尔）诱发的痉挛，以浓度依赖方式产生解痉作用，其相应的半数有效浓度（EC）值分别为1.44毫克/毫升（1.08 - 1.78）和1.27毫克/毫升（0.98 - 1.66）。罂粟碱，一种已知的磷酸二酯酶（PDE）抑制剂和钙通道阻滞剂（CCB），在类似的EC值8.72微摩尔（7.92 - 9.24）和8.14微摩尔（7.62 - 8.84）时，也抑制CCh和高钾诱导的收缩。与提取物和罂粟碱相反，维拉帕米在抑制高钾方面表现出明显更高的效力，相比之下，其对CCh诱发痉挛的EC值分别为0.16微摩尔（0.13 - 0.261）和2.54微摩尔（2.28 - 2.92）。当预孵育的提取物使异丙肾上腺素介导的舒张曲线（CRCs）向左移动时，进一步证实了（提取物）对PDE的抑制作用，这与罂粟碱类似，而当用（提取物）预孵育的组织在无钙培养基中构建的钙CRCs向右偏移并抑制最大反应时，证实了其类似CCB的作用。因此，本研究为（提取物）在治疗肠道功能亢进紊乱方面的药用提供了详细的机制支持。
