Diarrhea is a prevalent gastrointestinal problem associated with fatal implications. It is a huge public health concern that requires better alternatives to current drugs. This study investigated the mechanisms involved in the antidiarrheal activity of Anacardium occidentale (Ao) stem bark extract, a plant commonly used in the management of diarrhea in Nigeria. Methanolic stem bark extract of the plant was partitioned into three fractions: hexane fraction, ethyl acetate fraction (AoEF) and methanol fraction. In vitro studies on the effect of these fractions on guinea pig ileum (GPI) strips, as well as the modulatory effect of AoEF on standard agonists- and antagonists-induced GPI contraction and relaxation, revealed AoEF as the most active fraction. In vivo studies to assess the effect of AoEF on the dopaminergic, muscarinic, and serotonergic pathways were carried out using gastric emptying (GE) and gastrointestinal transit (GT) as experimental end points. AoEF was subjected to GC-MS analysis, while the identified compounds were docked with the muscarinic acetylcholine receptor M3 (CHRM3) using AutodockVina. Results indicated that AoEF inhibited GE and GT via inhibition of CHRM3. In addition, GC-MS analysis revealed the presence of 24 compounds in AoEF, while docking indicated that octadecanoic acid 2-(2-hydroxylethoxy) ethyl ester exhibited the highest binding affinity to CHRM3. This study indicated that the antidiarrheal activity of Ao is through its antimotility effect via the inhibition of the muscarinic pathway. And since none of the identified compounds exhibited higher binding affinity to CHRM3 relative to loperamide, the antimotility activity of these phytoconstituents may be via synergism.

腹泻是一种与致命影响相关的普遍胃肠道问题。这是一个巨大的公共卫生问题，需要更好的替代现有药物。本研究调查了Anacardium occidentale抗腹泻活性的机制(Ao) 茎皮提取物，一种在尼日利亚常用于治疗腹泻的植物。将植物的甲醇茎皮提取物分成三个部分：己烷部分、乙酸乙酯部分 (AoEF) 和甲醇部分。关于这些部分对豚鼠回肠 (GPI) 条的影响以及 AoEF 对标准激动剂和拮抗剂诱导的 GPI 收缩和松弛的调节作用的体外研究表明，AoEF 是最活跃的部分。使用胃排空 (GE) 和胃肠转运 (GT) 作为实验终点，进行了评估 AoEF 对多巴胺能、毒蕈碱和血清素能通路影响的体内研究。对 AoEF 进行 GC-MS 分析，同时使用 AutodockVina 将鉴定的化合物与毒蕈碱乙酰胆碱受体 M3 (CHRM3) 对接。结果表明，AoEF 通过抑制 CHRM3 来抑制 GE 和 GT。此外，GC-MS 分析显示 AoEF 中存在 24 种化合物，而对接表明十八烷酸 2-（2-羟基乙氧基）乙酯对 CHRM3 的结合亲和力最高。该研究表明，Ao 的止泻活性是通过其抑制毒蕈碱途径的抗运动作用。并且由于与洛哌丁胺相比，没有一种已鉴定的化合物对 CHRM3 表现出更高的结合亲和力，因此这些植物成分的抗运动活性可能是通过协同作用。而对接表明十八烷酸2-（2-羟基乙氧基）乙酯对CHRM3表现出最高的结合亲和力。该研究表明，Ao 的止泻活性是通过其抑制毒蕈碱途径的抗运动作用。并且由于与洛哌丁胺相比，没有一种已鉴定的化合物对 CHRM3 表现出更高的结合亲和力，因此这些植物成分的抗运动活性可能是通过协同作用。而对接表明十八烷酸2-（2-羟基乙氧基）乙酯对CHRM3表现出最高的结合亲和力。该研究表明，Ao 的止泻活性是通过其抑制毒蕈碱途径的抗运动作用。并且由于与洛哌丁胺相比，没有一种已鉴定的化合物对 CHRM3 表现出更高的结合亲和力，因此这些植物成分的抗运动活性可能是通过协同作用。