Medicinal Plants Research Center (NPPM), Federal University of Piauí, 64.049-550, Teresina, PI, Brazil.
Laboratory of Experimental Physiopharmacology (LAFFEX), Federal University of Piauí, 64.202-020, Parnaíba, PI, Brazil.
Biomed Pharmacother. 2019 Feb;110:631-640. doi: 10.1016/j.biopha.2018.11.131. Epub 2018 Dec 9.
Diarrhea is one of the leading causes of infant death in the world accounting for high child mortality rate. It is also present in different pathophysiologies related to several etiological agents. The aim of this study is to investigate the antidiarrheal effect of α -Terpineol (α-TPN) in different diarrhea models in rodents. The antidiarrheal effect of α-TPN in the treatment of acute diarrhea and enteropooling induced by castor oil or PGE in Swiss mice pretreated orally with saline (NaCl 0.9%), Loperamide (5 mg/kg) and α-TPN (6.25, 12.5, 25 and 50 mg/kg) was analyzed. Additionally, parameters of severity, total weight of faeces and post-treatment for 4 h were evaluated. Modulation of the opioid and cholinergic pathways was performed and intestinal transit model using activated charcoal as marker was also used. The effect of α-TPN on secretory diarrhea was investigated using the model of fluid secretion in intestinal loops isolated from cholera toxin-treated mice. α-TPN showed antidiarrheal effect (*p < 0.05), reducing the total stool amount (*55%, *48%, *44%, *24%) and diarrheal (*47%, *66%; *56%, 10%) respectively for the doses tested. All doses investigated in the enteropooling test presented significant changes (*46%, *78%, *66%, *41% respectively) in relation to the control. α-TPN through the muscarinic pathway reduced the gastrointestinal transit (*31%), besides inhibiting PGE-induced diarrhea (*39%). α-TPN also reduced fluid formation and loss of Cl ions, by interacting directly with GM1 receptors and cholera toxin, thus increasing the uptake of intestinal fluids. The results suggest an anti-diarrheal activity of α-TPN due to its anticholinergic action, ability to block PGE and GM1 receptors and interaction with cholera toxin in secretory diarrhea, making it a promising candidate drug for the treatment of diarrheal diseases.
腹泻是导致全球婴儿死亡的主要原因之一，也是导致儿童死亡率高的主要原因。它也存在于与几种病因有关的不同病理生理学中。本研究旨在探讨α-松油醇（α-TPN）在不同腹泻模型中的抗腹泻作用。通过在口服给予生理盐水（0.9%NaCl）、洛哌丁胺（5mg/kg）和α-TPN（6.25、12.5、25 和 50mg/kg）预处理的瑞士小鼠中，用蓖麻油或 PGE 诱导急性腹泻和肠液积聚，分析α-TPN 的抗腹泻作用。此外，还评估了严重程度、粪便总重量和治疗后 4 小时的参数。还进行了阿片和胆碱能途径的调节，并使用活性炭作为标志物进行了肠道转运模型。使用霍乱毒素处理的小鼠分离的肠环中的液体分泌模型研究了α-TPN 对分泌性腹泻的影响。α-TPN 表现出抗腹泻作用（*p<0.05），分别减少总粪便量（*55%、*48%、*44%、*24%）和腹泻（*47%、*66%；*56%，10%）对于测试的剂量。在肠液积聚试验中，所有研究剂量与对照组相比均有显著变化（*46%、*78%、*66%、*41%）。α-TPN 通过毒蕈碱途径降低胃肠道转运（*31%），此外还抑制 PGE 诱导的腹泻（*39%）。α-TPN 还通过直接与 GM1 受体和霍乱毒素相互作用，减少液体形成和氯离子的丢失，从而增加肠道液体的摄取。结果表明，α-TPN 具有抗腹泻活性，这是由于其抗胆碱能作用、阻断 PGE 和 GM1 受体的能力以及在分泌性腹泻中与霍乱毒素的相互作用，使其成为治疗腹泻病的有前途的候选药物。
