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.
Molecules. 2022 Dec 14;27(24):8880. doi: 10.3390/molecules27248880.
The study was performed to assess and rationalize the traditional utilization of the fruit part of Grewia tenax (G. tenax). The phytoconstituents present in the methanolic extract were analyzed using Gas-Chromatography-Mass Spectroscopy (GC-MS), while the anti-diarrheal activity was investigated in the Swiss albino mice against castor oil-provoked diarrhea in vivo. The antispasmodic effect and the possible pharmacodynamics of the observed antispasmodic effect were determined in an isolated rat ileum using the organ bath setup as an ex vivo model. GC-MS findings indicate that G. tenax is rich in alcohol (6,6-dideutero-nonen-1-ol-3) as the main constituent (20.98%), while 3-Deoxy-d-mannoic lactone (15.36%) was detected as the second major constituents whereas methyl furfural, pyranone, carboxylic acid, vitamin E, fatty acid ester, hydrocarbon, steroids, sesquiterpenes, phytosterols, and ketones were verified as added constituents in the methanolic extract. In mice, the orally administered G. tenax inhibited the diarrheal episodes significantly (p < 0.05) at 200 mg/kg (40% protection), and this protection was escalated to 80% with the next higher dose of 400 mg/kg. Loperamide (10 mg/kg), a positive control drug, imparted 100% protection, whereas no protection was shown by saline. In isolated rat ileum, G. tenax completely inhibited the carbamylcholine (CCh; 1 µM) and KCl (high K+; 80 mM)-evoked spasms in a concentrations-mediated manner (0.03 to 3 mg/mL) by expressing equal potencies (p > 0.05) against both types of evoked spasms, similar to papaverine, having dual inhibitory actions at phosphodiesterase enzyme (PDE) and Ca2+ channels (CCB). Similar to papaverine, the inhibitory effect of G. tenax on PDE was further confirmed indirectly when G. tenax (0.1 and 0.3 mg/mL) preincubated ileal tissues shifted the isoprenaline-relaxation curve towards the left. Whereas, pre-incubating the tissue with 0.3 and 1 mg/mL of G. tenax established the CCB-like effect by non-specific inhibition of CaCl2−mediated concentration-response curves towards the right with suppression of the maximum peaks, similar to verapamil, a standard CCB. Thus, the present investigation revealed the phytochemical constituents and explored the detailed pharmacodynamic basis for the curative use of G. tenax in diarrhea and hyperactive gut motility disorders.
该研究旨在评估和合理化对粗叶木（Grewia tenax）果实部分的传统利用。使用气相色谱-质谱联用（GC-MS）分析甲醇提取物中的植物成分，同时在体内研究瑞士白化病小鼠对蓖麻油诱导的腹泻的抗腹泻活性。使用器官浴装置作为离体模型，在分离的大鼠回肠中确定抗痉挛作用和观察到的抗痉挛作用的可能药效学。GC-MS 结果表明，粗叶木富含醇（6,6-二氘-壬-1-醇-3）作为主要成分（20.98％），而 3-脱氧-D-甘露酸内酯（15.36％）被检测为第二大成分，而甲基糠醛，吡喃酮，羧酸，维生素 E，脂肪酸酯，碳氢化合物，类固醇，倍半萜，植物甾醇和酮被确认为甲醇提取物中的添加成分。在小鼠中，口服给予粗叶木可显着抑制腹泻发作（p <0.05），在 200 mg/kg 时（40％保护），下一个更高剂量 400 mg/kg 时保护作用可提高至 80％。阳性对照药物洛哌丁胺（10 mg/kg）赋予 100％的保护，而生理盐水则无保护作用。在分离的大鼠回肠中，粗叶木以浓度依赖性方式完全抑制了烟碱（CCh; 1 μM）和高钾（KCl; 80 mM）引起的痉挛，其对两种类型的痉挛的等效效力（p> 0.05），类似于罂粟碱，对磷酸二酯酶（PDE）和钙通道（CCB）均具有双重抑制作用。与罂粟碱类似，当粗叶木（0.1 和 0.3 mg/mL）预孵育回肠组织时，通过向左移动异丙肾上腺素松弛曲线，间接证实了粗叶木对 PDE 的抑制作用。而，当组织用 0.3 和 1 mg/mL 的粗叶木预处理时，通过非特异性抑制 CaCl2介导的浓度反应曲线向右移动并抑制最大峰值，类似于维拉帕米（标准 CCB）建立了类似 CCB 的作用。因此，本研究揭示了植物化学成分，并探索了粗叶木在腹泻和高活性肠道运动障碍中的治疗用途的详细药效学基础。
