The antidiarrheal and spasmolytic activities of Phyllanthus emblica are mediated through dual blockade of muscarinic receptors and Ca2+ channels

Aim of the study

This study was aimed at providing the possible mechanisms for the medicinal use of Phyllanthus emblica in diarrhea.

Materials and methods

The in vivo studies were conducted in mice, while isolated rabbit jejunum and guinea-pig ileum were used for the in vitro experiments.

Results

The crude extract of Phyllanthus emblica (Pe.Cr), which tested positive for alkaloids, tannins, terpenes, flavonoids, sterols and coumarins, caused inhibition of castor oil-induced diarrhea and intestinal fluid accumulation in mice at 500-700 mg/kg. In isolated rabbit jejunum, Pe.Cr relaxed carbachol (CCh) and K⁺ (80 mM)-induced contractions, in a pattern similar to that of dicyclomine. The preincubation of guinea pig-ileum with Pe.Cr (0.3 mg/mL), caused a rightward parallel shift in the concentration-response curves (CRCs) of acetylcholine without suppression of the maximum response. While at the next higher concentration (1 mg/mL), it produced a non-parallel rightward shift with suppression of the maximum response, similar to that of dicyclomine, suggesting anticholinergic and Ca²⁺ channel blocking (CCB)-like antispasmodic effect. The CCB-like activity was further confirmed when pretreatment of the tissue with Pe.Cr, shifted the CRCs of Ca²⁺ to the right with suppression of the maximum response, similar to nifedipine or dicyclomine. The activity-directed fractions of Pe.Cr showed a combination of Ca²⁺ antagonist and anticholinergic like components in all fractions but with varying potency.

Conclusion

These results indicate that the Phyllanthus emblica fruit extract possesses antidiarrheal and spasmolytic activities, mediated possibly through dual blockade of muscarinic receptors and Ca²⁺ channels, thus explaining its medicinal use in diarrhea.     

Investigation on Antidiarrhoeal Activity of Aristolochia Indica Linn. Root Extracts in Mice

Background

The present study aimed at investigating the effect of ethanolic extract (EtAI), and aqueous extract (AqAI) of Aristolochia indica Linn roots on castor oil-induced diarrhoea and study on small intestinal transit. Phytochemical analysis of extracts was performed as per standard procedure.

Materials and Methods

The oral toxicity study using Swiss albino mice was performed in accordance with OECD guidelines. The EtAI and AqAI extracts of Aristolochia indica Linn were studied for antidiarrhoeal property using castor oil-induced diarrhoeal model and charcoal-induced gastrointestinal motility test in Swiss albino mice.

Results

Among the tested doses of 200 and 400 mg/kg body weight, the extracts reduced the frequency and severity of diarrhoea in test animals throughout the study period. At the same doses, the extract delayed the intestinal transit of charcoal meal in test animals as compared to the control and the results were statistically significant.

Conclusion

Experimental findings showed that ethanol extract of Aristolochia indica Linn root possess significant antidiarrheal activity and may be a potent source of anti-diarrhoeal drug in future.     

Antidiarrheal activity of Pyrenacantha staudtii Engl. (Icacinaceae) aqueous leaf extract in rodents

Ethnopharmacological relervance

Pyrenacantha staudtii Engl. (Icacinaceae) is a plant which is traditionally used for the treatment of blemnorrhea, hernia, insomnia, intestinal pain and diarrhea in Nigeria. Therefore the core aim of the present study is to evaluate antidiarrheal activity of Pyrenacantha staudtii aqueous extract (PSE).

Materials and methods

The antidiarrheal activity was evaluated using castor oil-induced diarrhea method. The effects of Pyrenacantha staudtii aqueous extract on gastrointestinal motility, intestinal transit and enteropooling were also examined in rodents. The acute toxicity effect of the aqueous extract of Pyrenacantha staudtii was also investigated.

Results

Pyrenacantha staudtii aqueous extract (PSE, 100-400 mg/kg, p.o.) produced dose-dependent and significant (P < 0.05-0.01) protection of rats and mice against castor oil-induced diarrhea, inhibited intestinal transit, and delayed gastric emptying. PSE, produced dose-dependent and significant (P < 0.05-0.01) antimotility effect, caused dose-related inhibition of castor-oil-induced enteropooling in animals, comparable to atropine (1 mg/kg, p.o.). Like loperamide (10 mg/kg, p.o.), PSE, dose-dependently and significantly (P < 0.05-0.01) delayed the onset of castor-oil induced diarrhea, decreased the frequency of defecation, and reduced the severity of diarrhea in the rodents. Compared with control animals, PSE, dose-dependently and significantly (P < 0.05-0.01) decreased the volume of castor oil-induced intestinal fluid secretion, and reduced the number, weight and wetness of fecal droppings.

Conclusion

The findings of this study indicate that PSE possesses antidiarrheal property in rats and mice. These findings confirm the ethnomedicinal use of Pyrenacantha staudtii leaf as a valuable natural remedy for the treatment, management and/or control of diarrhea.     

Antidiarrheal activity of extracts and compound from Trilepisium madagascariense stem bark

Objective:

The present study was performed to evaluate the preventive and curative antidiarrheal effects of the methanol extract, fractions and compound from the stem bark of Trilepisium madagascariense in rats.

Materials and Methods:

The methanol extract from the stem bark of T. madagascariense, its fractions (n-hexane, ethyl acetate, n-butanol and aqueous residue) and compound (obtained from further column chromatography of the ethyl acetate fraction) were evaluated for the antidiarrheal activity in rats. These test samples (at 100, 200 and 400 mg/kg for the extract and fractions and 2.5 mg/kg for compound) were assayed on the latent periods, purging indices and fecal frequencies in castor oil-induced diarrhea. Gastrointestinal transit and castor oil-induced enteropooling assays were conducted. Shigella-induced diarrhea was assayed. Blood chemistry and fecal Shigella load were examined.

Results:

The fractionation of the ethyl acetate fraction from the methanol extract of T. madagascariense afforded a known compound [isoliquiritigenin (1)]. Compound 1 increased the latent period of diarrhea induction (179.40 min) compared to the saline control (60.80 min). The purging indices, fecal frequencies and intestinal enteropooling decreased with an increase in the dose of test samples. The blood cell counts, sera creatinine and fecal Shigella load decreased significantly (P ≤ 0.05) in the plant extract-treated rats compared to the saline control.

Conclusion:

The results of our study, being reported for the first time, provide clear evidence that the methanol extract, fractions and isoliquiritigenin from T. madagascariense stem bark possess antidiarrheal activities.     

Byrsonima fagifolia: an integrative study to validate the gastroprotective, healing, antidiarrheal, antimicrobial and mutagenic action

Ethnopharmacological relevance

Ethnopharmacological survey indicated leaves of Byrsonima fagifolia Nied. (Malpighiaceae) against gastrointestinal disorders.

Aim of the study

The methanolic extract from the leaves of Byrsonima fagifolia (denominated BF) was evaluated for toxic, mutagenic, gastroprotective, antidiarrheal, antibacterial and immunomodulatory activities.

Materials and methods

The preventive and healing action of BF against gastric ulcer was evaluated in experimental models in rodents. We evaluated immunomodulatory (by murine peritoneal macrophages), antidiarrheal (by induced diarrhea with castor oil and intestinal motility) and antibacterial action of BF against standard strain of Escherichia coli, Staphylococcus aureus and Helicobacter pylori. The safety of use of BF was also evaluated by mutagenic (Ames assay) and by analyses of toxicity parameters.

Results

Phytochemical BF profile indicated the presence of phenolic compounds with antioxidant and radical-scavenging properties. BF significantly inhibited gastric lesions induced by ethanol and HCl/ethanol and endogenous mucosal sulphydryl groups (SHs) participated efficaciously in BF gastroprotection. BF blocked development of inflammation process and also has antidiarrheal actions. This extract accelerated the healing of the gastric ulcerated mucosa by stimulating proliferative factors and by increasing production of gastric mucus with no toxic action. The substances responsible for the protective action are concentrated in the ethyl acetate fraction that demonstrated no mutagenic action in vitro.

Conclusions

Byrsonima fagifolia presents gastroprotective, healing and antidiarrheal activities supporting previous claims that its traditional use by Brazilians can treat these gastrointestinal ailments.     

谈儿童用止泻类中成药的再评价

目的通过研究儿童用止泻类中成药的药品标准,提出对儿童用中成药再评价的建议。方法在已建立的中成药数据库中检索儿童用止泻类中成药品种,将收集到的84个品种的数据建立Excel表,应用中医药理论对其进行医学、药学的综合分析。结果 84个儿童用止泻类中成药品种共涉及7个剂型,仅有6个品种是由单味药组成,而毒性药朱砂也是常用药味,84个儿童用止泻类中成药品种中有62个品种未标明注意事项,占到了全部品种的73.81%。结论儿童用止泻类中成药的剂型、处方、适应证、用法用量等不同程度地存在问题,有必要对其进行再评价,并统一、规范、完善药品标准的相应项目。     

鸦葱对肠炎的影响

鸦葱18.2 g/kg、10.3 g/kg对蓖麻油、番泻叶所引起的小鼠腹泻具有显著的抑制作用。鸦葱(10.8 g/kg)对二甲苯所致小鼠耳壳肿胀,醋酸所引的小鼠腹腔毛细血管通透性增高也具有显著的抑制作用。体外实验表明鸦葱对免离体十二指肠有明显的抑制作用,鸦葱对大肠杆菌及金黄色葡萄球菌均无抑菌作用。     

Pharmacological and computer-aided studies provide new insights into Millettia peguensis Ali (Fabaceae)

Millettia peguensis, popular for its ethnopharmacological uses, was employed to evaluate its different pharmacological properties in this study. The analgesic studies of the plant have been performed by acetic acid-induced writhing and formalin-induced licking tests respectively, whereas the antidiarrheal experiment was done by castor oil-induced diarrheal test. Besides, antioxidant, cytotoxic, antimicrobial, thrombolytic evaluations were performed by DPPH scavenging with phenol content determination, brine shrimp lethality, disc diffusion and clot lysis methods respectively. Moreover, in silico study of the phytoconstituents was carried out by molecular docking and ADME/T analysis.The methanol extract of Millettia peguensis (MEMP) revealed significant biological activity in the analgesic and antidiarrheal test (p < 0.001) compared to the standards. Antioxidant assay displayed promising IC₅₀ values (15.96 μg/mL) with the total phenol content (65.27 ± 1.24 mg GAE/g). In the cytotoxicity study, the LC₅₀ value was found to be 1.094 μg/mL. Besides, MEMP was highly sensitive to the bacteria but less liable to clot lysis. Furthermore, phytoconstituents exposed potential binding affinity towards the selected receptors, whereas the ADME/T properties indicated the drug likeliness of the plant. The outcomes of these findings suggest the therapeutic potential of this plant against pain, diarrhea, inflammation, and tissue toxicity.     

粳米米汤止泻物质基础及其机制?

目的：探讨粳米米汤止泻物质基础及可能机制。方法从粳米中提取制备直链、支链淀粉,分别采用番泻叶致小鼠急、慢性腹泻模型和新斯的明致小鼠小肠运动亢进模型,评价其对小鼠腹泻次数、小肠推进率、血清中钠、钾离子水平的影响。结果与模型对照组比较,直链淀粉、支链淀粉均能不同程度减少急、慢性腹泻模型小鼠的稀便次数,并拮抗慢性腹泻模型小鼠及新斯的明引起的小肠运动亢进,且直链淀粉的作用较支链淀粉、粳米米汤更显著。结论直链淀粉与支链淀粉为粳米米汤止泻的主要物质基础,且直链淀粉的止泻作用优于支链淀粉,其止泻作用可能通过影响体内钠、钾转运及抗胆碱作用实现。     

CNS involvement in the antisecretory action of [Met]enkephalinamide on the rat intestine

The effects of the stable enkephalin, [D-Ala², Met⁵]enkephalinamide (DAMA) were examined on basal and stimulated fluid accumulation in intestinal loops of anesthetized Wistar-Furth rats. DAMA (0.1–3.0 μg, i.c.v.) dose-dependently increased basal fluid absorption in the medial ileum and decreased jejunal and proximal ileal fluid secretion after 4 h cholera toxin (1 μg/loop) pretreatment. The antisecretory effects of DAMA were blocked by naltrexone (1 mg/kg s.c.). Thus, the antisecretory effects of opioids may be partially mediated at CNS sites.