Presence of cholinergic and calcium antagonist constituents in Saussurea lappa explains its use in constipation and spasm

This study was carried out to provide a scientific basis for the traditional use of Saussurea lappa, in constipation and spasms. Isolated tissue preparations were used to see if the aqueous-methanol crude extract of the S. lappa root (Sl.Cr) contains gut stimulatory and inhibitory constituents. In isolated guinea-pig ileum, a quiescent preparation, Sl.Cr caused a concentration-dependent (0.3-5.0 mg/mL) spasmogenic effect, with the maximum effect reaching 91% of the acetylcholine maximum. A further increase in concentration caused a declining effect, indicating the presence of spasmolytic constituent(s). The spasmolytic effect was more marked in the spontaneously contracting rabbit jejunum and in the atropinized preparations. The spasmolytic effect was mediated through calcium channel blocking (CCB) activity, as evident by its inhibitory effect against high K(+) (80 mm)-induced contraction and displacement of the Ca(++) concentration-response curves to the right. These data indicate that the crude extract of Sl.Cr contains gut stimulatory constituent(s) of cholinergic-type providing a scientific basis for its use in constipation. The presence of spasmolytic constituents of CCB-type more evident in the spontaneous contracting gut preparation may explain its use in spasms.     

Presence of calcium antagonist activity explains the use of Syzygium samarangense in diarrhoea

Syzygium samarangense (Family; Myrtaceae) or 'makopa', as it is commonly known, is native to Malaysia, some islands of Indonesia and to Far East in general. This study was undertaken to rationalize the use of this plant in hypermotility states of the gut. The hexane extract of S. samarangense (Ss.Hex) was found to dose-dependently (10-3000 microg/mL) relax the spontaneously contracting isolated rabbit jejunum. When tested for a possible calcium channel blocking (CCB) activity, the extract (10-1000 microg/mL) relaxed the high K+-induced contractions and also decreased the Ca++ dose-response curves in a dose-dependent manner (30-100 microg/mL), confirming the CCB activity. Four flavonoids isolated from the hexane extract were tested for a possible spasmolytic activity. All flavonoids, identified as: 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (SS1), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (SS2), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (SS3) and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (SS4), showed dose-dependent (10-1000 microg/mL) spasmolytic activity with SS2 being the most potent. These results indicate that the presence of compounds with spasmolytic and calcium antagonist activity may be responsible for the medicinal use of the plant in diarrhoea.     

The calcium channel blocking and phosphodiesterase inhibitory activities of the extract of Andropogon muricatus explains its medicinal use in airways disorders

The present work was carried out to provide a pharmacological base for the medicinal use of Andropogon muricatus in airways disorders, such as asthma. In isolated guinea‐pig tracheal strips, the crude extract of Andropogon muricatus exhibited a non‐specific relaxant effect against carbachol (1 µ m ) and high K⁺ precontractions, with EC₅₀ values of 0.10 (0.07–0.11) and 0.15 mg/mL (0.11–0.18), respectively, similar to papaverine, while verapamil was more potent against high K⁺. This suggests the involvement of a non‐specific relaxant effect, mediated possibly through Ca⁺⁺ channel blockade and phosphodiesterase inhibition. The functional nature of the relaxant effect was further confirmed through indirect evidence when pretreatment of the tissues with the plant extract caused potentiation of the isoprenaline inhibitory response curves, similar to papaverine, while the effect of verapamil remained unchanged. These data indicate that the crude extract of Andropogon muricatus contains constituent(s) that mediate the tracheal relaxant effect, possibly through dual inhibition of Ca⁺⁺ channels and phosphodiesterase and provide pharmacological evidence for its medicinal use in airways disorders, particularly asthma. Copyright © 2011 John Wiley & Sons, Ltd.     

Calcium channel blocking activity of Mentha longifolia L. explains its medicinal use in diarrhoea and gut spasm

Mentha longifolia has a reputation in traditional medicine in the indications of diarrhoea and gut spasm. This study was carried out to provide a possible pharmacological basis for its medicinal use in hyperactive gut disorders. In a castor oil induced diarrhoeal model, the crude extract of Mentha longifolia (Ml.Cr), at doses of 100–1000 mg/kg, provided 31–80% protection, similar to loperamide. In isolated rabbit jejunum preparations, Ml.Cr caused inhibition of spontaneous and high K⁺‐induced contractions, with respective EC₅₀ values of 1.80 (1.34–2.24; n = 6–8) and 0.60 mg/mL (0.37–0.85; n = 6–8), which suggests spasmolytic activity, mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pretreatment of the tissue with Ml.Cr (0.3–1 mg/mL) caused a rightward shift in the Ca⁺⁺ concentration–response curves (CRCs), similar to verapamil. Loperamide also inhibited spontaneous and high K⁺‐induced contractions and shifted the Ca⁺⁺ CRCs to the right. Activity‐directed fractionation revealed that the petroleum spirit fraction was more potent than the parent crude extract and aqueous fraction. These data indicate that the antidiarrhoeal and spasmolytic effects of the crude extract of Mentha longifolia are mediated through the presence of CCB‐like constituent(s), concentrated in the petroleum spirit fraction and this study provides indirect evidence for its medicinal use in diarrhoea and spasm. Copyright © 2010 John Wiley & Sons, Ltd.     

Cholinomimetic and calcium channel blocking activities of Carthamus oxycantha

The crude extract of Carthamus oxycantha (Co.Cr) and its fractions were studied in vitro for their possible spasmogenic and spasmolytic activities. Co.Cr (0.03-10 mg/mL) caused an atropine sensitive spasmogenic effect in guinea-pig ileum. In spontaneously contracting rabbit jejunum preparations, Co.Cr caused a dose-dependent (0.03-3.0 mg/mL) spasmogenic effect, followed by relaxation at the next higher doses of 5.0-10.0 mg/mL. In the presence of atropine, the spasmogenic effect was blocked and the relaxant effect was observed at lower doses (0.1-5.0 mg/mL), shifting the inhibitory dose-response curves to the left. Co.Cr also inhibited K(+) (80 mm)-induced contractions in atropinized preparations at similar doses, suggesting calcium channel blockade (CCB) activity. The CCB effect was further confirmed when pretreatment of the tissue with Co.Cr produced a dose-dependent shift in the Ca(++) dose-response curves to the right, similar to that caused by verapamil. Activity-directed fractionation revealed that the spasmolytic effect was concentrated in organic fractions in the following order of potency: hexane > ethylacetate > chloroform, while the aqueous fraction exhibited spasmogenic and weak spasmolytic effects. These results indicate that Carthamus oxycantha contains a combination of spasmogenic (cholinergic) and spasmolytic (calcium antagonist) constituents.     

阻断钙离子通道对正畸牙齿移动的影响

目的研究阻断L型钙离子通道是否能减缓正畸牙齿的移动。方法选取60只雄性SD大鼠，分成加力组、加力＋硝苯地平I荆组和加力＋硝苯地平Ⅱ剂组，每组再按不同时间分为1天组、3天组、7天组、14天组和21天组。测量并比较牙齿石膏模型加力前后右侧上颌第一磨牙近中移动距离，对牙周组织切片采用HE染色和胶原特殊染色，再用计算机进行光密度分析。结果牙齿近中移动距离减少，牙周胶原量增多。结论阻断钙离子通道减缓了正畸牙齿移动的速度。     

黄槿化学成分和药理活性研究进展

黄槿为《全国中草药汇编》收载的两种半红树植物之一,具有清热解毒的功效,在海南黎族聚集地区作为药物使用.有关黄槿的化学成分研究起始于20世纪60年代,至今从中分离得到了大量的三萜、黄酮、倍半萜和酰胺类化合物,其中木栓烷型三萜和高度氧化的倍半萜类成分是该药用植物的特征性成分.药理研究主要集中在抗炎、抗肿瘤和抗氧化活性.现就该植物的化学成分和药理活性研究进展进行综述,为其进一步开发提供科学依据.     

胃肠动力中药在老年性便秘治疗中的应用

[目的]观察胃肠动力中药合枳术丸汤剂治疗老年性便秘的临床疗效。[方法]将符合诊断标准的112例随机分为试验组和对照组,试验组56例用胃肠动力中药合枳术丸汤剂治疗,对照组56例用莫沙必利治疗。[结果]试验组56例,总有效率98.2%(55),对照组56例,总有效率62.50%。[结论]应用胃肠动力中药合枳术丸汤剂治疗老年性便秘,具有调畅气机、润肠活血通降,既补益又通降,同时可减少老年性便秘患者的泻剂依耐和心脑血管疾病的发生。     

Pharmacological basis for the use of peach leaves in constipation

The aqueous crude extract (PPL.Cr) of peach leaves (Prunus persica) was studied for the possible presence of gut stimulatory constituent(s) to rationalize the folkloric use of the plant in constipation. PPL.Cr at the dose of 1-10 mg/ml caused a moderate degree of spasmogenic effect in isolated guinea-pig ileum. Pretreatment of the tissue with atropine (1 M) completely abolished the contractile effect of the plant extract similar to that of acetylcholine which is suggestive of a cholinergic mechanism. In isolated rabbit jejunum preparations, PPL.Cr produced a week spasmogenic effect followed by relaxation of the spontaneous contractions at higher doses. Bioassay-directed fractionation revealed that the spasmogenic activity was separated in the aqueous fraction, while the spasmolytic activity was concentrated in the ethyl acetate fraction. When tested against K(+)-induced contraction, both PPL.Cr and its ethyl acetate fraction (PPL.EtAc) caused a dose-dependent inhibition, suggesting calcium channel blockade (CCB). The presence of CCB in peach leaves was confirmed when pretreatment of the tissue with PPL.EtAc caused a dose-dependent rightward shift in the Ca(2+) dose-response curves, similar to that produced by verapamil. These data indicate that the plant contains spasmogenic (cholinomimetic) and spasmolytic (calcium antagonist) constituents, which are concentrated in the aqueous and ethyl acetate fractions, respectively. Furthermore, the laxative effect of the plant reported in the traditional system of medicine may be partially due to the cholinergic action, which was dominant over the spasmolytic component.     

Pharmacological basis for the use of Fumaria indica in constipation and diarrhea

The crude extract of Fumaria indica whole plant (Fi.Cr) and its fractions were studied in vitro for spasmogenic and spasmolytic effects to rationalize some of the traditional uses. Fi.Cr (1.0-5.0 mg/mL) caused a moderate degree of atropine-sensitive spasmogenic effect in guinea-pig ileum. In spontaneously contracting rabbit jejunum, Fi.Cr (0.03-0.3 mg/mL) caused a mild spasmogenicity followed by relaxation at the higher doses. In the atropinized preparations, Fi.Cr inhibited spontaneous and K(+)-induced contractions at the similar doses (0.1-1.0 mg/mL), which suggests calcium channel blockade (CCB). CCB effect was confirmed when pretreatment of the tissue with the Fi.Cr produced a dose-dependent shift in the Ca(2+) dose-response curves to the right, similar to that produced by verapamil. Activity-directed fractionation revealed that the spasmolytic effect is concentrated in the petroleum ether fraction, while dichloromethane fraction contains both spasmogenic and spasmolytic constituents. These data indicate that the presence of cholinergic and CCB constituents in Fi.Cr may explain the respective traditional use of Fumaria indica in constipation and diarrhoea.     

中医治疗阿片类药物所致便秘的研究进展

阿片类药物在治疗癌性疼痛方面起着极为重要的作用,然而阿片类药物引起的相关胃肠道反应也开始备受关注,其中以阿片类药物所致便秘(OIC)最为常见且最受关注.它不但出现在用药初期,并且会持续存在于阿片类药物止痛的全过程.因此,便秘已成为制约阿片类药物镇痛治疗应用的最大障碍,严重影响疾病的治疗及患者的生活质量.中医在治疗OIC...     

A review of traditional use,phytoconstituents and biological activities of Himalayan yew,Taxus wallichiana

Plants synthesize certain phytoconstituents for their protection, which, because they are not of primary need, are known as secondary metabolites. These secondary metabolites of plants, have often been found to have medicinal uses for human beings. One such gymnosperm having secondary metaboli tes of medicinal potential for humans is Taxus wallichiana(Himalayan yew). Besides being the source of taxol, this plant has been investigated for its essential oil, diterpenoids, lignans, steroids, sterols and biflavonoids. Traditionally, it is used to treat disorders of the digestive, respiratory, nervous and skeletal systems. Although pharmacologically underexplored, it has been used for antiepileptic, anti-inflammatory, anticancer, antipyretic, analgesic, immunomodulatory and antimicrobial activities. The present review compiles traditional uses, phytochemical constituents(specifically the secondary metabolites) pharmacological activities and the toxicity of T. wallichiana.     

Problems and possibilities in the use of traditional drugs

Research and development of traditional drugs, as tools in health care, need a special approach, preferably in a multidisciplinary setting. With special reference to the situation of the indigenous medicine in Sri Lanka, an ethnopharmacognostic approach which has been practised there during the last 4 years is outlined. Besides the study of literature data the significance and relevancy of a field inquiry into the nature, the position and the use of traditional drugs is stressed. In such field inquiries a questionnaire which covers the problems of an ethnobotanical, ethnopharmaceutical, ethnopharmacological and ethnomedical nature is used. The problems encountered are discussed according to four categories: the non-professional users, the professionals who prescribe the drugs and direct the medications, the professional producers and the non-professional preparation of drugs. The possibilities for advancement of traditional medicine is outlined as a programmed development aiming at standardization of the quality of ingredients and manufacturing processes and schemes of quality control. However, simultaneous clinical research along with experimentally based standardized production is of vital importance. Within the framework of such developmental endeavours serious scientific attention should be given to conceptual aspects of the traditional system and the context in which their drugs are used. Finally it is argued that major advancements of traditional medicine will only be achieved if research programmes are focused on clear-cut topics.     

Antidiarrhoeal and spasmolytic activities of the methanolic crude extract of Alstonia scholaris L. are mediated through calcium channel blockade

This study was aimed to provide a pharmacological basis to the medicinal use of Alstonia scholaris as an antidiarrhoeal and antispasmodic by using in vivo and in vitro techniques. In the in vivo study the crude extract of Alstonia scholaris (As.Cr), which tested positive for the presence of alkaloids, provided 31–84% protection against castor oil‐induced diarrhoea in mice at 100–1000 mg/kg doses, similar to loperamide. In isolated rabbit jejunum preparation, the As.Cr caused inhibition of spontaneous and high K⁺ (80 mm )‐induced contractions, with respective EC₅₀ values of 1.04 (0.73–1.48) and 1.02 mg/mL (0.56–1.84; 95% CI), thus showing spasmolytic activity mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pretreatment of the tissue with the As.Cr (0.3–1 mg/mL) caused a rightward shift in the Ca⁺⁺ concentration‐response curves similar to verapamil, a standard calcium channel blocker. Loperamide also inhibited spontaneous and high K⁺ precontractions as well as shifted the Ca⁺⁺ CRCs to the right. These results indicate that the crude extract of Alstonia scholaris possesses antidiarrhoeal and spasmolytic effects, mediated possibly through the presence of CCB‐like constituent(s) and this study provides a mechanistic base for its medicinal use in diarrhoea and colic. Copyright © 2009 John Wiley & Sons, Ltd.     

中药归经理论研究与中药现代化

本文分析了目前中药研究存在的问题及中药归经研究的现状,提出中药现代化即以中医药理论为指导,用现代科学方法来研究中药,将传统中医药的优势、特色与现代科技相结合。中药归经理论作为中医药理论的特色之一,其实质亦即药物的作用机制,研究归经即搞清中药通过何种途径对脏腑发挥作用。因此,中药归经理论的研究,是中药规范化、标准化研究的重要内容之一,是实现中药现代化的前提。     

魏志军从督脉论治成人顽固性便秘经验

成人顽固性便秘是消化系统疾病中的难治病,魏志军教授从《黄帝内经》中督脉生病治督脉的原则出发,依据正常排便的神经生理,从中、西医两个角度探索该病的发生机制,认为成人顽固性便秘与腰骶神经功能障碍存在密切关系,运用奇经八脉辨证法,从督脉辨证,创制了专方升督平木汤,通过临床观察,在该病的治疗中有独特疗效.     

Pharmacological basis for the medicinal use of Carissa carandas in constipation and diarrhea

Ethnopharmacological relevance

Carissa carandas Linn. commonly known as “Karaunda” (Apocynaceae) is a popular medicinal herb widely distributed in different parts of Pakistan. In addition to other medicinal uses, Carissa carandas is popular in indigenous system of medicine for its medicinal use in gut motility disorders like, constipation and diarrhea.

Objective

This study was planned to provide pharmacological basis to the medicinal use of Carissa carandas in constipation and diarrhea.

Materials and methods

The crude extract of the leaves of Carissa carandas (Cc.Cr) was prepared in methanol and its fractionation was carried out with ethylacetate, petroleum ether and n-butanol. In-vivo studies were conducted on mice, while isolated rabbit jejunum and guinea-pig ileum preparations were used for the in-vitro experiments. The spasmogenic and spasmolytic responses of gut tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system.

Results

The HPLC fingerprints of Cc.Cr, its petroleum (Cc.Pef), ethylacetate (Cc.Eaf) and n-butanol (Cc.Baf) fractions showed the presence of oleanolic acid, ursolic acid, stigmasterol and β-sitosterol. Oral administration of Cc.Cr to mice increased fecal output at lower doses (30 and 50 mg/kg), while it showed protection against castor oil-induced diarrhea at higher doses (300 and 600 mg/kg). In isolated guinea-pig ileum and rabbit jejunum, Cc.Cr and Cc.Baf exhibited stimulatory effect at 0.003–3 mg/ml, which was partially sensitive to atropine or pyrillamine or partially/fully sensitive to atropine+pyrillamine, followed by relaxation at higher tested concentrations, being more potent in rabbit tissues. The ethylacetate fraction (0.1–5 mg/ml) exhibited fully atropine-sensitive contractions in both guinea-pig and rabbit tissues, being more potent in guinea-pig while more efficacious in rabbit tissues. However, the petroleum fraction (0.003–1.0 mg/ml) showed only spasmolytic activity in spontaneously contracting rabbit tissues, similar to nifedipine. In guinea-tissue, Cc.Pef did not cause any stimulant effect. When studied against high K⁺ (80 mM)-induced contraction, the crude extract and its fractions caused a dose-dependent inhibition, with the following order of potency: Cc.Pef>Cc.Eaf>Cc.Cr≥Cc.Baf, similar to nifedipine indicating Ca⁺⁺ channel antagonist like activity, which was further confirmed when the plant extract displaced Ca⁺⁺ curves to the right with suppression of maximum effect similar to that of nifedipine.

Conclusion

This study demonstrates that the crude extract of Carissa carandas possesses a gut-stimulatory effect mediated primarily through the activation of muscarinic and histaminergic receptors while its spasmolytic effect was mediated possibly through Ca⁺⁺ antagonist pathway. Thus, this study provides a clear evidence for the dual effectiveness of Carissa carandas in constipation and diarrhea, thus validating its medicinal use.     

Phytochemicals from traditional medicinal plants used in the treatment of diarrhoea: modes of action and effects on intestinal function

Medicinal plants have been used as traditional treatments for numerous human diseases for thousands of years. Diarrhoeal diseases continue to be a major cause of morbidity and mortality throughout the world and there is renewed interest in the discovery of novel compounds that can be used to fight these diseases. Numerous studies have validated the traditional use of antidiarrhoeal medicinal plants by investigating the biological activity of extracts of such plants, which have antispasmodic effects, delay intestinal transit, suppress gut motility, stimulate water adsorption or reduce electrolyte secretion. Of the numerous phytochemicals (such as alkaloids, tannins, flavonoids and terpenes) present in active extracts, tannins and flavonoids are thought to be responsible for antidiarrhoeal activity by increasing colonic water and electrolyte reabsorption. Others act by inhibiting intestinal motility. As some of the active ingredients are potentially toxic, there is a need to evaluate the safety of plant preparations. A few clinical trials have evaluated the safety and tolerability of traditional and herbal medicine preparations used to treat diarrhoea and generally indicate that minimal side effects are observed. However, with the increased popularity of plant-derived and herbal medicines in Western society, the benefits and potential dangers of these medicines must be considered.     

Antibacterial activities of medicinal plants used for the treatment of diarrhoea in Limpopo Province, South Africa

The ethnobotanical survey conducted in this study showed that 21 plant species belonging to 14 families are used in traditional medical practice in Limpopo Province, South Africa, for the treatment of diarrhoea. Methanol, ethanol, acetone and hot water extract from different plant parts (leaves, roots, bark and stem rhizome), of several of these plants (Indigofera daleoides, Punica granatum, Syzygium cordatum, Gymnosporia senegalensis, Ozoroa insignis, Elephantorrhiza elephantina, Elephantorrhiza burkei, Ximenia caffra, Schotia brachypetala and Spirostachys africana), were screened for antibacterial activity against Vibro cholera, Escherichia coli and Staphylococcus aureus, Shigella spp., Salmonella typhi. The antibacterial activity was determined by agar-well diffusion method and expressed as the average diameter of the zone of inhibition of bacterial growth around the wells. The minimum inhibitory concentration (MIC) of active extracts was determined by using the micro-plate dilution assay. Most of the extracts showed relatively high antibacterial activity against most of the tested microorganisms with the diameter of inhibition zones ranging between 10 and 31 mm. Of the plants studied, the most active extracts were those obtained from Punica granatum and Indigofera daleoides. All extracts from two plants, namely, Punica granatum and Ozoroa insignis, were active against all bacterial strains while only organic extracts of Indigofera daleoides inhibited the growth of all tested microorganisms. Water extract of Punica granatum were equally active as organic extracts against bacteria such as Staphylococcus aureus, Shigella sonnei and Shigella flexneri. All extracts of Elephantorrhiza elephantina, Elephantorrhiza burkei and Ximenia caffra and Schotia brachypetala were not active against Escherichia coli and Salmonella typhi. The MIC values for active extracts ranged between 0.039 and 0.6 mg/ml. The results obtained appeared to confirm the antibacterial potential of the plants investigated, and their usefulness in the treatment of diarrhoea.