Pharmacological basis for the medicinal use of Holarrhena antidysenterica in gut motility disorders.

CONTEXT: Holarrhena antidysenterica Wall. (Apocynaceae) is widely used in traditional medical system for treatment of constipation, colic, and diarrhea. AIM: This study was carried out to provide pharmacological basis for medicinal use of Holarrhena antidysenterica in gastrointestinal disorders. MATERIALS AND METHODS: Hydro-ethanolic crude extract of Holarrhena antidysenterica (HaCE) and its fractions were studied in various gastrointestinal isolated tissue preparations. RESULTS: In guinea pig ileum tissues, HaCE at 0.3-10 mg/mL caused pyrilamine-sensitive spasmogenic effect. When tested in spontaneously contracting rabbit jejunum preparations, HaCE (0.01-3.0 mg/mL) caused moderate stimulation, followed by a relaxant effect at next higher concentrations. In presence of pyrilamine, the contractile effect was blocked and the relaxation was observed at lower concentrations (0.01-0.3 mg/mL). HaCE inhibited the high K(+) (80 mM)-induced contractions at concentration range of 0.01-1.0 mg/mL and shifted Ca(++) concentration response curves to the right, like that caused by verapamil. Activity-directed fractionation revealed that the spasmogenic component was concentrated in the aqueous fraction, while the spasmolytic component was concentrated in the organic fraction. DISCUSSION AND CONCLUSION: These results indicate that the gut stimulant and relaxant activities of Holarrhena antidysenterica are mediated possibly through activation of histamine receptors and Ca(++) channel blockade, respectively and this study provides sound mechanistic background for its usefulness in gut motility disorders such as constipation, colic, and possibly diarrhea.

Studies on antidyslipidemic effects of Morinda citrifolia (Noni) fruit, leaves and root extracts.

BACKGROUND: The objective of present study was to provide the pharmacological basis for the medicinal use of Morinda citrifolia Linn in dyslipidemia using the aqueous-ethanolic extracts of its fruits (Mc.Cr.F), leaves (Mc.Cr.L) and roots (Mc.Cr.R). RESULTS: Mc.Cr.F, Mc.Cr.L and Mc.Cr.R showed antidyslipidemic effects in both triton (WR-1339) and high fat diet-induced dyslipidemic rat models to variable extents. All three extracts caused reduction in total cholesterol and triglyceride levels in triton-induced dyslipidemia. In high fat diet-induced dyslipidemia all these extracts caused significant reduction in total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C), atherogenic index and TC/HDL ratio. Mc.Cr.R extract also caused increase in high density lipoprotein-cholesterol (HDL-C). The Mc.Cr.L and Mc.Cr.R reduced gain in body weight with a reduction in daily diet consumption but Mc.Cr.F had no effect on body weight and daily diet consumption. CONCLUSIONS: These data indicate that the antidyslipidemic effect of the plant extracts was meditated through the inhibition of biosynthesis, absorption and secretion of lipids. This may be possibly due partly to the presence of antioxidant constituents in this plant. Therefore, this study rationalizes the medicinal use of Morinda citrifolia in dyslipidemia.

Antispasmodic and vasodilator activities of Morinda citrifolia root extract are mediated through blockade of voltage dependent calcium channels.

BACKGROUND: Morinda citrifolia (Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders. METHODS: Isolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract of Morinda citrifolia roots (Mc.Cr). RESULTS: The Mc.Cr produced a concentration-dependent relaxation of spontaneous and high K(+) induced contractions in isolated rabbit jejunum preparations. It also caused right ward shift in the concentration response curves of Ca(++), similar to that of verapamil. In guinea-pig right atria, Mc.Cr caused inhibition of both atrial force and rate of spontaneous contractions. In rabbit thoracic aortic preparations, Mc.Cr also suppressed contractions induced by phenylephrine (1.0 µM) in normal- Ca(++) and Ca(++)-free kreb solutions and by high K(+), similar to that of verapamil. In rat thoracic aortic preparations, Mc.Cr also relaxed the phenylephrine (1.0 µM)-induced contractions. The vasodilatory responses were not altered in the presence of L-NAME (0.1 mM) or atropine (1.0 µM) and removal of endothelium. CONCLUSIONS: These results suggest that the spasmolytic and vasodilator effects of Mc.Cr root extract are mediated possibly through blockade of voltage-dependent calcium channels and release of intracellular calcium, which may explain the medicinal use of Morinda citrifolia in diarrhea and hypertension. However, more detailed studies are required to assess the safety and efficacy of this plant.

Antihypertensive, antidyslipidemic and endothelial modulating activities of Orchis mascula.

The objective of this study was to investigate the possible mode(s) of action for the medicinal use of Orchis mascula (OM) (family Orchidaceae) in hypertension and dyslipidemia. In spontaneously hypertensive rats (SHRs), OM significantly (P<0.05) reduced systolic blood pressure to 174.2+/-9.63 vs. 203.4+/-7.13 mm Hg (mean+/-s.e.m.; n=7-10) and improved endothelial dysfunction by increasing acetylcholine-induced relaxation. In normotensive anesthetized rats, the crude extract of OM (Om.Cr) at 10 and 30 mg kg(-1) caused a dose-dependent attenuation of mean arterial pressure. OM also decreased serum triglycerides to 29.28+/-6.99 vs. 93.84+/-5.7 mg per 100 ml (P<0.001), low-density lipoprotein-cholesterol to 5.99+/-1.27 vs. 21.9+/-3.5 mg per 100 ml (P<0.05) and atherogenic index to 0.096+/-0.017 vs. 0.36+/-0.08 mg per 100 ml (P<0.05). OM significantly reduced lipid levels in tyloxapol and high fat diet-induced hyperlipidemia. In a second model, OM also reduced gain in body weight with a reduction in daily diet consumption. In isolated rabbit aorta, Om.Cr caused concentration-dependent relaxation of both phenylephrine and high K(+) (80 mM)-induced contractions and a rightward shift of the calcium concentration-response curves similar to the effect seen with verapamil. In conclusion, OM shows antihypertensive and endothelial-modulating effects mediated through multiple pathways that include direct vasodilation by calcium channel blockade and reduction of plasma lipids by inhibition of biosynthesis, absorption and secretion. This study rationalizes the medicinal use of OM in hypertension and dyslipidemia. However, further studies are required to identify the active constituents of this plant.