Gut and airways relaxant effects of Carum roxburghianum

Ethnopharmacological relevance

Carum roxburghianum is traditionally used in hyperactive gastrointestinal and respiratory disorders. The present study was carried out to investigate the possible gut and airways relaxant potential of Carum roxburghianum to rationalize its folk uses.

Materials and methods

Crude extract of Carum roxburghianum (Cr.Cr) was studied in in vivo and in vitro techniques.

Results

Cr.Cr exhibited protective effect against castor oil-induced diarrhea in mice at 100–1000 mg/kg. In rabbit jejunum preparations, Cr.Cr (0.03–3.0 mg/mL) caused relaxation of spontaneous and K⁺ (80 mM)-induced contractions at similar concentrations, like papaverine. Pretreatment of tissues with Cr.Cr (0.1–1.0 mg/mL) shifted Ca⁺⁺ concentration–response curves (CRCs) to right, like verapamil. Cr.Cr (0.03 and 0.1 mg/mL) caused leftward shift of isoprenaline-induced inhibitory CRCs, similar to papaverine. In isolated guinea-pig ileum, Cr.Cr (0.01 and 0.03 mg/mL) produced rightward parallel shift of acetylcholine-curves, like atropine. Cr.Cr (1.0–30 mg/kg) caused suppression of carbachol (CCh, 100 μg/kg)-induced increase in inspiratory pressure of anaesthetized rats. In guinea-pig trachea, Cr.Cr (0.03–1.0 mg/mL) relaxed CCh and high K⁺-induced contractions, shifted isoprenaline-induced inhibitory CRCs to left at 0.1 and 0.3 mg/mL and CCh-curves parallel to right (0.01 and 0.03 mg/mL). Cr.Cr did not cause any mortality of mice up to 10 g/kg dose.

Conclusion

These results indicate that Carum roxburghianum possess combination of antidiarrheal, antispasmodic and bronchodilatory effects, which provides pharmacological basis to its traditional use in the disorders of gut and airways hyperactivity, like diarrhea, colic and asthma.     

Study on the mechanism of the bronchodilatory effects of Cynodon dactylon (Linn.) and identification of the active ingredient

Ethnopharmacological relevance

In the traditional medicine, Cynodon dactylon (Linn.) is used in asthma, but scientific studies to provide evidence for medicinal uses are sparse. Thus this study was undertaken to provide evidence for medicinal use in asthma as a bronchodilator, and to identify active ingredient(s).

Materials and methods

In vivo, acetylcholine (Ach)-induced bronchospasm was conducted in guinea pig while isolated rat tracheal strip was suspended in organ bath to measure the concentration response curve using multichannel data acquisition system.

Results

The chloroform extract of Cynodon dactylon (CECD) protected against Ach-induced bronchospasm in guinea pigs, similar to atropine. In the in vitro studies, CECD relaxed carbachol (CCh) and high K⁺-induced contraction of rat tracheal strip, similar to atropine and verapamil respectively, suggesting antimuscarinic and calcium channel blocking (CCB) activities, which were confirmed by right ward shifting of CCh and Ca⁺² concentration response curve (CRC). The phosphodiestrase (PDE) inhibitory activity was confirmed by potentiation of isoprenaline-induced inhibitory response, similar to papaverine. Densitometry analyses led to the identification of scopoletin as an active ingredient. Effectively, it significantly inhibited high K⁺, and Ca⁺² induced contractile response, similar to verapamil. The phosphodiestrase (PDE) inhibitory activity was confirmed by direct evidence of potentiation of isoprenaline-induced inhibitory response, similar to papaverine.

Conclusions

These results suggest that the bronchodilator activity of CECD is partly due to presence of scopoletin, and mediated possibly through CCB and PDE inhibition.     

Bronchodilatory effect of Acorus calamus (Linn.) is mediated through multiple pathways

Aim of the study

This study was undertaken to provide a pharmacological basis for traditional use of Acorus calamus in airways disorders.

Materials and methods

Isolated guinea-pig trachea and atria were suspended in organ baths bubbled with carbogen and mechanisms were found using different parameters.

Results

In isolated guinea-pig tracheal segments, crude extract of Acorus calamus was more effective than carbachol in causing relaxation of high K⁺ (80 mM) precontractions, similar to verapamil, suggesting blockade of calcium channels. The n-hexane fraction was equipotent against both precontractions, similar to papaverine, while ethylacetate fraction was more potent against carbachol precontractions but had a negligible dilator effect against K⁺, similar to atropine and or rolipram. Pretreatment of tracheal preparations with n-hexane or ethylacetate fractions potentiated isoprenaline-induced inhibitory concentration-response curves, similar to papaverine or rolipram. Pretreatment of tracheal preparations with ethylacetate fraction caused a rightward parallel shift in carbachol response curve at lower concentration (0.003 mg/mL) similar to atropine and a non-parallel shift at higher concentrations (0.01 mg/mL), with reduction of maximum response, similar to rolipram. In isolated guinea-pig atrial preparations, crude extracts, its fractions and papaverine inhibited force and rate of contractions at higher concentrations than the smooth muscle while verapamil was equipotent.

Conclusion

These data indicate the presence of unique combination of airways relaxant constituents in crude extract of Acorus calamus, a papaverine-like dual inhibitor of calcium channels and phosphodiesterase in n-hexane fraction and a novel combination of anticholinergic, rolipram-like phosphodiesterase4 inhibitor in ethylacetate fraction and associated cardiac depressant effect, provide a pharmacological basis for traditional use of Acorus calamus in disorders of airways.     

Diuretic activity of the ethanol and aqueous extracts of the surface layer of Poria cocos in rat

Ethnopharmacological relevance

Poria cocos Wolf (Polyporaceae) is a well-known traditional East-Asian medicinal fungus. the epidermis (“Fu-Ling-Pi” in Chinese) of the sclerotia is used as a diuretic. This study was conducted to evaluate of ethanol extract (EE) and aqueous extract (AE) of the diuretic activity of Fu-Ling-Pi in saline-loaded rats.

Material and methods

The EE and AE were orally administered to rats. Urinary excretion rate, pH and electrolyte excretion were measured in the urine of saline-loaded rats.

Results

Urinary excretion rates were significantly increased by the EE. The three doses of AE only produced a slight increase urinary output. The EE had little or no effect on K⁺ excretion, but did indeed induce a notable excretion of Na⁺, that was in agreement with the urinary excretion. The three doses of AE produced an increase Na⁺ and K⁺ excretion, but did not arrive at statistical significance.

Conclusions

The present study confirmed that the not aqueous but ethanol extracts of the epidermis of Poria cocos presents a remarkable diuretic effect.     

Evaluation of diuretic activity of Amaranthus spinosus Linn. aqueous extract in Wistar rats

Ethnopharmacological relevance

Traditional Siddha medicine literature claims that the Amaranthus spinosus Linn. (family: Amaranthaceae) whole plant possesses diuretic property.

Aim of the study

To evaluate the diuretic potential of Amaranthus spinosus aqueous extract (ASAE) in rats.

Material and methods

Different concentrations of ASAE (200, 500, 1000, 1500 mg/kg), thiazide (10 mg/kg) and vehicle were orally administered to rats (n = 6 animals per group) and their urine output was collected after 24 h. Volume, pH, Na⁺, K⁺ and Cl⁻ concentrations of urine were estimated.

Results

ASAE produced increase in Na⁺, K⁺, Cl⁻ excretion, caused alkalinization of urine, showed strong saluretic activity and carbonic anhydrase inhibition activity. These effects were observed predominantly at 500 mg/kg dose and there was no dose–response relationship.

Conclusion

Our study strongly suggests that the Amaranthus spinosus is acting as a thiazide like diuretic with carbonic anhydrase inhibitory activity which restates the claim as diuretic herb in Siddha medicine.     

Direct inhibition of calcineurin by caffeoyl phenylethanoid glycosides from Teucrium chamaedrys and Nepeta cataria

Ethnopharmacological relevance

Teucrium chamaedrys L. and Nepeta cataria L. (Lamiaceae) are species with traditional uses that relate to the treatment of inflammation. Extracts of both species were found to inhibit calcineurin; an important regulator of T-cell mediated inflammation that has received little attention in ethnopharmacological research.

Materials and methods

Extracts and isolated compounds were tested against calcineurin in its calmodulin-activated and basal un-activated state. Active compounds were isolated using Sephadex LH-20 gel filtration and HPLC then identified using NMR spectroscopy.

Results and conclusions

Activity-guided fractionation of Teucrium chamaedrys and Nepeta cataria led to the isolation of the caffeoyl phenylethanoid glycosides teucrioside, verbascoside and lamiuside A (teupolioside). The three compounds inhibited calcineurin both in the presence and absence of calmodulin, suggesting a direct interaction with calcineurin. Calcineurin inhibition should be considered as a potential mode of action when investigating the immunomodulatory activity of caffeoyl phenylethanoid glycoside containing plants.     

Withanolides from Whitania aristata and their diuretic activity

Aim of the study

Withania aristata is an endemic plant used traditionally in Canary Islands as a diuretic. In this paper, we report on this pharmacological activity in several extracts of the dry vegetal material collected and the identification and diuretic activity of two withanolides, one of them previously not reported, isolated from the most active fraction.

Material and methods

Four Whitania aristata extracts at 100 mg/kg were orally administered to laboratory animals to evaluate their diuretic activity. From the most active fraction, two withanolides were isolated. Both and a mixture of them at 5 and 10 mg/kg were analyzed too as diuretics. Water excretion rate and content of Na⁺ and K⁺ electrolytes were measured in the urine of saline-loaded animals.

Results

Whitania aristata water fraction, the two withanolides and the mixture of these compounds displayed high diuretic activity, with a significant excretion of sodium and potassium ions in laboratory animals.

Conclusions

This research supports the ethno-medicinal use of Whitania aristata as diuretic. This activity seems to be associated to the presence of a new type of natural diuretic agents, such as withaferin A and witharistatin.     

Antiulcer and gastric antisecretory effects of dichloromethane fraction and piplartine obtained from fruits of Piper tuberculatum Jacq. in rats

Ethnopharmacological relevance

Piper tuberculatum Jacq. (Piperaceae) is medicinally used as an analgesic and as a treatment for gastric complaints. Thus, the current study aimed to investigate the gastroprotective and antisecretory properties of the dichloromethane fraction of the fruit of Piper tuberculatum (DFPT) and piplartine, a compound isolated from the DFPT, in rats.

Materials and methods

Gastric ulcers were induced in fasted rats by oral administration of absolute ethanol and then mucus content and glutathione (GSH) levels were measured. Mechanisms underlying the antisecretory action were studied through gastric H⁺,K⁺-ATPase activity of highly purified rabbit gastric microsomes and pylorus ligature method in rats.

Results

In the acute toxicity test the values of estimated LD₅₀ for oral and intraperitoneal administration of DFPT were 1.6266 and 0.2684 g/kg, respectively. The DFPT (ED₅₀=29 mg/kg, p.o.) and piplartine (4.5 mg/kg, p.o.) promoted gastroprotection against acute lesions induced by ethanol, effect that could be related with the maintenance of GSH levels in the gastric mucosa. However, only DFPT stimulated gastric mucus secretion. In vitro, the DFPT and piplartine inhibited the H⁺,K⁺-ATPase activity and, in vivo DFPT and piplartine also reduced basal gastric acid secretion, as well as that stimulated by pentagastrin.

Conclusions

These results demonstrate that DFPT and piplatine cause marked gastroprotective effects accompanied by the increase and maintenance of gastric mucus and GSH levels, as well as a reduction in gastric acid secretion through the gastrinergic pathway.     

Hypotensive effect of Aspidosperma subincanum Mart. in rats and its mechanism of vasorelaxation in isolated arteries

Ethnopharmacological relevance

Aspidosperma subincanum is a medicinal herb that is known to be useful for the treatment of cardiovascular-related illnesses. However, its effects and pharmacological mechanisms of action have not been studied. The aim of the present study was to determine the effect of an ethanol extract of Aspidosperma subincanum (EEAS) on blood pressure (in vivo) and vascular tension (in vitro) in the rat thoracic aorta.

Materials and methods

Catheters were inserted into the right femoral vein and artery of anesthetized rats for EEAS infusion and the measurement of blood pressure, heart rate and aortic blood flow (flow probes were placed around the aorta). Moreover, the vasodilator effect of EEAS in isolated pre-contracted rat aortas was examined.

Results

Intravenous infusion of EEAS resulted in significant and dose-dependent hypotension, bradycardia and increased aortic blood flow. In isolated arteries, EEAS (0–27 μg/mL) induced a concentration-dependent relaxation of pre-contracted aortic rings; endothelial denudation potentiated this effect. Pre-treatment of the aortic rings with ODQ, an inhibitor of soluble guanylyl cyclase (sGC); MDL-12,330A, an inhibitor of adenylyl cyclase (AC); or CPA, a SERCA inhibitor, reduced EEAS-induced vasorelaxation. Treatment with an EEAS impaired contractions induced by phenylephrine (an adrenergic agonist) and Bay K 8644 (an L-type Ca²⁺ channel activator). The blockade of K⁺ channels with tetraethylammonium, clotrimazole, glibenclamide or 4-aminopyridine reduced the relaxation stimulated by EEAS.

Conclusions

These findings suggest that EEAS induces hypotension associated with bradycardia. EEAS induces endothelium-independent vascular relaxation. The sGC/cGMP and AC/cAMP pathways, SERCA activation and Ca²⁺ and K⁺ flux across the sarcolemma, are likely involved in this relaxation.     

Diuretic and anti-diuretic activities of the ethanol and aqueous extracts of Alismatis rhizoma

Ethnopharmacological relevance

Alismatis rhizoma or Alisma orientale (Zexie in Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a well-known traditional Chinese medicine and is used as an agent for diuresis and for excreting dampness in Asia and Europe. In this paper, we report the diuretic activities of the ethanol extract (EE) and the aqueous extract (AE) of A. rhizoma (AR).

Materials and methods

The EE and AE were orally administered to rats. The urinary excretion rate and pH, and electrolyte excretion were measured in the urine of saline-loaded rats.

Results

The results showed that EE could increase the urine output at 2.5, 5 and 10 mg/kg doses but decrease the urine output at 20, 40 and 80 mg/kg doses compared with the control group. The 5 and 10 mg/kg doses of EE increased the urine electrolyte excretion, but the effects on Na⁺/K⁺ values were too weak to reach statistical significance. The Na⁺ excretion and Cl⁻ excretion were markedly decreased with the 20, 40 and 80 mg/kg doses of EE, but the effect on K⁺ excretion was notably slight. All of the tested doses of AE produced an increase in urinary excretion, but the increase did not reach statistical significance.

Conclusions

This study identified that EE but not AE presents a notable diuretic effect, and EE had diuretic and anti-diuretic effects, which appears to be related to the sodium–chloride co-transporter in the renal distal convoluting tubule. This study demonstrated for the first time that the EE of AR has a dual effect on renal function, including promotion of diuretic activity at lower doses and inhibiting diuretic activity at higher doses, and the AR dose should be given more attention in clinical applications. This study will play a critical and guiding role in the dosing of AR as a diuretic drug in clinical applications.     

Diuretic activity of some fractions of the epidermis of Poria cocos

Ethnopharmacological relevance

Poria cocos Wolf (Polyporaceae) is a well-known medicinal fungus, the epidermis (“Fu-Ling-Pi” in Chinese) of the sclerotia is used as a diuretic for treating oedema and promoting the diuretic process. In this paper we report on the diuretic activity in rats of petroleum ether, ethyl acetate, n-butanol and the remaining fractions of the ethanol extract from the epidermis of Poria cocos.

Materials and methods

Petroleum ether, ethyl acetate, n-butanol and the remaining fractions of the ethanol extract of Fu-Ling-Pi were orally administered to rats. The urinary excretion rate and the pH and electrolyte excretion were measured in the urine of saline-loaded rats.

Results

In this study, all the tested fractions of Fu-Ling-Pi increased the urinary excretion rate. The three doses of the ethyl acetate fraction all produced remarkable urinary output in 6 h, and all produced a remarkable increase in Na⁺ excretion and Cl⁻ excretion. The Na⁺/K⁺ value in the experimental group was significantly enhanced compared with that of the control group, but the three doses of the ethyl acetate fraction had no effect on the K⁺ excretion. The 25-mg/kg and 50-mg/kg doses of the n-butanol fraction showed notable urinary output and produced a remarkable increase of Na⁺ excretion and Cl⁻ excretion, but the two doses did not produce a remarkable effect on the Na⁺/K⁺ value. The petroleum ether and remaining fractions did not show remarkable diuretic activities compared with the control group.

Conclusions

This study confirmed that the ethyl acetate and n-butanol fractions present a remarkable diuretic effect, showing that they are the diuretic bioactive fractions of Fu-Ling-Pi. This finding appears to indicate at least two mechanisms for the observed diuretic activity, and the K⁺-saving diuretic effect may be related to the triterpenoid components of intermediate polarity contained in this fungus, particularly the lanostanes tetracyclic triterpenoids.     

Anti-secretory,anti-inflammatory and anti-Helicobacter pylori activities of several fractions isolated from Piper carpunya Ruiz & Pav.

Ethnopharmacological relevance

The leaves of Piper carpunya Ruiz & Pav. (syn Piper lenticellosum C.D.C.) (Piperaceae), are widely used in folk medicine in tropical and subtropical countries of South America as an anti-inflammatory, anti-ulcer, anti-diarrheal and anti-parasitical remedy as well as an ailment for skin irritations.

Aims of the study

To study the anti-inflammatory, anti-secretory and anti-Helicobacter pylori activities of different fractions isolated from an ethanolic extract of the leaves of Piper carpunya, in order to provide evidence for the use of this plant as an anti-ulcer remedy. Moreover, to isolate the main compounds of the extract and relate their biological activity to the experimental results obtained with the fractions.

Materials and methods

Sixteen fractions were obtained from the ethanolic extract (F I–XVI) and 16 pure compounds were isolated and identified from these fractions. We studied the effects of the fractions (0.1–400 μg/mL) on the release of myeloperoxidase (MPO) enzyme from rat peritoneal leukocytes, on rabbit gastric microsomal H⁺, K⁺-ATPase activity and anti-Helicobacter pylori anti-microbial activity using the microdilution method (MM). The main compounds contained in the fractions were isolated and identified by ¹H- and ¹³C NMR spectra analysis and comparison with the literature data.

Results

Eight fractions showed inhibition of MPO enzyme (F I–IV, X, XII, XIV and XV). The highest inhibition was observed with F XIV (50 μg/mL, 60.9%, p < 0.001). F X and XII were the most active ones, inhibiting the gastric H⁺, K⁺-ATPase activity with IC₅₀ values equal to 22.3 μg/mL and 28.1 μg/mL, respectively. All fractions, except F XV, presented detectable anti-Helicobacter pylori activity, with a diameter of inhibition zones ranging from 11 mm up to 50 mm. The best anti-Helicobacter pylori activity was obtained with F III and V. Both fractions killed Helicobacter pylori with lowest concentration values, about 6.25 μg/mL. Sixteen pure compounds were isolated, five of them are flavonoids that possess strong anti-oxidant and free radical scavenging activity, e.g. vitexin, isovitexin, and rhamnopyranosylvitexin. Terpenoids like sitosterol, stigmasterol and phytol, which have shown gastroprotective activity, and dihydrochalcones, like asebogenin, with anti-bacterial activity, were also isolated. Furthermore, the rare neolignan 1, that is a DNA polymerase β lyase inhibitor, and (6S, 9S)-roseoside, that shows strong anti-bacterial activity, were isolated, for the first time, from the genus Piper.

Conclusions

We suggest that the flavonoids isolated from F I and II (vitexin, isovitexin, rhamnopyranosylvitexin and isoembigenin) contribute to the anti-MPO activity, as well as to their anti-Helicobacter pylori activity. These flavonoids may also be responsible for the important inhibition of H⁺, K⁺-ATPase activity. Also the phytosterols and phytol obtained from F XIV and XV could be involved in these gastroprotective activities. These results encourage us to continue phytochemical studies on these fractions in order to obtain full scientific validation for this species.     

Mechanisms underlying the diuretic effects of Tropaeolum majus L. extracts and its main component isoquercitrin

Ethnopharmacological relevance

Previous studies have shown that the extracts obtained from Tropaeolum majus L., and its main compound isoquercitrin (ISQ), exhibit pronounced diuretic effects, supporting the ethnopharmacological use of this plant. The aim of this study was to evaluate the efficacy and mechanisms underlying the diuretic action of an ethanolic extract of Tropaeolum majus (HETM), its purified fraction (TMLR), and its main compound ISQ, in spontaneously hypertensive rats (SHR).

Materials and methods

The diuretic effects of HETM (300 mg/kg; p.o.), TMLR (100 mg/kg; p.o.), and ISQ (10 mg/kg; p.o.), were compared with classical diuretics in 7 days repeated-dose treatment. The urinary volume, sodium, potassium, chloride, bicarbonate, conductivity, pH and density were estimated in the sample collected for 15 h. The plasmatic concentration of sodium, potassium, urea, creatinine, aldosterone, vasopressin, nitrite and angiotensin converting enzyme (ACE) activity were measured in samples collected at the end of the experiment (seventh day). Using pharmacological antagonists or inhibitors, we determine the involvement of bradykinin, prostaglandin and nitric oxide (NO) in ISQ-induced diuresis. In addition, reactive oxygen species (ROS) and the activity of erythrocytary carbonic anhydrase and renal Na⁺/K⁺/ATPase were evaluated in vitro.

Results

HETM, TMLR and ISQ increased diuresis similarly to spironolactone and also presented K⁺-sparing effects. All groups presented both plasmatic aldosterone levels and ACE activity reduced. Previous treatment with HOE-140 (a B2-bradykinin receptor antagonist), or indomethacin (a cyclooxygenase inhibitor), or L-NAME (a NO synthase inhibitor), fully avoided the diuretic effect of ISQ. In addition, the 7 days treatment with ISQ resulted in increased plasmatic levels of nitrite and reducing ROS production. Moreover, the renal Na⁺/K⁺/ATPase activity was significantly decreased by ISQ.

Conclusion

Our results suggest that the mechanisms through ISQ and extracts of Tropaeolum majus increase diuresis in SHR rats are mainly related to ACE inhibition, increased bioavailability of bradykinin, PGI2, and nitric oxide, besides an inhibitory effect on Na⁺/K⁺-ATPase.     

Coriander fruit exhibits gut modulatory,blood pressure lowering and diuretic activities

Aim of the study

Coriander (Coriandrum sativum) is traditionally used for various gastrointestinal and cardiovascular disorders and this study was designed to rationalize its use in dyspepsia, abdominal colic, diarrhea, hypertension and as diuretic.

Materials and methods

Coriander crude extract (Cs.Cr) was evaluated through in vitro and in vivo techniques.

Results

Cs.Cr caused atropine sensitive stimulatory effect in isolated guinea-pig ileum (0.1–10 mg/ml). In rabbit jejunum preparations, Cs.Cr evoked a similar contractile response but in the presence of atropine, it exhibited relaxation against both spontaneous and high K⁺ (80 mM)-induced contractions as well as shifted the Ca²⁺ concentration–response curves to right, similar to that caused by verapamil. Cs.Cr (1–30 mg/ml) caused fall in arterial blood pressure of anesthetized animals, partially blocked by atropine. Cs.Cr produced vasodilatation against phenylephrine and K⁺ (80 mM)-induced contractions in rabbit aorta and cardio-depressant effect in guinea-pig atria. Cs.Cr produced diuresis in rats at 1–10 mg/kg. Bio-assay-directed fractionation revealed the separation of spasmogenic and spasmolytic components in the aqueous and organic fractions respectively.

Conclusions

These results indicate that coriander fruit exhibits gut stimulatory, inhibitory and hypotensive effects mediating possibly through cholinergic, Ca²⁺ antagonist and the combination of these mechanisms respectively. Diuretic activity adds value to its use in hypertension.     

Korean red ginseng stimulates insulin release from isolated rat pancreatic islets

Ethnopharmacological relevance

Korean red ginseng (KRG), one of heat-processed Korean ginseng (Panax ginseng C.A. Meyer), has a long history as herbal remedy for antidiabetic effect.

Aim of the study

The effect and mechanism of KRG on stimulation of insulin release were investigated in isolated rat pancreatic islets.

Material and methods

Pancreatic islets isolated from rats were used to evaluate the insulinotropic action of KRG. The effect of Ca on the insulinotropic action of KRG was investigated.

Results

The aqueous ethanolic extract of KRG (AEE-KRG) (0.1–1.0 mg/ml) significantly evoked a stimulation of insulin release at 3.3 mM glucose compared to the control. Experiments at different glucose concentrations (8.4 and 16.7 mM) showed that AEE-KRG significantly stimulated on its own whereas it did not potentiate insulin secretion induced by glucose. The extracellular Ca²⁺-free condition, a L-type Ca²⁺ channel blocker and an ATP-sensitive K⁺ channel opener significantly inhibited insulin secretion evoked by AEE-KRG.

Conclusion

These findings suggest that KRG displays beneficial effects in the treatment of diabetes at least in part via the stimulation of insulin release in a glucose-independent manner.     

Anti-spasmodic effects of Zizyphus lotus (L.) Desf. extracts on isolated rat duodenum

Aim of the study

The present study deals with the anti-spasmodic activity of the aqueous and the methanolic extracts of the leaves and the root barks of Zizyphus lotus (L.) Desf. on male rats.

Materials and methods

This activity was assessed on contractions of isolated rat duodenum, induced by acetylcholine, KCl, and BaCl₂ and compared with the effect of atropine and papaverine.

Results

Both extracts of leaves and root barks caused significant relaxation of spontaneous contractions and produced a concentration-dependent inhibition (P < 0.01–0.001) of contraction induced by spasmogenic agents.

Conclusion

These results indicate that Zizyphus lotus extracts contain anti-spasmodic constituents mediating their effect through cholinergic receptors and blockade Ca²⁺ influx. This could explain the traditional use of Zizyphus lotus in the treatment of the intestinal diseases.     

Vasodilatory effects of ethanol extract of Radix Paeoniae Rubra and its mechanism of action in the rat aorta

Ethnopharmacological relevance

Radix Paeoniae Rubra (RPR) is an important traditional Chinese medicine (TCM) commonly used in clinic for a long history in China. RPR is the radix of either Paeonia lactiflora Pall. or Paeonia veitchii Lynch. RPR has a wide variety of pharmacological actions such as anti-thrombus, anti-coagulation, and anti-atherosclerotic properties, protecting heart and liver. However, the mechanisms involved are to be defined.

Aim of the study

The aim of the present study was to define the effect of Paeonia lactiflora Pall. extracts on vascular tension and responsible mechanisms in rat thoracic aortic rings.

Materials and methods

Ethanol extract of Paeonia lactiflora Pall. (EPL) was examined for their vascular relaxant effects in isolated phenylephrine-precontracted rat thoracic aorta.

Results

EPL induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Vascular relaxation induced by EPL was significantly inhibited by removal of the endothelium or pretreatment of the rings with N^G-nitro-l-arginine methylester (l-NAME) or 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ). Extracellular Ca²⁺ depletion or diltiazem significantly attenuated EPL-induced vasorelaxation. Modulators of the store-operated Ca²⁺ entry (SOCE), thapsigargin, 2-aminoethyl diphenylborinate and Gd³⁺, and an inhibitor of Akt, wortmannin, markedly attenuated the EPL-induced vasorelaxation. Further, the EPL-induced vasorelaxation was significantly attenuated by pretreatment with tetraethylammonium, a non-selective K_Ca channels blocker, or glibenclamide, an ATP-sensitive K⁺ channels inhibitor, respectively. Inhibition of cyclooxygenases with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on the EPL-induced vasorelaxation.

Conclusions

The present study suggests that EPL relaxes vascular smooth muscle via endothelium-dependent and Akt- and SOCE-eNOS-cGMP-mediated pathways through activation of both K_Ca and K_ATP channels and inhibition of L-type Ca²⁺ channels.     

Antinociceptive effect of ethanol extract of leaves of Lannea coromandelica

Ethnopharmacological relevance

Lannea coromandelica (Houtt.) Merr. is a plant locally called “Jiga”, found all over Bangladesh. Leaf of the plant is traditionally used in the treatment of local swellings, pains of body, toothache etc. This study evaluated the antinociceptive effect of the ethanol extract of L. coromandelica leaves (EELC).

Materials and methods

The antinociceptive activity of the extract (at the doses of 50, 100, and 200 mg/kg) was evaluated by using chemical- and heat-induced pain models such as acetic acid-induced writhing, hot plate, tail immersion, formalin, and glutamate test. To verify the possible involvement of opioid receptor in the central antinociceptive effect of EELC, naloxone was used to antagonize the effect. Besides, the involvements of ATP-sensitive K⁺ channel and cGMP pathway were also justified by using glibenclemide and methylene blue.

Results

EELC demonstrated significant dose-dependent antinociceptive activity in the chemical- and heat-induced nociception in mice models (p<0.05). These findings imply the involvement of both peripheral and central antinociceptive mechanisms. The use of naloxone confirmed the association of opioid receptors in the central antinociceptive effect. EELC also showed the involvements of ATP-sensitive K⁺ channel and cGMP pathway for antinociceptive activity.

Conclusions

This study reported the antinociceptive activity of the leaf of L. coromandelica and rationalized the traditional use of the leaf in the treatment of different painful conditions.     

Diuretic properties of Orthosiphon stamineus Benth

Ethnopharmacological relevance

Orthosiphon stamineus has been used in traditional medicine for centuries especially to treat diseases of the urinary system.

Aim of the study

To investigate the diuretic activity, to elucidate its possible mechanism and to evaluate the renal effects of Orthosiphon stamineus extract.

Materials and methods

Water extracts were administered orally at doses of 5 and 10 mg/kg to Sprague–Dawley rats and the control groups were given commercial diuretic drugs either furosemide or hydrochlorthiazide at 10 mg/kg. Urine volume, urine pH, urine density and urine electrolytes were determined every hour for 4 h. Blood was assayed for glucose, albumin, blood urea nitrogen (BUN) and creatinine.

Results

O. stamineus extract exhibited dose-dependent diuretic activity. However, excretion of Na⁺ and Cl⁻ was not markedly elevated, but urinary excretion of K⁺ was significantly increased. O. stamineus extracts slightly increased the serum BUN, creatinine and blood glucose level. Although these levels were statistically significant when compared to control, these levels were still within normal range.

Conclusions

O. stamineus exhibited diuretic activity, but was less potent than furosemide and hydrochlorothiazide. Care should be taken when consuming this herb as slight increase of kidney function enzymes was recorded.     

Role of prostaglandin/cAMP pathway in the diuretic and hypotensive effects of purified fraction of Maytenus ilicifolia Mart ex Reissek (Celastraceae)

Ethnopharmacological relevance

Although Maytenus ilicifolia is used in Brazilian folk medicine as a diuretic drug, no study has been conducted to this date in order to evaluate this ethnopharmacological statement. So, the aim of this study was to evaluate possible mechanisms involved in acute diuretic activity of the ethanolic supernatant of the infusion (SEI) obtained from Maytenus ilicifolia and to assess its relationship with a hypotensive activity by a bioassay-guided fractionation using normotensive Wistar rats.

Material and methods

The preparation obtained from the infusion (SEI) and their respective fractions (Fr·H₂O and Fr·EtOAc) were orally administered in a single dose to rats. The urine excretion rate, pH, density, conductivity and content of Na⁺, K⁺, Cl⁻ and HCO₃⁻ were measured in the urine of saline-loaded animals. Samples of the concentration of electrolytes, urea, creatinine, aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were evaluated in collected serum. The hypotensive activity and the involvement of nitric oxide, bradykinin and prostaglandin/cAMP pathway in the hypotensive and diuretic effects were also determined.

Results

Water and Na⁺ excretion rate were significantly increased by Fr·EtOAc and the arterial pressure was significantly reduced, while the urinary excretion of potassium and chloride were reduced. Pre-treatment with indomethacin or DDA (2′,5′-dideoxyadenosine) significantly reduced the hypotensive and diuretic activity observed. All other parameters evaluated were not affected by any treatment.

Conclusion

The present study reveals that Fr·EtOAc obtained from Maytenus ilicifolia may present compounds responsible for diuretic and hypotensive activities, and this effect, could involve the prostaglandin/cAMP pathway.