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Introduction: Zaringiah (Dracocephalum kotschyi) is an Iranian endemic herbal plant naturally growing in the Isfahan and Khorasan provinces. Hydroalcoholic extract of Zaringiah has anti-inflammatory, antispasmodic, and immunomodulatory properties. So far, the effect of Zaringiah extract on contraction induced by histamine and serotonin (5-HT) has not been reported. The objective of this research was to investigate the antispasmodic effect of hydroalcoholic, aqueous, chloroform, and ethyl acetate extracts of Zaringiah on rabbit ileum smooth muscle contractions induced by histamine and 5-HT. Methods: Khorasani variant of Zaringiah was used in this study. Aqueous extract was prepared by decoction, while hydroalcoholic extract was obtained by the maceration technique. Chloroform and ethyl acetate fractions were obtained using a solvent in solvent extraction technique. Rabbit isolated ileum was set up in an organ bath filled with Tyrode’s solution. The effects of the above extracts were examined on contractions induced by histamine or 5-HT and compared with each other. Results: Hydroalcoholic extract of Zaringiah inhibited the rabbit ileum contractions induced by histamine (IC50 = 76 ± 7.7 μg/mL) and 5-HT (IC50 = 60 ± 6.4 μg/mL), as well as spontaneous contractions (IC50 = 63 ± 15 μg/mL). The aqueous extract, as well as chloroform and ethyl acetate fractions, concentration-dependently inhibited spontaneous, histamine, and 5-HT induced contractions. Conclusion: There was not a significant difference among the inhibitory actions of hydroalcoholic, aqueous, chloroform, and ethyl acetate extracts of Zaringiah on rabbit ileum, indicating the distribution of active constituents in both polar and non-polar mediums.

Introduction: Zaringiah (Dracocephalum kotschyi) is a famous Iranian herbal plant with anti-inflammatory and spasmolytic activities. There is no standard drug dosage form for the D. kotschyi extract on the market. The objective of this project was to design a suitable oral dosage form for the hydroalcoholic extract of D. kotschyi. Methods: Standard granules were prepared using the moist granulation technique. Physical properties of the granules were determined before filling the capsule with fixed doses of the drug (25 mg and 50 mg). Syrup was prepared in sucrose solution at 5 mg/mL concentration. Bioactivity and phytochemical assays were used for dosage form stability and uniformity evaluations before and after 3- and 6- months incubation. Pharmacological bioassay method was designed to determine the bioactivity of the products before and after incubation. Pharmacological effects of the prepared capsule and syrup were determined on rat isolated ileum and intestinal meal transit, respectively. Results: In this study, D. kotschyi extract was effectively formulated as capsule and syrup for oral consumption. Environmental and aging factors had no significant effect on the total flavonoid or phenolic contents or bioactivity of the manufactured products. Furthermore, the ingredients used in the formulation had no effect on the bioactivity of the active substances in the extract. Conclusion: The standard oral dosage forms prepared from D. kotschyi extract can be used for clinical trials. In addition, we introduced a reliable bioassay technique, which might be applied for the evaluation of herbal medicines with antispasmodic activities.

Background: Dracocephalum kotschyi is one of the native medicinal plants of Iran with anti-inflammatory and spasmolytic properties. The aim of this study was to investigate the effects of D. kotschyi hydroalcoholic extract on blood biochemical and hematological parameters in rat.Methods: In this study, hydroalcoholic extract was prepared by maceration technique and its phenolic content was assessed by Folin-Ciocalteu method. The extract was then administered orally for 30 days (50, 100 & 200 mg/kg) in 3 different rat groups. A normal control group and vehicle treated group were also included for comparison. After a month of extract administration and qualitative observations, blood samples were taken from all the rats for quantitative determination of biochemical and hematological parameters. The liver and kidney sections were also prepared for microscopic pathological examination.Findings: According to our findings, oral consumption of hydroalcoholic extract of D. kotschyi over a month induced no substantial changes in the measured biochemical and hematological parameters. The high dose of hydroalcoholic extract of D. kotschyi caused a slight increase in the amount of some liver enzymes (AST, ALT and ALP) and the dose of 50 mg/kg elevated creatinine levels. However, examination of liver and kidney sections showed no microscopic tissue damage.Conclusion: Short term consumption of hydroalcoholic extract of D. kotschyi has no adverse effect on blood biochemical and hematological parameters. However, as long as the long term effect of the extract on liver and renal function is not fully understood, consumption of D. kotschyi in patients with hepatic or renal failure is not recommended.

Introduction: Naringenin is a flavonoid constituent of many herbal plants, including citreous fruits. Biological studies have suggested various therapeutic effects for naringenin, including protective effects on gastrointestinal (GI) motility. The present study was performed to investigate the involvement of ATP-sensitive K+ channels on the effect of naringenin in rat ileum motility. Methods: Ileum contractions were induced by either KCl or acetylcholine (ACh) in vitro. Inhibitory concentration-response curves were constructed for naringenin and diazoxide after exposure of rat isolated ileum to KCl (20mM) or ACh (500nM). The relaxant effects of naringenin and diazoxide were also examined in the presence of glibenclamide. Furthermore, oral effects of diazoxide (25 mg/kg) and naringenin (25, 50 mg/kg) were also assessed on the intestinal charcoal meal transit in mice (n=10) in the absence and presence of glibenclamide (50 mg/kg). Results: Diazoxide and naringenin in a concentration-dependent manner inhibited ileum contractions induced by low bath concentration of KCl (20mM). However, both drugs had no effect on contractions induced by a high concentration of KCl (160mM). The inhibitory effects of diazoxide and naringenin were blocked by glibenclamide. Oral administration of diazoxide and naringenin significantly reduced the intestinal transit of charcoal meal. The delay in the intestinal transit was blocked by the oral dose of glibenclamide. The effect of naringenin on the rat intestinal strip pre-contracted with the KCl was relatively similar to that of ATP-sensitive K+ channel opener (diazoxide). Conclusion: This research supports that ATP-sensitive K+ channels are involved in the rat small intestinal smooth muscles relaxation induced by naringenin.

Introduction: Honeysuckle (Lonicera japonica) is an ornamental flowering plant with numerous traditional medicinal uses. It has been claimed to have anti-spasmodic activities, but only limited studies have been done to support this. The objective of this research was to investigate anti-spasmodic effect of L. japonica flower extract on uterus contractions. Methods: Hydroalcoholic extract was prepared using the maceration technique. In addition, chloroform and ethyl acetate fractions were prepared using a solvent in solvent fractionation technique. Essential oils were collected using the hydro-distillation technique. Rat isolated uterus was suspended in an organ bath and contracted with oxytocin, acetylcholine (ACh), KCl, or application of electrical field stimulation (EFS). The relaxant effects of the extract, its fractions, and nifedipine were examined on uterine contrition induced by the above-mentioned stimuli. Results: Nifedipine in a concentration-dependent manner inhibited uterine contraction induced by oxytocin, KCl, ACh, and EFS. L. japonica flower extract also exhibited an inhibitory effect on the isolated rat uterus. Comparison of the hydroalcoholic extract with its chloroform and ethyl acetate fractions showed that the chloroform fraction was the most potent and the ethyl acetate the weakest part of the plant with antispasmodic activity. The relaxant effect of essential oil had close similarities to that of chloroform extract. Conclusion: Lipophilic compounds isolated by the chloroform partition of crude hydroalcoholic extract of L. japonica flower exhibited the most antispasmodic activity. Ethyl acetate partition of the same extract exhibited the least activity. Therefore, it can be concluded that the spasmolytic constituents of L. japonica flower reside in chloroform partitioning. The nonpolar essential oils may also have a contribution.

Introduction: Dracocephalum kotschyi is an Iranian traditional medicine with anti-inflammatory and bronchodilatory properties. The objective of this research was to investigate the preventive effect of D. kotschyi extract in bleomycin induced fibrosis. Methods: Fibrosis was induced by intratracheal administration of a single dose of bleomycin (5 mg/kg) in rat. One group received daily administration of normal saline. Other groups were treated daily with oral administration of either hydroalcoholic or aqueous extract of D. kotschyi (20, 40, & 80 mg/kg). Another group was treated with pirfenidone (100 mg/kg). After 4 weeks daily treatments, the animals were sacrificed and the whole lungs were dissected out for biochemical and histopathological examinations. The biochemical examination included assessment of hydroxyproline and malondialdehyde levels. Results: The lung tissues in bleomycin treated groups showed severe tissue injuries. However, lung tissues in the groups that received hydroalcoholic or aqueous extracts of D. kotschyi showed mild to moderate tissue injuries. Intratracheal instillation of bleomycin significantly increased hydroxyproline and malondialdehyde biomarker levels compared with the sham group. In the positive control group treated with pirfenidone, there was a marked reduction in both hydroxyproline and malondialdehyde levels. Both hydroalcoholic and aqueous extracts of D. kotschyi significantly prevented the elevation of hydroxyproline and malondialdehyde levels at the above oral doses in comparison to the vehicle treated control group. Conclusion: Prevention of hydroxyproline and malondialdehyde elevation levels in this experiment indicates that D. kotschyi extract might be a suitable remedy for the treatment of respiratory fibrosis induced by drugs such as bleomycin.

Introduction: Quercetin is a flavonoid compound found in many medicinal plants. Antispasmodic effect of quercetin has been reported in ileum and uterus smooth muscles but not in bladder. Therefore, the objective of this research was to investigate relaxant effect of quercetin in rabbit isolated bladder. Methods: Male rabbit was asphyxiated with carbon dioxide and then sacrificed. The whole bladder was dissected out and placed in oxygenated Tyrode’s solution. Isolated bladder was cut into longitudinal strips and placed in an organ bath for contraction studies. Contractions were induced with KCl (20mM), acetylcholine (5μM) and electrical field stimulation (EFS). Full inhibitory concentration–response curve was constructed for quercetin following addition of above spasmogens. Quercetin was added into the organ bath with 2 fold increments in concentration until maximum response was achieved. Nifedipine was used as positive control group and equivalent volume of quercetin vehicle (water + DMSO) was used as negative control group. Results: Quercetin (4 μg/mL to 640 μg/mL) in a concentration dependent manner inhibited isolated bladder strips contracted by KCl (IC50=159±25 μg/mL), acetylcholine (IC50=43±9.1 μg/mL) and EFS (IC50=38±9.3 μg/mL). In the highest used concentration, quercetin completely removed contractile responses to KCl, acetylcholine and electrical filed stimulation (EFS). Nifedipine totally inhibited KCl response (IC50=115±36 ng/mL) but only partially inhibited acetylcholine and EFS responses. Conclusion: These results confirm the relaxant effect of quercetin on rabbit bladder and if similar effects are seen in human studies, then quercetin would be a suitable drug candidate to be investigated for bladder incontinence.

Background and purpose: Dracocephalum kotschyi (Zaringiah) is a fragrant wild medicinal plant found in Iran. Traditionally, it is used for the treatment of rheumatism, asthma, and gastrointestinal ailments. So far no investigation has been done on the beneficial or side effects of D. kotschyi on peptic ulcer. Therefore, this research was performed to find out whether D. kotschyi extract would induce peptic ulcer or could alleviate existing peptic ulcer. Experimental approach: Effect of hydroalcoholic (DKHE) and flavonoid extracts (DKFE) of D. kotschyi were determined in normal or indomethacin-induced gastric ulcer rats (n = 6) and compared with the vehicle and ranitidine treated controls. All the treatments were carried out orally and 24 h later the stomach mucus was visually examined for peptic ulcers. A section of the stomach was taken for microscopic histopathological examinations while another section of the stomach was used for measurement of myeloperoxidase (MPO) and malondialdehyde (MDA) activities. Findings/Results: Oral administration of the DKHE and DKFE alone, did not cause any sign of gastric ulcer induction. The D. kotschyi extracts not only didn’t aggravate the induced ulcer but also significantly prevented the severity of gastric ulcer induction by indomethacin. In addition, DKHE and DKFE inhibited MPO (up to 58.2%) and MDA (up to 44.2%) activities indicating their anti-inflammatory and antioxidant potential action on the stomach-induced ulcer. Conclusion and implication: Usage of D. kotschyi extracts is not associated with gastric ulcer induction and its co-administration with NSAIDs would be beneficial for controlling both the inflammation and preventing gastric ulcer in diseases such as rheumatism.

Introduction: Dracocephalum kotschyi extract has antispasmodic activities on smooth muscle including ileum, uterus and trachea. The objective of this research was to investigate antispasmodic activity of hydroalcoholic and flavonoids extracts of D. kotschyi on rabbit bladder contractions. Methods: Rabbits were euthanized by carbon dioxide asphyxiation and the whole bladder was dissected out and immersed in the Tyrode’s solution. Longitudinal bladder strips were mounted vertically in an organ bath at 37°C and gassed continuously with O2 . Bladder strips were contracted with acetylcholine (ACh), KCl, or electrical field stimulation (EFS). Isotonic tension of the tissue was recorded before and after addition of hydroalcoholic or flavonoids rich extracts of D. kotschyi. Nifedipine and propantheline were used as standard drugs. Results: Standard drug propantheline, prevented bladder phasic contraction induced by ACh (1µM) without affecting KCl response. On the other hand, cumulative addition of nifedipine attenuated the tonic contractions induced by KCl (20mM) on bladder smooth muscle. Hydroalcoholic and flavonoids extracts of D. kotschyi at concentration ranges of 10-320 µg/ mL in a concentration dependent way inhibited bladder tonic contraction induced by KCl (n=6). Both extracts also in a concentration-dependent manner relaxed EFS and ACh-induced contractions (range, 20–1280 µg/mL) of bladder smooth muscle in vitro. Complete inhibition was achieved with the highest used concentrations of the extracts. The inhibitory effect of the extract was reversible following washing the tissues with fresh Tyrode’s solution. Conclusion: This study clearly demonstrated that D. kotschyi extracts were able to prevent contractions induced by ACh, KCl or EFS in isolated rabbit bladder. This means that people consuming this medicinal plant may face urinary retention which could be a problem for patients with prostate hypertrophy. On the other hand, this plant might be useful in patients with urinary incontinence. However, its usefulness must be assessed in the controlled clinical trials.

Background: The goal of the current research was to further elucidate the role of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in the motility and contractility force of gastric smooth muscle of diabetic rats. Materials and Methods: Male Wistar rats (190–230 g) were grouped into control and streptozotocin (STZ)-induced diabetes (55 mg/kg) rats. Thirty days later, gastric muscle contractility was measured using a myograph and a force transducer of antral segments immersed in a tissue bath. Gastric emptying response was measured through feeding of standard pellet. Furthermore, the expression of KATP channel subunits in antral smooth muscle was determined by western blot technique. Results: The amplitude of KCl-evoked twitch contractions of diabetic antral strips was about 25% more than control (P < 0.05). Application of minoxidil, a KATP channel opener, dose dependently decreased the force of twitch contractions in both normal and diabetic antral strips. Application of 10 μM glibenclamide, a KATP channel blocker, did not antagonize the minoxidil-induced relaxation of antral strips. Diabetic gastric emptying was faster than normal, although not significant. Despite the relaxant effect of minoxidil on gastric emptying rate in normal rats (P < 0.05), this effect was not observed in diabetic rats. Also, glibenclamide increased gastric emptying and antagonized minoxidil-induced relaxation in normal rats (P < 0.05). Furthermore, the expression of KATP Kir6.1 and SUR2B subunits was substantially reduced in antral smooth muscle in diabetic condition (P < 0.01). Conclusion: These results propose that KATP channels may contribute to the development of gastric motility disorders in diabetes.

Introduction: Pharmacological studies confirm antispasmodic activities of chamomile (Matricaria chamomilla) extract on intestinal smooth muscles and it has been suggested that chamomile increases uterus tone, but so far there is no scientific studies which support this assumption. Therefore, this study was designed to determine spasmodic and spasmolytic activities of M. chamomilla extracts on rat isolated uterus. Methods: Hydro-alcoholic extract of M. chamomilla was prepared by maceration technique. Flavonoids rich extract was prepared by liquid in liquid extraction technique. The spasmodic effects of the extracts were assessed on spontaneously contracting rat uterus. The myorelaxant effect of M. chamomilla extracts was validated on isolated uterus contractions induced by KCl, acetylcholine (ACh), electrical field stimulation (EFS) and oxytocin. Results: Hydro-alcoholic extract of M. chamomilla (0.8 and 1.6 mg/mL) enhanced spontaneous movement of rat isolated uterus smooth muscle suspended in an organ bath. On the other hand, flavonoids rich fraction only diminished uterus contractile activities. Flavonoids rich extract of the plant at bath concentration ranges of 40 μg/mL to 400 μg/mL attenuated uterus response to ACh, KCl, EFS and oxytocin. The hydro-alcoholic extract of M. chamomilla at higher concentration ranges (250 μg/mL to 1.5 mg/mL) inhibited uterus contractions induced by the above spasmogens. Conclusion: The present study confirms both spasmodic and spasmolytic activities M. chamomilla hydro-alcoholic extract. Therefore, medicinal use of the crude extract of M. chamomilla may initiate uterus contraction which could increase risk of spontaneous miscarriage or premature parturition.

Background: In traditional medicine, Lavender and Rosemary are referred as antispasmodic agents. However, so far their direct effects on uterus contraction have not been reported. This study aimed to assess antispasmodic effect of hydroalcoholic extracts of rosemary and lavender on rat isolated uterus contractions. Methods: In this research, the relaxant effect of hydroalcoholic extracts of these plants on rat isolated uterus contraction induced by KCl, acetylcholine, oxytocin, and electrical field stimulation (EFS) was determined and compared with nifedipine. Findings: Hydroalcoholic extracts of Lavender and Rosemary inhibited uterus contractions induced by KCl, acetylcholine, oxytocin, and EFS in a concentration-dependent manner. Conclusion: Hydroalcoholic extracts of Lavender and Rosemary have relaxant effects on uterus smooth muscle, and can be useful in prevention of premature labor.

Introduction: Dracocephalum kotschyi is a native Iranian plant with antispasmodic activities on smooth muscles such as ileum and uterus. However, so far antispasmodic effect of D. kotschyi on tracheal smooth muscle has not been reported. Therefore, the objective of this research was to investigate antispasmodic activity of D. kotschyi extract and two of its components luteolin and apigenin on rabbit tracheal contraction in vitro. Methods: Rabbits were euthanized by carbon dioxide and the trachea was dissected and immersed in a Tyrode’s solution. Tracheal rings were prepared and mounted vertically in an organ bath at 37°C and gassed continuously with O2. The tracheal ring preparations were contracted with acetylcholine (ACh) and KCl. The isotonic tension was recorded before and after addition of aminophylline, apigenin, luteolin or flavonoids rich extract of D. kotschyi. Flavonoids rich extract were prepared from D. kotschyi using solvent-solvent fractionation technique. Results: Standard drug aminophylline, prevented tracheal ring preparation contracted with ACh. Cumulative addition of aminophylline also attenuated tonic contraction induced by KCl on tracheal smooth muscle. D. kotschyi extract at concentration ranges of 32-512 μg/mL in a concentration dependent manner inhibited KCl and ACh induced tracheal contraction. Apigenin and luteolin (range 16–512 μg/mL) relaxed KCl and ACh-induced contraction of tracheal smooth muscle in vitro in a concentration-dependent manner. Conclusion: This study demonstrated that D. kotschyi extract is a relaxant of tracheal smooth muscle. The relaxant effect of D. kotschyi extract could be due to its flavonoids component such as apigenin and luteolin.

Introduction: Lavender (Lavandula angustifolia Mill) is a herbal medicine widely used for gastrointestinal (GI) disorders. However, its pharmacological action on isolated ileum has not been studied. In this research effect of hydroalcoholic extract of L. angustifolia on isolate ileum contractions was studies and compared with loperamide. Methods: Hydroalcoholic extract of the plant was prepared by percolation method. The total flavonoid contents were assessed by colorimetric technique. A portion of rat ileum was suspended in an organ bath containing Tyrode’s solution. The tissue was kept under 1 g tension at 37°C and continuously gassed with O2. The tissue was stimulated with KCl (80 mM), acetylcholine (ACh, 2 μM) and electrical field stimulation (EFS). Effect of the L. angustifolia extract was studied on ileum contractions and compared with that of loperamide. Results: The yield of hydroalcoholic extract was 17% with total flavonoid content of 185 μg/mL in the stock solution. Loperamide in concentration dependent manner inhibited ileum contractile response to KCl, ACh and EFS. Hydroalcoholic extract of L. angustifolia (8-512 μg/mL) concentration dependently inhibited ileum contraction induced by KCl (IC50 = 88 ± 21 μg/mL), ACh (IC50 = 119 ± 251 μg/mL) and EFS (IC50 = 87 ± 33 μg/mL). The vehicle had no significant effect on ileum contractions. Conclusion: From this study it was concluded that L. angustifolia extract at microgram concentration shows an inhibitory effect on rat ileum smooth muscle. Therefore, isolation and identification of active ingredients are recommended.

Introduction: Dracocephalum kotschyi is an Iranian indigenous herbal plant which has been reported to have antispasmodic activity in vitro. The antispasmodic activity of hydroalcoholic extract of D. kotschyi is reported to be due to its flavonoids constituents including apigenin and luteolin. The objective of this research was to compare antispasmodic activities of hydroalcoholic and flavonoids extracts of D. kotschyi on ileum contractions in vivo. In addition, spasmolytic activity of apigenin, luteolin and apigenin-4'-galactoside were compared. Methods: The hydroalcoholic extract was prepared by percolation method. Flavonoids extract was obtained by solvent-solvent extraction. Antispasmodic effect of the test compounds was assessed by measurement of percent small intestine transit following oral administration of a charcoal meal and compared with control group and standard drug loperamide. Results: Biochemical assessment of flavonoids content of the extracts showed that ethyl-acetate fraction contained higher quantity of flavonoids. Loperamide (2.5 mg/kg) reduced charcoal meal movement by 58% in comparison to control group. Hydroalcoholic extract of D. kotschyi (20 mg/kg) and its ethyl-acetate fraction (20 mg/kg) reduced the intestinal charcoal meal transit by 32% and 90%, respectively. Apigenin, luteolin and apigenen-4'-galactoside with oral dose of 20 mg/kg inhibited intestinal movement of the charcoal meal 93%, 89% and 45%, respectively in comparison with the vehicle treated control groups. Conclusion: This study confirms that both the hydroalcoholic and flavonoids extracts of D. kotschyi have antispasmodic properties in vivo. Antimotility of apigenen-4'-galactoside in mice is probably due to release of apigenin in the gastrointestinal tract.

Introduction: Aerial parts of Dracocephalum kotschyi have been used as antispasmodic agents in Iranian traditional medicine. Recent pharmacological studies confirmed antispasmodic activity of D. kotschyi extract. The objective of this research was to investigate antispasmodic activities of apigenin and luteolin to find out if they are responsible for the spasmolytic activity of hydroalcoholic extract of D. kotschyi. Methods: Aerial parts of D. kotschyi were extracted with ethanol. Antispasmodic effect of hydroalcoholic extract of D. kotschyi, apigenin and luteolin were examined on KCl and/or acetylcholine (ACh)-induced contractions in rat isolated ileum. Results: Hydroalcoholic extract of D. kotschyi concentrations-dependently inhibited KCl and ACh induced contractions with IC50 values of 41 ± 10 μg/mL and 133 ± 19 μg/mL, respectively. Apigenin concentrations-dependently inhibited KCl and ACh induced contractions with IC50 values of 57 ± 12 μM and 80 ± 18 μM, respectively. Luteolin concentrations-dependently inhibited KCl induced contractions with IC50 values of 68 ± 14 μM. Loperamide reduced both KCl and ACh induced contraction with IC50 values of 189 ± 44 nM and 82 ± 20 μM, respectively. Conclusion: In this study apigenin and luteolin were identified as two active ingredients responsible for antispasmodic activities of D. kotschyi extract.

Introduction: Zataria multiflora Boiss. is an indigenous herbal plant found in many parts of Iran. This herb is traditionally used as a remedy for treating gastrointestinal disorders including diarrhea. Despite the existence of few pharmacological evidences which support the antispasmodic action of Z. multiflora in vitro, there is no scientific report about therapeutic efficacy of Z. multiflora in animal models. The objective of this research was to investigate the antispasmodic activity of hydroalcoholic and hexane extracts of Z. multiflora on intestinal peristaltic movement as well as assessment of its antidiarrheal action in mice. Methods: Dried leafy branches of Z. multiflora were coarsely powdered and subjected to extraction by ethanol or hexane in a percolator apparatus. Antispasmodic activity of Z. multiflora in vivo was assessed by investigating effect of the extracts on intestinal charcoal meal transit. The antidiarrheal activity of Z. multiflora extracts was evaluated by castor oil and magnesium sulfate‑induced diarrhea. The inhibitory effects of the extracts were compared with the standard drug loperamide. Results: The antispasmodic activity of Z. multiflora (20 & 40 mg/kg) hydroalcoholic and hexane extracts was confirmed by a reduction in the distance traveled by charcoal meal alongside the small intestine. Z. multiflora extracts (20 & 40 mg/kg) also significantly attenuated the castor oil and magnesium sulfate‑induced diarrhea. Loperamide was more efficacious in reducing number of total stools in both models of diarrhea. Conclusion: The obtained results have established a pharmacological evidence for the folkloric use of the Z. multiflora as an antidiarrhoeal and spasmodic agent.

Introduction: Pycnocycla spinosa, a native plant of Iran with approved antispasmodic and antidiarrheal activities, could be a suitable candidate and an alternative remedy for the treatment of diarrhea and irritable bowel syndrome (IBS). Therefore, the aim of this study is formulation of an acceptable dosage form and development of a validated high-performance liquid chromatography (HPLC) method for analysis of active ingredients in its extract and pharmaceutical forms. Methods: Different formulations of P. spinosa tablets were prepared by wet granulation method. The prepared tablets were evaluated for hardness, friability, disintegration time and drug assay. HPLC was carried out based on the extract active ingredient: 6-(4-hydroxy-3-methoxyphenyl)-hexanoic acid (HMPHA) determination in P. spinosa extract and tablets. Results: The mean weight, friability, hardness, and disintegration time of selected formulation (tablet 5 mg) were 217.26 mg, 0.69%, 53.6 N and 95.8 seconds, respectively. Similar acceptable results were also found for 10 mg tablets. The assay test showed that the content of HMPHA in each 5 mg and 10 mg tablets were 1.64 μg and 3.59 μg, respectively. The HPLC method showed a good linearity and suitability in its working range: 4.5 to 15 μg/mL. Conclusion: The data showed that the selected formulation of P. spinosa tablets has acceptable physicochemical features.

Colitis is an inflammatory disease of the intestine with unknown etiology involving multiple immune, genetic, and environmental factors. We were interested to examine the effect of total extract from Dracocephalum Kotschyi (D. kotschyi) Boiss. on the experimental colitis. D. kotschyi hydroalcoholic extract (10, 20, and 40 mg/kg) or apigenin (5, 10, and 20 mg/kg) were administered orally 2 h prior to induction of colitis which was induced by intrarectal administration of acetic acid (4%) in rats. Prednisolone (4 m/kg) was used as the standard drug for comparison. Biochemical evaluation of inflamed colon was performed by measuring myeloperoxidase (MPO) activity. After 5 days treatment, mucosal ulceration was evaluated. Intrarectal instillation of acetic acid caused significant inflammatory reactions as indicated by macroscopic and microscopic changes. The activity of MPO increased in vehicle treated groups while recovered to normal level by pretreatment of animals with D. kotschyi extract, apigenin, or prednisolone. D. kotschyi and apigenin-treated groups showed significantly lower score values of macroscopic and microscopic characters when compared with the vehicle-treated negative control group. The beneficial effect of apigenin was comparable with that of prednisolone. This research has shown the anti-inflammatory potential of D. kotschyi extract and apigenin in experimentally induced colitis.

Hydroalcoholic extract and essential oil of aerial parts of Pycnocycla caespitosa have spasmolytic activity on rat ileum contractions. The objective of this research was to separate fractions of total hydroalcoholic extract of P. caespitosa guided by their spasmolytic activity on rat uterus. Aerial parts of P. caespitosa were extracted with ethanol. The concentrated extract was subjected to column chromatography and thin layer chromatography (TLC) for isolation fractions, then one of the bioactive fractions was subjected to further isolation to find its active components. Five fractions were obtained (Fr.1-Fr.5) and their anti-spasmodic activities were examined on uterus contraction induced by KCl (80 mM) and compared with ritodrine. In addition, spasmolytic effect of Fr.4 (one of the bioactive fractions) was determined on rat uterus induced by oxytocin (0.0005 IU/mL) and compared with ritodrine. Hydroalcoholic extract of P. caespitosa (0.032-2 mg/mL) reduced the responses to KCl but the inhibitory effect was not complete with 2 mg/mL extract in the bath. Four fractions (Fr.1, Fr.2, Fr.3 and Fr.4) (32-500 μg/mL) inhibited rat uterus contractions on the uterus while Fr.4 was slightly more active than others (IC50 = 146 ± 23 μg/mL). Falcarindiol and isoacetovanillone were identified from Fr.4 using phytochemical methods including high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and TLC. In conclusion, in this research bioactivity guided technique was successfully used for separation of active fraction of P. caespitosa. Falcarindiol and isoacetovanillone were identified from the active fraction which inhibited both tonic and rhythmic contractile responses in rat isolated uterus.

Pycnocycla caespitosa is an essential oil-containing plant naturally growing in southwest of Iran. The extract of this plant has been used as remedy in traditional medicine. Another species of Pycnocyla (P. spinosa) possessed antispasmodic activity. The pharmacological objective of this study was to look for relaxant effect of hydroalcoholic extract and essential oil of P. caespitosa on rat isolated ileum contractions for comparison with loperamide. The essential oil and the hydroalcoholic extract were prepared by hydrodistillation and percolation techniques, respectively. For antispasmodic studies a section of rat ileum was suspended in an organ bath containing Tyrode′s solution. The tissue was stimulated with electrical field stimulation (EFS), KCl (80 mM) and acetylcholine (ACh 0.5 μM). The tissue was kept under 1 g tension at 37 °C and continuously gassed with O 2 . The essential oil content in the aerial parts of P. caespitosa was found to be 0.16 % ml/g. The essential oil was analyzed by gas chromatography and gas chromatography-mass spectrometry. Seventy constituents, representing 97 % of the oil were identified. The major components of the oil were carvacrol (7.1%), β-eudesmol (6.4 %), ρ-cymene (5.7%), caryophyllene oxide (3.6%), α-pinine (1.4%) and α-phelandrene (1.1%). The hydroalcoholic extract of P. caespitosa inhibited the response to KCl (IC 50 = 48 ± 3 μg/ml), ACh (IC 50 = 61 ± 14.7 μg/ml) and EFS (IC 50 = 77 ± 17 μg/ml) in a concentration-dependent manner. The essential oil of P. caespitosa also inhibited rat ileum contractions. The IC 50 values for KCl, ACh and EFS were 9.2 ± 1.2 μg/ml, 7.6 ± 0.8 μg/ml and 6.4 ± 0.8 μg/ml, respectively. The inhibitory effect of both the essential oil and the extract were reversible. This research confirms the anti-spasmodic activity of both the essential oil and the extract of P. caespitosa on smooth muscle contraction of ileum.

Preterm contraction of uterus is a main cause of miscarriages and preterm labour. Euphorbia known as Ferphion in Iranian traditional medicine texts like Al-Hawi, is reported for prevention of preterm labour. Therefore, the objective of this research was to investigate the effect of Euphorbia spinidens Bornm. Ex Prokh. on motility of rat uterus. Uterine horns were isolated form non-pregnant female rats pretreated with estrogen. E. spinidens hydroalcoholic extract was examined on KCl (80 mM) induced and spontaneous periodic contraction in isolate uterine strips suspended in an organ bath and compared with nifedipine and ritodrine. In isolated rat uterine strips, E. spinidens extract (1-500 µg/mL) showed mixed effects. At lower concentrations, firstly potentiated the spontaneous periodic contraction, while in concentrations above 256 µg/mL the spontaneous periodic contractions were completely attenuated. These findings demonstrated that although lower concentrations of hydroalcoholic extract potentiated the spontaneous periodic contraction of rat uterine smooth muscle, but at higher concentrations it had inhibitory effect on rat uterus contraction.

Dracocephalum kotschyi Boiss. is a traditional medicine with antispasmodic activities. The objective of this research was to study antispasmodic activities of hydroalcoholic extract of D. kotschyi on rat isolated uterus contractions for comparison with isolated ileum. Hydroalcoholic extract was obtained from aerial part of D. kotschyi using percolation method. A portion of rat ileum or uterus was suspended in Tyrode′s solution at 37 °C and gassed with O 2 . Effect of D. kotschyi extract was assessed on ileum or uterus contractions induced by KCl (80 mM), acetylcholine (ACh, 500 nM), electrical field stimulation (EFS) or oxytocin (0.0005 IU/mL). The extract of D. kotschyi concentration-dependently inhibited ileum responses to KCl (IC 50 = 65 ± 18 μg/mL), ACh (IC 50 = 102 ± 18 μg/mL) and EFS (IC 50 = 117 ± 29 μg/mL). The extract of D. kotschyi also concentration-dependently inhibited uterus responses to KCl (IC 50 = 453 ± 64μg/mL), ACh (IC 50 = 58 ± 9 μg/mL), EFS (IC 50 = 22 ± 3 μg/mL) as well as oxytocin (IC 50 = 70 ± 11 μg/mL). From this experiment it was concluded that D. kotschyi extract possesses antispasmodic activities on both smooth muscle of ileum and uterus. In comparison, the extract was more effective inhibitor of ACh and EFS responses in rat uterus than on the ileum. On the other hand, the extract was a more potent inhibitor of KCl response on rat ileum. However, the extract was found to be a potent inhibitor of oxytocin-induced contraction of rat uterus. These results indicate that D. kotschyi extract may contain components that might be useful lead compounds for prevention of uterus spasm.

Dracocephalum kotschyi Boiss, a member of Labiatae family, is a native plant to Iran, which has been reported to have immunomodulatory, antihyperlipidemic and antispasmodic activities. The objective of this research was to study the antispasmodic and antidiarrhoeal activities of hydroalcoholic and hexane extracts of D. kotschyi in mice. Furthermore, the antidiarrhoeal and antispasmodic effect of apigenin, a flavonoid constituent of D. kotschyi, was also studied. Hydroalcoholic and hexane extracts were obtained from aerial part of D. kotschyi using percolation method. Antispasmodic effect of the test compounds was assessed by measurement of small intestine transit following oral administration of a charcoal meal. Diarrhoea was induced by administration of either castor oil (0.5 ml) or magnesium sulphate (MgSO4) (10% w/v solution). Both the hydroalcoholic and hexane extracts of D. kotschyi (10 and 20 mg/kg) reduced the intestinal charcoal meal transit. Loperamide (2 mg/kg) and apigenin (2 and 10 mg/kg) inhibited intestinal movement of the charcoal meal and also inhibited castor oil and MgSO4-induced diarrhoea. The hydroalcoholic and hexane extracts of D. kotschyi (10 and 20 mg/kg) also significantly inhibited the castor oil and MgSO4-induced diarrhoea in mice in comparison with the vehicle-treated control groups. This study confirms that both the hydroalcoholic and hexane extracts of D. kotschyi has antispasmodic and antidiarrhoeal properties in vivo and could be a suitable remedy for treatment of gastrointestinal disorders in which smooth muscle spasm and/or diarrhoea plays a significant roles.

It has been reported that Rosa damascena hydroalcoholic extract has inhibitory effect at higher concentration but stimulatory action at lower concentrations on ileum. This could be due to the presence of stimulatory components in the extract. R. persica Mich. is another species which belongs to Rose family but so far there is no report about pharmacological action of its extract. Therefore, the objective of this research was to investigate inhibitory effect of hydroalcoholic and hexane extract of this plant on ileum contraction to see which type of extract would be more appropriate as antispasmodic agents. Hydroalcoholic and hexane extracts were prepared by percolation method. A section of rat ileum was suspended in an organ bath containing Tyrode′s solution. The tissue was kept under 1 g tension at 37 °C and continuously gassed with O 2 . Effects of R. persica extracts or vehicle were studied on ileum contractions induced by electrical field stimulation (EFS), KCl or acetylcholine (ACh) and compared with that of atropine. Hydroalcoholic extracts of R. persica (10-640 μg/ml) concentration dependently inhibited ileum contraction induced by KCl (IC 50 = 244 ± 35 μg/ml), ACh (IC 50 = 129 ± 7.4 μg/ml) and EFS (IC 50 = 172 ± 18.7 μg/ml). Hexane extract of R. persica (10-320 μg/ml) concentration dependently inhibited ileum contraction induced by KCl (IC 50 = 117 ± 12.4 μg/ml), ACh (IC 50 = 78 ± 9.1 μg/ml) and EFS (IC 50 = 67 ± 10.5 μg/ml). Atropine only inhibited the responses to ACh and EFS. The vehicle had no significant effect on ileum contractions. From this experiment it was concluded that R. persica extract have inhibitory effect on rat isolated ileum. Therefore, separation and identification of active component is recommended.