Comparative pharmacokinetic study of paeoniflorin after oral administration of decoction of Radix Paeoniae Rubra and Radix Paeoniae Alba in rats

An investigation was designed and conducted to compare the pharmacokinetics difference of paeoniflorin after oral administration of the extracts of Radix Paeoniae Rubra and Radix Paeoniae Alba to rats on separate occasions. Quantification of paeoniflorin in rat plasma was achieved using a simple and rapid HPLC method for pharmacokinetic study. After oral administration of decoctions of Radix Paeoniae Rubra and Radix Paeoniae Alba, paeoniflorin was absorbed and reached a maximum concentration of 3.69 ± 1.46 and 1.46 ± 0.29 (p < 0.05) μg/ml at 1.67 ± 0.43 and 0.80 ± 0.35 h (p < 0.05), respectively. Compared to the AUC (18.85 ± 7.54 μg h/ml) after oral administration of the paeoniflorin solution, a smaller AUC (10.61 ± 1.51 μg h/ml, p < 0.05) and a larger AUC (24.89 ± 7.41 μg h/ml) of paeoniflorin after oral administration of the decoctions of Radix Paeoniae Alba and Radix Paeoniae Rubra were obtained, respectively. There were statistically significant differences in pharmacokinetic parameters of paeoniflorin including the t_max, C_max, AUC, t_1/2, CL, and V_d among the animals orally administered the decoctions of Radix Paeoniae Rubra and Radix Paeoniae Alba. In particular, the parameters of t_max, C_max, and AUC of paeoniflorin were remarkably increased (P < 0.05, P < 0.001) when oral administering paeoniflorin in the decoctions of Radix Paeoniae Rubra, but t_1/2, V_d, and CL were decreased (P < 0.05 or P < 0.01), in comparison of the decoction of Radix Paeoniae Alba.     

Effect of Brazilian green propolis on experimental gastric ulcers in rats

Propolis is a resinous hive product collected by honeybees from plants. The propolis produced in Southeastern of Brazil is known as green propolis because of its color. Modern herbalists recommend its use because it displays antibacterial, antifungal, antiviral, hepatoprotective, anti-inflammatory, immunomodulatory and anti-ulcer properties. The anti-ulcer activity of green propolis hydroalcoholic crude extract was evaluated by using models of acute gastric lesions induced by ethanol, indomethacin and stress in rats. Moreover, the effects of extract on gastric content volume, pH and total acidity, using pylorus ligated model were evaluated. Animals pretreated with propolis hydroalcoholic crude extract (50, 250 and 500 mg/kg) showed a significant reduction in lesion index, total affected area and percentage of lesion in comparison with control group (p < 0.05) in the ethanol-induced ulcer model. Green propolis extract, at a higher dose (500 mg/kg), displayed a significant protection by reducing (p < 0.05) the evaluated parameters in the gastric ulceration induced by indomethacin. In the stress-induced ulcer model it was observed a significant reduction (p < 0.05) in those parameters in animals treated with green propolis extract (250 and 500 mg/kg). Regarding the pylorus ligated model it was observed that green propolis extract (250 and 500 mg/kg) displayed an anti-secretory activity, which lead to a reduction in the gastric juice volume, total acidity and pH. These findings indicate that Brazilian green propolis displays good anti-ulcer activity, corroborating the folk use of propolis preparations, and contributing for its pharmacological validation.     

Anthelmintic activity of preparations derived from Myrsine africana and Rapanea melanophloeos against the nematode parasite,Haemonchus contortus,of sheep

Myrsine africana L. and Rapanea melanophloeos L. belong to the plant family Myrsinaceae. Various rural communities in Kenya, such as smallholder farmers and pastoralists, use them to treat their livestock. The anthelmintic effects/activities of leaves and fruits of M. africana and fruits of R. melanophloeos were tested in sheep experimentally infected with the nematode parasite Haemonchus contortus. Male lambs were infected with 3000–5000 third stage larvae of H. contortus and treated 28 days after inoculation with concoctions made from leaves or fruits of the plants. No significant reduction in faecal nematode egg counts was observed with any of the concoctions at any of the doses tested. Packed red cell volume decreased and live weight increased at similar rates in treated and control groups, thus there was no significant effect of treatment. The results showed that the tested extracts of the M. africana and R. melanophloeos were not efficacious against H. contortus in sheep.     

Comparative pharmacokinetics of baicalin after oral administration of pure baicalin, Radix scutellariae extract and Huang-Lian-Jie-Du-Tang to rats

Huang-Lian-Jie-Du-Tang (HLJDT) is an important “heat-clearing” multiherb remedy of traditional Chinese medicine, and Radix scutellariae (Scutellaria baicalensis Georgi, Labiatae) is a key ingredient herb in it. Baicalin and wogonoside are two main effective ingredients enriched in Radix scutellariae. In the present study, pharmacokinetic differences of baicalin following oral administration of pure baicalin, Radix scutellariae extract, baicalin co-administrated with extract of the other three herbs of HLJDT and HLJDT were investigated in male S.D. rats with approximately the same dose of 200 mg/kg baicalin. The pharmacokinetic comparison of wogonoside was conducted only in Radix scutellariae extract and HLJDT. Plasma concentrations of baicalin and wogonoside were determined using HPLC method. Unpaired Student's t-test was used for statistical comparison. The results indicated that baicalin and wogonoside demonstrated bimodal phenomenon in the plasma profile. Some ingredients in the other three herbs of HLJDT, not in Radix scutellariae itself, had pharmacokinetic interaction with baicalin and wogonoside and hence decreased their systematic exposure level (p < 0.01). The absorption site of baicalin was preliminary evaluated in rat using in situ absorption in stomach and different intestinal segments and results revealed the existence of double-site absorption of baicalin. The first absorption site was in upper intestinal, probably via directly absorption of baicalin; while the second absorption site was in colon in the form of aglygon.     

In vitro study of the effects of khat (Catha edulis Forsk) extract on isolated mouse interstitial cells

Isolated mouse interstitial cells were incubated with different concentrations of khat (Catha edulis) extract (0.06 mg/ml, 0.6 mg/ml, 6 mg/ml, 30 mg/ml and 60 mg/ml) and cell viability as well as testosterone concentration measured at 30 min intervals over a 3 h incubation period. High concentrations of khat extract (30 mg/ml and 60 mg/ml) significantly inhibited testosterone production while low concentrations (0.06 mg/ml, 0.6 mg/ml and 6 mg/ml) significantly stimulated (P < 0.05) testosterone production by mouse interstitial cells. Similarly, at concentrations of 30 mg/ml and 60 mg/ml, there was a significant decrease in interstitial cell viability, whereas at 0.06 mg/ml, 0.6 mg/ml and 6 mg/ml there was no significant decrease. There was only a weak correlation (r = 0.39) between testosterone production and viable interstitial cells. We postulate that khat extract at high concentrations may cause reproductive function impairment in the user but at low concentrations, may enhance testosterone production with accompanying effects on reproductive functions in male mice.     

Effects of an aqueous extract of Triticum repens on lipid metabolism in normal and recent-onset diabetic rats

The aim of this study was to demonstrate the effects of single and repeated oral administration of the aqueous rhizomes extract of Triticum repens (TR) (20 mg/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of TR induced a significant decrease in the plasma triglycerides concentrations 4 days (P<0.05) and 1 week after repeated oral administration (P<0.05). This reduction was abolished 2 weeks after once daily repeated oral administration. A significant decrease of plasma cholesterol levels was observed only 1 week (P<0.05) after repeated oral administration.

In diabetic rats, TR treatment caused a significant decrease in plasma triglycerides levels after a single (P<0.01) and repeated (P<0.001) oral administration. A strong decrease in cholesterol level was observed 6 h after a single oral administration of the aqueous extract TR (P<0.001). Four days after repeated oral administration of TR aqueous extract, the plasma cholesterol level was significantly decreased (P<0.05) and still dropped after 2 weeks (P<0.001).

On other hand, the repeated oral administration of aqueous TR extract caused a significant decrease in body weight 2 weeks after repeated oral treatment in diabetic rats (P<0.05).

We conclude that the aqueous extract of TR exhibits lipid and body weight lowering activities in severe hyperglycaemic rats after repeated oral administration of aqueous TR extract at a dose of 20 mg/kg.     

Effect of Retama raetam on lipid metabolism in normal and recent-onset diabetic rats

The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Retama raetam (Forssk) Webb (RR) (20 mg/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats. In normal rats, the aqueous extract of RR induced a significant decrease of the plasma triglycerides concentrations one week after repeated oral administration (P<0.05). This reduction was maintained two weeks after once daily repeated oral administration (P<0.05). A significant decrease of plasma cholesterol levels was also observed one week (P<0.05) and two weeks (0.05) after repeated oral administration.

In diabetic rats, RR treatment caused a significant decrease of plasma triglycerides levels after a single (P<0.05) and repeated (P<0.001) oral administration. A significant decrease of cholesterol levels was observed four hours after a single oral administration of the RR aqueous extract (P<0.05). One week after repeated oral administration of RR aqueous extract, the plasma cholesterol levels were significantly decreased (P<0.05) and still dropped after two weeks (P<0.005).

On the other hand, the repeated oral administration of RR aqueous extract caused a significant decrease of body weight one week after repeated oral treatment in diabetic rats (P<0.05). We conclude that the aqueous extract of RR exhibits lipid and body weight lowering activities in both normal and severe hyperglycemic rats after repeated oral administration of RR aqueous extract at a dose of 20 mg/kg.     

Antimetastatic activities of Selaginella tamariscina (Beauv.) on lung cancer cells in vitro and in vivo

Selaginella tamariscina is a traditional Chinese herb for the therapy of chronic trachitis and has been approved some anti-tumor activity. However, the anti-metastasis effects of Selaginella tamariscina in the lung cancer have not been understood clearly. The objectives of study were to investigate the effects of the Selaginella tamariscina extracts (STE) on the invasion and motility of highly metastatic A549 and Lewis lung carcinoma (LLC) cells. To further investigate the precise involvement of STE in tumor metastasis, A549 and LLC cells were treated with STE at various concentrations (0–100 μg/mL) for a specified period. The results from zymography showed that a STE treatment decreased (p < 0.05) the expressions of matrix metalloproteinase (MMP)-2, -9 and urokinase plasminogen activator (u-PA) in a dose-dependent manner in the A549 and LLC cell. Meanwhile, their endogenous inhibitors, which are tissue inhibitor of metalloproteinase-2 (TIMP-2) and plasminogen activator inhibitor-1 (PAI-1), were increased in the A549 cell. Furthermore, the inhibitory effect of STE on the growth and metastasis of LLC cells in vivo was also proven. These results demonstrated that STE could be a candidate antimetastatic agent against lung cancer.     

Ovicidal and larvicidal activity of crude extracts of Maesa lanceolata and Plectranthus punctatus against Haemonchus contortus

The widespread development of anthelmintic resistance and high cost of the conventional anthelmintic drugs, has limited the control of gastrointestinal nematode parasites of sheep and goats and hence led to evaluation of medicinal plants as an alternative source of anthelmintics. In the current study, in vitro ovicidal and larvicidal activity of the leaves and fruits of the aqueous and hydro-alcoholic extracts of Maesa lanceolata and aerial parts of Plectranthus punctatus were evaluated on the egg and larvae of Haemonchus contortus using egg hatch assay and larval development test. All extracts of plants tested have shown complete inhibition of egg hatching at or below 1 mg/ml. ED₅₀ for egg hatch inhibition ranged from 0.11 to 0.29 mg/ml, for both the aqueous and hydro-alcoholic extracts of Plectranthus punctatus and Maesa lanceolata. All extracts have shown dose dependent inhibition of larval development with variable results. The complete inhibition (100%) at the maximum concentration tested (50 mg/ml) was obtained only for hydro-alcoholic extract of the fruits of Maesa lanceolata and the lowest inhibition (50.33%) was recorded for the hydro-alcoholic extract of the leaves of the same plant. The overall findings of the present study has shown that Plectranthus punctatus and Maesa lanceolata contain possible anthelmintic compounds and further evaluation of different extracts and fractions of these plants should be carried out.     

Effect of polyherbal formulation on experimental models of inflammatory bowel diseases

A polyherbal ayurvedic formulation from an ancient authentic classical text of ayurveda was evaluated for its activity against inflammatory bowel disease (IBD). The polyherbal formulation contained four different drugs viz., Bilwa (Aegle marmeloes), Dhanyak (Coriandrum sativum), Musta (Cyperus rotundus) and Vala (Vetiveria zinzanioids).

The formulation has been tried before in clinical practice and was found to be useful in certain number of cases of IBD (ulcerative colitis), so was tried in the same form i.e., decoction (aqueous extract) in experimental animals to revalidate the claims of the same.

The formulation was tried on two different experimental animal models of inflammatory bowel disease, which are acetic acid-induced colitis in mice and indomethacin-induced enterocolitis in rats. Prednisolone was used as the standard drug for comparison.

The formulation showed significant inhibitory activity against inflammatory bowel disease induced in these experimental animal models. The activity was comparable with the standard drug prednisolone. The results obtained established the efficacy of this polyherbal formulation against inflammatory bowel diseases.     

Diuretic activity of some Withania aristata Ait. fractions

We previously reported on the significant dose-dependent diuretic effects produced in laboratory rats by hot water infusions and methanol extracts of Withania aristata Ait., where notable increases were observed in the excretion of water and sodium, with an interesting potassium-saving effect. The present study gives the results of the diuretic effects in rats of the hexane, dichloromethane, ethyl acetate, butanol and methanol–water fractions of the previously studied methanol extract.

Water excretion rate, pH, density, conductivity and content of Na⁺, K⁺ and Cl⁻ were measured in the urine of the rats when subjected to hypersaline conditions. Of the above fractions, the methanol:water extract (100 mg/kg) showed the most interesting diuretic activity (25%; ^**p < 0.01), which suggested that increase in the polarity of the extracting solvent led to an increase in the concentration of the polar compounds responsible for the diuretic effect. These data, together with previous results on the aqueous and methanol extracts, reaffirm assertions made regarding the effectiveness of the extracts of this plant against urinary pathologies in the Canary Islands folk medicine.     

In vivo study of propolis supplementation effects on antioxidative status and red blood cells

In vivo study has been conducted on 47 healthy women and men in order to investigate whether daily intake of powdered propolis extract during 30 days has any influence on the following blood parameters: activity of superoxide dismutase, glutathione peroxidase and catalase, concentration of plasma malondialdehyde, total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides, glucose, uric acid, ferritin and transferrin, together with routine red blood cell parameters.

The effect of daily propolis intake seems to be time and gender related. For the men test group after the initial 15 days of propolis treatment, 23.2% (p = 0.005) decrease in concentration of malondialdehyde was observed. After 30 days of treatment, statistically significant (p = 0.010) 20.9% increase in superoxide dismutase activity and change in some of the red blood cell parameters were detected. For the women test group, the propolis treatment did not induce a change in any of the measured parameters.     

In vitro anthelmintic activity of crude extracts of five medicinal plants against egg-hatching and larval development of Haemonchus contortus

Ethnopharmacological relevance

Senna occidentalis, Leonotis ocymifolia, Leucas martinicensis, Rumex abyssinicus, and Albizia schimperiana are traditionally used for treatment of various ailments including helminth infection in Ethiopia.

Materials and Methods

In vitro egg hatch assay and larval development tests were conducted to determine the possible anthelmintic effects of crude aqueous and hydro-alcoholic extracts of the leaves of Senna occidentalis, aerial parts of Leonotis ocymifolia, Leucas martinicensis, Rumex abyssinicus, and stem bark of Albizia schimperiana on eggs and larvae of Haemonchus contortus.

Results

Both aqueous and hydro-alcoholic extracts of Leucas martinicensis, Leonotis ocymifolia and aqueous extract of Senna occidentalis and Albizia schimperiana induced complete inhibition of egg hatching at concentration less than or equal to 1 mg/ml. Aqueous and hydro-alcoholic extracts of all tested medicinal plants have shown statistically significant and dose dependent egg hatching inhibition. Based on ED₅₀, the most potent extracts were aqueous and hydro-alcoholic extracts of Leucas martinicensis (0.09 mg/ml), aqueous extracts of Rumex abyssinicus (0.11 mg/ml) and Albizia schimperiana (0.11 mg/ml). Most of the tested plant extracts have shown remarkable larval development inhibition. Aqueous extracts of Leonotis ocymifolia, Leucas martinicensis, Albizia schimperiana and Senna occidentalis induced 100, 99.85, 99.31, and 96.36% inhibition of larval development, respectively; while hydro-alcoholic extracts of Albizia schimperiana induced 99.09 inhibition at the highest concentration tested (50 mg/ml). Poor inhibition was recorded for hydro-alcoholic extracts of Senna occidentalis (9%) and Leonotis ocymifolia (37%) at 50 mg/ml.

Conclusions

The overall findings of the current study indicated that the evaluated medicinal plants have potential anthelmintic effect and further in vitro and in vivo evaluation is indispensable to make use of these plants.     

Efficacy of Myrsine africana, Albizia anthelmintica and Hilderbrantia sepalosa herbal remedies against mixed natural sheep helminthosis in Samburu district, Kenya

Traditional livestock healers from Samburu and Turkana communities in Samburu District of Kenya were identified and recruited for participation in this study. Sheep with mixed gastrointestinal helminthosis were purchased from nomadic livestock owners in the area. Three herbal anthelmintic remedies, viz. Myrsine africana, Albizia anthelmintica and Hilderbrantia sepalosa were administered in the traditional way by the healers and their efficacy determined using percent fecal egg count reduction (percent FECR) test. The results indicate that all the herbal remedies had some efficacy against both nematodes and Monezia species of helminths. The group effect against nematodes was significantly different (P=0.002). Compared to an untreated control group, the efficacy against nematodes was 77, 89.8 and 90% for Myrsine afriacana, Albizia antihelmintica and Hilderbrantia sepalosa, respectively, while albendazole had 100% efficacy. The main nematodes encountered included Haemonchus spp., Trichostrogylus spp. and Oesophagostomum spp. With regard to Monezia species herbal remedies performed better than albendazole with an efficacy of 100% compared to 63% for albendazole. The group of sheep treated with Albizia anthelmintica showed a significant increase (P=0.003) in packed cell volume (PCV).     

Hypoglycemic effect of Egyptian Morus alba root bark extract: effect on diabetes and lipid peroxidation of streptozotocin-induced diabetic rats

The hypoglycemic activity of the flavonoids rich fraction of 70% alcohol extract of the Egyptian Morus alba root bark (MRBF-3) was evaluated after its oral administration to streptozotocin-induced diabetic rats. Diabetes was induced by injection of 60 mg kg⁻¹ i.p. The administration of MRBF-3 to streptozotocin (STZ)-diabetic rats for 10 days in a dose of 200 and 400 mg kg⁻¹ day⁻¹ was not significant. However, administration of MRBF-3 for 10 days (600 mg kg⁻¹ day⁻¹) significantly reduced the amount of the glucose from control level (379 ± 9 mg/dl) to a lower level (155 ± 8 mg/dl) and significantly increased the insulin level from control (10.8 ± 0.3 μU/ml) to a high level (15.6 ± 0.3 μU/ml). The measurement of produced lipid peroxides (expressed as the amount of thiobarbituric acid (TBA) reactive substance, nmol TBARS/ml serum) indicated antiperoxidative activity of MRBF-3. The oral administration of MRBF-3 to STZ-diabetic rats significantly decreased the lipid peroxides from 6.3 ± 0.8 to 5.1 ± 0.7 nmol TBARS/ml serum. The phytochemical investigation of MRBF-3 resulted in the isolation of four hydrophobic flavonoids with one or two isoprenoid groups (log P = 5–9): morusin, cyclomorusin, neocyclomorusin, and kuwanon E, a 2-arylbenzofuran, moracin M, and two triterpenes, betulinic acid and methyl ursolate. The data obtained from this study revealed that MRBF-3 may protect pancreatic β cells from degeneration and diminish lipid peroxidation. However, this is the first biological screening of the Egyptian Morus alba root bark; further future merit studies including clinical study will be necessary in order to confirm the results obtained from this study.     

Anti-inflammatory activity of Sedum kamtschaticum

Sedum kamtschaticum Fischer (Crassulaceae) has been used as a folk medicine in North-East Asia for treating inflammatory disorders. The present investigation was carried out to establish in vivo anti-inflammatory activity and cyclooxygenase-2 modulating activity of this plant material. The methanol extract of Sedum kamtschaticum significantly inhibited mouse croton oil-induced ear edema (24–47% inhibition at 50–400 mg/kg) and rat paw edema (24–30% inhibition at 400–800 mg/kg) by oral administration. Prednisolone (10 mg/kg) showed 54 and 36% inhibition in the same animal models, respectively. Sedum kamtschaticum also showed significant inhibitory activity against mouse ear edema induced by multiple treatment of phorbol ester for 3 days. In addition, Sedum kamtschaticum exhibited potent analgesic activity against mouse acetic acid-induced writhing (IC₅₀=125 mg/kg), while aspirin (200 mg/kg) showed 57% inhibition. Using lipopolysaccharide-treated RAW 264.7 cells, down-regulation of cyclooxygense-2 expression was found to be one of the cellular action mechanisms of anti-inflammation by Sedum kamtschaticum.     

Antiulcer and in vitro antioxidant activities of Jasminum grandiflorum L

The study was aimed at evaluating the antiulcer and antioxidant activities of 70% ethanolic axtract of leaves of Jasminum grandiflorum L. (JGLE). The leaves of Jasminum grandiflorum L. (Family: Oleaceae) is used in folk medicine for treating ulcerative stomatitis, skin diseases, ulcers, wounds, corns—a hard or soft hyperkeratosis of the sole of the human foot secondary to friction and pressure (Stedman's Medical Dictionary, 28th ed. Lippincott Williams & Wilkins, Philadelphia. p. 443), etc., Antiulcerogenic activity of JGLE (100 and 200 mg/kg, b.w., orally) was evaluated employing aspirin + pylorus ligation (APL) and alcohol (AL) induced acute gastric ulcer models and ulcer-healing activity using acetic acid-induced (AC) chronic ulcer model in rats. Both the antisecretory and cytoprotection hypothesis were evaluated. The antioxidant activity of JGLE has been assayed by using in vitro methods like 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH) assay, reductive ability, superoxide anion scavenging activity, nitric oxide scavenging activity and total phenolic content, in order to explain the role of antioxidant principles in the antiulcerogenic activity of the extract. There was a significant (P < 0.01) dose-dependent decrease in the ulcerative lesion index produced by all the three models in rats as compared to the standard drug famotidine (20 mg/kg, b.w. orally). The reduction in gastric fluid volume, total acidity and an increase in the pH of the gastric fluid in APL rats proved the antisecretory activity of JGLE. Additionally, JGLE completely healed the ulcer within 20 days of treatment in AC model as evidenced by histopathological studies. Like antiulcer activity, the free radical scavenging activities of JGLE depends on concentration and increased with increasing amount of the extract. These results suggest that leaves of Jasminum grandiflorum possess potential antiulcer activity, which may be attributed to its antioxidant mechanism of action.     

Evaluation of ethnobotanically selected Benin medicinal plants for their in vitro antiplasmodial activity

Twenty extracts from nine Benin medicinal plants, traditionally used to treat malaria, were screened for in vitro antiplasmodial activity towards Plasmodium falciparum K1 chloroquine resistant and 3D7 chloroquine sensitive strains. All plants showed antiplasmodial activity below 10 μg/ml. Nine extracts exhibited IC₅₀ values below 5 μg/ml towards one or both of the two strains. The most active extract towards the sensitive 3D7 strain was the methanolic extract of Croton lobatus aerial part, with an IC₅₀ value of 0.38 μg/ml. The best inhibition of the growth of Plasmodium falciparum resistant K1 strain was observed with the methylene chloride extract of Hybanthus enneaspermus and with the methanolic extract of Croton lobatus roots (IC₅₀=2.57 and 2.80 μg/ml, respectively).     

Antispasmodic and blood pressure lowering effects of Valeriana wallichii are mediated through K+ channel activation

Crude extract of Valeriana wallichii rhizome (Vw.Cr) and its fractions were studied for possible antispasmodic and blood pressure lowering activities to rationalize some of the folkloric uses. In rabbit jejunum preparations, Vw.Cr (0.1–3.0 mg/mL) caused relaxation of spontaneous contractions. When tested against high K⁺ (80 mM)-induced contractions it produced weak inhibitory effect, while caused complete relaxation of the contractions induced by low K⁺ (20 mM). In the presence of glibenclamide (3 μM), the inhibitory effect of low K⁺ was shifted to the right, similar to that produced by cromakalim while, verapamil caused no differentiation in its inhibitory effect against low and high K⁺-induced contractions. In guinea pig ileum, the plant extract produced similar results as in rabbit jejunum. Intravenous administration of Vw.Cr, produced fall in arterial blood pressure in normotensive anaesthetized rats and this effect was partially blocked by glibenclamide. In rabbit aortic preparations, plant extract also caused a selective and glibenclamide-sensitive relaxation of low K⁺ (20 mM)-induced contractions. Activity-directed fractionation studies revealed that the observed activity was distributed both in the chloroform and aqueous fractions. These results indicate that the antispasmodic and hypotensive effects of Valeriana wallichii are mediated possibly through K_ATP channel activation, which justify its use in gastrointestinal and cardiovascular disorders.     

Anti-inflammatory,analgesic activity and acute toxicity of Glaucium grandiflorum extract

The species of Glaucium have been used in Iranian herbal medicine as laxative, hypnotic, antidiabetic agents and also in the treatment of dermatitis. The anti-inflammatory and analgesic effects of the aerial parts of Glaucium grandiflorum Boiss & Huet (Papaveraceae), a native plant of Iran, were studied using carrageenan induced edema, formalin and hot plate tests. The G. grandiflorum extract at the dose of 200 mg/kg had more edema inhibition than indomethacin at the doses of 10 (P<0.01) and 8 mg/kg (P<0.001) in the carrageenan test. The ED₅₀ (i.p.) in the edema induced by carrageenan was 13.59 mg/kg. In formalin test, the extract (60–90 mg/kg, i.p.) caused graded inhibition of both phases of formalin-induced pain. In hot plate test, the i.p. administration of the extract at the doses of 60, 70, 80 and 90 mg/kg significantly raised the pain threshold at a observation time of 45 min in comparison with control (P<0.001). The extract, at the antinociceptive doses, did not affect motor coordination of animals when assessed in the rotarod model. The 72 h acute LD₅₀ value of this extract after i.p. administration in mice was 797.94 mg/kg.