Anti-nociceptive and anti-inflammatory effects of methanolic extract of Asparagus pubescens root in rodents.

The effect of methanolic extract of Asparagus pubescens was investigated on chemical, thermal-induced pain as well as fresh egg albumin-induced inflammation and pentylenetetrazol (PTZ)-induced convulsion in rodents. The extract dose-dependently (0.25-1.5 g/kg) inhibited acetic acid-induced writhing, formalin-induced pain licking and hot plate-induced pain in mice. The extract significantly inhibited both the fresh egg albumin-induced inflammation in rats as well as PTZ-induced convulsion in mice. These inhibitions were statistically significant (P < 0.02-0.001). It increased the latencies of both clonic and tonic convulsions and delayed their mortalities. Its ability to reduce both neurogenic and non-neurogenic pains may be related to its active constituents such as tannins, saponins, steroid and flavonoids.

Antitrypanosomal effect of the aqueous extract of Brassica oleracea.

The in vitro antitrypanosomal activity of the aqueous extract of Brassica oleracea, was investigated in Trypanosoma brucei brucei 'Lafia' strain. The extract was found to be effective by immobilizing the trypanosomes within the 3-h incubation period and thereafter rendering them not infective to mice.

Effect of methanolic extract of Cassia nigricans leaves on rat gastrointestinal tract.

The effects of the methanolic extract of Cassia nigricans leaves were investigated on experimentally-induced diarrhoea and ulceration in rat. The extract dose-dependently reduced both the small intestinal propulsive movement (P<0.01-0.001), and castor oil-induced fluid accumulation (P<0.05-0.001). Its inhibitory effects on intestinal propulsive movement and fluid accumulation were significantly (P<0.05) antagonised by yohimbine. However, castor oil-induced diarrhoea was increased. The extract also reduced significantly (P<0.05-0.001) the ulcers induced by both indomethacin and ethanol. The results indicate that the observed antidiarrhoeal effect might in part be due to alpha(2)-adrenoceptor stimulation.

Antidiarrhoeal and antiulcerogenic effects of methanolic extract of Asparagus pubescens root in rats.

The effect of methanolic extract of Asparagus pubescens root on experimentally-induced diarrhoea and ulceration was investigated in rats. The extract (500-1500 mg/kg) dose-dependently, reduced significantly the intestinal propulsive movement, castor oil-induced diarrhoea and intestinal fluid accumulation. Yohimbine an alpha(2)-adrenoceptor blocker attenuated the antidiarrhoeal effect of the extract. The extract also reduced the ulcer indices induced by indomethacin and ethanol in a dose-related manner. The results indicate that its antidiarrhoeal and antiulcerogenic effects might in part be due to its alpha(2)-adrenoceptor stimulation and its active constituents respectively.

Chemical, pathological and toxicological studies of the effects of RICOM-1013-J of Ricinus communis var minor on women volunteers and rodents.

RICOM-1013-J (Ricinus communis var minor) administered orally once to each of 12 women volunteers at a dose of 2.5-2.7 g per 8 months, protected against pregnancy over a period of 7-8 months of study. A study of the effect of a contraceptive dose (20 mg/kg) on metabolic parameters in rat (food and water in-take, urine and faecal output and body weight) over a period of 4 months showed a slight decrease in all the parameters in the first 1-8 weeks. This effect was reversible attaining pretreatment levels from week 16. The LD(50) in an acute toxicity test in mice was 63.1 +/- 16.0 g/kg s.c. Determination of blood urea, sodium (Na(+)), potassium (K(+)), chloride (Cl(-)) and bicarbonate (HCO$_¿3¿ ¿-¿$)as a measure of renal function and alkaline phosphatase (ALP), transaminases (GPT and GOT) and transpeptidases (GGT) as a measure of liver function showed that liver function profiles in pretreated rats were not significantly different from control (p < 0.05) on day 21 to day 150. However, serum levels of ALP and GGT at day 120 to day 150 were moderately but significantly elevated (p > 0.05) compared with the control. There were no significant changes in renal function profiles in pretreated rats (p < 0.05) compared with the control. The results of the liver and renal function profiles in women volunteers showed that there were no significant (p < 0.05) changes in renal functions on day 206 following RICOM-1013-J administration. However, serum levels of ALP and GGT showed a slight rise in about 70% of volunteers, whereas bilirubin and transaminases levels were normal. The present results indicate a very high efficacy and margin of safety of RICOM-1013-J in women volunteers. The increase in ALP and GGT in both animal and women volunteers suggest mild intrahepatic cholestatic changes which may be attributed to an oestrogenic effect of RICOM-1013-J.

Preliminary clinical investigation of the contraceptive efficacy and chemical pathological effects of RICOM-1013-J of Ricinus communis var minor on women volunteers.

The seeds of Ricinus communis Linn, RICOM-1013-J, administered as a single oral dose of 2.3-2.5 g once per 12 months protected against pregnancy in 50 women volunteers for a period of one year. The antifertility and contraceptive efficacy of the seed was demonstrated in this study. Clinical observation revealed very minimal side effects. Some of the side effects investigated included headache, nausea, vomiting, weight gain, loss of appetite, raised blood pressure and dysmenorrhoea. Furthermore, both the renal and liver functions were not affected as revealed by urea, electrolyte and creatinine values as well as total bilirubin, conjugated bilirubin, serum albumin, total protein and transaminases values when compared with control values. In addition cholesterol and phospholipids were not significantly altered. When all these results are considered together, it seems unlikely that the antifertility and contraceptive efficacy of RICOM-1013-J is due to hormonal mechanisms alone since side effects, renal and liver function, and cholesterol effects attributable to oestrogen and/or progesterone were minimal in the volunteers.

Uterotonic properties of the methanol extract of Monechma ciliatum.

The oxytocic activity of the hot methanol extract (HME) of the leaves of Monechma ciliatum was compared with other uterine stimulants like ergometrine, oxytocin, 5-hydroxytryptamine (5-HT), acetylcholine (ACh) and prostaglandins (PGs) E2 and F2alpha (PGE2 and PGF2alpha) in the presence of some antagonists in an attempt to explain the mechanism of action of the extract. The effects of the reference drugs on uteri isolated from rats pretreated with HME for 2 weeks were also observed. Atropine blocked the effect of ACh and partially blocked those of HME while L-366-948 blocked only the effect of oxytocin. Indomethacin inhibited the effects of HME as well as all the other drugs, except the PGs and ACh. D-600 blocked the effect of all the drugs including HME. Methysergide antagonised only the effect of 5-HT and partially blocked ergometrine. Prolonged treatment altered the uterine musculature and the activity profile of the reference drugs. These results suggest that the HME may be acting by more than one mechanism to contract the uterus and explains the mechanism of the anti-implantation activity of the plant.

Contraceptive and non-estrogenic effects of methanolic extract of Asparagus pubescens root in experimental animals.

The methanolic extract of Asparagus pubescens Bak root was investigated for its contraceptive activity in mice, rats and rabbits. The extract dose-dependently (0.5-1.5 g/kg) protected the animals from conception for 4-14 gestational periods in rabbits, rats and mice. It inhibited fetal implantation, as was confirmed by laparotomy on day 10 of pregnancy. The pups showed significant change in weight and length (P < 0.05-0.001) with 1.5 g/kg compared to the control fetal defects. In ovariectomized immature young rats and mice, there was a dose-dependent decrease in uterine wet weight (P < 0.001). The extract did not induce any uterotrophic effects or immature vaginal opening when compared to estrogen treated groups. Its contraceptive effect may in part be due to its anti-implantation and/or a direct effect on the uterus.

Inhibitory effects of the aqueous extract of Pavetta crassipes leaves on gastrointestinal and uterine smooth muscle preparations isolated from rabbits, guinea pigs and rats.

The effects of the aqueous extract of Pavetta crassipes leaves were studied on gastrointestinal and uterine smooth muscle preparations isolated from rabbit jejunum, guinea pig ileum and rat uterus. The extract produced a concentration-dependent inhibition of the spontaneous motility or elevated tone in these preparations. The inhibitory effects of the extract were not affected by pretreatment with propranolol or yohimbine, but were completely blocked by verapamil pretreatment. The results indicate the presence of biologically active substances whose action might be mediated through calcium channels. A preliminary phytochemical screening of the leaf extract of P. crassipes revealed the presence of flavonoids, tannins and anthraquinones as possible candidates for such inhibitory substances.

The skeletal muscle relaxant action of Portulaca oleracea: role of potassium ions.

An aqueous extract of the stems and leaves of Portulaca oleracea abolishes the twitch contraction of the directly stimulated rat hemidiaphragm preparation. The effects of the extract mimic qualitatively the action of potassium oxalate--a known constituent of Portulaca oleracea--on the diaphragm. Removal of K+ ions from the methanol extract by passing it through a cation exchange resin reduced the inhibitory effect of the extract. There was a positive correlation between the concentration of K+ ions in the extract and the effects of potassium chloride of similar molarity. It is concluded that the K+ ion content of Portulaca oleracea is at least partly responsible for the relaxant effect observed on the isolated rat diaphragm.

Anticonceptive and estrogenic effects of a seed extract of Ricinus communis var. minor.

An ether-soluble fraction of a methanol extract of Ricinus communis var. minor seeds administered subcutaneously to adult female rats and rabbits at doses up to 1.2 g/kg and 600 mg/kg, respectively, in divided doses showed anti-implantation and anticonceptive activities. Laparotomy performed on Day 10 and Day 15 of pregnancy on mated female rats and rabbits treated with the extract did not reveal any uterine implantation sites. The animals were protected against pregnancy for over three gestation periods and among those that later delivered, there was no evidence of abnormality in the pups. In ovariectomized young female rats as well as in immature mice, the extract dose-dependently increased uterine wet weight. Furthermore, the extract induced premature opening of the vagina, increased the number of epithelial cells and cornified cells and decreased the leucocyte number in the vaginal smear. The estrogen-like activities exhibited by the extract were dose-dependent and the anticonceptive effect may be due at least in part to such estrogenic action.

Mode of inhibitory actions of acute and chronic chloroquine administration on the electrically stimulated mouse diaphragm in vitro.

1. The effects of bath applied chloroquine (Chlo) and of acute and chronic Chlo administration on skeletal muscle reactivity to electrical stimulation and to drugs have been studied on mouse hemidiaphragm preparations in vitro. 2. Chlo (0.15-150 micrograms) produced a concentration-dependent inhibition twitch and tetanic contractions due to direct muscle stimulation (MS). Acute and chronic administration of Chlo (45 mg kg-1, i.p. daily, for 3-28 days) progressively shifted the concentration-response curve to bath-applied Chlo to the right, with maximum effect occurring from day 14 of Chlo pretreatment. 3. Acute and chronic administration of Chlo decreased the twitch and tetanus tension, raised the minimal fusion frequency (MFR) for tetanic contraction to occur and did not alter the twitch/tetanus tension ratio. Tetanus tension unlike twitch tension was not significantly decreased on day 3. 4. Caffeine (5-500 microM)--and isoprenaline (0.001-0.8 microM)-induced potentiations of twitch contraction were attenuated in a concentration-dependent manner by bath-applied Chlo and by acute and chronic administration of Chlo. Higher concentrations of caffeine (0.1-5 microM) and KCl (10 mM-130 mM) produced contracture of the muscle which was sensitive to inhibition by Chlo (50-150 microM). Moreover, the spike contractions superimposed on caffeine contracture were more sensitive to the inhibitory effect of Chlo than the contracture. 5. The inhibitory effects of dantrolene sodium and (+)-tubocurarine on MS and on indirectly stimulated hemidiaphragm respectively were not significantly altered by acute and chronic administration of Chlo. In contrast, the inhibitory concentration-response curve to procaine was shifted to the right. 6. The inhibitory effect of bath-appled Chlo, or acute and chronic pretreatment on twitch tension (MS) was not significantly antagonized by stepwise increase in extracellular Ca2 + (0.05-2.5 mM). Sodium thiocyanate (1-5 mM) reversed in a concentration-dependent manner the inhibitory effects of Chlo. 7. Complete recovery of twitch contractions occurred after 3 days of stopping daily Chlo administration, with partial recovery to tetanic tension after 28 days and no recovery of MFR. The reactivity of the diaphragm to bath applied Chlo was progressively restored, whereas the tension curve area to caffeine and KCI was still attenuated even 28 days after stopping Chlo pretreatment. 8. It is concluded that acute and chronic Chlo administration results in changes in reactivity of the hemidiaphragm muscle to electrical stimulation and to drugs such that there is a decrease in muscle strength and tolerance to Chlo in vitro. These effects are dependent on its direct inhibitory action on skeletal muscle and may result from interference with Ca2 + mobilization within the muscle.

Skeletal muscle relaxant action of an aqueous extract of Portulaca oleracea in the rat.

The aqueous extract of Portulaca oleracea produced skeletal muscle relaxation in rats following i.p. or oral administration, as assessed by the prolongation of pull-up time. The i.p. route of administration was more effective. When compared with chlordiazepoxide (20 mg/kg, i.p.), diazepam (40 mg/kg, i.p.) and dantrolene sodium (30 mg/kg, oral), the extract (200-1000 mg/kg, i.p.) proved a more effective skeletal muscle relaxant. With 1000 mg/kg i.p., 80% lethality was seen. The LD50 in an acute toxicity test in mice was 1040 mg/kg i.p.

Effects of Olax gambecola methanol extract on smooth muscle and rat blood pressure.

A methanol extract of the roots of Olax gambecola induced a biphasic contractile response consisting of a transitory initial rapid contraction (Phase I), followed by a slowly developing sustained increase in basal tone (Phase II) on rat fundus, antrum, guinea pig taenia coli, rabbit jejunum and aorta. The Phase I contraction was abolished by atropine, attenuated significantly by indomethacin and potentiated by physostigmine while the Phase II response was unaffected. Hexamethonium, morphine, serotonin (5-HT) antagonists or desensitization of 5-HT receptors did not alter either the Phase I or the Phase II contractions. Calcium channel blockers and procedures affecting calcium translocation abolished the Phase I contraction while only reducing the Phase II contractions. Transmural electrical stimulation produced contractions of the fundus which were attenuated by the extract. Single bolus injections of extract produced a rapid fall in blood pressure in both normotensive and spontaneously hypertensive rats but intravenous infusion resulted in a sustained fall in blood pressure which was maintained throughout the infusion period. Chronic i.p. administration of extract to spontaneously hypertensive rats reduced blood pressure markedly but did not alter the blood pressure of normotensive animals. The hypotensive response to single bolus injections was abolished by atropine and potentiated by physostigmine. The activity profile of the extract suggests the presence of at least two active principles in the crude extract of Olax gambecola used in this study.

Effects of various intracranial fluids on smooth muscle.

Samples of cerebrospinal fluid (CSF) drawn from patients with subarachnoid hemorrhage, subdural hemorrhage, or brain tumor, as well as control samples from patients without a known cerebral pathological condition, were tested for their ability to contract smooth muscle. Canine middle cerebral artery, canine basilar artery, and rat stomach fundus were used, and contractions were expressed as the percentage of the contraction elicited by a standard dose of 5-hydroxytryptamine. All samples that contained blood produced contractions of the smooth muscle preparations, and despite a large sample no significant differences were observed in the magnitude of the contractions either between preparations or between samples from different groups of patients. Control samples were generally without significant effect. Neither methysergide, a 5-hydroxytryptamine antagonist, nor indomethacin, an inhibitor of prostaglandin synthesis, significantly diminished the contractions induced by bloody CSF, although the calcium antagonist D600 successfully antagonized the response in all groups. D600 was a better antagonist of the action of blood-containing CSF on cerebral artery than on stomach fundus. Samples obtained from patients with angiographic evidence of vasospasm were significantly more active than those obtained from patients without vasospasm, but the latter retained considerable activity.

The effect of metoclopramide on intestinal muscle responses and the peristaltic reflex in vitro.

Metoclopramide (Mcp) is known to facilitate gastrointestinal emptying in vivo and to stimulate various isolated intestinal muscle preparations. On the guinea pig ileum, taenia coli, rabbit ileum and rat duodenum, Mcp increased the tone and responses to acetylcholine, carbachol and nicotine; had no effect on responses to histamine, potassium chloride and prostaglandin E1; decreased responses to 5-hydroxytryptamine (5-HT). Atropine, methysergide, morphine, and tetrodotoxin, alone or in combination, partially blocked the stimulatory responses to Mcp, but hexamethonium, mepyramine and indomethacin did not. Mcp (1.0 muM) lowered the threshold for elicitation of the peristaltic reflex to a sub-threshold intraluminal pressure (2.5 cm water), facilitated the peristaltic response to threshold pressures (3-4 cm water) and restored the reflex in fatigued preparations, but not that depressed by cooling to 24 degrees C. During block of peristalsis by atropine, hexamethonium or methysergide (applied serosally) 5-HT (0.25 muM) but not Mcp (1.0 muM)) effectively restored the peristaltic reflex, but neither antagonized the inhibition by morphine or procaine acting serosally. However, Mcp (1.0 muM) re-established peristalsis inhibited by a high concentration of 5-HT ((4 X 10 muM). These results do not support the hypotheses that the stimulatory action of Mcp is entirely dependent on either peripheral sensitization of muscarinic receptors or an action on tryptaminergic mechanisms but are consistent with our previous conclusion that an additional component may be a blockade of some intrinsic inhibitory (possibly purinergic) substance normally restraining intestinal motility or tone.