Antiinflammatory, analgesic and hypoglycemic effects of Mangifera indica Linn. (Anacardiaceae) stem-bark aqueous extract

Previous studies in our laboratories and elsewhere have shown that some members of Anacardiaceae family possess antiinflammatory, analgesic and hypoglycemic effects in man and mammalian experimental animals. The present study was, therefore, undertaken to examine the antiinflammatory, analgesic and antidiabetic properties of the stem-bark aqueous extract of Mangifera indica Linn., M. indica a member of the Anacardiaceae family, in rats and mice. The stem-bark powder of M. indica was Soxhlet extracted with distilled water and used. The analgesic effect of the plant's extract was evaluated by the hot-plate and acetic acid test models of pain in mice, while the antiinflammatory and antidiabetic effects of the stem-bark extract were investigated in rats, using fresh egg albumin-induced paw edema, and streptozotocin (STZ)-induced diabetes mellitus, respectively. Morphine (MPN, 10 mg/kg i.p.), diclofenac (DIC, 100 mg/kg i.p.), and chlorpropamide (250 mg/kg p.o.) were used respectively as reference analgesic, antiinflammatory, and hypoglycemic agents for comparison. M. indica stem-bark aqueous extract (MIE, 50-800 mg/kg i.p.) produced dose-dependent and significant (p<0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain stimuli in mice. MIE (50-800 mg/kg i.p.) also significantly (p<0.05-0.001) inhibited fresh egg albumin-induced paw edema, and caused significant (p<0.05-0.001) hypoglycemic effects in rats. It is suggested that the analgesic effects of MIE (50-800 mg/kg i.p.) may be peripherally and centrally mediated. The different chemical constituents of the plant, especially the polyphenolics, flavonoids, triterpenoids, mangiferin, and other chemical compounds present in the plant may be involved in the observed antiinflammatory, analgesic, and hypoglycemic effects of the plant's extract. However, the results of this experimental animal study lend pharmacological credence to the suggested folkloric uses of the plant in the management and control of painful, arthritic and other inflammatory conditions, as well as in the management of adult-onset type 2 diabetes mellitus in some rural African communities.     

Analgesic, antiinflammatory and hypoglycemic effects of Sutherlandia frutescens R. BR. (variety Incana E. MEY.) [Fabaceae] shoot aqueous extract

Previous studies on the pharmacology of South African medicinal plants in our laboratories and elsewhere have shown that some plants possess therapeutic attributes. One such ethnomedically useful plant is Sutherlandia frutescens R. BR. (family: Fabaceae). S. frutescens is widely used in South African traditional medicine for the management and/or control of a plethora of human ailments. In order to scientifically appraise some of the ethnomedical uses of S. frutescens, the present study was undertaken to investigate the analgesic, antiinflammatory and antidiabetic properties of the plant's shoot aqueous extract in experimental animal models. The analgesic effect of the herb's shoot extract was evaluated using the hot-plate and acetic acid test models of pain in mice, while the antiinflammatory and hypoglycemic effects of the plant's shoot aqueous extract were investigated in rats, using fresh egg albumin-induced pedal (paw) edema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac (100 mg/kg) and chlorpropamide (250 mg/kg) were used, respectively, as reference drugs for comparison. S. frutescens shoot aqueous extract (50-800 mg/kg i.p.) produced significant (p < 0.05-0.001) analgesic effects against thermally- and chemically-induced nociceptive pain stimuli in mice. The plant extract (50-800 mg/kg p.o. or i.p.) also significantly (p < 0.05-0.001) inhibited fresh egg albumin-induced acute inflammation and caused significant (p < 0.05-0.001) hypoglycemia in rats. The various chemical constituents and secondary metabolites of the herb are speculated to account for the observed analgesic, antiinflammatory and hypoglycemic effects of the plant. The results of this experimental animal study suggest that S. frutescens shoot aqueous extract possesses analgesic, antiinflammatory, and hypoglycemic properties, and thus lend pharmacological credence to the suggested folkloric uses of the herb in the management and/or control of painful, arthritic and other inflammatory conditions, as well as for adult-onset, type-2 diabetes mellitus in some communities of South Africa.     

Antiinflammatory and analgesic effects of Psidium guajava Linn. (Myrtaceae) leaf aqueous extract in rats and mice

In many parts of Africa, the leaf, stem-bark, and roots of Psidium guajava Linn. (Family: Myrtaceae) are used traditionally for the management, control, and/or treatment of an array of human disorders. In an effort to scientifically appraise some of the ethnomedical properties of P. guajava leaf, and probe its efficacy and safety, the present study was undertaken to examine the antiinflammatory and analgesic properties of the plant's leaf aqueous extract in some experimental animal paradigms. The antiinflammatory property of the aqueous leaf extract was investigated in rats, using fresh egg albumin-induced pedal (paw) edema, while the analgesic effect of the plant extract was evaluated by the "hot-plate" and "acetic acid" test models of pain in mice. Diclofenac (100 mg/kg, i.p.) and morphine (10 mg/kg, i.p.) were used respectively as standard, reference antiinflammatory and analgesic agents for comparison. P. guajava leaf aqueous extract (PGE, 50-800 mg/kg, i.p.) produced dose-dependent and significant (p < 0.05-0.001) inhibition of fresh egg albumin-induced acute inflammation (edema) in rats. The plant extract (PGE, 50-800 mg/kg, i.p.) also produced dose-dependent and significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain in mice. The numerous tannins, polyphenolic compounds, flavonoids, ellagic acid, triterpenoids, guiajaverin, quercetin, and other chemical compounds present in the plant are speculated to account for the observed antiinflammatory and analgesic effects of the plant's leaf extract. In summary, the findings of this experimental animal study indicate that the leaf aqueous extract of P. guajava possesses analgesic and antiinflammatory properties, and thus lend pharmacological credence to the suggested ethnomedical, folkloric uses of the plant in the management and/or control of painful, arthritic and other inflammatory conditions in some rural communities of Africa.     

Hypoglycemic and hypotensive effects of Psidium guajava Linn. (Myrtaceae) leaf aqueous extract

The leaf of Psidium guajava Linn. (family, Myrtaceae) is used traditionally in African folk medicine to manage, control, and/or treat a plethora of human ailments, including diabetes mellitus and hypertension. In order to scientifically appraise some of the anecdotal, folkloric, ethnomedical uses of P. guajava Linn., the present study was undertaken to investigate the hypoglycemic and hypotensive effects of P. guajava leaf aqueous extract (PGE, 50-800 mg/kg) in rat experimental paradigms. The hypoglycemic effect of the plant's extract was examined in normal and diabetic rats, using streptozotocin (STZ)-induced diabetes mellitus model. Hypertensive Dahl salt-sensitive rats were used to investigate the hypotensive (antihypertensive) effect of the plant's extract. Chlorpropamide (CPP; 250 mg/kg, p.o.) was used as the reference hypoglycemic agent for comparison. Acute oral administrations of the plant's extract (PGE; 50-800 mg/kg, p.o.) caused dose-related, significant (p < 0.05-0.001) hypoglycemia in normal (normoglycemic) and STZ-treated, diabetic rats. Moreover, acute intravenous administrations of the plant's extract (PGE, 50-800 mg/kg i.v.) produced dose-dependent, significant reductions (p < 0.05-0.001) in systemic arterial blood pressures and heart rates of hypertensive, Dahl salt-sensitive rats. Although the exact mechanisms of action of the plant's extract still remain speculative at present, it is unlikely that the extract causes hypotension in the mammalian experimental animal model used via cholinergic mechanisms, since its cardiodepressant effects are resistant to atropine pretreatment. The numerous tannins, polyphenolic compounds, flavonoids, pentacyclic triterpenoids, guiajaverin, quercetin, and other chemical compounds present in the plant are speculated to account for the observed hypoglycemic and hypotensive effects of the plant's leaf extract. However, the results of this experimental animal study indicate that the leaf aqueous extract of P. guajava possesses hypoglycemic and hypotensive properties, and thus lend pharmacological credence to the suggested folkloric, ethnomedical uses of the plant in the management or control of adult-onset, type 2 diabetes mellitus and hypertension in some rural African communities.     

Potentiation of the antiinflammatory effect of Anacardium occidentale (Linn.) stem-bark aqueous extract by grapefruit juice

In an attempt to scientifically appraise some of the ethnomedical uses of Anacardium occidentale Linn. (family: Anacardiaceae), the present study was undertaken to examine the antiinflammatory effect of the plant's stem-bark aqueous extract in rats. Young adult male Wistar rats weighing 250-300 g were used. The antiinflammatory effect of A. occidentale stem-bark aqueous extract alone and in combination with grapefruit (Citrus paradisi Macf.) juice was investigated on fresh egg albumin-induced rat paw edema. Like diclofenac (100 mg/kg p.o.), aqueous extract of A. occidentale stem-bark (800 mg/kg p.o.) produced time-related, sustained and significant reduction (p < 0.05-0.001) of the fresh egg albumin-induced acute inflammation of the rat hind paw. However, the antiinflammatory effect of the plant extract was found to be approximately 8-15 times less than that of diclofenac. Coadministration of grapefruit juice (5 ml/kg p.o.) with A. occidentale stem-bark aqueous extract (800 mg/kg p.o.) or diclofenac (100 mg/kg p.o.) significantly potentiated (p < 0.05-0.001) the antiinflammatory effects of the crude plant extract and diclofenac on fresh egg albumin-induced rat paw edema. Although A. occidentale stem-bark aqueous extract is less potent than diclofenac as an antiinflammatory agent, the results of this experimental animal study indicate that the plant extract possesses antiinflammatory activity, and thus lend pharmacological support to the folkloric use of the plant in the management and/or control of arthritis and other inflammatory conditions among the Yoruba-speaking people of western Nigeria.     

Analgesic, anti-inflammatory and hypoglycaemic effects of Securidaca longepedunculata (Fresen.) [Polygalaceae] root-bark aqueous extract

The present study was undertaken to investigate the analgesic, anti-inflammatory and hypoglycaemic properties of Securidaca longepedunculata (Fresen.) root-bark aqueous extract (SLE) in mice and rats. The analgesic effect of SLE was evaluated by 'hot-plate' and 'acetic acid' analgesic test methods in mice; while its anti-inflammatory and hypoglycaemic effects were examined in rats, using fresh egg albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes mellitus models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used as reference drugs for comparison. SLE (50-800 mg/kg i. p.) produced dose-dependent, significant (p < 0.05-0.001) analgesic effects against thermally- and chemically-induced nociceptive pain in mice. The plant's extract (SLE, 50-800 mg/kg p. o.) also dose-dependently and significantly inhibited (p < 0.05-0.001) fresh egg albumin-induced acute inflammation, and caused significant hypoglycaemia (p < 0.05-0.001) in normal (normoglycaemic) and STZ-treated diabetic (hyperglycaemic) rats. The results of this experimental animal study indicate that S. longepedunculata root-bark aqueous extract (SLE) possesses analgesic, anti-inflammatory and hypoglycaemic properties. These findings lend pharmacological credence to the anecdotal, folkloric and ethnomedical uses of S. longepedunculata root-bark in the treatment, management and/or control of painful, arthritic, inflammatory conditions, as well as in the management and/or control of type 2 diabetes mellitus in some rural communities of South Africa.     

Laboratory evaluation of the hypoglycemic effect of Anacardium occidentale Linn (Anacardiaceae) stem-bark extracts in rats

This study evaluated the hypoglycemic effect of stem-bark extracts of Anacardium occidentale Linn., of the Anacardiaceae family, in normal (normoglycemic) and in streptozotocin-treated diabetic rats. Young adult, male Wistar rats weighing 250-300 g were used. Diabetes mellitus was induced in the test rats by intraperitoneal injections of streptozotocin (STZ, 90 mg/kg). In one set of experiments, graded doses of the aqueous and methanolic stem-bark extracts of A. occidentale (100-800 mg/kg p.o.) were separately administered to groups of fasted normal and fasted diabetic rats. In another set of experiments, 800 mg/kg p.o. of the aqueous or methanolic extract of the plant, a dose which produced maximal hypoglycemic effects in both fasted normal and diabetic rats in the previous set of experiments, were used. The hypoglycemic effects of single doses (i.e., 800 mg/kg p.o.) of A. occidentale stem-bark aqueous and methanolic extracts were compared with those of insulin (5 microU/kg s.c.) and glibenclamide (0.2 mg/kg p.o.) in both fasted normal and fasted diabetic rats. Following acute treatment, relatively moderate-to-high doses of A. occidentale stem-bark extracts (100-800 mg/kg p.o.) produced dose-dependent, significant reductions (p< 0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. On their own, both insulin (5 microU/kg s.c.) and glibenclamide (0.2 mg/kg p.o.) produced significant reductions (p< 0.01-0.001) in the blood glucose concentrations of the fasted normal and fasted diabetic rats. At single doses of 800 mg/kg p.o., A. occidentale stem-bark aqueous and methanolic extracts significantly reduced (p< 0.001) the mean basal blood glucose concentrations of fasted normal and fasted diabetic rats. The hypoglycemic effect of the methanolic plant extract was found to be slightly more pronounced than that of the aqueous plant extract in both the normal and diabetic rats examined. A. occidentale contains a diverse group of chemical compounds. Since methanol extractives of plants usually contain many chemical compounds, each of which is capable of producing definite biological activities via different mechanisms, it is difficult to draw any logical conclusion on the mechanism of the hypoglycemic effect of such a diverse mixture of chemical compounds contained in the plant extracts used in this study. While it is possible that the hypoglycemic effects of the plant extracts may be due, at least in part, to their terpenoid and/or coumarin contents, the mechanism of their hypoglycemic action remains largely speculative. However, this is unlikely to be due to the stimulation of pancreatic beta-cells and subsequent secretion of insulin. Although A. occidentale stem-bark aqueous or methanolic extract is less potent than insulin as an antidiabetic agent, the results of this experimental animal study indicate that it possesses hypoglycemic activity, and thus lends credence to the folkloric use of the plant in the management and/or control of adult-onset, type-2 diabetes mellitus among the Yoruba-speaking people of Western Nigeria.     

Antinociceptive and antiinflammatory activities of Artemisia copa extracts.

The aqueous extract from aerial parts of Artemisia copa Phil. (Compositae), was evaluated for antinociceptive activity using writhing, formalin, and hot-plate tests in mice. A dose-related antinociceptive response was obtained in the writhing test at doses of 500 and 1000 mg/kg p.o. (percentage of inhibition 23.3 and 52.70, respectively). The extract also inhibited the second phase of formalin test (38.81%) and this effect was not antagonized by pretreatment with naloxone 5mg/kg i.p. Furthermore, no significant effect was obtained in the hot-plate test. Dichloromethane and ethanolic extracts, were analyzed for antiinflammatory activity with the carrageenan-induced paw edema in rats and the ear edema induced by 12-O-tetradecanoylphorbol-13 acetate (TPA) and arachidonic acid (AA) in mice. Both extracts showed antiinflammatory activity in the TPA (88 and 54%), and the ethanolic extract showed a 37% inhibition in AA test. No effects were seen at doses of 300 mg/kg p.o. and 100 mg/kg i.p. in the carrageenan test. The results obtained indicate that A. copa has analgesic and topical antiinflammatory activities that supports the folk medicinal use of the plant.     

Hypoglycemic effect of Hypoxis hemerocallidea corm (African potato) aqueous extract in rats

Diabetes mellitus has been recognized as a clinical syndrome since ancient times, and remains a crippling global health problem today. It is a group of heterogeneous, autoimmune, hormonal and metabolic disorders, often accompanied by hypertension, hyperlipidemia and obesity. Current estimates suggest that approximately 150 million people worldwide suffer from diabetes mellitus. The present study was undertaken to examine the hypoglycemic effect of aqueous extract of Hypoxis hemerocallidea (family: Hypoxidaceae) corm (locally known as "African Potato") in normal (normoglycemic) and in streptozotocin (STZ)-treated, diabetic rats. Young adult, male Wistar rats weighing 250-300 g were used. Diabetes mellitus was induced in the group of diabetic test rats by intraperitoneal injections of STZ (90 mg/kg). In one set of experiments, graded doses of the aqueous extract of African Potato (100-800 mg/kg p.o.) were administered to 12-h fasted normal and diabetic rats. In another set of experiments, 800 mg/kg of African potato extract, a dose of the plant extract that produced maximal hypoglycemic effects in fasted normal and diabetic rats in our pilot experiments, was used. The hypoglycemic effect of this single dose was compared with those of insulin (5 micro U/kg s.c.) and glibenclamide (5 mg/kg p.o.) in 12-h fasted normal and diabetic rats. Following acute treatment, relatively moderate to high doses of African potato extract (100-800 mg/kg p.o.) produced dose-dependent, significant reductions (p < 0.05-0.001) in the blood glucose concentrations of fasted normal and diabetic rats. Similarly, insulin (5 micro U/kg s. c.) and glibenclamide (5 mg/kg p.o.) produced significant reductions (p < 0.01-0.001) in the blood glucose concentrations of the fasted normal and diabetic rats. At a dose of 800 mg/kg, the plant extract caused 30.20% and 48.54% reductions in the blood glucose concentrations of fasted normal and STZ-treated diabetic rats, respectively. While it is likely that the hypoglycemic effect of the plant extract is largely due to its phytosterols and/or sterolin content, the exact mechanism of its hypoglycemic action is still obscure and will have to await further studies. However, the results of this experimental animal study indicate that African potato possesses hypoglycemic activity; and thus lends credence to the suggested folkloric use of the herb in the control and/or management of adult-onset, type 2 diabetes mellitus in some communities of South Africa.     

GABAergic and cholinergic mediation in the antinociceptive action of homotaurine.

1. The role of GABAergic and cholinergic mechanisms in the antinociceptive effect of homotaurine (22.25-111.24 mg/kg i.p.) in chemical (acetic acid) and thermal (tail flick, tail immersion) tests has been studied by means of the interaction with baclofen and anticholinergic drugs. 2. Baclofen (2 mg/kg p.o.) and scopolamine sulfate (2.5 mg/kg i.p.) potentiate the antinociceptive effect of the amino acid in the chemical test. 3. Bicuculline (1 mg/kg i.p.) pretreatment does not modify the antinociceptive effect of homotaurine in the tail immersion and tail flick tests. 4. Scopolamine sulfate and methylnitrate (1 mg/kg i.p.) antagonise the effect of homotaurine (111.24 mg/kg i.p.) in the tail flick test. 5. The above results imply that peripheral GABAB and central cholinergic mechanisms play a role in the antinociceptive effect of homotaurine.     

Modification of formalin-induced nociception by different histamine receptor agonists and antagonists.

The present study evaluated the effects of different histamine receptor agonists and antagonists on the nociceptive response in the mouse formalin test. Intracerebroventricular (20-40 microg/mouse i.c.v.) or subcutaneous (1-10 mg/kg s.c.) injection of HTMT (H(1) receptor agonist) elicited a dose-related hyperalgesia in the early and late phases. Conversely, intraperitoneal (20 and 30 mg/kg i.p.) injection of dexchlorpheniramine (H(1) receptor antagonist) was antinociceptive in both phases. At a dose ineffective per se, dexchlorpheniramine (10 mg/kg i.p.) antagonized the hyperalgesia induced by HTMT (40 mug/mouse i.c.v. or 10 mg/kg s.c.). Dimaprit (H(2) receptor agonist, 30 mg/kg i.p.) and ranitidine (H(2) receptor antagonist, 20 and 40 mg/kg i.p.) reduced the nociceptive responses in the early and late phases. No significant change in the antinociceptive activity was found following the combination of dimaprit (30 mg/kg i.p.) with ranitidine (10 mg/kg i.p.). The antinociceptive effect of dimaprit (30 mg/kg i.p.) was prevented by naloxone (5 mg/kg i.p.) in the early phase or by imetit (H(3) receptor agonist, 25 mg/kg i.p.) in both early and late phases. The histamine H(3) receptor agonist imetit was hyperalgesic following i.p. administration of 50 mg/kg. Imetit-induced hyperalgesia was completely prevented by treatment with a dose ineffective per se of thioperamide (H(3) receptor antagonist, 5 mg/kg i.p.). The results suggest that histamine H(1) and H(3) receptor activations increase sensitivity to nociceptive stimulus in the formalin test.     

Mechanisms involved in the antinociception caused by ethanolic extract obtained from the leaves of Melissa officinalis (lemon balm) in mice

The present study examined the antinociceptive effect of the ethanolic extract from Melissa officinalis L. and of the rosmarinic acid in chemical behavioral models of nociception and investigates some of the mechanisms underlying this effect. The extract (3-1000 mg/kg), given orally (p.o.) 1 h prior to testing, produced dose-dependent inhibition of acetic acid-induced visceral pain, with ID50 value of 241.9 mg/kg. In the formalin test, the extract (30-1000 mg/kg, p.o.) also caused significant inhibition of both, the early (neurogenic pain) and the late (inflammatory pain), phases of formalin-induced licking. The extract (10-1000 mg/kg, p.o.) also caused significant and dose-dependent inhibition of glutamate-induced pain, with ID50 value of 198.5 mg/kg. Furthermore, the rosmarinic acid (0.3-3 mg/kg), given p.o. 1 h prior, produced dose-related inhibition of glutamate-induced pain, with ID50 value of 2.64 mg/kg. The antinociception caused by the extract (100 mg/kg, p.o.) in the glutamate test was significantly attenuated by intraperitoneal (i.p.) treatment of mice with atropine (1 mg/kg), mecamylamine (2 mg/kg) or l-arginine (40 mg/kg). In contrast, the extract (100 mg/kg, p.o.) antinociception was not affected by i.p. treatment with naloxone (1 mg/kg) or d-arginine (40 mg/kg). It was also not associated with non-specific effects, such as muscle relaxation or sedation. Collectively, the present results suggest that the extract produced dose-related antinociception in several models of chemical pain through mechanisms that involved cholinergic systems (i.e. through muscarinic and nicotinic acetylcholine receptors) and the l-arginine-nitric oxide pathway. In addition, the rosmarinic acid contained in this plant appears to contribute for the antinociceptive property of the extract. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.     

Hypoglycemic effect of methanolic extract of Musa paradisiaca (Musaceae) green fruits in normal and diabetic mice

Diabetes mellitus is a debilitating hormonal disorder in which strict glycemic control and prevention of associated complications are of crucial importance. This study was designed to evaluate the hypoglycemic effect of methanolic extract of mature, green fruits of Musa paradisiaca (MEMP) in normal (normoglycemic) and streptozotocin (STZ)-treated, diabetic (hyperglycemic) mice, using chlorpropamide as the reference antidiabetic agent. MEMP (100-800 mg/kg p.o.) induced significant, dose-related (p < 0.05-0.001) reductions in the blood glucose concentrations of both normal and diabetic mice. Chlorpropamide (250 mg/kg p.o.) also produced significant (p < 0.01-0.001) reductions in the blood glucose concentrations of normal and diabetic mice. The results of this experimental study indicate that, in the mammalian model used, MEMP possesses hypoglycemic activity. Although the precise mechanism of the hypoglycemic action of MEMP is still unclear and will have to await further studies, it could be due, at least in part, to stimulation of insulin production and subsequent glucose utilization. Nevertheless, the findings of this experimental animal study indicate that MEMP possesses hypoglycemic activity, and thus lends credence to the suggested folkloric use of the plant in the management and/or control of adult-onset, type-2 diabetic mellitus among the Yoruba-speaking people of South-Western Nigeria.     

Dopamine D(2) receptor antagonists prevent delta(9)-tetrahydrocannabinol-induced antinociception in rats

Delta(9)-Tetrahydrocannabinol (1 and 5 mg/kg, i.p.) produced, dose-dependently, antinociceptive effects using hot plate and tail flick tests in rats. These effects were suppressed not only by the cannabinoid CB(1) receptor antagonist SR 141716A (0.5 mg/kg; i.p.) but also by the dopamine D(2) receptor antagonists S(-)-sulpiride (5 and 10 mg/kg; i.p.) and S(-)-raclopride (1.5 and 3 mg/kg; i.p.). Conversely, Delta(9)-tetrahydrocannabinol antinociceptive effects were potentiated by the dopamine D(2) receptor agonists (-)-quinpirole (0.025 mg/kg, s.c.) and (+)-bromocriptine (0.5 and 1 mg/kg; i.p.). Our results indicate that the antinociceptive effects of Delta(9)-tetrahydrocannabinol are mediated by the concomitant activation of cannabinoid CB(1) and dopamine D(2) receptors and that dopamine D(2) receptor agonists may be useful in improving the analgesic effects of cannabinoids.     

Effects of various nonopioid receptor antagonists on the antinociceptive activity of Muntingia calabura extracts in mice

This study was carried out in mice to determine the nonopioid receptor signaling pathway(s) that might modulate the antinociceptive activity of the aqueous and chloroform extracts of Muntingia calabura (M. calabura) leaves, using the hot-plate test. The leaves of M. calabura were sequentially soaked [1:2 (w/v); 72 h] in distilled water (dH(2)O) and chloroform. The 50% concentration extracts were selected for this study based on the plant's previously established antinociceptive profiles. The mice (n = 7) were pretreated (s.c.) for 10 min with the selected nonopioid receptor antagonists, followed by the (s.c.) administration of the respective extract. The latency of discomfort was recorded at the interval time of 0.5, 1, 2, 3, 4 and 5 h after the extract administration. The 5 mg/kg atropine, 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol, 1 mg/kg haloperidol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the aqueous extract-induced antinociceptive activity. The 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the chloroform extract-induced antinociceptive activity. In conclusion, the central antinociceptive activity of M. calabura leaves appears to be involved in the modulation of various nonopioid receptor signaling pathways. Its aqueous extract antinociceptive activity is mediated via modulation of the muscarinic, alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic, dopaminergic and GABAergic receptors, while its chloroform extract activity is mediated via modulation of the alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic and GABAergic receptors.     

Mechanisms of L-NG-nitro arginine methyl ester-induced antinociception in mice: a role for serotonergic and adrenergic neurons.

1. The mechanisms involved in the antinociceptive action of L-NG-nitro arginine methyl ester (L-NAME) were investigated in mice. 2. Intraperitoneal administration of L-NAME produced a dose-dependent antinociception in the tail-flick, hot-plate and phenyl-p-quinone-induced writhing tests. 3. Pretreatment with the catecholamine depletors 6-hydroxydopamine (5 micrograms i.c.v.) or reserpine (5 mg/kg i.p.) or the serotonin synthesis inhibitor, p-chlorophenylalanine methyl ester (200 mg/kg i.p. on 2 consecutive days) resulted in a significant decrease in the antinociceptive effect of L-NAME. 4. Similarly, pretreatment with the selective alpha 1-adrenoceptor antagonist prazonin (2.5 mg/kg, i.p.), or the non-selective alpha-adrenoceptor blocker, phentolamine (5 mg/kg, i.p.) antagonized the antinociceptive effect of L-NAME. 5. However, the administration of the selective alpha 2-adrenoceptor antagonist, idazoxan (2.5 mg/kg i.p.) was without effect. 6. Likewise, pretreatment with the serotonin 5-HT2 receptor blocker, ketanserin (1 mg/kg, i.p.), the D2 dopamine receptor antagonist (+/-) sulpiride (30 mg/kg, i.p.) or the opioid antagonist naloxone (5 mg/kg, i.p.) did not inhibit the antinociceptive effect of L-NAME. 7. These results suggest that L-NAME produces antinociception in the mouse probably by an action on adrenergic and serotonergic synapses.     

Stachyose extract from Rehmannia glutinosa Libosch. to lower plasma glucose in normal and diabetic rats by oral administration

The hypoglycemic effects of water extract and stachyose extract (Part III) from Rehmannia glutinosa Libosch. were investigated in this paper by oral administration to normal, glucose- and adrenaline-induced hyperglycemic and alloxan-induced diabetic rats. The results showed that Part III had the effect of lowering fasted plasma glucose level and partially preventing hyperglycemia induced by glucose (2.5 g x kg(-1), i.p.) and adrenaline (300 microg x kg(-1), i.p.), respectively, but no obvious dose-dependent effect was found when it was administered at the doses of 100, 200 and 400 mg x kg(-1) for 6 days, i.g. In alloxan-induced diabetic rats, Part III (200 mg x kg(-1) for 15 days, i.g.) gave a significant decrease in blood glucose level. The results suggested that Part III, which is mainly composed of stachyose from Rehmannia glutinosa Libosch., had a significant hypoglycemic effect in glucose- and adrenaline-induced hyperglycemic and alloxan-induced diabetic rats.     

The involvement of endogenous opioid mechanisms in the antinociceptive effects induced by antidepressant drugs, desipramine and trimipramine

The present study was designed to investigate the involvement of endogenous opioid systems in the antinociception induced by the antidepressant drugs, desipramine and trimipramine. For this purpose, the antinociceptive effects of desipramine (7.5 and 15.0 mg/kg i.p.) and trimipramine (5.0 and 10.0 mg/kg i.p.) were compared to that induced by morphine (0.2 and 2.0 mg/kg i.p.) in the tail-clip model in mice. Naloxone (0.3 and 3.0 mg/kg i.p.), a non-specific opioid receptor antagonist, inhibited morphine-induced antinociception in mice, whereas the antinociceptive effects of antidepressant drugs were found to be resistant to naloxone blockade to some extent, since only the higher concentration of naloxone (3.0 mg/kg i.p.) caused significant inhibition of the effects of antidepressant drugs. In contrast, naltrindole (1.0 mg/kg i.p.), a specific delta-receptor antagonist, inhibited antinociception induced by desipramine and trimipramine in this test, while it inhibited the antinociceptive effect of morphine only partly. None of the opioid antagonists produced a significant effect in the tail-clip experiment when they were injected alone. Based on these findings, we concluded that endogenous opioids are involved in the antinociceptive effects of the antidepressant drugs using different mechanisms.     

Modification of antinociceptive action of Ukrain by endogenous nitric oxide in the writhing syndrome test in mice

The effects of L-arginine, the physiological precursor of nitric oxide (NO), and inhibitors of NO-synthase on the antinociceptive action of Ukrain (4.75, 9.5, and 19.0 mg/kg i.p.) were investigated using the writhing syndrome test in mice. It was found that L-arginine (0.1 or 1.0 mg/kg i.p.) significantly decreased or enhanced the antinociceptive effect of Ukrain, depending on the combination administered. In addition, the inhibitors of NO-synthase NG-nitro-L-arginine methyl ester (L-NAME) (1.0 and 10 mg/kg i.p.), 7-nitroindazole (1.0 mg/kg i.p.) and NG-monomethyl-L-arginine acetate (L-NMMA) (1.0 mg/kg i.p.) significantly enhanced Ukrain-induced antinociception. These results suggest that endogenous NO can modify the antinociceptive effect of Ukrain.     

Methanol extract from mycelium of endophytic fungus Rhizoctonia sp. induces antinociceptive and anti-inflammatory activities in mice

The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100?mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8?h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10?mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition in a carrageenan-induced edema model at a dose of 10?mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.