Modulating Effects of the Hydroethanolic Leaf Extract of Persicaria lanigera R. Br. Soják (Polygonaceae) against Acute Inflammation.

Plant species have been used traditionally to treat numerous inflammatory disorders because of their known medicinal properties. This study aimed to assess the anti-inflammatory effect of aqueous ethanolic leaf extract of Persicaria lanigera using acute inflammatory models. The safety profile of the Persicaria lanigera extract was assessed using an acute toxicity model. The anti-inflammatory effect of the Persicaria lanigera leaf extract (100-600 mg·kg-1, p.o.) was studied in carrageenan-induced paw oedema, zymosan-induced knee joint arthritis, and histamine-induced paw oedema in Sprague-Dawley rats (n = 5). It was observed that the Persicaria lanigera leaf extract administered prophylactically significantly inhibited paw oedema from 99.01 ± 12.59 to 59.10 ± 4.94%, 56.08 ± 3.65%, and 48.62 ± 3.27% at 100 mg·kg-1, 300 mg·kg-1, and 600 mg·kg-1, while the standard drug, aspirin, showed 41.84 ± 9.25% in carrageenan-induced paw oedema, respectively. Furthermore, the extract decreased knee joint inflammation significantly from 62.43 ± 5.73% to 32.07 ± 2.98% and 24.33 ± 8.58% at 300 mg·kg-1 and 600 mg·kg-1 in zymosan-induced knee joint inflammation, respectively. In the histamine-induced paw oedema model, the extract significantly inhibited oedema to 61.53 ± 9.17%, 54.21 ± 9.38%, and 54.22 ± 9.37% at the same doses. Aqueous ethanolic leaf extract of Persicaria lanigera is safe and attenuates inflammation in acute inflammation models.

Gestational iron supplementation reverses depressive-like behavior in post-partum Sprague Dawley rats: Evidence from behavioral and neurohistological studies.

Background: Postpartum depression is a mood disorder that affects about 9-20% of women after child birth. Reports suggest that gestational iron deficiency can cause a deficit in behavioral, cognitive and affective functions and can precipitate depressive symptoms in mothers during the postpartum period. The present study examined the effect of iron supplementation on depressive behavior during postpartum period in a rat model. Method: Female Sprague-Dawley rats were crossed. Pregnant rats received iron, fluoxetine, desferrioxamine or vehicle throughout the period of gestation. During the postpartum period, mothers from all groups were taken through the open field test (OFT), forced swim test (FST), novelty-induced hypophagia (NIH) and sacrificed for histological examination of the brains. Results: Results showed that rats treated with iron-chelating agent, desferrioxamine, and vehicle during gestation exhibited increased immobility scores in the FST, increased latency to feed and reduced feeding in the NIH with corresponding decreased number of neurons and dendritic branches in the cortex of the brain. These depression-related effects were attenuated by perinatal iron supplementation which showed decreased immobility scores in the FST comparable to rats treated with fluoxetine, a clinically effective antidepressant. Iron treatment also decreased latency to feeding while increasing feeding behavior in the NIH. Iron-treated dams had a higher number of neurons with dendritic connections in the frontal cortex compared to vehicle- and desferrioxamine-treated groups. Conclusion: The results suggest that, iron supplementation during gestation exerts an antidepressant-like effect in postpartum Sprague-Dawley rats, attenuates neuronal loss associated with depression and increases dendritic spine density.

The Anticonvulsant Effect of Hydroethanolic Leaf Extract of Calotropis procera (Ait) R. Br. (Apocynaceae).

A number of currently used drugs have been obtained from medicinal plants which are a major source of drugs. These drugs are either used in their pure form or modified to a semisynthetic drug. Drug discovery through natural product research has been fruitful over the years. Traditionally, Calotropis procera is used extensively in the management of epilepsy. This study is conducted to explore the anticonvulsant effect of a hydroethanolic leaf extract of Calotropis procera (CPE) in murine models. This effect was evaluated using picrotoxin-induced convulsions, strychnine-induced convulsions, and isoniazid- and pilocarpine-induced status epilepticus in mice of both sexes. The results showed that CPE (100-300 mg/kg) exhibited an anticonvulsant effect against strychnine-induced clonic seizures by significantly reducing the duration (p = 0.0068) and frequency (p = 0.0016) of convulsions. The extract (100-300 mg/kg) caused a profound dose-dependent delay in the onset of clonic convulsions induced by picrotoxin (p < 0.0001) and tonic convulsions (p < 0.0001) in mice. The duration of convulsions was reduced significantly also for both clonic and tonic (p < 0.0001) seizures as well. CPE (100-300 mg/kg), showed a profound anticonvulsant effect and reduced mortality in the pilocarpine-induced convulsions. ED50 (~0.1007) determined demonstrated that the extract was less potent than diazepam in reducing the duration and onset of convulsions but had comparable efficacies. Flumazenil-a GABAA receptor antagonist-did not reverse the onset or duration of convulsions produced by the extract in the picrotoxin-induced seizure model. In isoniazid-induced seizure, CPE (300 mg kg1, p.o.) significantly (p < 0.001) delayed the onset of seizure in mice and prolonged latency to death in animals. Overall, the hydroethanolic leaf extract of Calotropis procera possesses anticonvulsant properties.

Anti-inflammatory, anti-nociceptive and antipyretic activity of young and old leaves of Vernonia amygdalina.

BACKGROUND: Both young and old leaves of Vernonia amygdalina (VA) are traditionally used to treat inflammation, pain and fever. However, the efficacy of young and old leaves for treating these ailments have not been compared till date. AIM: To ascertain the effect of young and old leaves of VA in managing inflammation, pain and fever. METHODS: Both quantitative and qualitative phytochemical screening of ethanol extracts of young (EthYL) and old (EthOL) leaves of VA were performed. The anti-inflammatory activity of orally administered EthYL and EthOL (50-200 mg/kg) and Diclofenac (10 mg/kg) were evaluated in carrageenan-induced inflammation model in rats. Antipyretic activity of EthYL, EthOL and Aspirin (25 mg/kg) were assessed in the Baker's yeast-induced pyrexia model. Anti-allodynic effect of both extracts were evaluated by inserting inflamed paws of rats in cold water. Antinociceptive property of the extracts were assessed using tail withdrawal and formalin-induced nociception test. Histopathological examination of the paws was performed, in addition to formalin test to understand the possible mechanism of action of the extracts. Negative control rats received 2 ml/kg normal saline in all tests. RESULTS: The amount of flavonoids, alkaloids, tannins, and phenolics were significantly (p < 0.05) higher in EthOL than EthYL, while saponins were significantly higher (p < 0.05) in EthYL than EthOL. The antioxidant ability and total antioxidant capacity were significantly (p < 0.05) higher in EthYL than EthOL. However, this was significantly (p < 0.05) lower than the anti-oxidant activity of Ascorbic acid. A dose-dependent increase in anti-inflammatory, antipyretic and antinociceptive properties were observed in both EthYL and EthOL, similar to the standard drugs. Mast cell degranulation accompanied by vasodilatation and high leukocytosis were observed in the negative control, but were markedly low in extract treated groups. Both extracts mediated their analgesic effect through opioidergic and nitric oxide pathways with EthYL additionally implicating the muscarinic cholinergic system. CONCLUSION: Although both EthYL and EthOL alleviate inflammation, pyrexia and nociception, EthYL of VA was found to be more potent than EthOL.

An isobolographic analysis of the anti-nociceptive effect of geraniin in combination with morphine or diclofenac.

BACKGROUND: Geraniin, a dehydroellagitannin, is a major component of the aqueous extract of the aerial parts of Phyllanthus muellerianus (Kuntze) Exell. (Euphorbiaceae). Several Phyllanthus species are traditionally used for painful disorders. The anti-nociceptive effects of the aqueous extract of the aerial parts of P. muellerianus and of geraniin have been scientifically established. The aim of the paper is to determine whether a combination of geraniin and diclofenac or geraniin and morphine leads to better anti-nociceptive effects. METHODS: The nature of the interactions of morphine and diclofenac with geraniin was evaluated by undertaking the isobolographic analysis. Mice were treated with geraniin (3-30 mg/kg), morphine (1-10 mg/kg), and diclofenac (10-100 mg/kg) to obtain the ED50 values of the agents in the formalin test. Dose-response curves were then obtained and analyzed after the co-administration of geraniin with morphine or diclofenac in fixed ratio (1:1) combinations based on specific fractions (1/2, 1/4, and 1/8) of their respective ED50 values for the formalin test. RESULTS: Geraniin was less potent than morphine but more potent than diclofenac in the formalin-induced nociception. The isobolographic analysis of geraniin/morphine (G/M) and geraniin/diclofenac combinations (G/D) at different fractions revealed the potentiation of their anti-nociceptive effects. The degrees of potentiation, which were calculated as interaction indices, showed synergism for both combinations in both phase I (G/M: 0.040, G/D: 0.017) and phase II (G/M: 0.004, G/D: 0.002) of the formalin test. CONCLUSIONS: The present study demonstrates synergism for the co-administration of geraniin with both morphine and diclofenac.

Possible mechanisms involved in the anti-nociceptive effects of hydro-ethanolic leaf extract of Ziziphus abyssinica.

CONTEXT: Various parts of Ziziphus abyssinica Hochst ex. A. Rich (Rhamnaceae) have been used in Ghanaian and African traditional medicine as an analgesic. However, there are little scientific data to support the anti-nociceptive effects of the hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) as well as the possible mechanisms involved in its anti-nociceptive effects. PURPOSE: To predict possible nociceptive pathways involved in the anti-nociceptive effects of EthE. MATERIALS AND METHODS: The effect of EthE (30, 100 and 300 mg/kg) on intraplantar injection of pain mediators such as interleukin-1ß, tumour necrosis factor-α, prostaglandin E2 and bradykinin was evaluated in male Sprague Dawley rats using Randall-Selitto test for 5 h. The effect of specific antagonists to the opioidergic, adenosinergic, ATP-sensitive K+ channels, nitric oxide, serotonergic, muscarinic, adrenergic and voltage-gated calcium channel on the anti-nociceptive effect of EthE (100 mg/kg) was evaluated using the formalin test in male imprinting control region (ICR) mice for 1 h. RESULTS: Pretreatment of the rats with EthE significantly reversed the hypernociception induced by intraplantar injection of TNF-α (F4,120 = 10.86, p < 0.0001), IL-1ß (F4,120 = 14.71, p < 0.0001), bradykinin (F4,80 = 12.52, p < 0.0001) and prostaglandin E2 (F5,144 = 6.165, p = 0.0001). The anti-nociceptive effect exhibited by EthE in the formalin test was reversed by systemic administration of NG-l-nitro-arginine methyl ester, naloxone, theophylline and glibenclamide. CONCLUSIONS: EthE inhibits hypernociception induced by TNF-α, IL-1ß, bradykinin and prostaglandin E2. EthE exhibited anti-nociceptive effects possibly mediated through opioidergic, adenosinergic, ATP-sensitive potassium channels and nitric oxide cyclic GMP pathways.

Hydro-ethanolic leaf extract of Ziziphus abyssinica Hochst Ex A. Rich (Rhamnaceae) exhibits anti-nociceptive effects in murine models.

BACKGROUND: Despite substantial advances in pain research and treatment, millions of people continue to suffer from pain and this has been attributed mainly to the unavailability of effective and safer analgesics. The use of plants as medicines is still widespread and plants constitute a large source of novel phytocompounds that might become leads for the discovery of newer, effective and safer alternatives. Various parts of Ziziphus abyssinica have been used in folk medicine in several African countries as painkillers. However, there is no report on the possible anti-nociceptive effects of this plant especially the leaves, hence the need for this current study. METHODS: The possible anti-nociceptive activity of hydro-ethanolic leaf extract of Ziziphus abyssinica (EthE) was assessed in rodents using chemical (acetic acid, formalin and glutamate), thermal (tail-immersion test) and mechanical/inflammatory (carrageenan) models of nociception. RESULTS: EthE (30-300 mg/kg, p.o.) dose-dependently and significantly inhibited chemical-induced nociception with a maximum inhibition of 86.29 ± 2.27%, 76.34 ± 5.67%, 84.97 ± 5.35%, and 82.81 ± 5.97% respectively for acetic acid, formalin (phase 1), formalin (phase 2) and glutamate tests at its highest dose. EthE also dose-dependently and significantly increased reaction times in both tail-immersion and carrageenan-induced hypernociceptive tests. The activities of the extract in the various models were comparable with the effect of morphine hydrochloride and diclofenac sodium used as standard analgesic drugs. CONCLUSION: Oral administration of hydro-ethanolic leaf extract of Ziziphus abyssinica ameliorates nocifensive behaviours associated with chemical-, thermal- and mechanical/inflammatory - induced nociceptive pain.

In vivo efficacy of top five surveyed Ghanaian herbal anti-malarial products.

BACKGROUND: Anti-malarial herbal preparations (HPs) continue to enjoy high patronage in Ghana despite reports that the artemisinin-based combination therapy (ACT), the recommended first choice for treatment of uncomplicated malaria in the country, remains efficacious. A major issue with the use of these preparations is inadequate or unreliable data on their efficacy and quality. An assessment of the potency and quality of the most popular commercial anti-malarial HPs in Ghana was, therefore, carried out. The outcome of this investigation is herein discussed preceded by a short literature review of herbal medicines in Ghana. METHODS: Using a questionnaire survey of 344 individuals in parts of Ghana, five of the most frequently used HPs were identified and selected for test of their efficacy and quality. The effect of the selected compounds on Plasmodium berghei in vivo was assessed using standard methods. RESULTS: All five tested HPs (HP-A, HP-B, HP-C, HP-D and HP-E) showed chemo-suppressive activity against P. berghei in vivo. However the degree of parasites inhibition is significantly lower compared to the WHO-recommended artemether-lumefantrine combination (p < 0.05, 99.9% chemosuppression/activity, 28 days survival). Using the Solomon Saker's Test, two of the preparations were found to contain chloroquine or compounds with chemical properties like that of chloroquine. CONCLUSION: Popular anti-malarial HPs used in southern Ghana were found to have chemo-suppressive properties. Intentional addition of chloroquine or SCs to these preparations in order to enhance their effectiveness has serious public health concerns as it may induce cross resistance to amodiaquine, one of the partner drugs in the recommended ACT for use in Ghana.

Effects of an ethanol extract and the diterpene, xylopic acid, of Xylopia aethiopica fruits in murine models of musculoskeletal pain.

CONTEXT: Fruits of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) are used traditionally to manage arthritis, headache and other pain disorders. OBJECTIVE: The analgesic properties of the X. aethiopica ethanol fruit extract (XAE) and xylopic acid (XA) were evaluated in musculoskeletal pain models. MATERIALS AND METHODS: Acute muscle pain was induced in gastrocnemius muscle of Sprague-Dawley rats with 3% carrageenan (i.m.). Rats received XAE (30-300 mg/kg), XA (10-100 mg/kg) or morphine (1-10 mg/kg) after 12 h. Effects of XAE and XA on muscle pain were assessed by measuring post-treatment grip strength of the rats. Chronic muscle pain was similarly induced, but drug treatment was on the eighth day and effects of XAE and XA assessed with Randall-Selitto test for hyperlagesia. Acute-skeletal pain was induced in knee joints of rats with 3% carrageenan-kaolin mixture and effects determined 12-h later. Similar induction protocol was used for chronic knee pain with treatment and measurement as done for chronic muscle pain. RESULTS: XAE and XA significantly and dose-dependently ameliorated both acute muscle (ED50 mg/kg: XAE = 22.9; XA = 6.2) and skeletal hyperalgesia (XAE = 39.9; XA = 17.7) induced by 3% carrageenan. Similarly, chronic skeletal hyperalgesia was reduced by XAE and XA treatment similar to morphine (ED50: XAE = 13.0; XA = 4.6). This reduction was also seen in chronic muscle hyperalgesia (ED50: XAE = 79.1; XA = 42.7). XAE and XA significantly reduced the spread of hyperalgesia to contralateral limbs in both models of chronic hyperalgesia. CONCLUSION: These findings establish analgesic properties of the ethanol fruit extract of X. aethiopica and xylopic acid in musculoskeletal pain.

Antidiabetic Effect of Young and Old Ethanolic Leaf Extracts of Vernonia amygdalina: A Comparative Study.

The young leaves of Vernonia amygdalina are often utilized as vegetable and for medicinal purpose compared to the old leaves. This study was designed to evaluate and compare the antidiabetic effects between ethanolic leaf extracts of old and young V. amygdalina on streptozotocin (STZ) induced diabetic rat for four weeks. Preliminary screening of both young and old ethanolic extracts revealed the presence of the same phytochemicals except flavonoids which was only present in the old V. amygdalina. Difference in antioxidant power between the young and old leaf extracts was statistically significant (p < 0.05). Both leaf extracts produced a significant (p < 0.05) antihyperglycaemic effect. Also results from treated rats revealed increasing effect in some haematological parameters. Similarly, the higher dose (300 mg/kg) of both extracts significantly (p < 0.05) reduced serum ALT, AST, and ALP levels as compared to the diabetic control rats. Results also showed significant (p < 0.05) decrease in LDL-C and VLDL-C in the extract-treated rats with a corresponding increase in HDL-C, as compared to the diabetic control rats. Moreover histopathological analysis revealed ameliorative effect of pathological insults induced by the STZ in the pancreas, liver, and spleen, most significantly the regeneration of the beta cells of the islets of Langerhans in treated rats.

Analgesic properties of aqueous leaf extract of Haematostaphis barteri: involvement of ATP-sensitive potassium channels, adrenergic, opioidergic, muscarinic, adenosinergic and serotoninergic pathways.

BACKGROUND: Pain is the most common cause of patients seeking medical advice as a result of its association with different pathologies. This study evaluated the antinociceptive property of Haematostaphis barteri as well as the possible mechanism(s) associated with its antinociceptive property. METHODS: Mice were administered H. barteri (30-300 mg kg-1; p.o.), followed by intraplantar injection of 10 µL of 5% formalin into the hind paws. The pain score was determined for 1 h in the formalin test. The possible nociceptive pathways involved in the antinociceptive action of H. barteri were determined by pre-treating mice with theophylline (5 mg kg-1, a non-selective adenosine receptor antagonist), naloxone (2 mg kg-1, a non-selective opioid receptor antagonist), glibenclamide (8 mg kg-1; an ATP-sensitive K+ channel inhibitor), and atropine (3 mg kg-1; non-selective muscarinic antagonist). RESULTS: H. barteri (30-300 mg kg-1) significantly and dose dependently precluded both first and second phases of nociception. Pre-treatment with naloxone had no effect on the analgesic activities of H. barteri in the first phase. Again, pre-treatment with atropine and glibenclamide did not significantly reverse the neurogenic antinociception of the extract in phase 1. However, theophylline reversed the analgesic effect of the extract in the first phase. In phase 2, theophylline had no effect on the analgesic activities of the extract. Naloxone, atropine, and glibenclamide significantly blocked the antinociception of H. barteri in the inflammatory phase of the formalin test. CONCLUSIONS: H. barteri possesses antinociceptive property mediated via the opioidergic, adrenergic, muscarinic, ATP-sensitive K+ channels, and adenosinergic nociceptive pathways.

Anxiolytic-like effect of the leaves of Pseudospondias microcarpa (A. Rich.) Engl. in mice.

BACKGROUND: Pseudospondias microcarpa is a plant used for managing various diseases including CNS disorders. Previous studies showed sedative and anticonvulsant effects, suggesting possible anxiolytic activity. This study therefore assessed the anxiolytic effects of P. microcarpa hydroethanolic leaf extract (PME) in mice. METHODS: In the present study, anxiolytic-like effect of the extract in behavioural paradigms of anxiety - the elevated plus maze (EPM), light/dark box (LDB), social interaction test and stress-induced hyperthermia (SIH) - was evaluated. RESULTS: Mice treated with PME (30-300 mg kg-1, p.o.) exhibited anxiolytic-like activity similar to diazepam in all the anxiety models used. The extract increased open arm activity (p<0.05) in the EPM as well as increasing the time spent in the lit area in relation to the time spent in the dark area of the LDB. Sociability and preference for social novelty significantly (p<0.05-0.001) increased in mice treated with PME. In the SIH paradigm in mice, both PME and the benzodiazepine receptor agonist, diazepam, significantly (p<0.05) reduced the stress-induced increase in rectal temperature. The extract did not impair motor coordination and balance in the beam walk test. CONCLUSIONS: Results of the present study indicate that PME possesses anxiolytic-like effects in mice.

Antidepressant-Like Effect of the Leaves of Pseudospondias microcarpa in Mice: Evidence for the Involvement of the Serotoninergic System, NMDA Receptor Complex, and Nitric Oxide Pathway.

Depression continues to be a major global health problem. Although antidepressants are used for its treatment, efficacy is often inconsistent. Thus, the search for alternative therapeutic medicines for its treatment is still important. In this study, the antidepressant-like effect of Pseudospondias microcarpa extract (30-300 mg kg(-1), p.o.) was investigated in two predictive models of depression--forced swimming test and tail suspension test in mice. Additionally, the mechanism(s) of action involved were assessed. Acute treatment with the extract dose dependently reduced immobility of mice in both models. The antidepressant-like effect of the extract (100 mg kg(-1), p.o.) was blocked by p-chlorophenylalanine and cyproheptadine but not prazosin, propranolol, or yohimbine. Concomitant administration of D-cycloserine and the extract potentiated the anti-immobility effect. In contrast, D-serine, a full agonist of glycine/NMDA receptors, abolished the effects. Anti-immobility effects of PME were prevented by pretreatment of mice with L-arginine (750 mg kg(-1), i.p.) and sildenafil (5 mg kg(-1), i.p.). On the contrary, pretreatment of mice with L-NAME (30 mg kg(-1), i.p.) or methylene blue (10 mg kg(-1), i.p.) potentiated its effects. The extract produces an antidepressant-like effect in the FST and TST that is dependent on the serotoninergic system, NMDA receptor complex, and the nitric oxide pathway.

A hydro-ethanolic extract of Synedrella nodiflora (L.) Gaertn ameliorates hyperalgesia and allodynia in vincristine-induced neuropathic pain in rats.

BACKGROUND: The hydro-ethanolic extract of Synedrella nodiflora (L.) Gaertn whole plant has demonstrated analgesic effects in acute pain models. The extract has also demonstrated anticonvulsant effects in murine models of experimental epilepsy. The present study illustrates an evaluation of the hydro-ethanolic extract of the plant for possible analgesic properties in hyperalgesia and allodynia associated with vincristine-induced neuropathy in rats. METHODS: Neuropathic pain was induced in Sprague-Dawley rats by injecting 100 µg/kg of vincristine sulphate on alternative days for 6 days (days 0, 2, 4, 8, 10 and 12). Vincristine-induced cold allodynia, mechanical hyperalgesia and thermal hyperalgesia were measured pre-vincristine administration and on days 15, 17 and 19 post-vincristine administration. The rats were then treated with S. nodiflora extract (SNE) (100, 300 and 1000 mg/kg), pregabalin (10, 30 and 100 mg/kg) and distilled water as vehicle daily for 5 days and pain thresholds were measured on alternate days for 3 days. RESULTS: SNE and pregabalin produced analgesic properties observed as increased paw withdrawal latencies to mechanical, tactile, cold water stimuli and thermal hyperalgesic tests during the 5 days of treatment. CONCLUSIONS: The findings suggest that hydro-ethanolic extract of S. nodiflora possesses anti-hyperalgesic and anti-allodynic effects in vincristine-induced neuropathic pain in rats.