Ameliorative effects of probiotic Limosilactobacillus fermentum and Enterococcus lactis isolated from cameroonian traditionally processed milk and palm wine against chronic constriction injury induced neuropathic pain in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Fermented milk and palm wine are regularly used by several ethnic groups in Cameroon in traditional treatment rituals for infections, inflammatory, cardiovascular disorders, and even metabolic diseases such as diabetes, hypercholesterolemia etc. Reports from many studies have demonstrated that fermented milk and palm wine are potential sources of probiotic bacteria. However, the capacity of probiotics isolated from these natural sources to alleviate neuropathic pain has not been experimentally tested. AIM OF THE STUDY: This study aimed at investigating the ameliorative potential of lactic acid bacteria isolated from palm wine and traditional fermented cow milk on the chronic constriction injury (CCI) induced neuropathic pain in mice. MATERIALS AND METHODS: Pour plating technique on De Man Rogasa (MRS) agar was utilised for isolation of lactic acid bacteria from fermented cow milk and palm wine, and identified using the 16S r RNA gene sequencing. Neuropathic pain was induced by chronic constriction injury of the sciatic nerve. These bacteria were orally administered at different concentrations to Balb/c mice by gavage for 14 consecutive days. Cold allodynia, mechanical hyperalgesia and exploratory behaviour were evaluated on day 0, 7th and 14th respectively. The total level of calcium, oxidative stress markers and myeloperoxidase were also quantified in the sciatic nerve homogenate. Cyclooxygenase-2(COX-2) and cytokine profile were determined from serum. RESULTS: Lactic acid bacteria were isolated from fermented cow milk and palm wine and two isolates were chosen according to their probiotic potentials and identified as strain of Limolactobacillus fermentum and Enterococcus lactis. Their 16 S rRNA gene sequences were deposited in NCBI genbank with accession number of OP896078 and OR619545, respectively. Pretreatment with Limosilactobacillus fermentum and Enterococcus lactis significantly alleviated mechanical hyperalgesia and cold allodynia with similar effect to the reference drug, morphine. These two isolates ameliorated CCI induced neuropathic pain by increasing antioxida776nts (GSH, CAT and SOD, P < 0.01) and decreasing pro-oxidants (MDA and NO, P < 0.01). Also, they inhibited the release of proinflammatory cytokines (IL-1ß, TNF-α, IFN-γ, and IL-6; P < 0.01) and IL-10 level was significantly (P < 0.01) increased when compared to the negative control. Treatment with these bacteria significantly dropped the level of total calcium (P < 0.01), COX-2 (P < 0.01) and MPO (P < 0.01) when compared with the negative control. CONCLUSION: The neuroprotective potentials of these selected lactic acid bacteria against CCI induced neuropathic pain may be attributed to their anti-oxidant, anti-inflammatory properties and reduced calcium deposition in sciatic nerve.

Dichrocephala integrifolia Aqueous Extract Antagonises Chronic and Binges Ethanol Feeding-Induced Memory Dysfunctions: Insights into Antioxidant and Anti-Inflammatory Mechanisms.

Ethanol consumption is widely accepted despite its addictive properties and its mind-altering effects. This study aimed to assess the effects of Dichrocephala integrifolia against, memory impairment, on a mouse model of chronic and binges ethanol feeding. Mice were divided, into groups of 8 animals each, and received distilled water, Dichrocephala integrifolia aqueous extract (25; 50; 100; or 200 mg/kg) or memantine (200 mg/kg) once a day, while fe, with Lieber-DeCarli control (sham group only) or Lieber-DeCarli ethanol diet ad libitum for 28 days. The Y maze and the novel object recognition (NOR) tests were used to evaluate spatial short-term and recognition memory, respectively. Malondialdehyde, nitric oxide, glutathione levels, and proinflammatory cytokines (Il-1ß, TNF-α, and Il-6) were evaluated in brain homogenates following behavioral assessments. The results showed that chronic ethanol administration in mice was associated with a significant (p < 0.001) reduction in the spontaneous alternation percentage and the discrimination index, in the Y maze and the NOR tests, respectively. It significantly (p < 0.01) increased oxidative stress and inflammation markers levels in the brain. Dichrocephala integrifolia (100 and 200 mg/kg) as well as memantine (200 mg/kg) significantly (p < 0.001) increased the percentage of spontaneous alternation and the discrimination index, in the Y maze and NOR tests, respectively. Dichrocephala integrifolia (100 and 200 mg/kg) likewise memantine (200 mg/kg) significantly (p < 0.01) alleviated ethanol-induced increase, in the brain malondialdehyde level, nitric oxide, Il-1ß, TNF-α, and Il-6. From these findings, it can be concluded that Dichrocephala integrifolia counteracted memory impairment, oxidative stress, and neuroinflammation induced by chronic ethanol consumption in mice.

Anticonvulsant effects of Senna spectabilis on seizures induced by chemicals and maximal electroshock.

Senna spectabilis (Fabaceae) is one of the medicinal plants used in Cameroon by traditional healers to treat epilepsy, constipation, insomnia, anxiety. The present study aimed to investigate the anticonvulsant effects of Senna spectabilis decoction on seizures induced by maximal electroshock (MES), pentylenetetrazole (PTZ), pilocarpine (PC) and its possible action mechanisms in animal models using flumazenil (FLU), methyl-ß-carboline-3-carboxylate (BC) and bicuculline (BIC). Senna spectabilis decoction (106.5 and 213.0mg/kg) antagonized completely tonic-clonic hind limbs of mice induced by MES. The lowest plant dose (42.6mg/kg) provided 100% of protection against seizures induced by PTZ (70mg/kg). Administration of different doses of the plant decoction antagonized seizures induced by PC up to 75%, causing a dose dependent protection and reduced significantly the mortality rate induced by this convulsant. Both FLU and BC antagonize strongly the anticonvulsant effects of this plant and are unable to reverse totally diazepam or the plant decoction effects on inhibiting seizures. The animals did not present any sign of acute toxicity even at higher doses of the plant decoction. In conclusion, Senna spectabilis possesses an anticonvulsant activity. We showed that its decoction protects significantly mice against seizures induced by chemicals and MES, delays the onset time and reduces mortality rate in seizures-induced. It also appears that the oral administration of the decoction of S. spectabilis is more active than the intraperitoneal administration of the ethanolic extract on inhibiting seizures induced by MES and PTZ. Moreover, the plant decoction could interact with GABAA complex receptor probably on the GABA and benzodiazepines sites.

Biomimetic synthesis of Tramadol.

Tramadol has recently been isolated from the roots and bark of Nauclea latifolia. A plausible biosynthetic pathway has been proposed and the product-precursor relationship has been probed by (13)C position-specific isotope analysis. By further exploring this pathway, we demonstrate that a key step of the proposed pathway can be achieved using mild conditions that mimic in vivo catalysis.

Antipsychotic and sedative effects of the leaf extract of Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) has been used as a medicine for the treatment of epilepsy, insomnia, dementia and psychotic disorders in Cameroonian traditional medicine. AIM OF THE STUDY: This study was designed to examine whether the aqueous extract and the alkaloid fraction prepared from the leaves of Crassocephalum bauchiense possess antipsychotic and sedative properties in rodents. MATERIALS AND METHODS: The rectal temperature of mice was recorded with a probe thermometer at a constant depth. Novelty-induced rearing behavior is used to evaluate a central excitatory locomotor behavior in mice. The antipsychotic effects of the extracts were assessed using the apomorphine animal model of psychosis. The catalepsy test was tested based on the ability of the leaves extracts of Crassocephalum bauchiense to alter the duration of akinesia by placing the naive mice with both forelegs over a horizontal bar. The extracts of Crassocephalum bauchiense effects were evaluated on sodium pentobarbital-induced sleeping time. In addition, gamma-aminobutyric acid concentrations in the brain treated mice were also estimated. RESULTS: The aqueous extract and the alkaloid fraction from Crassocephalum bauchiense caused dose-dependent inhibition of novelty-induced rearing behavior, decreased the apomorphine-induced stereotypy and fighting, and had significant fall of the body temperature. The aqueous extract prolonged the sodium pentobarbital sleeping time. This prolongation was not reversed by bicuculline, a light-sensitive competitive antagonist of GABA(A) receptors complex. However, the effect of the aqueous extract on sodium pentobarbital-induced sleeping time was blocked by N-methyl-ß-carboline-3-carboxamide, a partial inverse agonist of the benzodiazepine site in the GABA(A) receptor complex and flumazenil, a specific antagonist of the benzodiazepine site in the GABAA receptor complex. In biochemical experiments, the concentration of the inhibitory amino acid, gamma-aminobutyric acid, was significantly increased in the brain of animals treated with the aqueous extract of Crassocephalum bauchiense and sodium valproate. CONCLUSIONS: The results show that the antipsychotic and sedative properties of Crassocephalum bauchiense are possibly mediated via the blockade of dopamine D-2 receptors and GABAergic activation, respectively. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for these neuropharmacological actions and also to identify the active substances present in the extracts of Crassocephalum bauchiense.