Germain Sotoing Taïwe

Antipyretic and antinociceptive effects of Nauclea latifolia root decoction and possible mechanisms of action.

Context: Nauclea latifolia Smith (Rubiaceae) is a small tree found in tropical areas in Africa. It is used in traditional medicine to treat malaria, epilepsy, anxiety, pain, fever, etc. Objective: The aim of this study was to investigate the effects of Nauclea latifolia roots decoction on the peripheral and central nervous systems and its possible mechanisms of action. Materials and methods: The analgesic investigation was carried out against acetic acid-induced writhing, formalin-induced pain, hot-plate and tail immersion tests. The antipyretic activity was studied in Brewer’s yeast-induced pyrexia in mice. Rota-rod test and bicuculline-induced hyperactivity were used for the assessment of locomotor activity. Results: Nauclea latifolia induced hypothermia and had antipyretic effects in mice. The plant decoction produced significant antinociceptive activity in all analgesia animal models used. The antinociceptive effect exhibited by the decoction in the formalin test was reversed by the systemic administration of naloxone, Nω-l-nitro-arginine methyl ester or glibenclamide. In contrast, theophylline did not reverse this effect. Nauclea latifolia (antinociceptive doses) did not exhibit a significant effect on motor coordination of the mice in Rota-rod performance. Nauclea latifolia protected mice against bicuculline-induced behavioral excitation. Discussion and conclusion: Overall, these results demonstrate that the central and peripheral effects of Nauclea latifolia root decoction might partially or wholly be due to the stimulation of peripheric opioid receptors through the action of the nitric oxide/cyclic monophosphate guanosin/triphosphate adenosine (NO/cGMP/ATP)-sensitive- K+ channel pathway and/or facilitation of the GABAergic transmission.

Occurrence of the Synthetic Analgesic Tramadol in an African Medicinal Plant

moderate to severe pain without any known side effects. [8, 9] It was designed by a simplification of the structure of morphine that kept the pharmacophoric elements responsible for the analgesic effect. Herein, we describe the isolation of tramadol from the root bark of N. latifolia, and the different methods used to prove the authenticity of its natural origin. The

A retro-biosynthetic approach to the prediction of biosynthetic pathways from position-specific isotope analysis as shown for tramadol

Significance The extraction of tramadol from the roots of Nauclea latifolia excited great interest worldwide. This was the first time that a widely marketed synthetic drug was found as an apparently natural product at high abundance. In this article, we describe the position-specific distribution of 13C in this tramadol. As a conventional approach to study its probable biosynthetic precursors, enzymatic steps, and intermediate metabolites is not currently feasible, we herein propose the concept of a retro-biosynthesis by examining the position-specific isotope distribution within the molecule and rationally interpreting the data in terms of known plant biochemical processes that may be involved in a biosynthesis of tramadol. Thus, clear guidance is given for future labeling studies. Tramadol, previously only known as a synthetic analgesic, has now been found in the bark and wood of roots of the African medicinal tree Nauclea latifolia. At present, no direct evidence is available as to the biosynthetic pathway of its unusual skeleton. To provide guidance as to possible biosynthetic precursors, we have adopted a novel approach of retro-biosynthesis based on the position-specific distribution of isotopes in the extracted compound. Relatively recent developments in isotope ratio monitoring by 13C NMR spectrometry make possible the measurement of the nonstatistical position-specific natural abundance distribution of 13C (δ13Ci) within the molecule with better than 1‰ precision. Very substantial variation in the 13C positional distribution is found: between δ13Ci = −11 and −53‰. Distribution is not random and it is argued that the pattern observed can substantially be interpreted in relation to known causes of isotope fractionation in natural products. Thus, a plausible biosynthetic scheme based on sound biosynthetic principals of precursor–substrate relationships can be proposed. In addition, data obtained from the 18O/16O ratios in the oxygen atoms of the compound add support to the deductions made from the carbon isotope analysis. This paper shows how the use of 13C NMR at natural abundance can help with proposing a biosynthetic route to compounds newly found in nature or those difficult to tackle by conventional means.

Evaluation of antinociceptive effects of Crassocephalum bauchiense Hutch (Asteraceae) leaf extract in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE The leaves of Crassocephalum bauchiense have long been used in traditional Cameroonian medicine for the treatment of epilepsy, pain, inflammatory disorders, arthritis and intestinal pain. AIM OF THE STUDY In this study, we attempted to identify the possible antinociceptive action of the aqueous extract and the alkaloid fraction prepared from the leaves of Crassocephalum baucheiense. MATERIALS AND METHODS Using acetic acid induced abdominal constrictions, formalin-, capsaisin- and glutamate-induced nociception, and hot plate assay procedures, the antinociceptive effects of the aqueous extract and the alkaloid fraction was assessed after oral administration in mice. Morphine sulfate was used as reference analgesic agent. Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of the extracts of Crassocephalum bauchiense. Male and female Swiss mice were used to assess acute toxicity of these extracts. RESULTS The aqueous extract and the alkaloid fraction of Crassocephalum bauchiense produced a significant antinociceptive effects in the acetic acid, formalin, glutamate, capsaicin and hot plate tests. These antinociceptive effects of Crassocephalum bauchiense were significantly attenuated by pretreatment with naloxone. The extracts of Crassocephalum bauchiense did not alter the locomotion of animals in the open-field or rotarod tests, which suggest a lack of a central depressant effect. The animals did not exhibit any acute toxicity to the aqueous extract and the alkaloid fraction, so it was not possible to calculate the LD(50). CONCLUSION The results confirm the popular use of Crassocephalum bauchiense as an antinociceptive, and contribute to the pharmacological knowledge of this species because it was shown that the aqueous extract and the alkaloid fraction of Crassocephalum bauchiense produced dose related antinociception in models of chemical and thermal nociception through mechanisms that involve an interaction with opioidergic pathway.

Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats.

ETHNOPHARMACOLOGICAL RELEVANCE The leaves of Kalanchoe pinnata (Crassulaceae) are used in Cameroon folk medicine to manage many diseases such as cardiovascular dysfunctions. In this work, we aimed to evaluate the activities of aqueous leaf extract of Kalanchoe pinnata on the blood pressure of normotensive rat (NTR) and salt hypertensive rats (SHR), as well as its antioxidant properties. MATERIALS AND METHODS Hypertension was induced in rats by oral administration of 18% NaCl for 4 weeks. For the preventive study, three groups of rats received 18% NaCl solution and the plant extract at 25 mg/kg/day, 50 mg/kg/day or 100 mg/kg/day by gavage. Two positive control groups received 18% NaCl solution and either spironolactone (0.71 mg/kg/day) or eupressyl (0.86 mg/kg/day) by gavage for 4 weeks. At the end of this experimental period, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR) were measured by the invasive method. Some oxidative stress biomarkers (reduced glutathione (GSH), superoxide dismutase (SOD), nitric monoxide (NO) were evaluated in heart, aorta, liver and kidney. NO level was indirectly evaluated by measuring nitrite concentration. RESULTS Kalanchoe pinnata extract prevented significantly the increase of systolic and diastolic arterial pressures in high salt-loaded rats (SHR). In SHR, concomitant administration of Kalanchoe pinnata at 25, 50 and 100 mg/kg/day significantly prevented the increase in blood pressure by 32%, 24% and 47% (for SAP); 35%, 33% and 56% (for DAP), respectively. No significant change was recorded in heart rate of those rats. The plant extract improved antioxidant status in various organs, but more potently in aorta. Thus, antioxidant and modulatory effects of Kalanchoe pinnata at the vasculature might be of preponderant contribution to its overall antihypertensive activity. CONCLUSION The work demonstrated that the concomitant administration of high-salt and the aqueous extract of Kalanchoe pinnata elicits prevention of salt-induced hypertension in rat. This antihypertensive activity is associated with an improvement of antioxidant status. Overall, results justify and support the use of Kalanchoe pinnata as antihypertensive medicine.

Anticonvulsant activity of an active fraction extracted from Crinum jagus L. (Amaryllidaceae), and its possible effects on fully kindled seizures, depression-like behaviour and oxidative stress in experimental rodent models.

ETHNOPHARMACOLOGICAL RELEVANCE The leaf extract of Crinum jagus L. (Amaryllidaceae) is widely used in traditional Cameroonian medicine as antiepileptic remedy and for the treatment of convulsion, depression and mood disorders associated with epilepsy. AIM OF THE STUDY Hence, this study was conducted to evaluate the effects of an active fraction extracted from the leaves of Crinum jagus against seizures, depression-like behaviour and oxidative stress in pentylenetetrazole (PTZ)-induced kindling in mice. MATERIALS AND METHODS Bioactive-guided fractionation of the leaf extract of Crinum jagus by using 70mg/kg PTZ-induced convulsions in mice, afforded a potent anticonvulsant fraction (flavonol kaempferol; C4.4). The effects of C4.4 on 30mg/kg PTZ-induced kindling, kindling-induced depression like-behaviour and oxidative stress was evaluated. Mice were injected PTZ (30mg/kg, i.p.) once every alternate day (48±1h) until the development of kindling. Depression was assessed using tail suspension test and forced swim test while the oxidative stress parameters were estimated in the whole brain at the end of experiments. Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of C4.4. Acute toxicity of C4.4 was also assessed in mice. RESULTS Convulsions-induced by 70mg/kg PTZ were strongly antagonized by C4.4. Oral administration of C4.4 significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure mean stage and decreased the number of myoclonic jerks in PTZ-kindled mice. The data indicated also that C4.4 significantly reduced the immobility times in the tail suspension test and the forced swim test. This active fraction has also antioxidant properties by decreasing the lipid peroxidation, and augmenting endogenous antioxidant enzymes in brain. C4.4 administered (12.5-50mg/kg) did not alter the locomotion of animals in the open-field or rotarod tests, which suggest a lack of a central depressant effect. The animals did not exhibit any acute toxicity to C4.4 at the therapeutic doses. CONCLUSION These results suggest that pretreatment with C4.4 ameliorates convulsions-induced by PTZ, protects mice against kindling development, depression-like behaviour and oxidative stress in PTZ-kindled mice. These finding provides scientific rationale for the use of Crinum jagus extracts for the amelioration of epilepsy observed in traditional medicine in Cameroon.

Extracts of Feretia apodanthera Del. demonstrated anticonvulsant activities against seizures induced by chemicals and maximal electroshock

Extracts of Feretia apodanthera Del. (Rubiaceae) have been extensively used in traditional Cameroonian medicine to treat a variety of diseases, including some neurological disorders. The present study was aimed to tests the anticonvulsant properties of the aqueous extract and the alkaloid fraction of the stem barks of Feretia apodanthera. The anticonvulsant investigation was carried out against bicuculline-, picrotoxin-, pentylenetetrazol-, Methyl-β-carboline-3-carboxylate-, N-Methyl-D-aspartate-, 4-aminopyridine-, and maximal electroshock-induced seizures or turning behavior in mice. The aqueous extract protected mice against bicuculline-, picrotoxin-, pentylenetetrazol-, Methyl-β-carboline-3-carboxylate-, N-methyl-D-aspartate -, 4-aminopyridine- and maximal electroshock-induced seizures or turning behavior. Also, N-Methyl-D-aspartate-, 4-aminopyridine- and maximal electroshock- induced seizures or turning behavior, were significantly antagonized by the alkaloid fraction (80mg/kg) from Feretia apodanthera. The total protection of mice provided by the aqueous extract against convulsions induced by pentylenetetrazol or picrotoxin was anagonized by flumazenil, a specific antagonist of the benzodiazepine site in the GABAA receptor complex. The aqueous extract of Feretia apodanthera (but not the alkaloid fraction) increased the brain GABA content and inhibited the GABA transaminase activity. In conclusion, Feretia apodanthera was revealed possessing anticonvulsant effects in mice, likely via the GABAergic neurotransmission.

Acute and sub-chronic toxicity studies of three plants used in Cameroonian ethnoveterinary medicine: Aloe vera (L.) Burm. f. (Xanthorrhoeaceae) leaves, Carica papaya L. (Caricaceae) seeds or leaves, and Mimosa pudica L. (Fabaceae) leaves in Kabir chicks.

ETHNOPHARMACOLOGICAL RELEVANCE Aloe vera (L.) Burm. f. (Xanthorrhoeaceae), Carica papaya L. (Caricaceae) and Mimosa pudica L. (Fabaceae) are widely used in the Cameroonian ethnoveterinary medicine as a panacea, and specifically for gastrointestinal disorders as well as an anthelmintic and antibacterial. AIM OF THE STUDY The present study evaluated the potential toxicity of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds, and Mimosa pudica leaves after acute and sub-chronic administration in chicks. MATERIALS AND METHODS For the acute toxicity test a single administration of each of the four hydroalcoholic extracts was given orally at doses ranging from 40 to 5120 mg/kg (n=5/group/sex). In the sub-chronic study, these extracts were given orally as a single administration to chicks at doses of 80, 160, 320 and 640 mg/kg/day for 42 days. The anti-angiogenic properties of these extracts (5-320 µg/mg) were investigated in the chick chorioallantoic membrane in vivo. RESULTS In the acute toxicity test, none of the four studied hydroalcoholic extracts induced mortality or significant behavioural changes. The sub-acute treatment with the four plant extracts did not alter either the body weight gain or the food and water consumption. However, the results indicated that Aloe vera leaf extract acute treatment by oral route at doses up to 2560 mg/kg did not produce death in 50% (5/10) of chicks during 24h or 14 days of observation, but 20% (2/10) chicks died. The haematological and biochemical analyses did not show significant differences in any of the parameters examined in female or male groups, with the exception of a transient rise in white blood cell counts at high doses (640 mg/kg). Additionally, these extracts did not have the potential for anti-angiogenic effects through the inhibition of neo-angiogenesis in the chick chorioallantoic membrane in vivo. CONCLUSION The results showed that the therapeutic use of the hydroalcoholic extracts of Aloe vera leaves, Carica papaya leaves or seeds and Mimosa pudica leaves had very low toxicity in oral acute high dose administration and no toxicity in oral sub-chronic low dose administration and indicate that the plants could be considered safe for oral medication in chicks.

Malaria, Moderate to Severe Anaemia, and Malarial Anaemia in Children at Presentation to Hospital in the Mount Cameroon Area: A Cross-Sectional Study

Background. Malaria remains a major killer of children in Sub-Saharan Africa, while anaemia is a public health problem with significant morbidity and mortality. Examining the factors associated with moderate to severe anaemia (MdSA) and malarial anaemia as well as the haematological characteristics is essential. Methodology. Children (1–14 years) at presentation at the Regional Hospital Annex-Buea were examined clinically and blood samples were collected for malaria parasite detection and full blood count evaluation. Results. Plasmodium falciparum, anaemia, and malarial anaemia occurred in 33.8%, 62.0%, and 23.6% of the 216 children, respectively. Anaemia prevalence was significantly higher in malaria parasite positive children and those with fever than their respective counterparts. MdSA and moderate to severe malarial anaemia (MdSMA) were detected in 38.0% and 15.3% of the participants, respectively. The prevalence of MdSA was significantly higher in children whose household head had no formal education, resided in the lowland, or was febrile, while MdSMA was significantly higher in febrile children only. Children with MdSMA had significantly lower mean white blood cell, lymphocyte, and platelet counts while the mean granulocyte count was significantly higher. Conclusion. Being febrile was the only predictor of both MdSA and MdSMA. More haematological insult occurred in children with MdSMA compared to MdSA.

Antiepileptogenic and Neuroprotective Effects of Pergularia daemia on Pilocarpine Model of Epilepsy

In this study, we investigated antiepileptogenic and neuroprotective effects of the aqueous extract of Pergularia daemia roots (PDR) using in vivo and in vitro experimental models. In in vivo studies, status epilepticus caused by pilocarpine injection triggers epileptogenesis which evolves during about 1–2 weeks. After 2 h of status epilepticus, mice were treated during the epileptogenesis period for 7 days with sodium valproate and vitamin C (standards which demonstrated to alter epileptogenesis), or Pergularia daemia. The animals were then, 1 week after status epilepticus, challenged with acute pentylenetetrazole (PTZ) administration to test behaviorally the susceptibility to a convulsant agent of animals treated or not with the plan extract. Memory was assessed after PTZ administration in the elevated plus maze and T-maze paradigms at 24 and 48 h. Antioxidant and acetylcholinesterase activities were determined in the hippocampus after sacrifice, in vitro studies were conducted using embryonic rat primary cortical cultures exposed to L-glutamate. Cell survival rate was measured and apoptotic and necrotic cell death determined. The results showed that chronic oral administration of PDR significantly and dose-dependently increased the latency to myoclonic jerks, clonic seizures and generalized tonic–clonic seizures, and the seizure score. In addition, PDR at all doses (from 4.9 to 49 mg/kg) significantly decreased the initial and retention transfer latencies in the elevated plus maze. Interestingly PDR at the same doses significantly increased the time spent and the number of entries in T-maze novel arm. PDR significantly increased the activities of acetylcholinesterase and antioxidant enzymes superoxide dismutase, catalase, and total glutathione and proteins, and decreased malondialdehyde level. Furthermore, PDR increased viability rate of primary cortical neurons after L-glutamate-induced excitotoxicity, in a dose dependent manner. Altogether these results suggest that PDR has antiepileptogenic and neuroprotective effects, which could be mediated by antioxidant and antiapoptotic activities.