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Background Malaria still constitutes a major public health menace, especially in tropical and subtropical countries. Close to half a million people mainly children in Africa, die every year from the disease. With the rising resistance to frontline drugs (artemisinin-based combinations), there is a need to accelerate the discovery and development of newer anti-malarial drugs. A systematic review was conducted to identify the African medicinal plants with significant antiplasmodial and/or anti-malarial activity, toxicity, as wells as assessing the variation in their activity between study designs (in vitro and in vivo). Methods Key health-related databases including Google Scholar, PubMed, PubMed Central, and Science Direct were searched for relevant literature on the antiplasmodial and anti-malarial activities of African medicinal plants. Results In total, 200 research articles were identified, a majority of which were studies conducted in Nigeria. The selected research articles constituted 722 independent experiments evaluating 502 plant species. Of the 722 studies, 81.9%, 12.4%, and 5.5% were in vitro, in vivo, and combined in vitro and in vivo, respectively. The most frequently investigated plant species were Azadirachta indica, Zanthoxylum chalybeum, Picrilima nitida, and Nauclea latifolia meanwhile Fabaceae, Euphorbiaceae, Annonaceae, Rubiaceae, Rutaceae, Meliaceae, and Lamiaceae were the most frequently investigated plant families. Overall, 248 (34.3%), 241 (33.4%), and 233 (32.3%) of the studies reported very good, good, and moderate activity, respectively. Alchornea cordifolia, Flueggea virosa, Cryptolepis sanguinolenta, Zanthoxylum chalybeum, and Maytenus senegalensis gave consistently very good activity across the different studies. In all, only 31 (4.3%) of studies involved pure compounds and these had significantly (p = 0.044) higher antiplasmodial activity relative to crude extracts. Out of the 198 plant species tested for toxicity, 52 (26.3%) demonstrated some degree of toxicity, with toxicity most frequently reported with Azadirachta indica and Vernonia amygdalina. These species were equally the most frequently inactive plants reported. The leaves were the most frequently reported toxic part of plants used. Furthermore, toxicity was observed to decrease with increasing antiplasmodial activity. Conclusions Although there are many indigenous plants with considerable antiplasmodial and anti-malarial activity, the progress in the development of new anti-malarial drugs from African medicinal plants is still slothful, with only one clinical trial with Cochlospermum planchonii (Bixaceae) conducted to date. There is, therefore, the need to scale up anti-malarial drug discovery in the African region.

The leaf extracts of Nauclea latifolia (Smith) were investigated for its bioactive constituents to validate it reported ethnomedicinal uses (infectious and oxidative stress related diseases). Isolation of antioxidant compounds from the ethyl acetate fraction was achieved by a DPPH directed fractionation, which resulted in trans-3,4-dihydroxycinnamic acid (caffeic acid) (1), quercetin (2), quercetin-3-O-β-glycopyranoside (3), 3-caffeoylquinic acid (chlorogenic acid) (4), and 3,5-O-dicaffeoylquinic acid (5). The extracts and isolated compounds were evaluated for antioxidant activities using five complementary assays: total antioxidant capacity (TAC), inhibition of nitric oxide (NO) radical activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, ferric reducing antioxidant potential (FRAP) and metal chelating ability (MCA) spectrophotometrically. The total phenolic content (TPC) was also determined. Antimicrobial activities of the samples were evaluated using agar cup plate diffusion and broth microdilution method. Compound (2) was more potent in the DPPH assay [IC50 = 0.59 ± 0.04 to 21.3 ± 1.01 µg/mL] than the ascorbic acid [8.82 ± 0.23 µg/mL] used as a standard. All the isolated compounds exhibited a higher degree of inhibition of NO radical than the standard. The IC50 ranged from 5.17 ± 2.59 to 55.2 ± 0.66 µg/mL compared with the standard, ascorbic acid [IC50 = 69.3 ± 1.78 µg/mL]. In the metal chelating ability (MCA) assay, compound (5) had better activity [IC50 = 105 ± 2.73 µg/mL] than the standard, EDTA [IC50 = 122 ± 1.17 µg/mL]. Compound (2) had the best TAC and FRAP results, 10.9 ± 2.14 mg AAE/g and 1.68 ± 0.09 mg AAE/g respectively. N. latifolia extracts exhibited less antibacterial activities than the isolated compounds. The MIC of quercetin (2) against S. aureus was 0.156 mg/mL while quercetin 3-O-β-glucopyranose exhibited wider spectrum of activities with MIC in the range of 1 mg/mL for most of the bacteria strains. Also, 3,5-O-dicaffeoylquinic acid had an MIC of 1.25 mg/mL against P. aeruginosa. Compounds 4 and 5 are reported from N. latifolia for the first time. This study concluded that some of the isolated compounds had strong antioxidant and moderate antimicrobial activities.

Objective: To explore the immunomodulatory, anti-inflammatory, anti-oxidant and anti-arthritic activity of aqueous and methanolic extracts of Nauclea pobeguinii stem bark. Methods: For in vitro assays, the production of reactive oxygen species (chemiluminescence technique), the proliferation of T cells (liquid scintillation counter method), as well as the inhibition of cyclooxygenase, lipoxygenase, protein denaturation, and free radicals [DPPH, ABTS and nitric oxide (NO) inhibition methods] were evaluated. For in vivo assays, a polyarthritis model was induced by complete Freund’s adjuvant in rats. The aqueous and methanolic extracts of Nauclea pobeguinii stem bark were administered orally at 150 and 300 mg/kg. After 28 days of treatment, the total blood was taken to quantify the hematological parameters and the serum was used to evaluate the biochemical parameters (alanine aminotransferase, aspartate transaminase, phenylalnine ammonialyase, and proteins) and oxidative stress parameters (malondialdehyde, catalase, superoxide dismutase, glutathione and NO), and then the knee joint was removed for histological analysis. Results: The extracts of Nauclea pobeguinii significantly reduced the production of intra- and extracellular reactive oxygen species and decreased T cell proliferation. They had an inhibitory effect on cyclooxygenase, lipoxygenase, and protein denaturation, and both extracts had antioxidant capacity on DPPH, ABTS and NO. Both extracts alleviated joint inflammation and pain sensitivity after complete Freund’s adjuvant injection, reduced alanine aminotransferase, aspartate transaminase, alkaline phosphatase, NO and malondialdehyde levels, increased protein concentration, superoxide dismutase, catalase and glutathione activity, and restored the cytoarchitecture of the joint after complete Freund’s adjuvant injection. Conclusions: The aqueous and methanolic extracts of Nauclea pobeguinii have immunomodulatory, anti-inflammatory, anti-oxidant and anti-arthritic properties.

Bioactive peptides are known for health-promoting properties due to several pharmacological effects they modulate in physiological systems. Herein, the presence of peptides particularly cyclic peptides, was investigated in two Rubiaceae members; Nauclea diderichii (De Wild. and T. Durand) Merrill and Ixora brachypoda DC by thin layer chromatography (TLC) chemical detection, and their multifunctional bioactivity evaluated. Crude and pre-purified peptides were obtained from both plants using aqueous and solid-phase extractions, respectively. The peptide fraction of N. diderrichii showed good DPPH scavenging activity (IC50 = 3.43 µg/mL) compared to the standard Gallic acid (IC50 = 1.44 µg/mL). Peptide fractions of both plants displayed inhibitory effects (MIC = 6.25 μg/mL) against bacteria and fungi strains except Escherichia coli, relative to standard drugs (MIC = 0.31 µg/mL). Both displayed significant toxicity to brine shrimp nauplii (LC50 ≤ 220.8 μg m L−1) as well as MCF-7 and RD cancer cells (IC50 ≤ 34.0 μg m L−1). The enterovirus species B and C tested were remarkably susceptible to the peptide fractions (IC50 ≤ 3.20 μg/mL).

The greatest common and devastating complication of diabetes is painful neuropathy that can cause hyperalgesia and allodynia. It can disturb psychosocial functioning by increasing levels of anxiety and depression. This work was designed to evaluate the antihyperalgesic, antidepressant, and anxiolytic-like effects of the aqueous and methanol extracts of Nauclea pobeguinii stem-bark in diabetic neuropathy induced by streptozotocin in mice. Diabetic neuropathy was induced in mice by the intraperitoneal administration of 200 mg/kg streptozotocin (STZ) to provoke hyperglycemia. Nauclea pobeguinii aqueous and methanol extracts at the doses of 150 and 300 mg/kg were administered by oral route, and their effects were evaluated on antihyperalgesic activity (Von Frey filaments, hot plate, acetone, and formalin tests), blood glucose levels, body weight, serum, sciatic nerve proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and sciatic nerve growth factor (IGF and NGF) rates, depression (open field test, forced swimming test, tail suspension test), and anxiety (elevated plus maze, light-dark box test, social interaction). Oral administration of Nauclea pobeguinii stem-bark aqueous and methanol extracts (150 and 300 mg/kg) produced antihyperalgesic, antidepressant, and anxiolytic-like effects in STZ-induced diabetic neuropathic mice. Extracts also triggered a decrease in glycaemia and increased body weight in treated animals. They also significantly ( p p

Nauclea latifolia root (NLR) extract is one of phytochemicals used to treat various ailments in most of developing countries. This investigation focuses on modelling, optimization and computer-aided simulation of phenolic solid-liquid extraction from NLR. The extraction experiments were conducted at extraction temperature (ET: 33.79-76.21 °C), process time (PT: 2.79-4.21 h) and solid-liquid ratio (SLC: 0.007929-0.018355 g/ml). Regression models (RM) were developed, using Response Surface Methodology (RSM) in Design Expert software, for predicting and optimizing total phenolic content (TPC) and total flavonoid content (TFC) and also compared with adaptive neuro-fuzzy inference system (ANFIS) modelling in Matlab environment. Aspen Batch Process Developer (ABPD) V10 was used to simulate phenolic extract production and perform material balance of the process. Both Coefficients of determination (R2) of RSM (TFC: 0.9996, TPC: 0.9932) and ANFIS models (TFC: 0.99998, TPC: 0.9982) were compared and predicted satisfactorily. Optimization results show: ET (2.79 h), PT (38.8 °C), SLC (0.0198 g/ml), TFC (25.92 25.92 μg RE/g) and TPC (8.47 mg GAE/g). The phenolic extraction base case simulation results gave batch throughput, annual throughput, number of batches per year 0.0089 g/batch, 0.139 g/year and 1019 batches, respectively. The ABPD predicted TPC and experimental TPC results were compared and gave mean relative deviation error of 3.75%. Thus, ABPD simulation model is reasonably reliable for the scale-up design engineering of the phenolic extract production from NLR.

Traditional herbal medicines are potentially rich sources of new drugs against malaria and other infectious diseases. However, phytochemicals extracted from a medicinal plant is strongly dependent on the nature of the extracting solvent. This study therefore aimed to investigate the antimalarial activity of three plants traditionally used to treat malaria using solvents of different polarities as solvents of extraction. The leaves of Lawsonia inermis, Tithonia diversifolia, and stem barks of Nauclea latifolia were extracted with water, n-hexane, ethanol and dichloromethane: methanol (1:1). The extracts were thereafter investigated for their antiplasmodial activity against Plasmodium berghei in infected mice using Peter’s 4-days suppressive test. In N. latifolia stem bark, the aqueous extract showed the highest percentage chemosuppression (79.04%) followed by the dichloromethane: methanol (1:1), ethanolic and hexane extracts with percentage chemosuppressions of 74.66%, 61.47% and 8.81% respectively. The dichloromethane: methanol (1:1) extract of T. diversifolia leaves exhibited moderate antiplasmodial activity with percentage chemosuppression of 43.90% while its other extracts showed weak activity. Only dichloromethane: methanol (1:1) extract of L. inermis showed good antiplasmodial activity with percentage chemosuppression of 61.57% while the other extracts had between weak to inactivity. The antimalarial activity exhibited by these plants, most especially N. latifolia and L. inermis, against P. berghei suggests that these plants have active principles against malarial as claimed by the folklore, and further work is necessary to isolate, identify and characterize the active components of the plants.

Fruit juices are liable to spoilage as a result of fermentation by microorganisms. This study is intended to provide information on preservative of fruit juices with plant extracts. The preservative effects of Gmelina arborea fruit and Nauclea latifolia stem bark extracts in apple and pineapple juices were assessed in comparison to chemical preservative (sodium benzoate) as a positive control and refrigeration at 4 °C as a negative control measures. Decrease in microbial load during storage was observed in the prepared juice samples. G. arborea fruit extract in microbial inhibition was more potent followed by sodium benzoate and N. latifolia stem bark extract. G. arborea preserved juices were of better choice in sensory evaluation for acceptability than N. latifolia and sodium benzoate preserved juices. Phytochemical screened from the extracts are saponins, tannins, flavonoids, alkaloids and steroids. The titratable acidity of the prepared juices evaluated G. arborea of lower titratable acidity value than N. latifolia. The results has provided a partial support for the use of G. arborea fruits and N. latifolia stem bark extracts for preservation of fruit juices. The use of N. latifolia and G. arborea as preservative agents have not been documented and could be potential sources of natural preservative agents for future use in preservation of alcoholic and non alcoholic beverages.

Background The resistance of some medico-veterinary parasite strains as well as the unavailability and toxicity of synthetic anthelminthics on humans, animals and the impacts of their residues in the environment have pushed scientists to turn to plants with anthelminthic properties. Hence, the aim of this work was to contribute to the fight against helminths of medical and veterinary importance in general, and also to clear the environment of their free living stages. Methods Fresh eggs of Heligmosomoides bakeri were obtained from the faeces of experimentally infected mice. L1 and L2 larval stages were obtained after 48 and 72 h of coproculture respectively. Methylene Chloride-Methanol (1:1) extracts of Annona senegalensis and Nauclea latifolia were diluted in DMSO or Tween 80 to prepare the following concentrations: 625, 1250, 2500, 3750 and 5000 μg/ml. The effects of extract solutions were evaluated on the embryonation of eggs, egg hatching and on L1 and L2 survival after 48, 10 and 24 h of incubation. Negative controls were 1.5% DMSO, 4% Tween 80 and a mixture of these solvents. The TLC was carried out and the profiles of secondary metabolites were made. Results Negative controls had no effect on the embryonation, eggs hatching and on larval mortality. However, it was found that, the extracts affected the free living stages of H. bakeri in a concentration-dependant manner. At the highest concentration (5000 μg/ml), the rate of inhibition of embryonation obtained were 20.80%, 38.15% and 84.83% for Methylene Chloride-Methanol of Annona senegalensis (MCM As), Nauclea latifolia (MCM Nl) extracts and mixture of Annona senegalensis and Nauclea latifolia (MCM As-Nl) extract respectively. For egg hatch, the inhibition rate was 16.10%, 46.24% and 87.07% for the above three extracts respectively at the same concentration of 5000 μg/ml. On L1 and L2 larval stages after 24 h of exposure to extracts, the mortality rates of 100%, 54.76% and 96.77% against 98%, 51.44% and 100% were obtained for MCM As, MCM Nl and MCM As-Nl respectively at the highest concentration. The Methylene Chloride-Methanol of A.senegalensis, N. latifolia extracts showed the presence of alkaloids except in N. latifolia extract, flavonoids, sterols, triterpens, tanins, polyphenols, anthraquinons, saponins and terpenoids. Conclusion These findings suggest that, the mixture of the two plant extracts showed an additive (synergetic effect) ovicidal effect and a slight larval mortality on L1 as compared to the effect of MCM As extract alone. These effects were due to the presence ao secondary metabolites identifies in the plant extracts. Thus, they may be used as possible «disinfectants» for soil transmitted nematodes.

International audience

Three previously undescribed indole alkaloids, named latifolianine A (1) and latifoliaindoles A and B (2 and 3), along with 10 known compounds (4-13), were isolated from the heartwood of Nauclea latifolia. Their structures were elucidated based on the analysis of their NMR and MS data. Latifolianine A (1) represents an unusual and unprecedented monoterpene indole alkaloid unit condensed with an ursane-type pentacyclic triterpenoid moiety. Plausible biogenetic routes toward latifolianine A (1) and latifoliaindoles A and B (2 and 3) were proposed. All the isolates were assessed in vitro for their inhibitory effects on Haemophilus influenzae. Naucleidinal (7) exhibited potent antibacterial activity (MIC value of 3.1 mug/mL) as compared to a reference drug, ciprofloxacin (MIC value of 1.6 mug/mL).

Various combinations of Nauclea latifolia root, Artocarpus altilis stem bark, Murraya koenigii leaf and Enantia chlorantha stem bark used in African ethnomedicine as decoctions for malaria and fevers, and combinations with standard drugs, were investigated for antiplasmodial activities using Plasmodium berghei berghei-infected mice. The respective prophylactic and curative ED50 values of 189.4 and 174.5 mg/kg for N. latifolia and chemosuppressive ED50 value of 227.2 mg/kg for A. altilis showed that they were the best antimalarial herbal drugs. A 1.6-fold increase of the survival time given by the negative control was elicited by M. koenigii, thereby confirming its curative activity. Pyrimethamine with an ED50 of 0.5 ± 0.1 mg/kg for the prophylactic, and chloroquine with ED50 = 2.2 ± 0.1 and 2.2 ± 0.0 mg/kg for the chemosuppressive and curative tests, respectively, were significantly (p < 0.05) more active. Co-administrations of N. latifolia with the standard drugs significantly reduced their prophylactic, chemosuppressive and curative actions, possibly increasing the parasites’ resistance. Binary combinations of N. latifolia or M. koenigii with any of the other plants significantly increased the prophylactic and suppressive activities of their individual plants, respectively. Also, E. chlorantha with A. altilis or N. latifolia enhanced their respective prophylactic or curative activities, making these combinations most beneficial against malaria infections. Combinations of three and four extracts gave varied activities. Hence, the results justified the combinations of ethnomedicinal plants in antimalarial herbal remedies and showed the importance of the three in vivo models in establishing antimalarial activity.

Covering up to 2016, Nauclea latifolia (syn. Sarcocephalus latifolius, Rubiaceae), commonly called the African pincushion tree, is a plant widely used in folk medicine in different regions of Africa for treating a variety of illnesses, including malaria, epilepsy and pain. N. latifolia has not only drawn the interest of traditional healers but also of phytochemists, who have identified a range of bioactive indole alkaloids in its tissue. More recently, following up on the traditional use of extracts in pain management, a bio-guided purification from the roots of the tree led to the identification of the active ingredient as tramadol, available as a synthetic analgesic since the 1970s. The discovery of this compound as a natural phytochemical was highlighted worldwide. This review focuses on the correlation between extracted compounds and pharmacological activities, paying special attention to infectious diseases and neurologically-related disorders. A critical analysis of the data reported so far on the natural origin of tramadol and its proposed biosynthesis is also presented.

Microbial infections till date remain a scourge of humanity due to lack of vaccine against some infections, emergence of drug resistant phenotypes, and the resurgence of infections amongst others. Continuous quest for novel therapeutic approaches remains imperative. Here we (i) assessed the effects of extracts/hydrolates of some medicinal plants on pathogenic microorganisms and (ii) evaluated the inhibitory potential of the most active ones in combination with antibiotics. Extract E03 had the highest DZI (25 mm). Extracts E05 and E06 were active against all microorganisms tested. The MICs and MBCs of the methanol extracts ranged from 16.667 × 103 μg/mL to 2 μg/mL and hydrolates from 0.028 to 333333 ppm. Extract E30 had the highest activity especially againstS. saprophyticus(MIC of 6 ppm) andE. coli(MIC of 17 ppm). Combination with conventional antibiotics was shown to overcome resistance especially with E30. Analyses of the extracts revealed the presence of alkaloids, flavonoids, triterpenes, steroids, phenols, and saponins. These results justify the use of these plants in traditional medicine and the practice of supplementing decoctions/concoctions with conventional antibiotics.Nauclea pobeguinii (E30), the most active and synergistic of all these extracts, and some hydrolates with antimicrobial activity need further exploration for the development of novel antimicrobials.

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.

This study was carried out to investigate thein vitroantioxidant potentials of the leaves and fruits ofNauclea latifolia, a straggling shrub or small tree, native to tropical Africa and Asia. Hot water extracts of the leaves and fruits ofNauclea latifoliawere assessed for their total polyphenolic, flavanol, and flavonol contents as well as 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability, ferric reducing antioxidant power (FRAP), Trolox equivalence antioxidant capacity (TEAC), and oxygen radical absorbance capacity (ORAC) assays. The aqueous extract of the leaves was found to contain higher level of total polyphenols (11.63±0.023 mg GAE/g), flavanol (1.45±0.10 mg CE/g), and flavonol (2.22±0.37 mg QE/g) than the extract of the fruits with values of1.75±0.02 mg GAE/g (total polyphenol),0.15±0.01 mg CE/g (flavanol), and1.00±0.13 mg QE/g (flavonol). Similarly, the aqueous extract of the leaves also exhibited higher DPPH (IC5020.64 mg/mL), FRAP (86.10±3.46 μmol AAE/g), TEAC (94.83±3.57 μmol TE/g), and ORAC (196.55±0.073 μmol TE/g) than the extract of the fruits with DPPH (IC50120.33 mg/mL), FRAP (12.23±0.40 μmol AAE/g), TEAC (12.48±0.21 μmol TE/g), and ORAC (58.88±0.073 μmol TE/g). The present study showed thatNauclea latifoliahas strong antioxidant potentials with the leaves demonstrating higherin vitroantioxidant activities than the fruits.

International audience; ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Nauclea latifolia Smith (Rubiaceae) popularly known as "koumkouma" is used in traditional Cameroonian medicine as neuropathic pain remedy and for the treatment of headache, inflammatory pain and convulsion. This study was conducted to evaluate the antinociceptive effects of the alkaloid fraction isolated from Nauclea latifolia in neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rat. MATERIALS AND METHODS: Bioactive-guided fractionation of the root extracts of Nauclea latifolia using the Von Frey in a rat model of neuropathic pain (Benett model), afforded a potent anti-hyperalgesic fraction IV. Further fractionation of this fraction was performed by high-performance liquid chromatography (HPLC), yielded eight sub-fractions (F1-F8) which were tested for antinociceptive effects. The alkaloid fraction (F3) collected by HPLC, exhibited potent antinociceptive effects, and the anti-allodynic and anti-hyperalgesic effects of this fraction (8, 16, 40 and 80 mg/kg) were determined using the von Frey and acetone tests respectively in a rat model of neuropathic pain. Rota-rod performance and catalepsy tests were used for the assessment of motor coordination. RESULTS: The alkaloid fraction (80 mg/kg) administered intraperitoneally induced a completely decreased hyperalgesia 90 min post-dosing. In the acetone test, the Nauclea latifolia fraction at 80mg/kg showed its maximal anti-allodynic effects 120 min post-injection. The areas under the curve (AUC) of the anti-allodynic or anti-hyperalgesic effects produced by the alkaloid fraction at 80 mg/kg were significantly (p

Background Nauclea latifolia Smith, a shrub belonging to the family Rubiaceae is a very popular medicinal plant in Cameroon and neighboring countries where it is used to treat jaundice, yellow fever, rheumatism, abdominal pains, hepatitis, diarrhea, dysentery, hypertension, as well as diabetes. The ethno-medicinal use against yellow fever, jaundice and diarrhea prompted us to investigate on the antiviral activity of the root bark of N. latifolia. In this study, HSV-2 was chosen as a viral model because of its strong impact on HIV transmission and acquisition. Methods The crude extract under study was prepared by maceration of air-dried and powdered roots barks of N. latifolia in CH2Cl2/MeOH (50:50) mixture for 48 hours, then it was subjected to filtration and evaporation under vacuum. A phytochemical analysis of the crude extract was performed by High Performance Liquid Chromatography coupled with a photodiode array and mass spectrometry (HPLC-PDA-ESI-qMS). The anti-HSV-2 activity was assayed in vitro by plaque reduction and virus yield assays and the major mechanism of action was investigated by virucidal and time of addition assays. Data values were compared using the Extra sum of squares F test of program GraphPad PRISM 4. Results The main components detected in the extract belong to the class of indole alkaloids characteristic of Nauclea genus. Strictosamide, vincosamide and pumiloside were tentatively identified together with quinovic acid glycoside. N. latifolia crude extract inhibited both acyclovir sensitive and acyclovir resistant HSV-2 strains, with IC50 values of 5.38 μg/ml for the former and 7.17 μg/ml for the latter. The extract was found to be most active when added post-infection, with IC50 of 3.63 μg/ml. Conclusion The results of this work partly justify the empirical use of N. latifolia in traditional medicine for the treatment of viral diseases. This extract could be a promising rough material for the development of a new and more effective modern anti-HSV-2 medication also active against acyclovir-resistant HSV-2 strains.

The aim of this study was to evaluate the short-term safety and tolerability of an antimalarial herbal medicinal product (PR 259 CT1) consisting of a quantified 80 % ethanol extract from the stem bark of Nauclea pobeguinii when given orally to healthy adult male volunteers. The amount of the major alkaloid strictosamide in the extract was determined by a validated HPLC method and was shown to be 5.6 %. The herbal preparation was formulated in a gelatine capsule form containing 500 mg of PCR 259 CT1. A sample of 15 healthy male volunteers, selected using the Lot Quality Assurance of Sampling (LQAS) method, was eligible for inclusion after fulfilment of the inclusion criteria and clinical examination by a physician. The volunteers were treated in an outpatient clinic with a drug regimen of two 500 mg capsules three times daily (each eight hours) for seven days, during meals. Safety and tolerability were monitored clinically, haematologically, biochemically and by electrocardiographic (ECG) examination at days 0, 1, 3, 7 and 14. Adverse effects were recorded by self-reporting of the participants or by detection of abnormalities in clinical examinations by a physician. The oral administration of PR 259 CT1 at high doses of 2 × 500 mg/capsule/day for 7 days was found to induce no significant changes in the concentration levels of all investigated haematological, biochemical, electrocardiogram and vital sign parameters and physical characteristics after 14 days of treatment compared to those seen in the baseline data. The concentration levels of all evaluated parameters were within the normal limits as reported in the literature. All adverse events noted were mild and self-resolving including increase of appetite (33 %), headache (20 %) and nausea (20 %). Other minor side effects were insomnia, somnolence and asthenia (7 %). Thus, PR 259 CT1 presented a significant safety and tolerability in healthy volunteers to allow its further development by starting a phase II clinical trial.

International audience; 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, N(ω)-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.

International audience; The neuropharmacological effects of the decoction of Nauclea latifolia Smith (Rubiaceae) roots were studied in mice Different experimental models (forced swimming test, horizontal wire test and hole-board test) were used for detecting antidepressant, myorelaxant and anxiolytic properties The results revealed that Nauclea latifolia induced a reduction of immobility, in a similar way to that of fluoxetine, along with a significant increase in the percentage of spent time in swimming behavior Nauclea latifolia displayed a myorelaxant activity in the horizontal wire test In the hole-board test, Nauclea laufolta significantly increased the number and duration of head-dips In addition, anxiolytic-like properties of Nauclea laufolta were blocked by anxiogenic agents as examined in the hole-board test This was the case for N-methyl-beta-carboline-3-carboxamide (FG7142), a partial Inverse agonist at the benzodiazepine site of the GABA(A) receptor complex, flumazenil (RO151788), a central benzodiazepine receptor antagonist and bicuculline, a light-sensitive competitive antagonist of GABA(A) receptors These results suggest that Nauclea latifolia roots decoction possess antidepressant, myorelaxant and anti-anxiety-like properties in the models employed The extracts might potentially act by GABAergic activation and/or by modulating the serotoninergic levels in the central nervous system However, further studies were still required

The hepatoprotective activity of the root bark extract of Nauclea latifolia was tested in vivo. The root bark was defatted with diethyl ether and then extracted with methanol and the methanolic extract was recovered on a 9.3 % w/w yield. The LD50 of the methanolic extract in rats was 300 mg/kg (i.p). It showed no significant effect on pentobarbital-induced sleep in rats after i.p. injection. The extract significantly reduced pentobarbital-induced sleep in paracetmol and carbon tetrachloride (CCl4) intoxicated rats. The elevataion of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and alkaline phosphatase (AP) induced by paracetamol and CCl4 intoxication in rats was also significantly (P Agro-Science Vol. 7 (1) 2008: pp. 72-77

The antibacterial activities of the plants, Mitragyna inermis, Morinda lucida, Khaya senegalensis and Nauclea latifolia were investigated using an indicator-based microdilution technique. The extracts of the plants in water, methanol, chloroform and petroleum ether inhibited growth of bacteria in broth cultures. M. inermis with the lowest minimal inhibitory concentration (MIC) of 0.03g/ml was the bacteriologically most active plant. The chi-square value (10.25) and F-statistic value (4.36) were significant at less than 0.05 level and implied that inhibition of bacterial growth was significantly associated with the type of plant investigated. The R value obtained on regressing bacterial inhibition on the independent variables – type of plant, plant part (leaf or stem bark) and extraction solvent used - was 0.57 (p < 0.01 level), and means that the independent variables put together influenced inhibition of bacterial growth . The findings of this study suggest the effectiveness of the microdilution technique in the phytochemical screening of plants for antibacterial activities. Key words: indicator-based, microdilution technique, antibacterial, Mitragyna inermis, Morinda lucida, Khaya senegalensis, Nauclea latifolia Afr. J. Trad. Comp. Alt. Med. Vol.2(3) 2005: 238 – 243

Objective To investigate the traditional antidiabetic uses of some indigenous Sudanese plants on streptozotocin-induced diabetes rats. Methods Diabetic rats were treated with a 400 mg/kg dose of aqueous extracts of five plant species orally for 2 h (acute) or 14 days (chronic). In acute model blood glucose levels were monitored at specific intervals. In the chronic model blood samples were collected from overnight fasted diabetic rats on day 15 to estimate blood glucose level. And the body weight, serum lipid profile and activities of liver and kidney enzymes were measured. Histopathological observations of liver sections were also studied. Results In the case of acute treatment, aqueous extracts of Tinospora bakis ( T. bakis ), Nauclea latifolia ( N. latifolia ) and Randia nilotica ( R. nilotica ) at 400 mg/kg significantly lowered ( P 0.05) blood glucose levels in diabetic rats whereas, chronic treatment of diabetic rats with 400 mg/kg of T. bakis, N. latifolia, R. nilotica and Mitragyna inremis proved to have significant ( P 0.05) antihyperglycemic effect and have the capacity to correct the metabolic disturbances associated with diabetes. Histopathological studies showed that the aqueous extracts of these four plants reinforced the healing of liver. However, Striga hermonthica aqueous extract did not exert any antihyperglycemic effect to diabetic rats. Conclusions This study demonstrated that T. bakis, N. latifolia, R. nilotica and Mitragyna inremis have therapeutic value in diabetes and related complications and thus supporting the traditional uses of these plants in Sudanese traditional medicine.

Background Bacterial Infections involving multi-drug resistant (MDR) phenotypes constitute a worldwide health concern. The present work was designed to assess the antibacterial properties of the methanol extracts of six medicinal plants (Anthocleista schweinfurthii, Nauclea latifolia, Boehmeria platyphylla, Caucalis melanantha, Erigeron floribundus and Zehneria scobra) and the effects of their associations with antibiotics on MDR Gram-negative bacteria over-expressing active efflux pumps. Methods The antibacterial activities and the ability to potentiate antibiotic effects of the methanol extracts the tested plants were evaluated in vitro against twenty eight Gram-negative bacteria expressing MDR phenotypes, using broth microdilution method. The phytochemical screening of these extracts was also performed using standard methods. Results All tested extracts displayed moderate to low antibacterial activity on at least 14.3 % of the 28 tested bacteria, with MIC values ranged from 128 to 1024 μg/mL. The best antibacterial spectrum was observed with Naulcea latifolia bark extract. Extracts from A. schweinfurthii fruits, N. latifolia stem bark, Z. scobra and N. latifolia leaves showed synergistic effects with many antibiotics against MDR bacteria. Conclusion The overall results of the present study provide information for the possible use of the studied plants, especially Nauclea latifolia in the control of Gram-negative bacterial infections including MDR species as antibacterials as well as resistance modulators. Electronic supplementary material The online version of this article (doi:10.1186/s12906-016-1105-1) contains supplementary material, which is available to authorized users.

International audience; BACKGROUND: Populations in Africa mostly rely on herbal concoctions for their primarily health care, but so far scientific studies supporting the use of plants in traditional medicine remain poor. The present study was undertaken to evaluate the anti-hyperglycemic effects of Picralima nitida (seeds), Nauclea latifolia (root and stem) and Oxytenanthera abyssinica (leaves) commonly used, in diabetic pregnancy. METHODS: Pregnant wistar rats, rendered diabetic by multiple low injections of streptozotocin, were treated with selected plant extracts based on their antioxidant activities. Vitamin C concentrations, fatty acid compositions and phytochemical analysis of plants extracts were determined. Effect of selected plant extracts on human T cell proliferation was also analysed. RESULTS: All analysed plant extracts exhibited substantial antioxidant activities probably related to their content in polyphenols. Picralima nitida exhibited the highest antioxidant capacity. Ethanolic and butanolic extracts of Picralima nitida, butanolic extract of Nauclea latifolia and ethanolic extract of Oxytenanthera abyssinica significantly decreased hyperglycemia in the diabetic pregnant rats. Butanolic extract of Picralima, also appeared to be the most potent immunosuppressor although all of the analysed extracts exerted an immunosuppressive effect on T cell proliferation probably due to their linolenic acid (C18:3n-3) and/or alkaloids content. Nevertheless, all analysed plants seemed to be good source of saturated and monounsaturated fatty acids. CONCLUSION: By having antioxidant, anti-hyperglycemic and immunosuppressive activities, these plants could be good candidates in the treatment of diabetes and diabetic pregnancy.

Background Malignacies are still a major public concern worldwide and despite the intensive search for new chemotherapeutic agents, treatment still remains a challenging issue. This work was designed to assess the cytotoxicity of six selected Cameroonian medicinal plants, including Nauclea pobeguinii and its constituents 3-acetoxy-11-oxo-urs-12-ene (1), p-coumaric acid (2), citric acid trimethyl ester (3), resveratrol (4), resveratrol β-D-glucopyranoside (5) and strictosamide (6), against 8 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. Methods The resazurin reduction assay was used to evaluate the cytotoxicity of the crude extracts and compounds, whilst column chromatography was used to isolate the constituents of Nauclea pobeguinii. Structural characterization of isolated compounds was performed using nuclear magnetic resonance (NMR) spectroscopic data. Results Preliminary experiments on leukemia CCRF-CEM cells at 40 μg/mL showed that the leaves and bark extracts from Tragia benthamii, Canarium schweinfurthii, Myrianthus arboreus, Dischistocalyx grandifolius and Fagara macrophylla induced more than 50 % growth of this cell line contrary to the leaves and bark extracts of N. pobeguinii. IC50 values below or around 30 μg/mL were obtained with leaves and bark extracts of N. pobeguinii towards two and five, respectively, of the 8 tested cancer cell lines. The lowest IC50 value was obtained with the bark extract of N. pobeguinii against HCT116 (p53−/−) colon cancer cells (8.70 μg/mL). Compounds 4 and 6 displayed selective activity on leukemia and carcinoma cells, whilst 1–3 were not active. IC50 values below 100 μM were recorded with compound 5 on all 9 tested cancer cell lines as well as with 4 against 7 out of 8 and 6 against 2 out of 8 cell lines. Collateral sensitivity was observed in CEM/ADR5000 leukemia cells, MDA-MB-231-BCRP breast adenocarcinoma cells (0.53-fold), HCT116 (p53+/+) cells, human U87MG.ΔEGFR glioblastome multiforme cells to the methanolic bark extract of N. pobeguinii, as well as in MDA-MB-231-BCRP cells and HCT116 (p53+/+) cells and U87MG.ΔEGFR cells (0.86-fold) to compound 5. Conclusions The results of this study demonstrate the cytotoxicity of six Cameroonian medicinal plants, Canarium schweinfurthii, Dischistocalyx grandifolius, Tragia benthamii, Fagara macrophylla, Myrianthus arboreus and Nauclea pobeguinii. We also demonstrated the antiproliferative potential of Nauclea pobeguinii against drug-resistant cancer cell lines. Resveratrol and its glucoside are the major cytotoxic constituents in the bark of Nauclea pobeguinii. Electronic supplementary material The online version of this article (doi:10.1186/s12906-015-0841-y) contains supplementary material, which is available to authorized users.