Markhamia lutea leaves aqueous and ethanolic extract with curative anti-inflammatory activity attenuates paclitaxel toxicity in rat's intestine.

OBJECTIVES: Markhamia lutea (M. lutea, Bignoniaceae) is mainly found in tropical/neotropical regions of America, Africa and Asia. The plant's leaves, stems or roots are used to treat anaemia, bloody diarrhoea, parasitic and microbial infections. This study evaluates anti-inflammatory properties (in vitro) of Markhamia lutea and their curative effects on paclitaxel-induced intestinal toxicity (in vivo). METHODS: The anti-inflammatory potential of Markhamia lutea was tested over cytokines (TNF-alpha, IL-6, IL-1ß, IL-10), reactive oxygen species (ROS) and enzymes (cyclooxygenase and 5-lipoxygenase). While in vivo, intestinal toxicity was induced for 10 days by oral administration of paclitaxel (3 mg/kg, 0.05 mL). Animals in each group were further treated with aqueous (300 mg/kg) and ethanolic (300 mg/kg) leaves extracts of Markhamia lutea during 7 days and clinical symptoms were recorded, hematological, biochemical and histological analysis were subsequently performed. RESULTS: In vitro, aqueous (250 µg/mL) and ethanolic (250 µg/mL) extracts of Markhamia lutea inhibited the activities of cyclooxygenase 1 (56.67 % and 69.38 %), cyclooxygenase 2 (50.67 % and 62.81 %) and 5-lipoxygenase (77.33 % and 86.00 %). These extracts inhibited the production of intracellular ROS, extracellular ROS and cell proliferation with maximum IC50 of 30.83 µg/mL, 38.67 µg/mL and 19.05 µg/mL respectively for the aqueous extract, then 25.46 µg/mL, 27.64 µg/mL and 7.34 µg/mL respectively for the ethanolic extract. The extracts also inhibited the production of proinflammatory cytokines (TNFα, IL-1ß and IL-6) and stimulated the production of anti-inflammatory cytokines (IL-10). In vivo, after administration of paclitaxel, the aqueous and ethanolic extracts of Markhamia lutea significantly reduced the weight loss, the diarrheal stools and the mass/length intestines ratio of the treated animals compared to the animals of the negative control group. Biochemically, the extracts lead to a significant drop in serum creatinine and alanine aminotransferase levels, followed by a significant increase in alkaline phosphatase. In addition to bringing the haematological parameters back to normal values after disturbance by paclitaxel, the extracts caused tissue regeneration in the treated animals. CONCLUSIONS: In vitro, aqueous and ethanolic extracts of Markhamia lutea showed anti-inflammatory properties (inhibition of COX1, COX2, 5-LOX activities, inhibition of ROS production and cell proliferation); in vivo, the same extracts showed curative properties against intestinal toxicity caused by paclitaxel.

Gastroprotective and ulcer healing effects of Nauclea pobeguinii (Rubiaceae) on experimentally induced gastric ulcers in male Wistar rats.

OBJECTIVES: In this study, we determined the gastroprotective and ulcer-healing effects of extracts (aqueous and methanolic) of Nauclea pobeguinii stem-back. METHODS: Gastroprotective and healing activity were evaluated following a HCl/ethanol and an indomethacin-induced acute ulcers models; acetic acid, pylorus-ligature, pylorus ligature/histamine and pylorus ligature/acetylcholine-induced chronic ulcers models. RESULTS: It emerges from this study that, at 100, 200 and 400 mg/kg, the extracts significantly reduced the various ulceration parameters. Compared to negative control male rats, the aqueous (100 mg/kg) and methanolic (400 mg/kg) extracts of Nauclea pobeguinii inhibited the ulcers induced by HCl/ethanol by 80.76 % and 100 % respectively, as well as ulcers induced by indomethacin by 88.28 % and 93.47 % respectively. Animals that received 200 mg/kg of both extracts showed a significant reduction in the levels of monocytes, lymphocytes, nitric oxide, MDA and a significant increase in the activities of SOD and catalase. Histological analysis showed repaired mucous epithelium at all doses of both extracts. Aqueous and methanol extracts inhibited ulceration indices by 89.33 % and 88.53 % for pylorus ligature, 83.81 % and 61.07 % for pylorus ligature/acetylcholine and 87.29 % and 99.63 % for pylorus ligature/histamine respectively. Both extracts protected the stomach lining with percentages inhibition of 79.49 % and 81.73 %, respectively in the ethanol test. The extracts induced a significant increase in mucus mass (p<0.001). CONCLUSIONS: The aqueous and methanol extracts of Nauclea pobeguinii healed ulcers thanks to their anti-inflammatory, anti-oxidant, anti-secretory and cytoprotective properties.

In Vitro and In Vivo Anti-Inflammatory Properties of the Hydroethanolic Extract of the Roots of Vernonia guineensis (Asteraceae).

In traditional Cameroonian medicine, to relieve many inflammations, parts of Vernonia guineensis, are very widely used. This study considered the evaluation of acute toxicity and anti-inflammatory properties of the hydroethanolic extract of the roots of Vernonia guineensis. In an acute toxicity study, 250, 2500, and 5000 mg/kg were administered orally to mice in a single dose, and general behavior, adverse effects, and mortality were monitored. In vitro and in vivo anti-inflammatory tests were performed, and then histological, serum, hematological, and oxidative stress parameters have been evaluated. In an acute toxicity, all groups revealed neither mortality nor any significant alteration in behavior; only drowsiness, sedation, and lethargy were observed at 5000 mg/kg. For in vitro tests, the extract inhibited anti-inflammatory activity. In the formalin test, at 250 mg/kg, the extract inhibited edema with a percentage of 56.41% (4th hour) in an acute treatment and 74.44% (10th day). Joint edema was reduced by 67.24% (24th hour) in a single treatment and by 74.25% (7th day) in repeated treatment. The extract caused an increase in red blood cell, hemoglobin, and serum protein levels and reduced the white blood cells as well as the activities of alkaline phosphatase and alanine aminotransferase. The extract modulated oxidative stress parameters in the brain, spinal cord, liver, and kidneys. The extract protected the joint by reducing the bone and cartilage erosion. The present work highlights the anti-inflammatory, antioxidant, and antianemic properties of the hydroethanolic extract of the roots of Vernonia guineensis, which supports its empirical use in traditional medicine for the treatment of inflammatory pathologies.

Anti-Helicobacter pylori, anti-Inflammatory, and Antioxidant Activities of Trunk Bark of Alstonia boonei (Apocynaceae).

An ulcer is an erosion of the gastric mucosa that occurs following an imbalance between the aggression and protective factors and/or an infection with Helicobacter pylori (H. pylori). About 90-100% of duodenal ulcers and 70-80% of gastric ulcers are caused by H. pylori. The objective of this work was to evaluate in vitro the anti-H. pylori activity and then the anti-inflammatory and antioxidant properties of aqueous and methanol extracts of Alstonia boonei. The anti-H. pylori tests (CMI and antiureasic activity) were determined using the agar well diffusion method, the microbroth dilution method, and the measurement of ammonia production by the indophenol method; the anti-inflammatory properties were evaluated by inhibition of proteinases, denaturation of albumin, production of NO by macrophages, cell viability, and hemolysis of red blood cells by heat; then, the antioxidant properties were evaluated by the FRAP method (ferric reducing antioxidant power) and the DPPH (1,1-diphenyl-2-picrylhydrazyl) test. The results show that the best trapping of the DPPH radical was obtained with the methanol extract (EC50 = 8.91 µg/mL) compared to the aqueous extract (EC50 = 19.86 µg/mL). The methanol extract also showed greater iron-reducing activity than the aqueous extract and vitamin C. Furthermore, at the concentration of 200 µg/mL, the methanol extract showed a percentage (96.34%) strains of H. pylori higher than that of the aqueous extract (88.52%). The MIC90 of the methanol extract was lower than that of the aqueous extract. The methanol extract showed a higher percentage inhibition (85%) of urease than the aqueous extract (73%). The methanol extract at a concentration of 1000 µg/mL showed the greatest ability to inhibit proteinase activity, albumin denaturation, and red blood cell hemolysis; on the other hand, maximum cell viability and greater production of nitrite oxide by macrophages were obtained with the aqueous extract. Aqueous and methanol extracts of Alstonia boonei possess anti-H. pylori which would probably be linked to their antioxidant and anti-inflammatory properties.

Scyphocephalione A isolated from the stem bark of Scyphocephalium ochocoa (Myristicaceae) attenuate acute and chronic pain through the antiinflammatory activity.

In the treatment of cancer, patients that receive anti-cancer drugs such as Vincristine develop peripheral neuropathic pain. Scyphocephalione A is a new bioactive compound isolated from Scyphocephalium ochocoa (Myristicaceae), a medicinal plant traditionally used in African countries. Recently, an in vitro study has shown its anti-inflammatory and cytotoxic activities on MCF-7 cell line of mammary carcinoma. The purpose of the present study was to assess the in vitro anti-inflammatory and in vivo anti-nociceptive activities of Scyphocephalione A. In vitro tests were carried out on cyclooxygenase and 5-lipoxygenase activities, and on protein denaturation; while in vivo tests were performed on acute and chronic pain models. It was noticed that Scyphocephalione A (1000 µg/ml), inhibits proteins denaturation, cyclooxygenase and 5-lipoxygenase activities respectively by 74.21%, 75.80% and 64.43%. The dose 50 mg/kg of Scyphocephalione A, inhibits acetic acid (63.43%, p < 0.001) and formalin (42.12%, p < 0.001) within first phase and 67.53% (p < 0.001) within second phase)-induced pains. At the same dose, Scyphocephalione A significantly inhibited mechanical and heat hyperalgesia, as well as cold allodynia induced by vincristine. In addition, the compound restored haematological, biochemical and oxidative stress parameters which were altered following Vincristine administration. These results suggest that Scyphocephalione A is endowed with anti-inflammatory potential and antinociceptive properties. Therefore, Scyphocephalione A can be classified as a promising molecule for the management of peripheral neuropathic pain triggered by anti-cancer drug.

A new dibenzofuran derivative from the stem bark of Scyphocephalium ochocoa with anti-inflammatory and cytotoxic activities.

The phytochemical investigation of the dichloromethane/methanol (1:1) extract of the stem bark of Scyphocephalium ochocoa, led to the isolation of one new dibenzofuran derivative, named scyphocephalione A (1), along with three other compounds, including epicatechin (2), gentisic acid (3) and myo-inositol (4). The structures of all the compounds were established with help of spectroscopic data including IR, UV, MS, 1 D- and 2 D-NMR, as well as by comparison with previously reported data in literature, and chemical modification. All the compounds were obtained from the genus Scyphocephalium for the first time. The anti-inflammatory activity (using chemiluminescence technique) of the crude extract and compound 1, together with NO inhibition (using ELISA), TNF-α (using ELISA) and MCF-7 cells cytotoxicity effects (using MTT assay) of compound 1 were assessed. From the results obtained, compound 1 could be considered as a promising chemotherapeutic agent for the treatment of inflammatory diseases.

Antihypernociceptive and Neuroprotective Effects of the Aqueous and Methanol Stem-Bark Extracts of Nauclea pobeguinii (Rubiaceae) on STZ-Induced Diabetic Neuropathic Pain.

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-1ß, 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 <0.001) reduced tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), and IL-6 and significantly (p <0.001) increased nerve growth factor (NGF) and insulin-like growth factor (IGF) in sciatic nerves. The results of this study confirmed that Nauclea pobeguinii aqueous and methanol extracts possess antihyperalgesic, antidepressant, and anxiolytic activities and could be beneficial therapeutic agents.

Methanolic Extract of Distemonanthus benthamianus (Caesalpiniaceae) Stem Bark Suppresses Ethanol/Indomethacin-Induced Chronic Gastric Injury in Rats.

Distemonanthus benthamianus (Caesalpiniaceae) is a plant from the Cameroon pharmacopoeia very widely used in the treatment of many pathologies among which are gastrointestinal disorders. The main purpose of this study was to assess the healing properties of gastric ulcer from the methanolic extract of Distemonanthus benthamianus and its mechanisms of action. The healing properties of gastric ulcers (chronic ulcer model induced by ethanol and indomethacin) were evaluated in vivo in adult male rats, while the mechanisms of action were evaluated in vitro by anti-inflammatory assay (protein denaturation, cyclooxygenase, and lipoxygenase assays) and immunomodulatory assay (ROS production (using technical chemiluminescence), cytokine (TNF-α, IL-1ß, IL-6) production (using ELISA), proliferation of T cells (using liquid scintillation counter), and cytotoxicity (using MTT assay)). The methanolic extract of Distemonanthus benthamianus inhibited protein denaturation (75.63%) and the activities of cyclooxygenase (78.92%) and 5-lipoxygenase (81.54%). The extract also significantly (p < 0.001) inhibited intracellular and extracellular ROS production and T cell proliferation and reduced significantly (p < 0.01, p < 0.001) TNF-α, IL-1ß, IL-6, and PGE2 production. At all doses (125, 250, and 500 mg/kg), the extract significantly reduces the ulceration index and the area of ulceration and significantly increases the mass of gastric mucus. In addition, the extract significantly decreases the level of MDA, significantly increases the activities of catalase and glutathione, and then improves the hematological parameters in sick animals. Histological micrographs show that in the presence of the extract, there is advanced reepithelialization with recovery of the ulcerated epithelium. Thus, the extract of Distemonanthus benthamianus has healing properties against gastric ulcers which are associated with its anti-inflammatory, immunomodulatory, and antioxidant effects.

Antihypernociceptive, Anxiolytic, and Antidepressant Properties of Aqueous and Ethanol Extracts of Dissotis thollonii Cogn. (Melastomataceae) in Mice.

Diabetic neuropathy, which affects 7 to 9% of the world's population and that is usually accompanied by anxiety and depression, is chronic pain that results from impaired function of the central or peripheral nervous system. This study aimed at evaluating the antihypernociceptive, antiallodynic, anxiolytic, and antidepressant effects of Dissotis thollonii extracts. Diabetic neuropathy was induced by intraperitoneal injection of streptozotocin (200 mg/kg) in mice. The aqueous and ethanol extracts (250 and 500 mg/kg) were administered orally. Hyperalgesia (thermal and chemical), allodynia (mechanical and thermal), anxiety (high plus labyrinth, light-dark box, and social interaction), and depression (open field test, suspension test tail, and forced swimming test) were evaluated, and then the levels of some cytokines and growth factors were determined. The aqueous and ethanol extracts of Dissotis thollonii demonstrated significant antihypernociceptive (inhibition of hyperalgesia and allodynia), anxiolytic, and antidepressant activities in mice made diabetic by STZ. The extracts also significantly inhibited (p < 0.001) the levels of TNF-α, IL-1ß, and IL-6 in the blood as well as the levels of TNF-α, IL-1ß, IL-6, IGF, and NGF in the sciatic nerve. This study shows that the extracts of Dissotis thollonii have antihypernociceptive and neuroprotective effects which could be linked to the inhibition of proinflammatory cytokines and growth factors in the blood and the sciatic nerve.

Cytoprotective and antisecretory properties of methanolic extract of Distemonanthus benthamianus (Caesalpiniaceae) stem bark on acute gastric ulcer in rats.

OBJECTIVES: In African traditional medicine, Distemonanthus benthamianus (Caesalpiniaceae) is used to treat many diseases including gastric ulcers. We evaluated in this study, the cytoprotective and antisecretory properties of the methanolic extract of the stem bark of this plant using different technics of gastric lesion induction. METHODS: Cytoprotective and antisecretory activity of the methanolic extract of D. benthamianus stem bark was evolved through six methods of gastric lesion induction in experimental Wistar male rats (150-200 g): (1) gastric lesions induced by HCl/ethanol, (2) gastric lesions induced by Indomethacin- HCl/ethanol, (3) gastric lesion induced by Indomethacin, (4) gastric lesions induced by Pylorus ligation, (5) gastric lesions induced by histamine-Pylorus ligation, (6) gastric lesions induced by carbachol-Pylorus ligation. Mucus and gastric mucosal ulceration were evaluated. pH, gastric volume, and acidity were quantified in all pylorus ligation induction technics. Nitric oxide (NO) level was determined in indomethacin induced gastric ulcers. RESULTS: At different doses (125, 250 and 500 mg/kg), extract reduced significantly the ulcer index. In all models used, that is 100.00% with HCl/ethanol; 100.00% with HCl/ethanol/indomethacin; 95.70% with Indomethacin; 74.79% with pylorus ligation, 95.94% histamine-Pylorus ligation, 99.54% carbachol-Pylorus ligation at the highest dose of 500 mg/kg. The lesion formation reduces in all the methods used followed by a significant increase of mucus production. The pylorus ligation technic revealed that the extract has an antisecretory activity. CONCLUSIONS: The methanolic extract of D. benthamianus stem bark has both cytoprotective and antisecretory effects. This extract exerts its antisecretory effect trough cholinergic and histaminergic pathways.

Effects of Aqueous and Methanolic Extracts of Stem Bark of Alstonia boonei De Wild. (Apocynaceae) on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Wistar Rats.

Among the most exploited species in Cameroon, Alstonia boonei is widely used in African medicine for the relief of several pathologies including gastrointestinal disorders. This study was conducted in order to assess the effects of aqueous and methanol stem-bark extracts of Alstonia boonei on DSS- (dextran sodium sulfate-) induced intestinal colitis and to determine its antioxidant potential. The classes of secondary metabolites present in these extracts were determined by chemical screening. The production of TNF-α, IL-6, IL-1ß, and PGE2 was performed by in vitro ELISA analysis. Anticolitis effects were determined using an in vivo model of ulcerative colitis induced by DSS. The colitis was induced with a double dose of DSS (3% and 1%), and the aqueous and methanol extracts were administered orally from the 6th day after commencement of induction. The phytochemical screening revealed the presence of six classes of secondary metabolites in these crude extracts: tannins, saponins, alkaloids, steroids, flavonoids, and phenols. Methanol and aqueous extracts of Alstonia boonei significantly (P < 0.001) inhibited TNF-α, IL-6, IL-1ß, and PGE2 production stimulated by LPS. Both extracts at all doses significantly reduced (P < 0.01, P < 0.001) the signs of DSS-induced colitis in the Wistar rats by decreasing inflammation and chronic colon damage. In addition, the extracts significantly (P < 0.001) reduced malondialdehyde and nitric oxide levels in the colon and significantly (P < 0.01) increased superoxide dismutase and catalase and reduced glutathione (P < 0.05). Both extracts showed greater activity than the reference substance (prednisolone 4 mg/kg) used in this study. This study has demonstrated that aqueous and methanol extracts of Alstonia boonei stem bark have healing properties against colitis experimentally induced by DSS in rats.

In vitro anti-inflammatory, anti-oxidant and in vivo anti-arthritic properties of stem bark extracts from Nauclea pobeguinii (Rubiaceae) in rats

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.

In Vitro Anti-Inflammatory and In Vivo Antiarthritic Activities of Aqueous and Ethanolic Extracts of Dissotis thollonii Cogn. (Melastomataceae) in Rats.

Dissotis thollonii Cogn. (Melastomataceae) is a tropical plant widely used in traditional Cameroonian medicine to relieve and treat many pathologies. It is widespread in the western region where it is used to treat typhoid fever, gastrointestinal disorders, and inflammatory diseases. The purpose of this study is to scientifically demonstrate the anti-inflammatory and antiarthritic properties of the aqueous and ethanolic extracts of the leaves of Dissotis thollonii. The anti-inflammatory properties were evaluated in vitro by inhibition tests for cyclooxygenase, 5-lipoxygenase, protein denaturation, extracellular ROS production, and cell proliferation; while antiarthritic properties were evaluated in vivo in rats using the zymosan A-induced monoarthritis test and the CFA-induced polyarthritis model. This study shows that aqueous and ethanolic extracts at a concentration of 1000 µg/ml inhibit the activity of cyclooxygenase (47.07% and 63.36%) and 5-lipoxygenase (66.79% and 77.7%) and protein denaturation (42.51% and 44.44%). Similarly, both extracts inhibited extracellular ROS production (IC50 = 5.74 µg/ml and 2.96 µg/ml for polymorphonuclear leukocytes, 7.47 µg/ml and 3.28 µg ml for peritoneal macrophages of mouse) and cell proliferation (IC50 = 16.89 µg/ml and 3.29 µg/ml). At a dose of 500 mg/kg, aqueous and ethanolic extracts significantly reduce edema induced by zymosan A (69.30% and 81.80%) and CFA (71.85% and 79.03%). At the same dose, both extracts decreased sensitivity to mechanical hyperalgesia with 69.00% and 70.35% inhibition, respectively. Systemic and histological analyzes show that both extracts maintain the studied parameters very close to normal and greatly restored the normal architecture of the joint in animals. Dissotis thollonii would therefore be a very promising source for the treatment of inflammatory diseases.

Antihypernociceptive and neuroprotective effects of Combretin A and Combretin B on streptozotocin-induced diabetic neuropathy in mice.

Painful diabetic neuropathy (PDN) is known to adversely affect psychosocial functioning by enhancing levels of anxiety and depression. This study was designed to verify the antihypernociceptive, anxiolytic, and antidepressant-like effects of Combretin A and Combretin B (two triterpenes cycloartane-type isolated from the leaves of Combretum fragrans) in streptozotocin-induced diabetic neuropathy in mice. PDN was induced in mice by the administration of streptozotocin (STZ, 200 mg/kg, i.p.). The effect of oral administration of Combretin A (25 and 50 mg/kg) and Combretin B (25 and 50 mg/kg) on nociception (mechanical allodynia, thermal hyperalgesia, cold allodynia, and chemical hyperalgesia), anxiety (elevated plus maze, light-dark box test, social interaction), and depressant (open field test, forced swimming test, tail suspension test) was evaluated. Combretin A (25 and 50 mg/kg) and Combretin B (25 and 50 mg/kg) caused antihypernociceptive, anxiolytic, and antidepressant-like effects in in STZ-induced diabetic neuropathy in mice. Both compounds also caused a decrease in blood glucose and improved body weight in treated animals. They also significantly (p < 0.001) reduced tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), malondialdehyde (MDA), and nitric oxide (NO) production in serum and sciatic nerves, and, significantly (p < 0.001) increased superoxide dismutase (SOD) and catalase (CAT) activity in serum, sciatic nerves, and brain. Combretin A and Combretin B also showed a great systemic effect, conserving values of evaluated parameters close to normal in treated mice. The results of this study confirm the antihypernociceptive, antianxiety, and antidepressant activities of Combretin A and Combretin B.

Antidiarrheal potential of Distemonanthus benthamianus Baillon. extracts via inhibiting voltage-dependent calcium channels and cholinergic receptors

Objective: To evaluate spasmolytic mechanisms of aqueous and methanolic extracts from Distemonanthus benthamianus trunk-bark. Methods: Spasmolytic activities of extracts were evaluated in vitro on spontaneous and potassium chloride-induced jejunum contractions, or against cholinergic [acetylcholine (0.3μmol/L)] stimulations. High performance liquid chromatography analysis of both extracts was performed in reference to standard compounds. Results: Extracts developed concentration-dependent inhibitory activities. The methanolic extract, which revealed better activity, produced spasmolytic and myorelaxant effects at concentrations of 0.01-0.30 mg/mL with EC50 of 0.06 and 0.09 mg/mL (95％ CI: 0.03-0.3 mg/mL), respectively. Its anticholinergic effect was obtained at the same concentrations with EC50 of 0.11 mg/mL (95％ CI:0.03-0.3 mg/mL). Chromatograms showed the presence of gallic acid in both extracts, rutin being only detected in the aqueous extract. Conclusions: Distemonanthus benthamianus extracts exhibit verapamil and atropine-like activities, thus highlighting calcium channels and muscarinic receptors blocking potentials, which may be conveyed by some phenolic compounds. These results confirm the antidiarrheal activity of Distemonanthus benthamianus extracts.

Anti-inflammatory and anti-arthritic effects of methanol extract of the stem bark of Boswellia dalzielii Hutch (Burseraceae) in rats.

Boswellia dalzielii is a tall tree (more than 13 m high) that produces aromatic white flowers. This plant is commonly used in indigenous medicine across Africa against diarrhea, malaria, vomiting, inflammation and arthritis. The present study focuses on the anti-inflammatory and anti-arthritis potential of methanol extract of Boswellia dalzielii (BDME). Anti-inflammatory activity was evaluated in inflammatory models induced by carrageenan, arachidonic acid, histamine, serotonin, prostaglandin and bradykinin. Anti-arthritis activity was measured using complete Freund's adjuvant model. Intracellular and extracellular ROS production and proliferation of T-cells were evaluated using chemiluminescence and liquid scintillation counter techniques, respectively. TNF-α and IL-1ß production were assessed using ELISA and MTT assay performed for cytotoxicity. BDME revealed a significant anti-inflammatory effect by preventing the development of edema caused by carrageenan, arachidonic acid, histamine, serotonin, prostaglandin and bradykinin. For anti-arthritic properties of BDME, the results showed a significant reduction of the joint diameter and a decrease in pain in the treated animals. The extract also showed a noticeable systemic effect, maintaining the values of the evaluated parameters close to normal in treated rats with an inhibition of joint destruction as shown in histopathological analysis. Furthermore, BDME exhibited significant inhibition of extracellular and intracellular ROS production. Still, the extract displayed significant inhibitory activity on T-cell proliferation as well as a reduced production of TNF-α and IL-1ß. Boswellia dalzielii could be considered as a promising tract in the prevention and/or management of inflammatory diseases.

Flavonoids and triterpenes from Combretum fragrans with anti-inflammatory, antioxidant and antidiabetic potential.

Despite the well-documented benefits of Combretum fragrans in Cameroon, only few scientific works have been done on it. In this study we isolated eight compounds from the leaves extract of C. fragrans: velutin (1), belamcanidin (2), cirsilineol (3), cirsimaritin (4), 3ß-acetoxy-20,24-epoxy-11,25-hydroxy-dammarane (5), combretin A (6), combretin B (7) and a mixture of arjunolic acid (8a) and asiatic acid (8b). Compounds 6 and 7 presented potent anti-inflammatory, antioxidant and antidiabetic activities. Compounds 1, 3, 5 and the mixture of 8a and 8b were significantly active, and compounds 2 and 4 presented moderate activity for reactive oxygen species inhibitory and free-radical scavenging. All compounds were isolated using chromatographic techniques; their structures were elucidated by spectroscopic techniques and their spectroscopic data compared with those of the literature. Anti-inflammatory activity was evaluated via the oxidative burst assay using a luminol-amplified chemiluminescence technique, antioxidant activity by free-radical scavenging activity (DPPH) and antidiabetic activity via α-glucosidase inhibition. All of the isolated compounds (1-8) were reported to exhibit significant antioxidant activity. Compounds 1, 3, and 5-8 exhibited potent chemiluminescence inhibition effect, and only compounds 6 and 7 inhibited α-glucosidase. Thus, C. fragrans can be used as an effective natural source of anti-inflammatory, antioxidant and antidiabetic compounds.

Analgesic, anti-inflammatory and anticancer activities of Combretin A and Combretin B isolated from Combretum fragrans F. HOFFM (Combretaceae) leaves.

Previous pharmacological and phytochemical studies showed that, Combretum fragrans F. HOFFM (Combretaceae) is a Cameroonian medicinal plant possessing numerous therapeutic virtues and rich in various active secondary metabolites. In this study, we investigate in vivo anti-nociceptive and anti-inflammatory activity and, in vitro anticancer, anti-TNFα, ROS and NO-inhibitory activities of Combretum A and Combretin B, two triterpenes cycloartane-type isolated from the leaves of Combretum fragrans. The effect on ROS, TNF-α and NO production, anticancer activity and cytotoxicity assay were done using chemiluminescence technique, ELISA kit, colorimetric method, MCF-7 cells and MTT assay, respectively. Antinociceptive and anti-inflammatory activities were estimated using a model of acetic acid, formalin and carrageenan. Combretin A and Combretin B significantly (p < 0.001) inhibited extracellular ROS production. These compounds also significantly (p < 0.001) reduced TNF-α and NO production. Moreover, these compounds decreased cell viability of MCF-7 cell lines. For acetic acid- or formalin-induced pain, as well as carrageenan-induced acute inflammation, Combretin A and Combretin B exhibited significant (p < 0.001) anti-nociceptive and anti-inflammatory activities. Anti-nociceptive, anti-inflammatory and anticancer potential associated with inhibitory effects on ROS, TNFα and NO production in this study show that, Combretin A and Combretin B could be considered as the promising chemotherapeutic agents in breast cancer treatment and inflammatory disease.

NO-cGMP-K channel-dependent anti-nociceptive activities of methanol stem bark extract of Piptadeniastrum africanum (Mimosaceae) on rats

Objective: To explore anti-hyperalgesic properties of methanol extract of Piptadeniastrum africanum stem bark (PAME) and it possible action mechanism. Methods: PAME was tested on carrageenan induced hyperalgesia using plantar test (thermal) and analgesymeter (mechanical) in rats, on prostaglandin E

Anti-arthritic property of crude extracts of Piptadeniastrum africanum (Mimosaceae) in complete Freund's adjuvant-induced arthritis in rats.

BACKGROUND: Rheumatoid arthritis, disease of unknown causes is a rheumatic and autoimmune pathology, recognised for its increasing frequency and its adverse consequences. It is a disease that occurs in most cases between 50 and 60 years and women are more affected than men. This study aimed at evaluating immunomodulatory and anti-arthritis capacity of aqueous and methanol extracts of stem bark of Piptadeniastrum africanum (Mimosaceae). METHODS: ROS production from phagocytes, proliferation of T-cells, TNF-α and IL-1ß production and cytotoxicity were performed by using chemiluminescence technique, liquid scintillation counter, ELISA and MTT assay, respectively. Anti-arthritic activity was evaluated using a model of adjuvant induced arthritis. RESULTS: Methanol and aqueous extracts of Piptadeniastrum africanum significantly (P < 0.001) inhibited extracellular and intracellular ROS production. These extracts also possess significant (P < 0.001) inhibitory activity on T-cell proliferation other than reduced TNF-α and IL-1ß production. Piptadeniastrum africanum also significantly exhibited antiarthritic activity in complete Freund's adjuvant induced arthritis in rat associated with a significant anti-inflammatory and anti-hyperalgesia activity. CONCLUSIONS: Immunomodulatory, anti-inflammatory, antihyperalgesia and anti-arthritis potential revealed in this study approve that, Piptadeniastrum africanum is a plant rich in compounds with anti-arthritic properties.