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.

The Aqueous Lyophilisate of Alchemilla Kiwuensis Engl. (Rosaceae) Displays Antiepileptogenic and Antiepileptic Effects on PTZ-induced Kindling in rats: Evidence of Modulation of Glutamatergic and GABAergic Pathways Coupled to Antioxidant Properties.

Alchemilla kiwuensis Engl. (Rosaceae) (A. kiwuensis) is an herbaceous plant traditionally used by Cameroonians to treat epilepsy and other central nervous system disorders. The present study evaluated the antiepileptogenic and antiepileptic effects of A. kiwuensis (40 mg/kg, 80 mg/kg) following Pentylenetetrazole (PTZ)-induced kindling as well as its sub-chronic toxicity. Following an initial i.p administration of a challenge dose (70 mg/kg), Wistar rats of both sexes received sub convulsive doses (35 mg/kg) of PTZ every other day, one hour after the oral gavage of animals with treatments, until two consecutive stage 4, in all animals of negative control. Seizure progression, latency, duration, and repetition were noted. Twenty-four hours later, animals were dissected to extract their hippocampi. The resulting homogenates were used to evaluate Malondialdehyde, reduced glutathione, catalase activity, GABA, GABA-Transaminase, glutamate, glutamate transporter 2, IL-1ß and TGF-1 ß. Sub-chronic toxicity was conducted according to OECD 407 guidelines. The lyophilisate of A. kiwuensis significantly increased the latency of seizure appearance, delayed seizure progression and decreased seizure repetition and duration. Biochemical analysis revealed that the lyophilisate significantly increased the catalase activity, reduced glutathione, GABA, glutamate transporter 2 and TGF-1B levels. The lyophilisate equally caused a significant decreased in the GABA-Transaminase activity, malondialdehyde, and IL-1 ß levels. There was no noticeable sign of toxicity. A. kiwuensis possesses antiepileptic and antiepiletogenic effects by enhancing GABAergic neurotransmission and antioxidant properties, coupled to modulation of glutamatergic and neuroinflammatory pathways and is innocuous in a sub-chronic model. These justifies its local use for the treatment of epilepsy.

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.

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.

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.

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.

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

Piptadenin, a Novel 3,4-Secooleanane Triterpene and Piptadenamide, a New Ceramide from the Stem Bark of Piptadeniastrum africanum (Hook.f.) Brenan.

Piptadenin (1), a new triterpene along with piptadenamide (10), a new ceramide, have been isolated from the AcOEt-soluble fraction of the MeOH extract of the stem bark of Piptadeniastrum africanum along with nine known compounds, 1-O-[(3ß,22ß)-3,22-dihydroxy-28-oxoolean-12-en-28-yl]-ß-d-glucopyranose (2), 22ß-hydroxyoleanic acid (3), oleanic acid (4), lupeol (5), betulinic acid (6), 5α-stigmasta-7,22-dien-3ß-ol (7), 5α-stigmasta-7,22-dien-3-one (8), (3ß)-stigmast-5-en-3-yl ß-d-glucopyranoside (9) and 2,3-dihydroxypropyl hexacosanoate (11). Except for compound 11, all the isolated compounds are reported for the first time from this plant. The structures of the isolated compounds were elucidated by spectroscopic data including 1D and 2D NMR. The pure compounds 1 - 11 were subjected to the pharmacological screening and compounds 2, 5 - 7 and 9 exhibited potent urease inhibitory activity with IC50 value of 25.8, 28.9, 30.1, 31.8 and 32.7 µm, respectively, whereas compound 1 showed moderate activity (IC50 = 98.7 µm). The potent urease inhibitory activity supplemented the previous literature reports and medicinal uses of this plant.

Antinociceptive Activities of the Methanolic Extract of the Stem Bark of Boswellia dalzielii Hutch. (Burseraceae) in Rats Are NO/cGMP/ATP-Sensitive-K+ Channel Activation Dependent.

Boswellia dalzielii (B. dalzielii) is traditionally used in the treatment of rheumatism, pain, and inflammation. The present investigation evaluates the property and possible mechanism of action of the methanolic extract of B. dalzielii (BDME) on inflammatory and neuropathic pain models. Effects of BDME (250 and 500 mg/kg), orally administered, were verified in mechanical hypernociception induced by LPS or PGE2. Mechanical hyperalgesia, cold allodynia, and heat hyperalgesia were used in vincristine-induced neuropathic pain. NW-nitro-L-arginine methyl ester (inhibitor of nitric oxide synthase), glibenclamide (ATP-sensitive potassium channel blocker), methylene blue (cGMP blocker), or naloxone (opioid antagonist receptor) has been used to evaluate the therapeutic effects of BDME on PGE2-induced hyperalgesia. Chemical profile of BDME was determined by using HPLC-XESI-PDA/MS. BDME showed significant antinociceptive effects in inflammatory pain caused by LPS and PGE2. The extract also significantly inhibited neuropathic pain induced by vincristine. The antinociceptive property of BDME in PGE2 model was significantly blocked by L-NAME, glibenclamide, methylene blue, or naloxone. The present work reveals the antinociceptive activities of BDME both in inflammatory and in neuropathic models of pain. This plant extract may be acting firstly by binding to opioid receptors and secondly by activating the NO/cGMP/ATP-sensitive-K+ channel pathway.

Gastroprotective and ulcer healing effects of Piptadeniastrum Africanum on experimentally induced gastric ulcers in rats.

BACKGROUND: Gastric peptic ulcer is one of the common disorders of gastrointestinal tract, which occur due to an imbalance between the offensive and defensive factors. It is an illness that affects a considerable number of people worldwide. This study was conducted to evaluate the antiulcerogenic and antiulcer effects and recognize the basic mechanism of action of Piptadeniastrum africanum stem bark extracts. METHODS: The aqueous and methanol extracts of Piptadeniastrum africanum were administered at the doses 125, 250 and 500 mg/kg to evaluate their effects on gastric ulcer induced by the HCl/ethanol mixture, indomethacin and acetic acid in Wistar strain male adult rats, aged between 12 and 16 weeks and weighing between 180 and 220 g. Ranitidine, Maalox and Misoprostol were used as standard drugs. Histopathological examination and nitric oxide level were performed to evaluate the basic mechanism of action of Piptadeniastrum africanum. Phytochemical screening was carried out to identify known phytochemicals present in these extracts. RESULTS: The aqueous and methanol extracts of stem bark of Piptadeniastrum africanum significantly inhibited (p < 0.01) gastric ulceration induced by HCl/ethanol to the percentages of inhibition of 81.38; 98.75 and 100 % for the aqueous extract and then 75.83, 89.76 and 96.52 % for the methanol extract, and with the Indomethacin-induced ulcers, aqueous and methanol extracts of bark of Piptadeniastrum africanum reduce significantly (p < 0.01) induced gastric lesions in rats, with percentage of cure 35.75; 52.33 and 98.58 % for the aqueous extract, and 33.7; 51.97; and 65.93 to the methanol extract. The results revealed a significant reduction of ulcerated surface in both extracts and increase of nitric oxide (NO) level with methanol extract. When compared to methanol extract, aqueous extract showed more pronounced effects, corresponding to percentages of healing of 59. 92; 84.12 and 59.65 % for the aqueous extract; and 70.43; 55.49 and 57.59 % for the methanol extract in the ulcer induced by acetic acid, all at the respective doses of 125, 250 and 500 mg/kg. Histopathological observations also demonstrated curative effect. As such, both extracts were found to exhibit preventive and curative effects through the release of NO and growth factors. This could also be due to the presence of phytochemicals such as alkaloids, flavonoids, phenols and saponins which act as antisecretory agents. CONCLUSIONS: Piptadeniastrum africanum stem bark extracts thus have gastroprotective and ulcer healing effects, which could result from their activities by stimulating important cellular mechanisms such as migration and proliferation of epithelial cells that may have a cytoprotective effect by stimulating the release of prostaglandins. These results are required to confirm the ethnopharmacological use of Piptadeniastrum africanum stem bark in the treatment of ulcer.

Anti-ulcerogenic properties of the aqueous and methanol extracts from the leaves of Solanum torvum Swartz (Solanaceae) in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum torvum (Solanaceae) is a plant currently used in Cameroon ethnomedicine for the treatment of stomach ailments. AIM OF THE STUDY: The present study was undertaken to determine the anti-ulcer potential of the aqueous and methanol extracts from the leaves of Solanum torvum. MATERIALS AND METHODS: The aqueous and methanol extracts from the leaves of Solanum torvum were tested orally at the doses of 250, 500 and 750 mg/kg, on gastric ulcerations experimentally induced by HCl/ethanol, indomethacin, pylorus ligation and stress. The fractionation of the methanol extract through silica gel column chromatography produced seven different fractions (A-G) which were tested orally at the dose of 100mg/kg against HCl/ethanol-induced ulceration. RESULTS: The methanol extract at the dose of 750 mg/kg produced 98.12, 99.16, 98.70 and 96.03% inhibition when gastric ulcerations were induced by HCl/ethanol, indomethacin, pylorus ligation and stress, respectively. The aqueous extract at the same dose produced 96.55, 96.86, 98.63 and 98.63% inhibition on ulcerations induced respectively by HCl/ethanol, indomethacin, pylorus ligation and stress. All the fractions of the methanol extract significantly inhibited ulcer formation. Fraction F which contains flavonoids and triterpens was the most active and exhibited an inhibitory percentage of 84.74. Both extracts significantly increased mucus production and reduced gastric acid secretion. CONCLUSIONS: The aqueous and methanol extracts of the leaves of Solanum turvum possess anti-ulcerogenic properties that may be due to cytoprotective mechanism. These results support the ethnomedical uses of the plant in the treatment of gastric ulcer.