Antinociceptive, anti-inflammatory and antioxidant effects of Boerhavia coccinea extracts and fractions on acute and persistent inflammatory pain models.

Background Boerhavia coccinea (Nyctaginaceae) is an herbaceous plant used for the treatment of pain. The aim of this study was to evaluate the antinociceptive and anti-inflammatory activities of the aqueous (AEBC) and ethanol (EEBC) extracts of Boerhavia coccinea as well as the major fractions (F1, F2 and F3) from EEBC. Methods The antinociceptive effect of the extracts and fractions was evaluated using formalin test. AEBC, EEBC and F1 were selected and further evaluated acutely (24 h) and chronically (16 days) in Complete Freund's Adjuvant (CFA)-induced persistent inflammatory pain for their antihyperalgesic and anti-inflammatory effects. They were administered orally (100 and 200 mg/kg/day) from 48 h following the intraplantar injection of 100 µL of CFA. After the 16 days of chronic treatment, rats' spinal cord and brain were collected for the evaluation of oxidative stress parameters namely nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT). Results AEBC, EEBC and F1 significantly inhibited the first and second phases of the formalin-induced pain. They significantly reduced the hyperalgesia both in acute and chronic treatments. These extracts showed no acute anti-inflammatory effect. AEBC and EEBC exhibited anti-inflammatory activities after repeated administration. AEBC, EEBC and F1 significantly reduced MDA level and significantly increased SOD and catalase activities, mainly in the spinal cord. AEBC and EEBC also reduced the NO production in the spinal cord. Conclusions Boerhavia coccinea extracts and F1 possess potent antinociceptive activity which is not related to their anti-inflammatory properties. Their antioxidant effects may contribute to these activities in chronic treatment.

Aqueous and methanol extracts of Paullinia pinnata L. (Sapindaceae) improve inflammation, pain and histological features in CFA-induced mono-arthritis: Evidence from in vivo and in vitro studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Paullinia pinnata L. (Sapindaceae) is an African woody vine, traditionally used for the treatment of itch and pain-related conditions such as rheumatoid arthritis. AIM: This work evaluates, in vitro and in vivo, the anti-inflammatory and analgesic effects of aqueous (AEPP) and methanol (MEPP) extracts from Paullinia pinnata leaves. METHODS: AEPP and MEPP (100, 200 and 300 mg/kg/day) were administered orally in monoarthritic rats induced by a unilateral injection of 50 µl of Complete Freund's Adjuvant (CFA) in the ankle joint. During the 14 days of treatment, pain and inflammation were evaluated alternatively in both ankle and paw of the CFA-injected leg. Malondialdehyde (MDA) and glutathione (GSH) levels were assessed in serum and spinal cord. Histology of soft tissue of the ankle was also analyzed. For in vitro studies, AEPP and MEPP (10, 30 and 100 µg/ml) were evaluated against nitric oxide (NO) production by macrophages that were either non-stimulated or stimulated with LPS, 8-Br-AMPc and the mixture of both substances after 8 h exposure. These extracts were also evaluated on TNF-α and IL-1ß production in cells stimulated with LPS for 8 h. Finally, the ability of the extracts to bind to neuroactive receptors was evaluated in vitro using competitive binding assays with >45 molecular targets. RESULTS: AEPP and MEPP significantly reduced by 20-98% (p < 0.001) the inflammation and pain sensation in both the ankle and paw. AEPP significantly increased glutathione levels (p < 0.05) in serum. Both extracts reduced MDA production in serum and spinal cord (p < 0.001), and significantly improved tissue reorganization in treated arthritic rats. P. pinnata extracts did not affect NO production in non-stimulated macrophages but significantly reduced it by 47-88% in stimulated macrophages. AEPP and MEPP also significantly inhibited TNF-α (35-68%) and IL-1ß (31-36%) production in LPS stimulated macrophages. No cytotoxic effect of plant extracts was observed. MEPP showed concentration-dependent affinity for Sigma 2 receptors with an IC50 of 50 µg/ml. CONCLUSION: These results demonstrate the analgesic and anti-inflammatory effects of P. pinnata extracts on monoarthritis and further support its traditional use for pain and inflammation. These activities are at least partly due to the ability of these extracts to inhibit the production of NO, TNF-α, IL-1ß and to likely modulate Sigma 2 receptors.

Anti-hyperalgesic activity of the aqueous and methanol extracts of the leaves of Pittosporum mannii Hook on CFA-induced persistent inflammatory pain.

BACKGROUND: Previous study showed that aqueous (AEPM) and methanol (MEPM) extracts from the leaves of Pittosporum mannii have analgesic effects in acute pain models. The present study evaluates the acute and chronic anti-hypernociceptive and anti-inflammatory effects of AEPM and MEPM in a model of persistent inflammatory pain. METHODS: The third day after induction of inflammatory pain by subplantar injection of 100 µL of CFA in Wistar rats, AEPM and MEPM were administered orally (75, 150 and 300 mg/kg/day) and their anti-hyperalgesic and anti-inflammatory effects were follow in acute (1-24 h) and chronic (for 14 days) treatments. At the end of the chronic treatment, oxidative stress and liver parameters were assessed. Effects of plant extracts were also evaluated on nociception induced by Phorbol 12-Myristate 13-Acetate (PMA) and 8-bromo 3',5'-cAMP (8-Br-cAMP) in mice. RESULTS: AEPM and MEPM significantly reversed the mechanical hyperalgesia caused by CFA in acute and chronic treatment. Moreover, AEPM and MEPM also significantly reduced the nociception caused by PMA (60%) and 8-Br-cAMP (87%). Nevertheless, AEPM and MEPM failed to inhibit the paw edema caused by CFA. Plant extracts significantly reduced the nitric oxide content in the spinal cord and the plasmatic concentration of alanine aminotransferase. MEPM also significantly increased the glutathione content in the spinal cord. CONCLUSION: AEPM and MEPM given orally are effective in inhibiting mechanical hyperalgesia in persistent inflammatory pain caused by CFA. Their mechanisms of action seem to involve an interaction with PKC, PKA and nitric oxide pathways. These extracts might be devoid of hepatotoxic effects.

Cycloartanes from Oxyanthus pallidus and derivatives with analgesic activities.

BACKGROUND: The leaves of Oxyanthus pallidus Hiern (Rubiaceae) are extensively used in the west region of Cameroon as analgesic. These leaves are rich in cycloartanes, a subclass of triterpenes known to possess analgesic and anti-inflammatory properties. The present study aimed at evaluating the analgesic properties of three cycloartanes isolated from Oxyanthus pallidus leaves as well as their aglycones and acetylated derivatives. METHODS: Three cycloartanes OP3, OP5 and OP6 obtained by successive chromatography of the crude methanol extract of the leaves were hydrolysed to yield respective aglycone AOP1, AOP2, AOP3 and acetylated to HOP1, HOP2 and HOP3 respectively. Formalin-induced pain model was used to evaluate the acute anti-nociceptive properties of these cycloartanes (5 mg/kg, p.o) in mice and to determine the structure-activity relationship. Acute (24 h) and chronic (10 days) anti-hyperalgesic and anti-inflammatory activities of OP5 were evaluated at the doses of 2.5 and 5 mg/kg/day administered orally. OP6 was also evaluated in acute experiments. The antioxidant and hepato-protective activities of OP5 were evaluated at the end of the chronic treatment. RESULTS: The mixture and the individual isolated cycloartanes significantly inhibited both phases of formalin-induced pain with percentage inhibition ranging from 13 to 78%. Acid hydrolysis did not significantly affect their antinociceptive activities while acetylation significantly reduced the effects of these compounds during the second phase of pain. OP5 and OP6 induced acute anti-hyperalgesic activity in formalin-induced mechanical hyperalgesia but not an anti-inflammatory effect. Repeated administration of OP5 for 10 days did not induce any anti-hyperalgesic effect. The evaluation of in vivo antioxidant properties showed that OP5 significantly reduced malondialdehyde and increased superoxide dismutase levels in liver without significantly affecting other oxidative stress and hepatotoxic parameters. Chronic administration of OP5 did not cause gastric ulceration. CONCLUSION: Cycloartanes isolated from Oxyanthus pallidus possess analgesic effects but lack anti-inflammatory activities. This analgesic effect especially on inflammatory pain may be due to the presence of hydroxyl group in front of the plane. OP5 is devoid of ulcerogenic effect and possess antioxidant properties that might be of benefit to its analgesic properties.

Antinociceptive properties of the aqueous and methanol extracts of the stem bark of Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous maceration from the stem barks of Petersianthus macrocarpus (P. Beauv.) Liben (Lecythidaceae) is taken orally in the central Africa for the management of various ailments, including pain. AIM OF THE STUDY: This work was carried out to evaluate in mice, the antinociceptive effects of the aqueous and methanol extracts of the stem bark of P. macrocarpus. MATERIALS AND METHODS: The chemical composition of the aqueous and methanol extracts prepared as cold macerations was determined by high performance liquid chromatography coupled with mass spectrometry (LCMS). The antinociceptive effects of these extracts administered orally at the doses of 100, 200 and 400 mg/kg were evaluated using behavioral pain model induced by acetic acid, formalin, hot-plate, capsaicin and glutamate. The rotarod test was also performed at the same doses. The oral acute toxicity of both extracts was studied at the doses of 800, 1600, 3200 and 6400 mg/kg in mice. RESULT: The LCMS analysis revealed the presence of ellagic acid as the major constituent in the methanol extract. Both extracts of P. macrocarpus significantly and dose dependently reduced the time and number of writhing induced by acetic acid. They also significantly inhibited the two phases of formalin-induced pain. These effects were significantly inhibited by a pretreatment with naloxone, except for the analgesic activity of the methanol extract at the earlier phase. In addition, nociception induced by hot plate, intraplantar injection of capsaicin or glutamate was significantly inhibited by both extracts. Acute toxicity test showed no sign of toxicity. CONCLUSION: These results demonstrate that aqueous and methanol extracts of P. macrocarpus are none toxic substances with good central and peripheral antinociceptive effects that are at least partially due to the presence of ellagic acid. These extracts may induce their antinociceptive effect by interfering with opioid, capsaicin and excitatory amino acid pathways.