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ETHNOPHARMACOLOGICAL RELEVANCE: Qualea parviflora Mart. is a medicinal species commonly found in the Brazilian Cerrado biome. AIM OF THE STUDY: Based on ethnopharmacological data, methanolic extract from Qualea parviflora (QP) bark was evaluated for its antiulcer, analgesic, anti-hemorrhagic, mutagenic and anti-Helicobacter pylori activities. MATERIAL AND METHODS: The gastroprotective action of the extract was evaluated in rodent experimental models (HCl/ethanol, ethanol or NSAID). We also evaluated mutagenic effect (Ames assay), anti-Helicobacter pylori, anti-hemorrhagic action, analgesic and inflammatory effects (hot-plate test and carrageenin-induced hind paw edema) of methanolic extract from Qualea parviflora. RESULTS: QP (500 mg/kg, p.o.) was able to protect gastric mucosa against HCl/ethanol solution (77%), absolute ethanol (97%), and also against injurious effect of NSAID (36%). When QP was challenged with sulfhydryl depletor compound, the gastroprotective action of extract was abolished. QP treatment was able to maintain the GSH level and show a concentration-dependent inhibition effect on the lipid peroxidation. QP present anti-Helicobacter pylori effect (MIC=75 microg/mL), anti-hemorrhagic and antidiarrheal action but not present analgesic or anti-inflammatory effect. CONCLUSION: methanolic extract from Qualea parviflora had gastroprotective effect related to the increase of gastric mucosa defensive factors such PGE(2) levels and maintain the basal gastric glutathione levels. The methanolic extract also showed anti-Helicobacter pylori activity, anti-hemorrhagic effect and antioxidant action, but absence of analgesic, mutagenic and toxic effects, a profile that adds safety to its use. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) is a biological blood-derived therapeutic obtained from whole blood that contains higher levels of platelets. PRP has been primarily used to mitigate joint degeneration and chronic pain in osteoarthritis (OA). This clinical applicability is based mechanistically on the release of several proteins by platelets that can restore joint homeostasis. Platelets are the primary source of brain-derived neurotrophic factor (BDNF) outside the central nervous system. Interestingly, BDNF and PRP share key biological activities with clinical applicability for OA management, such as anti-inflammatory, anti-apoptotic, and antioxidant. However, the role of BDNF in PRP therapeutic activities is still unknown. Thus, this work aimed to investigate the implications of BDNF in therapeutic outcomes provided by PRP therapy in vitro and in-vivo, using the MIA-OA animal model in male Wistar rats. Initially, the PRP was characterized, obtaining a leukocyte-poor-platelet-rich plasma (LP-PRP). Our assays indicated that platelets activated by Calcium release BDNF, and suppression of M1 macrophage polarization induced by LP-PRP depends on BDNF full-length receptor, Tropomyosin Kinase-B (TrkB). OA animals were given LP-PRP intra-articular and showed functional recovery in gait, joint pain, inflammation, and tissue damage caused by MIA. Immunohistochemistry for activating transcriptional factor-3 (ATF-3) on L4/L5 dorsal root ganglia showed the LP-PRP decreased the nerve injury induced by MIA. All these LP-PRP therapeutic activities were reversed in the presence of TrkB receptor antagonist. Our results suggest that the therapeutic effects of LP-PRP in alleviating OA symptoms in rats depend on BDNF/TrkB activity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Osteoarthritis (OA) is a chronic disease that may lead to joint structure degeneration, cartilage destruction, osteophyte formation, subchondral bone disruption, and pain. In this scenario, a higher proportion of the proinflammatory macrophage type 1 (M1) than the anti-inflammatory macrophage type 2 (M2) could be highlighted as a hallmark of OA progression. The balance between these two macrophage types emerges as a new therapeutic target in OA. This study aimed to evaluate the analgesia and macrophage profile in the treatment of experimental osteoarthritis (EOA) with systemic dimethyl fumarate (DMF) or local intra-articular monomethyl fumarate (MMF)., Results: DMF via gavage or MMF via intra-articular in the right knee of EOA rats showed improvements in gait parameters and the nociceptive recovery of the mechanical threshold assessment by adapted electronic von Frey treatment on the twenty-first day (long-lasting phase). DMF treatment decreased proinflammatory TNF-α while increasing anti-inflammatory IL-10 cytokines from the macerated capsule on the fifth day (inflammatory phase). MMF treatment showed joint capsule mRNA extraction downregulating iNOS and TNF-α gene expression while upregulating IL-10 and MCP-1. However, CD206 was not significant but higher than untreated EOA rats' joints on the seventh day (inflammatory phase)., Conclusions: Our studies with EOA model induced by MIA suggest a new perspective for human treatment committed with OA based on macrophage polarization as a therapeutic target, switching the proinflammatory profile M1 to the anti-inflammatory profile M2 with DMF systematic or by MMF locally treatment according to the OA severity., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Pannexin1 (Panx1) is a membrane channel expressed in different cells of the nervous system and is involved in several pathological conditions, including pain and inflammation. At the central nervous system, the role of Panx1 is already well-established. However, in the periphery, there is a lack of information regarding the participation of Panx1 in neuronal sensitization. The dorsal root ganglion (DRG) is a critical structure for pain processing and modulation. For this reason, understanding the molecular mechanism in the DRG associated with neuronal hypersensitivity has become highly relevant to discovering new possibilities for pain treatment. Here, we aimed to investigate the role of Panx1 in acute nociception and peripheral inflammatory and neuropathic pain by using two different approaches., Methods: Rats were treated with a selective Panx1 blocker peptide (10Panx) into L5-DRG, followed by ipsilateral intraplantar injection of carrageenan, formalin, or capsaicin. DRG neuronal cells were pre-treated with 10Panx and stimulated by capsaicin to evaluate calcium influx. Panx1 knockout mice (Panx1-KO) received carrageenan or capsaicin into the paw and paclitaxel intraperitoneally. The von Frey test was performed to measure the mechanical threshold of rats' and mice's paws before and after each treatment., Results: Pharmacological blockade of Panx1 in the DRG of rats resulted in a dose-dependent decrease of mechanical allodynia triggered by carrageenan, and nociception decreased in the second phase of formalin. Nociceptive behavior response induced by capsaicin was significantly lower in rats treated with Panx1 blockade into DRG. Neuronal cells with Panx1 blockage showed lower intracellular calcium response than untreated cells after capsaicin administration. Accordingly, Panx1-KO mice showed a robust reduction in mechanical allodynia after carrageenan and a lower nociceptive response to capsaicin. A single dose of paclitaxel promoted acute mechanical pain in wildtype (WT) but not in Panx1-KO mice. Four doses of chemotherapy promoted chronic mechanical allodynia in both genotypes, although Panx1-KO mice had significant ablation in the first eight days., Conclusion: Our findings suggest that Panx1 is critical for developing peripheral inflammatory pain and acute nociception involving transient receptor potential vanilloid subtype 1 (TRPV1) but is not essential for neuropathic pain chronicity., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Stress substantially increases the risk of developing painful temporomandibular disorders (TMDs) by influencing the release of endogenous catecholamines. Propranolol, an antagonist of β-adrenergic receptors, has shown potential in alleviating TMD-associated pain, particularly when the level of catecholamines is elevated. The aim of this study was to explore whether intra-articular propranolol administration is effective in diminishing temporomandibular joint (TMJ) pain during repeated stress situations. Additionally, we investigated the effect of repeated stress on the expression of genes encoding β-adrenoceptors in the trigeminal ganglion. In the present study, rats were exposed to a stress protocol induced by sound, then to the administration of formalin in the TMJ (to elicit a nociceptive response), followed immediately afterward by different doses of propranolol, after which the analgesic response to propranolol was evaluated. We also assessed the levels of beta-1 and beta-2 adrenergic receptor mRNAs (Adrb1 and Adrb2, respectively) using reverse transcription-quantitative PCR (RT-qPCR). Our findings revealed that propranolol administration reduces formalin-induced TMJ nociception more effectively in stressed rats than in non-stressed rats. Furthermore, repeated stress decreases the expression of the Adrb2 gene within the trigeminal ganglion. The findings of this study are noteworthy as they suggest that individuals with a chronic stress history might find potential benefits from β-blockers in TMD treatment., (© 2023 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Temporomandibular disorder (TMD) is a common painful condition of the temporomandibular joint (TMJ) and associated structures. Stress is a significant risk factor for developing this painful condition that predominantly affects women. This study aimed to test the hypothesis that stress increases the risk of developing TMJ pain by facilitating inflammatory mechanisms in female and male rats. To test this hypothesis, we evaluated TMJ carrageenan-induced expression of pro-inflammatory cytokines and migration of inflammatory cells and TMJ formalin-induced nociception in female and male rats submitted to a repeated stress protocol induced by sound. We found that sound-induced repeated stress facilitates TMJ inflammation and contributes to TMJ nociception development equally in females and males. We conclude that stress is a risk factor for developing painful TMJ conditions in males and females, at least in part, by favoring the inflammatory process similarly in both sexes., (© 2023 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.)

Inflammation is a vital process for the injured tissue restoration and one of its hallmarks is inflammatory hyperalgesia. The cyclooxygenase (COX) pathway is strongly related to the inflammatory and painful process. Usually, the COX-1 isoform is described as homeostatic, while COX-2 is characterized as inducible in inflammatory conditions. Although it is well known that neutrophil cells are the first to arrive at the inflamed site and the major source of COX-2 is still unknown, the specific role of neutrophil-derived COX-2 in the pain process is. Thus, in the present study, we demonstrate for the first time that neutrophil-derived COX-2 plays a key role in peripheral inflammatory hyperalgesia. Conditional knockout mice for COX-2 in neutrophils (COX-2  fl/fl: Mrp8cre± ) exhibited higher pain sensitivity after carrageenan (CG) injection and long-lasting IL-1β-induced hyperalgesia compared with the control group (COX-2  fl/fl ). Also, CG-induced inflammation in COX-2  fl/fl: Mrp8cre± mice showed COX-1 overexpression, and increased neutrophil migration and pro-inflammatory cytokines (e.g., IL-1β and CXCL1). These findings revealed that neutrophil COX-2 has an important role in the regulation of inflammatory hyperalgesia., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Several recent studies have established the efficacy of photobiomodulation therapy (PBMT) in painful clinical conditions. Diabetic neuropathy (DN) can be related to activating mitogen-activated protein kinases (MAPK), such as p38, in the peripheral nerve. MAPK pathway is activated in response to extracellular stimuli, including interleukins TNF-α and IL-1β. We verified the pain relief potential of PBMT in streptozotocin (STZ)-induced diabetic neuropathic rats and its influence on the MAPK pathway regulation and calcium (Ca 2+ ) dynamics. We then observed that PBMT applied to the L4-L5 dorsal root ganglion (DRG) region reduced the intensity of hyperalgesia, decreased TNF-α and IL-1β levels, and p38-MAPK mRNA expression in DRG of diabetic neuropathic rats. DN induced the activation of phosphorylated p38 (p-38) MAPK co-localized with TRPV1 + neurons; PBMT partially prevented p-38 activation. DN was related to an increase of p38-MAPK expression due to proinflammatory interleukins, and the PBMT (904 nm) treatment counteracted this condition. Also, the sensitization of DRG neurons by the hyperglycemic condition demonstrated during the Ca 2+ dynamics was reduced by PBMT, contributing to its anti-hyperalgesic effects., (© 2022. The Author(s).)

The mechanism underlying the role of tumor necrosis factor alpha (TNF-α) in the development of inflammatory hyperalgesia has been extensively studied, mainly the role of TNF-α in the release of pro-inflammatory cytokines. The current concept relies in the fact that TNF-α stimulates the cascade release of other pro-inflammatory cytokines, such as IL-1β, IL-6, and IL-8 (CINC-1 in rats), triggering the release of the final inflammatory mediator prostaglandin E 2 (PGE 2 ) and sympathetic amines that directly sensitize the nociceptors. However, this may not be the sole mechanism involved as the blockade of TNF-α synthesis by thalidomide prevents hyperalgesia without interrupting the synthesis of IL-1β, IL-6, and CINC-1. Therefore, we hypothesized that activation of TNF-α receptor type 1 (TNFR1) by TNF-α increases nociceptors' susceptibility to the action of PGE 2 and dopamine. We have found out that intrathecal administration of oligodeoxynucleotide-antisense (ODN-AS) against TNFR1 or thalidomide prevented carrageenan-induced hyperalgesia. The co-administration of TNF-α with a subthreshold dose of PGE 2 or dopamine that does not induce hyperalgesia by itself in the hind paw of Wistar rats pretreated with dexamethasone (to prevent the endogenous release of cytokines) induced a robust hyperalgesia that was prevented by intrathecal treatment with ODN-AS against TNFR1. We consider that the activation of neuronal TNFR1 by TNF-α decisively increases the susceptibility of the peripheral afferent neuron to the action of final inflammatory mediators - PGE 2 and dopamine - that ultimately induce hyperalgesia. This mechanism may also underlie the analgesic action of thalidomide., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

: Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as "jacaranda de espinho" or "espinheira santa nativa" is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using in vivo experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, L-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE 2 ) showed involvement of the COX pathway, based on observed decreases in PGE 2 levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, β-amyrin, allantoin, apigenin-7-methoxy-6- C -β-D-glucopyranoside, and apigenin-6- C -β-D-glucopyranosyl-8- C -β-D-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE 2 levels., Competing Interests: The authors declare that they have no conflicts of interest.

Peripheral diabetic neuropathy (PDN) manifests in 50-60% of type I and II diabetic patients and is the major cause of limb amputation. Adequate therapy for PDN is a current challenge. There are evidences that the activation of the P2X4 receptor (P2X4R) expressed on microglial cells of the central nervous system takes part in the development of neuropathic pain. However, there is an open question: Is P2X4R activation on dorsal root ganglia (DRG) involved in the development of neuropathic pain? To answer this question, this study verified the involvement of P2X4R expressed in DRG cells on diabetes-induced neuropathic mechanical hyperalgesia in rats. We found that intrathecal or ganglionar (L5-DRG) administration of a novel P2X4R antagonist (PSB-15417) or intrathecal administration of oligodeoxynucleotides (ODN)-antisense against the P2X4R reversed diabetes-induced neuropathic mechanical hyperalgesia. The DRG of the diabetic neuropathic rats showed an increase in P2X4R expression, and the DRG immunofluorescence suggested that P2X4R is expressed mainly in satellite glial cells (SGC). Finally, our study showed a functional expression of P2X4R in SGCs of the rat's DRG, because the P2X4R agonist BzATP elicits an increase in intracellular calcium concentration in SGCs, which was reduced by PSB-15417. These findings indicate that P2X4R activation in DRG is essential to diabetes-induced neuropathic mechanical hyperalgesia. Therefore, this purinergic receptor in DRG could be an interesting therapeutic target for quaternary P2X4R antagonists that do not cross the hematoencephalic barrier, for the control of neuropathic pain, preserving central nervous system functions., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice. We also investigated the involvement of TRPV1 (transient receptor potential vanilloid 1), TRPA1 (transient receptor potential ankyrin 1), TRPM8 (transient receptor potential melastatin 8), and ASIC (acid-sensing ion channel), as well as the opioidergic, glutamatergic, and supraspinal pathways. Moreover, the nociceptive response was reduced (30 mg/kg) in the early and late phase of the formalin test. DEAB activity appears to involve the opioid system, TRPM8, and ASIC receptors, clearly showing that the DEAB alleviates acute pain in mice and suggesting the involvement of the TRPM8 and ASIC receptors and the opioid system in acute pain relief., Competing Interests: The authors declare no conflict of interest.

The interference between external magnetic fields and neurophysiology is not new, however, the role of the neuronal magnetic field remains unclear. This study aimed at investigating a possible role of the neuronal magnetic field in nociception. Highly and poorly magnetic reduced graphene oxide (rGO) was injected intrathecally in rats. Nociceptive responsiveness was greater in rats that received highly magnetic-rGO in von Frey electronic or intraplantar capsaicin tests. Furthermore, in vitro experiments demonstrated that the number of KCl-responsive DRG-neurons was greater when treated with highly magnetic-rGO when compared with non-magnetic-rGO. Our data also suggested that the mechanism underlying the increased nociceptive responsiveness involves increased Ca 2+ v activity. Complementary experiments excluded the cytotoxic and inflammatory effects of the magnetic-rGO in neuronal responsiveness. These data suggest that the disturbance of the neuronal magnetic field in spinal cord increases nociceptive responsiveness, suggesting an importance of the magnetic component of the electromagnetic field in neuronal transmission., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity.

Ethnopharmacological Relevance: An ethnopharmacological survey indicated that leaves from Eugenia punicifolia (Kunth) DC. (Myrtaceae) are popularly used as a natural therapeutic agent to treat pain and inflammation., Aim of the Study: The overall objective of the present study was to evaluate the antinociceptive, anti-inflammatory and gastroprotective activities of a hydroalcoholic extract of leaves from Eugenia punicifolia (HEEP) in rodents., Material and Methods: The antinociceptive effects of HEEP were evaluated in mice after oral administration in chemical (formalin and glutamate) and thermal (hot-plate) tests. We evaluated the involvement of the glutamatergic, opioidergic and nitrergic pathways in the antinociception of HEEP and the effect of HEEP on the inhibition of p38α MAPK. The anti-inflammatory effect of HEEP was evaluated in mice and rats using xylene-induced ear edema and carrageenan-induced paw edema, respectively. Furthermore, the gastroprotective effect of HEEP was evaluated in rats with acute gastric lesions induced by ethanol or indomethacin. Finally, we performed a phytochemical analysis of HEEP., Results: The oral administration of HEEP (125, 250 and 500mg/kg, p.o.) significantly inhibited the neurogenic and inflammatory phases of formalin-induced licking, and HEEP (250mg/kg, p.o.) also significantly inhibited the nociception caused by glutamate. The antinociceptive effects of HEEP were significantly reversed by l-arginine (500mg/kg, i.p.) but not by naloxone (1mg/kg, i.p.) in the formalin test. HEEP did not affect animal motor performance in the rotarod model. In addition, HEEP also increased the paw withdraw latency in the hot-plate test. HEEP significantly inhibited ear edema induced by xylene (64%) and paw edema induced by carrageenan (50%) compared to the control group. Furthermore, HEEP (3-30mg/mL) also inhibited the phosphorylation of p38α MAPK by approximately 90%. In addition, HEEP (125, 250 and 500mg/kg, p.o.) protected the rats against ethanol (88.4-99.8%) and indomethacin (53-72.3%) and increased the mucus levels of the gastric mucosa without producing an antisecretory effect. The phytochemical profile of HEEP obtained using HPLC-PDA showed secondary metabolites already reported for the genus, mostly flavonoids, gallotannins and proanthocyanidins., Conclusions: These data show for the first time that HEEP has significant antinociceptive and anti-inflammatory effects, which appear to be related to the inhibition of the glutamatergic system, the synthesis of nitric oxide and the inhibition of the phosphorylation of p38α MAPK. HEEP also has interesting gastroprotective effects related to the maintenance of protective factors, such as mucus production. These results support the use of Eugenia punicifolia in popular medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive, anti-inflammatory and gastroprotective properties., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Citral (3,7-dimethyl-2,6-octadienal) is an open-chain monoterpenoid present in the essential oils of several medicinal plants. The aim of this work was to evaluate the effects of orally administered citral in experimental models of acute and chronic nociception, inflammation, and gastric ulcers caused by non-steroidal anti-inflammatory drugs (NSAIDs). Oral treatment with citral significantly inhibited the neurogenic and inflammatory pain responses induced by intra-plantar injection of formalin. Citral also had prophylactic and therapeutic anti-nociceptive effects against mechanical hyperalgesia in plantar incision surgery, chronic regional pain syndrome, and partial ligation of sciatic nerve models, without producing any significant motor dysfunction. In addition, citral markedly attenuated the pain response induced by intra-plantar injection of glutamate and phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator), as well as by intrathecal (i.t.) injection of ionotropic and metabotropic glutamate receptor agonists (N-methyl-D-aspartic acid [NMDA] and 1-amino-1,3-dicarboxycyclopentane [trans-ACPD], respectively), substance P, and cytokine tumour necrosis factor-α. However, citral potentiated behaviours indicative of pain caused by i.t., but not intra-plantar, injection of a transient receptor potential vanilloid receptor type 1 (TRPV1) agonist. Finally, the anti-nociceptive action of citral was found to involve significant activation of the 5-HT2A serotonin receptor. The effect of citral was accompanied by a gastro-protective effect against NSAID-induced ulcers. Together, these results show the potential of citral as a new drug for the treatment of pain., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Davilla elliptica and Davilla nitida are species commonly found in the Brazilian Cerrado biome., Aim of the Study: Based on ethnopharmacological and phytochemical analyses, methanolic extracts from leaves of Davilla elliptica (EDE) and Davilla nitida (EDN) were evaluated for their anti-ulcer, anti-inflammatory, immunological and anti-Helicobacter pylori activities., Materials and Methods: The gastroprotective action of both extracts was evaluated in rodent experimental models (HCl/ethanol, ethanol or NSAID). We also evaluated anti-inflammatory (carrageenin-induced rat hind paw edema), immunomodulatory (murine peritoneal macrophages) and antibacterial action of both extracts against a standard strain of Helicobacter pylori., Results: EDE and EDN (500 mg/kg) were able to protect gastric mucosa against HCl/ethanol solution (EDE 63%; EDN 59%), absolute ethanol (EDE 95%; EDN 88%), and also against injurious effect of NSAID (EDE 77%; EDN 67%). When EDE and EDN were challenged with sulfhydryl depleter compound, the gastroprotective action of both extracts was completely abolished. EDE had gastroprotective effect related to increase of glutathione bioavailability and stimulated higher levels of NO, H2O2 and TNF-alpha production. Otherwise EDN showed better anti-Helicobacter pylori action than EDE. Neither extracts presented anti-inflammatory activity by oral route., Conclusion: The phytochemical investigation showed that both extracts possess phenolic acid derivatives, acylglycoflavonoids and condensed tannins with evident quantitative variations that probably influenced the pharmacological differences between extracts.

Around 20,000 snakebites are reported annually in Brazil and 90% of them are inflicted by species of the genus Bothrops. Intravenous administration of antibothropic antivenom neutralizes the systemic actions, but it is of little effect on the reversal of local symptoms and often induces adverse reactions, a context that drives the search for complementary treatments for snakebite accidents. Vegetable extracts with a range of antiophidian activities constitute an excellent alternative. In this study, we investigated the anti-hemorrhagic effects of Mouriri pusa Gardn. (Melastomataceae), Byrsonima crassa Niedenzu (Malpighiaceae), Davilla elliptica St. Hill. (Dilleniaceae) and Strychnos pseudoquina St. Hil. (Loganiaceae) against Bothrops jararaca venom. The methanolic extracts from M. pusa (leaves), B. crassa (leaves) and D. elliptica (leaves) showed total neutralization capacity against local hemorrhages. The amenthoflavone and quercetin fractions from B. crassa and the flavonoids fractions (quercetin and myricetin) from M. pusa and D. elliptica also showed total neutralization capacity. We conclude that flavonoids derived from myricetin, quercetin and amenthoflavone play an important role in the anti-hemorrhagic potential of these Brazilian vegetables species against B. jararaca venom.

Aim of the Study: Cissus sicyoides L. is a medicinal plant popularly known in Brazil against various diseases and the research interest in this plant is justifiable because of its potential medicinal value in stomachache and gastric ulcer., Materials and Methods: The methanolic extract obtained from the leaves of Cissus sicyoides (Cc) was evaluated for the ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% EtOH, absolute ethanol, piroxicam and pylorus ligature) in rodents. We also evaluated microcirculation, antioxidant action and participation of NO (nitric oxide) and sulfhydryls (SH) groups in the Cc gastroprotective action., Results: Administration of Cc significantly reduced gastric lesions induced by different ulcerogenic agents in rodents. This extract administered by oral route significantly increased gastric volume without exerting antisecretory effect. The Cc effect involved an increase of the defense mechanism of the gastrointestinal mucosa such as NO and SH groups that prevent and attenuate the ulcer process. The Cc also has antioxidant property against oxidative stress but does not modify microcirculation response in gastric mucosa., Conclusions: These results confirmed the traditional use of Cissus sicyoides for the treatment of gastric ulcer.