Antidiarrheal effect of Psidium guajava L. extract in acute diarrhea: a systematic review.

BACKGROUND: Acute diarrheal diseases are a leading cause of childhood mortality and morbidity worldwide. Psidium guajava has been globally used for its antidiarrheal potential. Carry out a systematic review of scientific articles published up to the year 2021, which included in vivo pre-clinical tests and clinical trials involving patients with acute infectious diarrhea to verify the antidiarrheal, antibacterial, and antispasmodic effects of galenic preparations or phytopharmaceuticals from P. guajava. PRISMA and Rayyan were used as tools for the selection of studies collected in four databases (Pubmed, Scopus, Web of Science, and Science Direct). The keywords used to carry out the search were: "Psidium guajava", "guava", "antidiarrhea*", "diarrhe*", joined by Boolean operators "OR" or "AND". The characteristics of studies in animal models of acute diarrhea induction, as well as in vivo and in vitro motility and microbiological tests linked with its main pathophysiological mechanisms, were collected. RESULTS AND CONCLUSION: Twenty-three articles were included. Twenty (87%) of theirs reported heterogenic preclinical studies, predominating pharmacological studies of efficacy against conventional antidiarrheal agents, which utilized relevant outcomes and models of infectious diarrhea from the top pathogens in the clinic along with classical castor oil-induced diarrhea associated with motility tests. Only three of them (13%) corresponded to clinical trials to study the efficacy, dose, and safety of these preparations. Most studies reported positive results and significant mechanistic evidence from antibacterial, anti-motility, anti-secretory, and protective/anti-inflammatory perspectives. However, further studies are needed to define the clinical significance and safety treatment with P. guajava extracts. This article is protected by copyright. All rights reserved.

Effects of urbanization and accessibility to sanitation services on water quality in urban streams in Uruguay.

The world's urban population is growing rapidly, and threatening natural ecosystems, especially streams. Urbanization leads to stream alterations, increased peak flow frequencies, and reduced water quality due to pollutants, morphological changes, and biodiversity loss, known as the urban stream syndrome. However, a shift towards recognizing urban streams as valuable natural systems is occurring, emphasizing green infrastructure and nature-based solutions. This study in Uruguay examined water quality in various watersheds with different urbanization levels and socio-environmental characteristics along a precipitation gradient. Using Geographic Information Systems (GIS) and in situ data, we assessed physicochemical parameters, generated territorial variables, and identified key predictors of water quality. We found that urbanization, particularly urban areas, paved areas, and populations without sanitation, significantly influenced water quality parameters. These factors explained over 50% of the variation in water quality indicators. However, the relationship between urbanization and water quality was non-linear, with abrupt declines after specific urban intensity thresholds. Our results illustrate that ensuring sanitation networks and managing green areas effectively are essential for preserving urban stream water quality. This research underscores the importance of interdisciplinary teams and localized data for informed freshwater resource management.

Modified pectin with anticancer activity in breast cancer: A systematic review.

Breast cancer is the most commonly diagnosed cancer among women worldwide. The current pharmacological treatments for breast cancer have numerous adverse effects and are not always effective. Recently, the anticancer activity of modified pectins (MPs) against various types of cancers, including breast cancer, has been investigated. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model, including scientific articles from the last 22 years that measured the anticancer activity of MPs on breast cancer. The articles were searched in four databases with the terms: "modified pectin" and "breast cancer". Nine articles were included, five in vitro and four mixed (in vitro and in vivo). Different models and methods by which anticancer activity was measured were analyzed. All the studies reported positive results in both cell lines and in vivo murine models of breast cancer. The extracted data suggest a positive effect and provide mechanistic evidence of MPs in the treatment of breast cancer. However, as limited number of studies were included, further in vivo studies are required to obtain more conclusive preclinical evidence.

ESTUDIO METAGENÓMICO DE LA MICROBIOTA INTESTINAL EN PACIENTES CON OBESIDAD MÓRBIDA SOMETIDOS A CIRUGÍA BARIÁTRICA / METAGENOMIC STUDY OF THE INTESTINAL MICROBIOTA IN PATIENTS WITH MORBID OBESITY UNDERGOING BARIATRIC SURGERY

Introducción: La cirugía bariátrica (CB) es un tratamiento quirúrgico de la obesidad, cuyo objetivo es lograr el descenso de peso, de masa grasa y alcanzar un impacto metabólico a largo plazo. Se ha observado que ciertos pacientes no responden tan efectivamente a la cirugía, teniendo un descenso de peso inefectivo o recuperando peso tardíamente, y los mecanismos por lo que esto ocurre aún no están bien caracterizados. La microbiota intestinal tiene un rol esencial en varios de los procesos metabólicos asociados a la obesidad. El objetivo de este estudio fue caracterizar el metagenoma intestinal de pacientes candidatos para CB y otros que fueron operados, así como también evaluar las diferencias entre aquellos pacientes que tuvieron un resultado exitoso de la CB y los que no. Material y método: Se extrajo el ADN de 200 mg de heces de pacientes que cumplen criterios de CB, divididos en 3 grupos, basal (preoperatorio), 12 meses y más de 24 meses postoperatorios, con el fin de estudiar y comparar el perfil taxonómico de las comunidades bacterianas de la microbiota intestinal. Resultados: Mientras que la riqueza específica de los grupos de estudio no presentó diferencias significativas, la diversidad beta, que considera las abundancias relativas de los miembros de las comunidades bacterianas estudiadas, evidenció una composición global significativamente diferente entre los grupos de estudio. Sin embargo, nuestro análisis no identificó taxones específicos que pudieran dar explicación a la distinta evolución postoperatoria de los pacientes. Discusión: En la estructura de las comunidades microbianas, se observaron diferencias numéricas entre los grupos en cuanto a la riqueza y abundancia de taxones así como la comparación cuanti y cualitativa. Esta última presentó significativa disimilitud. Los resultados muestran que la principal diferencia entre los grupos de estudio se basó en la abundancia relativa de los gérmenes, cuyo estudio integral podría revelar patrones más consistentes y significativos vinculados a los mecanismos de respuesta terapéutica en sujetos sometidos a CB

Introduction: Bariatric surgery (BS) is a surgical treatment of obesity, which aims to achieve weight loss, fat mass loss and achieve a long-term metabolic impact. It has been observed that certain patients do not respond as effectively to surgery, having ineffective weight loss or regaining weight late, and the mechanisms by which this occurs are not yet well characterized. The intestinal microbiota plays an essential role in several of the metabolic processes associated with obesity. The objective of our study was to characterize the intestinal metagenome of candidate patients for CB and others who underwent surgery, as well as evaluate the differences between those patients who had a successful outcome from CB and those who did not. Material and method: DNA was extracted from 200 mg of feces from patients who met the criteria for surgical indication divided into 3 groups, baseline (preoperative), 12 months and more than 24 months postoperatively, in order to analyze and compare the taxonomic profile of the bacterial communities of the intestinal microbiota. Results: While the specific richness of the study groups did not present significant differences, beta diversity, which considers the relative abundances of the members of the bacterial communities studied, showed a significantly different global composition between the study groups. Nevertheless, our study did not identify specific taxa that could explain the different postoperative evolution of the patients. Discussion: In the structure of the microbial communities, numerical differences were observed between the groups in terms of the richness and abundance of taxa as well as the quantitative and qualitative comparison. The latter evidenced significant dissimilarity. The results show that the main difference between the study groups was based on the relative abundance of the germs, whose comprehensive study could reveal more consistent and significant patterns linked to the therapeutic response mechanisms in subjects subjected to CB. Bariatric surgery (BS) is a surgical treatment of obesity, whose objective is to achieve weight loss, fat mass and achieve a longterm metabolic impact. However, it has been observed that certain patients do not respond as effectively to surgery, having ineffective weight loss or late weight regain, and the mechanisms by which this occurs are not yet well characterized. The intestinal microbiota plays an essential role in several of the metabolic processes associated with obesity. The aim of this study was to characterize the intestinal metagenome of patients who will and who underwent BS, as well as to assess the differences between those patients who had a successful BS outcome and those who did not. Our results did not identify specific taxa that could explain the different evolution of the patients. While the specific richness of the study groups did not present significant differences, the beta diversity, which considers the relative abundances of the members of the studied bacterial communities, showed a significantly different global composition between the study groups

Gastroprotective Role of Fruit Extracts in Gastric Damage Induced by Non-Steroidal Anti-Inflammatory Drugs: A Systematic Review.

The aim of this study was to systematically review the scientific literature, with Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines, of the articles found in the past 11 years on the gastroprotective role of fruit extracts in gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). Scientific articles published between 2010 and 2020 were included in this systematic review, including in vitro and in vivo models, to define the gastroprotective role of fruit extracts. Studies were selected by Rayyan using PubMed, Web of Science, Scopus, and Science Direct databases. The keywords for the search strategy were: "gastric injury," "gastric ulcer," "fruit," "indomethacin," and "aspirin." Twenty-two articles with animal models of gastric ulcers were included. The NSAIDs used were aspirin and indomethacin. To know the damage caused by these, the ulceration index and biomarkers, such as aggressive/defensive factors involved in the gastric ulceration process, were measured. Most studies have shown that fruit extracts have antiulcer activity, with the most abundant metabolites being flavonoids, followed by terpenes and alkaloids. Possible antiulcer activities such as antioxidant, cytoprotective, gastric acid antisecretory, anti-inflammatory, or angiogenesis stimulant were declared, manifested mainly as a reduction of lipid peroxidation products, an increase in antioxidant enzymes and prostaglandins, and by the formation of a protective film through protein precipitation in the ulcer area. This systematic review demonstrates the importance of fruit extracts as gastric protectors.

Integrated analysis of the transcriptome and its interaction with the metabolome in metabolic associated fatty liver disease: Gut microbiome signatures, correlation networks, and effect of PNPLA3 genotype.

Interactions between communities of the gut microbiome and with the host could affect the onset and progression of metabolic associated fatty liver disease (MAFLD), and can be useful as new diagnostic and prognostic biomarkers. In this study, we performed a multi-omics approach to unravel gut microbiome signatures from 32 biopsy-proven patients (10 simple steatosis -SS- and 22 steatohepatitis -SH-) and 19 healthy volunteers (HV). Human and microbial transcripts were differentially identified between groups (MAFLD vs. HV/SH vs. SS), and analyzed for weighted correlation networks together with previously detected metabolites from the same set of samples. We observed that expression of Desulfobacteraceae bacterium, methanogenic archaea, Mushu phage, opportunistic pathogenic fungi Fusarium proliferatum and Candida sorbophila, protozoa Blastocystis spp. and Fonticula alba were upregulated in MAFLD and SH. Desulfobacteraceae bacterium and Mushu phage were hub species in the onset of MAFLD, whereas the activity of Fonticula alba, Faecalibacterium prausnitzii, and Mushu phage act as key regulators of the progression to SH. A combination of clinical, metabolomic, and transcriptomic parameters showed the highest predictive capacity for MAFLD and SH (AUC = 0.96). In conclusion, faecal microbiome markers from several community members contribute to the switch in signatures characteristic of MAFLD and its progression towards SH.

Systematic review on the anxiolytic and hypnotic effects of flower extracts in in vivo pre-clinical studies published from 2010 to 2020.

Anxiety disorders are prevalent conditions in the world population, whose standard approaches include pharmacotherapy, psychotherapy, and combinations of these interventions. Different classes of psychopharmaceuticals are recommended as the first line of drugs to treat these disorders, which can have several adverse effects, treatment resistance, dependence, and drug-drug interactions making it necessary to search for new therapeutic agents. In particular, diazepam (DZP), a prototype drug from the group of benzodiazepines, has been commonly used and evaluated for its efficacy and safety in different anxiety disorders in clinical trials. DZP is also the most widely used reference standard in in vivo pharmacological assays of natural compounds. However, translating the results obtained in different rodent species and physiological anxiety tests instead of psychopathological animal models that can be of clinical application remains challenging. A systematic review of scientific articles published between 2010 and 2020 that included in vivo pre-clinical tests to define the anxiolytic, sedative and/or hypnotic effect of flower extracts is proposed. PRISMA and Rayyan were used for the selection of studies using four databases (Pubmed, Scopus, Web of Science, and QInsight), using the keywords: "Animals," "Anxiolytic," "Diazepam," "Elevated Plus Maze," "Flower Extracts," "Insomnia," "In vivo," "Mice," "Open Field Test," "Pre clinical" and "Sedative." The characteristics of anxiety studies in animal models, other studies related to locomotor activity, and the hypnotic effect of the extracts were compiled. Twenty-four articles were included, 21 of them performed the animal model of anxiety-like behavior of the elevated plus maze, seven the open field test, and six the light-dark box test. The locomotor activity was evaluated in 10 studies after the administration of the extracts to the animals to define their sedative effect, where only one defined that the extract (Matricaria chamomilla) had a sedative effect. The plants declared with this type of activity were Achyranthes aspera, Alcea aucheri, Brassica nigra, Cananga odorata, Carthamus tinctorius, Chrysanthemum indicum, Citrus aurantium, Couroupita guianensis, Echium amoenum, Erythrina berteroana, Gardenia jasminoides, Hibiscus tilliaceus, Lavandula officinalis, Lawsonia inermis, Matricaria chamomilla, Melia azedarach, Nerium oleander, Passiflora incarnata, Plumeria rubra, Salix aegyptiaca, Syzygium aromaticum, Tagetes erecta, Tilia americana. Although this review showed that some flower extracts have an anxiolytic effect as effective as diazepam, their therapeutic utility in anxiety disorders remains to be extensively demonstrated. Hence, more reliable and predictive behavioral tests and appropriate strategies for the experimental designs are needed to obtain more conclusive evidence with clinical significance.

Reactogenic sleepiness after COVID-19 vaccination. A hypothesis involving orexinergic system linked to inflammatory signals.

Coronavirus disease 2019 (COVID-19) represents a global healthcare crisis that has led to morbidity and mortality on an unprecedented scale. While studies on COVID-19 vaccines are ongoing, the knowledge about the reactogenic symptoms that can occur after vaccination and its generator mechanisms can be critical for healthcare professionals to improve compliance with the future vaccination campaign. Because sleep and immunity are bidirectionally linked, sleepiness or sleep disturbance side effects reported after some of the COVID-19 vaccines advise an academic research line in the context of physiological or pathological neuroimmune interactions. On the recognized basis of inflammatory regulation of hypothalamic neurons in sickness behavior, we hypothesized that IL-1ß, INF-γ and TNF-α pro-inflammatory cytokines inhibit orexinergic neurons promoting sleepiness after peripheral activation of the innate immune system induced by the novel COVID-19 vaccines. In addition, based on knowledge of previous vaccines and disease manifestations of SARS-CoV-2 infection, it also suggests that narcolepsy must be included as potential adverse events of particular interest to consider in pharmacovigilance studies.

Reliability and clinical utility of the chronic pain classification in the 11th Revision of the International Classification of Diseases from a global perspective: results from India, Cuba, and New Zealand.

ABSTRACT: Chronic pain affects 1 in 5 persons and contributes substantially to the global burden of disease. The 11th Revision of the International Classification of Diseases (ICD-11) includes a comprehensive classification of chronic pain. The aim of this ecological implementation field study was to evaluate the classification's interrater reliability and clinical utility in countries with different income levels. The study was conducted in 4 pain clinics in Cuba, India, and New Zealand. Twenty-one clinicians used the ICD-11 to diagnose and code n = 353 patients with chronic pain. Of these, 111 were assessed by 2 clinicians, and Fleiss' kappa was calculated to establish interrater reliability for any diagnosis assigned to ≥15 patients. The clinicians rated the clinical utility of all diagnoses. The interrater reliability could be calculated for 11 diagnoses. It was substantial for 10 diagnoses and moderate for 1 (kappa: 0.596-0.783). The mean clinical utility of the ICD-11 chronic pain diagnoses was rated as 8.45 ± 1.69/10. Clinical utility was rated higher for ICD-11 than for the commonly used classification systems (P < 0.001, η2 = 0.25) and differed between all centers (P < 0.001, η2 = 0.60). The utility of the ICD-11 diagnoses was rated higher than the commonly used diagnoses in Dunedin and Havana, and no difference was found in Kolkata and Hyderabad. The study showed the high interrater reliability of the new chronic pain diagnoses. The perceived clinical utility of the diagnoses indicates their superiority or equality compared with the classification systems currently used in pain clinics. These results suggest the global applicability of the classification in specialized pain treatment settings.

Synergistic interaction between amitriptyline and paracetamol in persistent and neuropathic pain models: An isobolografic analysis.

The current study was designed to evaluate the transient antinociceptive interaction between amitriptyline and paracetamol in the formalin test. In addition, considering other long-term neuroprotective mechanisms of these drugs, we hypothesized that this combination might exert some synergistic effects on neuropathic pain linked with its possible ability to prevent Wallerian degeneration (WD). The effects of individual and fixed-ratio of 1:1 combinations of orally administered amitriptyline and paracetamol were assayed in the two phases of the formalin test and in the chronic constriction injury (CCI) model in rats. Isobolographic analysis was employed to characterize the synergism produced by the combinations. Amitriptyline, paracetamol, and fixed-ratio amitriptyline-paracetamol combinations produced dose-dependent antinociceptive effects mainly on the inflammatory tonic phase. Repeated doses of individual drugs and their combination decreased CCI-induced mechanical allodynia in a dose-dependent manner. ED30 (formalin) and ED50 (CCI) values were estimated for the individual drugs, and isobolograms were constructed. Theoretical ED30/50 values for the combination estimated from the isobolograms were 16.5 ± 3.9 mg/kg and 26.0 ± 7.2 mg/kg for the single and repeated doses in persistent and neuropathic pain models, respectively. These values were significantly higher than the actually observed ED30/50 values, which were 0.39 ± 0.1 mg/kg and 8.2 ± 0.8 mg/kg in each model, respectively, indicating a synergistic interaction. Remarkably, CCI-induced sciatic nerve WD-related histopathological changes were prevented by this combination compared to either drug administered alone.

Anti-hypernociceptive and anti-inflammatory effects of JM-20: A novel hybrid neuroprotective compound.

The present study examines the possible effect of the novel hybrid molecule JM-20 (3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-411-dihydro-1H-pyrido[2,3-b] [1,5] benzodiazepine) on pain-related behaviours in a persistent pain model (5% formalin test) and in the neutrophil migration events during the inflammatory process. It further introduces JM-20 in a chronic constriction injury (CCI) model to clarify the possible subjacent mechanisms with its consequent clinical relevance. A single administration of JM-20 (20 or 40 mg/kg, per os [p.o.]) decreased licking/biting exclusively in the tonic phase of the formalin test in a GABA/benzodiazepine (BZD) receptor antagonist flumazenil-sensitive manner. JM-20 reduced in vivo neutrophil migration, rolling and adhesion to the endothelium induced by intraperitoneal administration of carrageenan in mice. In addition, plasma extravasation and tumour necrosis factor alpha production in the peritoneal fluid were decreased. Treatment with JM-20 (20 mg/kg, p.o.) for 7 days after CCI reduced mechanical hypersensitivity in a NG-monomethyl-l-arginine (L-NMMA)/methylene blue/glibenclamide-sensitive manner. Histopathological signs of Wallerian degeneration (WD) of the sciatic nerve were also attenuated, as well as interleukin-1 beta release in the spinal cord. The nitrate/nitrite concentration was increased centrally and did not show differences at the peripheral nerve level. The findings of this study suggest JM-20 can decrease persistent pain. A transient activity of its BDZ portion on nociceptive pathways mediated by GABA/BDZ receptors in association with its anti-inflammatory properties could be at least partially involved in this effect. JM-20 decreased CCI-induced mechanical hypersensitivity via the l-arginine/nitric oxide (NO)/cyclic GMP-sensitive ATP-sensitive potassium channel pathway. Its neuroprotective ability by preventing WD could be implicated in its anti-neuropathic mechanisms.

Mangiferin: Possible uses in the prevention and treatment of mixed osteoarthritic pain.

Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such as Mangifera indica L. Previous studies have documented its analgesic, anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.

Anti-allodynic Effect of Mangiferin in Rats With Chronic Post-ischemia Pain: A Model of Complex Regional Pain Syndrome Type I.

The present study reproduces chronic post-ischemia pain (CPIP), a model of complex regional pain syndrome type I (CRPS-I), in rats to examine the possible transient and long-term anti-allodynic effect of mangiferin (MG); as well as its potential beneficial interactions with some standard analgesic drugs and sympathetic-mediated vasoconstriction and vasodilator agents during the earlier stage of the pathology. A single dose of MG (50 and 100 mg/kg, p.o.) decreased mechanical allodynia 72 h post-ischemia-reperfusion (I/R). MG 100 mg/kg, i.p. (pre- vs. post-drug) increased von Frey thresholds in a yohimbine and naloxone-sensitive manner. Sub-effective doses of morphine, amitriptyline, prazosin, clonidine and a NO donor, SIN-1, in the presence of MG were found to be significantly anti-allodynic. A long-term anti-allodynic effect at 7 and 13 days post-I/R after repeated oral doses of MG (50 and 100 mg/kg) was also observed. Further, MG decreased spinal and muscle interleukin-1ß concentration and restored muscle redox status. These results indicate that MG has a transient and long-term anti-allodynic effect in CPIP rats that appears to be at least partially attributable to the opioid and α2 adrenergic receptors. Additionally, its anti-inflammatory and antioxidant mechanisms could also be implicated in this effect. The association of MG with sub-effective doses of these drugs enhances the anti-allodynic effect; however, an isobolographic analysis should be performed to define a functional interaction between them. These findings suggest the possible clinical use of MG in the treatment of CRPS-I in both early sympathetically maintained pain and long-term sympathetically independent pain.

Anti-hypernociceptive effect of mangiferin in persistent and neuropathic pain models in rats.

The present study examines the possible effect of the glucosylxanthone mangiferin (MG) on pain-related behaviors in a tonic acute pain model (formalin test at 5%) and in a chronic constriction injury (CCI) model to clarify the underlying transient and long-term mechanisms. Acute administration of MG (10-100mg/kg, i.p.) reduced licking/biting exclusivity in the tonic phase of formalin test in a naloxone and yohimbine-sensitive manner. This effect was enhanced by a nonselective nitric oxide synthase (NOS) inhibitor (NG-monomethyl-L-arginine) and by a non-competitive N-methyl-D-aspartate (NMDA) antagonist (ketamine), but it was reversed by the NOS substrate (L-arginine). Pre-treatment with intrathecal yohimbine prevented the anti-hypernociceptive effect of systemic MG. Pre-treatment during 4 days before surgical and 3 days after CCI with MG (50mg/kg, i.p.) reduced mechanical hypernociception and decreased the signs of Wallerian degeneration (WD) of the sciatic nerve. MG improved the PC-12 cellular viability exposure to glutamate-mediated neuronal death, also involved in neuropathic pain. The findings of this study suggest that MG shows ability to decrease tonic pain in the formalin test. A transient activity of this xanthone on nociceptive pathways mediated by α2 adrenergic receptors in cooperation with the opioid system could be involved, at least in part, in this effect. Its neuroprotective effect by preventing WD in mononeuropathic rats could be implicated in the mechano-antihypernociceptive long term mechanisms.

Antihyperalgesic effects of an aqueous stem bark extract of Mangifera indica L.: role of mangiferin isolated from the extract.

This study aimed to assess the effects of a Mangifera indica stem bark extract (MSBE) and mangiferin (MG) on pain-related acute behaviors in the formalin 5% test. Rats received repeated oral MSBE (125-500 mg/kg) once daily for 7 days before formalin injection. Other four groups with the same treatments were performed in order to study the effect of MSBE on the formalin-induced long-term secondary mechano-hyperalgesia at 7 days after the injury by means of the pin-prick method. Additional groups received a single oral MSBE dose (250 mg/kg) plus ascorbic acid (1 mg/kg, i.p.). Also, repeated oral MG doses (12.5-50 mg/kg) during 7 days were administered. MSBE decreased licking/biting and flinching behaviors only in phase II and reduced the long-term formalin injury-induced secondary chronic mechano-hyperalgesia. The combination of MSBE plus ascorbic acid produced a reinforcement of this effect for flinching behavior, advising that antioxidant mechanisms are involved, at least in part, in these actions. Chronic administration of MG reproduced the effects of MSBE. For the first time, the antihyperalgesic effects of MSBE and MG in formalin 5% test, a recommended concentration for studying the antinociceptive activity of nitric oxide-related and N-methyl-d-aspartate-related compounds, were reported. These results could represent an important contribution to explain the analgesic ethnobotanical effects recognized to M. indica and other species containing MG.

Combination of Mangifera indica L. extract supplementation plus methotrexate in rheumatoid arthritis patients: a pilot study.

The purpose of the present study was to evaluate the possible therapeutic effects and the safety of Mangifera indica extract (Vimang tablets, 300 mg) combined with methotrexate (MTX) on reducing disease activity in rheumatoid arthritis (RA). Twenty patients with active RA underwent a year of treatment with MTX (12.5 mg/week) associated to non-steroidal anti-inflammatory drugs (NSAIDs) and/or prednisone (5-10 mg/day) were randomly allocated to the experimental group (n=10), that received the extract supplementation (900 mg/day) or preceding usual treatment (n=10) during 180 days. RA activity was evaluated using the tender and swollen joint counts, erythrocyte sedimentation rate, disease activity score-28 (DAS 28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Treatment's efficacy was demonstrated with ACR criteria. Only the patients of MTX-Vimang group revealed statistically significant improvement in DAS 28 parameters with respect baseline data but no differences were observed between groups. ACR improvements amounted 80% only in MTX-Vimang group at the 90 days (p<0.001). In MTX-Vimang group, 100% of patients decreased NSAIDs administration (p<0.01) and 70% of those eradicated gastrointestinal side effects (p<0.01) ensuing of the preceding treatment. Other adverse effects were not reported.