Chemopreventive and immunomodulatory effects of phenolic-rich extract of Commiphora leptophloeos against inflammatory bowel disease: Preclinical evidence.

ETHNOPHARMACOLOGY RELEVANCE: Commiphora leptophloeos (Mart.) J.B. Gillet (Burseraceae) is a medicinal plant native to Brazil, popularly known as "imburana". Homemade leaf decoction and maceration were used to treat general inflammatory problems in the Brazilian Northeast population. Our previous research confirmed the anti-inflammatory activity of the C. leptophloeos hydroalcoholic leaf extract. AIM OF THE STUDY: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut with no ideal treatment to maintain the remissive status. This work aimed to characterize the phytochemical composition and physicochemical properties of the C. leptophloeos hydroalcoholic leaf extract and its efficacy in chemopreventive and immunomodulatory responses in inflammatory bowel disease in non-clinical models. MATERIALS AND METHODS: Mass spectrometry and physicochemical tests determined the phytochemical profile and physicochemical characteristics of the Commiphora leptophloeos (CL) extract. The chemopreventive and immunomodulatory effects of CL extract (50 and 125 µg/mL) were evaluated in vitro in the RAW 264.7 lipopolysaccharide (LPS) induced cell assay and in vivo in the model of intestinal inflammation induced by 2,4-Dinitrobenzenesulfonic acid (DNBS) in mice when they were treated with CL extract by intragastric gavage (i.g.) at doses of 300, 400 and 500 mg/kg. RESULTS: Phytochemical annotation of CL extract showed a complex phenolic composition, characterized as phenolic acids and flavonoids, and satisfactory physicochemical characteristics. In addition, CL extract maintained the viability of RAW macrophages, reduced ROS and NO production, and negatively regulated COX-2, iNOS, TNF-α, IL-1ß, IL-6, and IL-17 (p < 0.05). In the intestinal inflammation model, CL extract was able to downregulate NF-κB p65/COX-2, mTOR, iNOS, IL-17, decrease levels of malondialdehyde and myeloperoxidase and cytokines TNF-α, IL-1ß and IL-6 (p < 0.05). CONCLUSION: Based on these findings, CL extract reduced inflammatory responses by down-regulating pro-inflammatory markers in macrophages induced by LPS and DNBS-induced colitis in mice through NF-κB p65/COX-2 signaling. CL leaf extract requires further investigation as a candidate for treating inflammatory bowel disease.

Toxicity and Anti-Inflammatory Activity of Phenolic-Rich Extract from Nopalea cochenillifera (Cactaceae): A Preclinical Study on the Prevention of Inflammatory Bowel Diseases.

Phenolic compounds have been scientifically recognized as beneficial to intestinal health. The cactus Nopalea cochenillifera, used as anti-inflammatory in traditional medicine, is a rich source of these bioactive compounds. The present study aimed to investigate the phytochemical profile of N. cochenillifera extract and evaluate its acute toxicity and anti-inflammatory effect on 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis in rats. The total phenolic content per gram of dry extract was 67.85 mg. Through HPLC-IES-MSn, a total of 25 compounds such as saccharides, organic acids, phenolic acids and flavonoids were characterized. The dose of 2000 mg/kg of extract by an oral route showed no signs of toxicity, mortality or significant changes in biochemical and hematological parameters. Regarding intestinal anti-inflammatory effects, animals were treated with three different doses of extract or sulfasalazine. Macroscopic analysis of the colon indicated that the extract decreased the disease activity index. Levels of IL-1ß and TNF-α decreased, IL-10 increased and MDA and MPO enzyme levels decreased when compared with the control group. In addition, a down-regulation of MAPK1/ERK2 and NF-κB p65 pathway markers in colon tissue was observed. The epithelial integrity was improved according to histopathological and immunohistological analysis. Thus, the extract provided strong preclinical evidence of being effective in maintaining the remission of colitis.

Comparative study of royal jelly, propolis, and photobiomodulation therapies in 5-fluorouracil-related oral mucositis in rats.

PURPOSE: This study aimed to evaluate the effects and mechanisms of action of royal jelly (RJ) and propolis compared to photobiomodulation therapy (PBMT) in an animal model of 5-fluorouracil-related oral mucositis (OM). METHODS: Seventy-two male Wistar rats were randomly allocated to four groups (n = 18 each): control (no treatment), PBMT (intraoral laser, 6 J/cm2), RJ, and propolis. On days 0 and 2, the animals received an injection of 5-fluorouracil (5-FU). The buccal mucosa was scratched (days 3 and 4) and the treatments were initiated on day 5. Six animals of each group were euthanized on days 8, 10, and 14. Phytochemical analysis (thin-layer chromatography, TLC) and clinical, histopathological, and immunohistochemical analysis of pS6, pAKT, and NF-κB were performed, and oxidative stress markers were also investigated. RESULTS: TLC revealed the presence of large amounts of sucrose (Rf 0.34) in RJ and of flavonoids in propolis. Lower clinical OM scores were observed on day 8, and improved morphological data were observed on day 10 in the PBMT, RJ, and propolis groups (p < 0.05). On day 8, immunoexpression of pS6, pAKT, and NF-κB was increased compared to control. On day 14, reduced glutathione (GSH) antioxidant levels were increased in the propolis group compared to control (p < 0.05). CONCLUSIONS: Our results showed that RJ and propolis, as well as PBMT, are effective in the treatment of OM. Considering that some patients who develop OM do not have access to PBMT, the present study demonstrated that topical application of RJ and propolis may be an important alternative for the treatment of OM.

Gastric Ulcer Healing Property of Bryophyllum pinnatum Leaf Extract in Chronic Model In Vivo and Gastroprotective Activity of Its Major Flavonoid.

Gastric ulcer is a common disease that develops complications such as hemorrhages and perforations when not properly treated. Extended use of drugs in the treatment of this pathology can provoke many adverse effects. Therefore, finding medicinal plants with gastroprotective and mucosal healing properties has gained increasing interest. Bryophyllum pinnatum (Crassulaceae), popularly known in Brazil as "saião" or "coirama," has been used to treat inflammatory disorders. It is rich in flavonoids, and quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside-Bp1 is its major compound. In this study, we aimed to investigate ulcer healing properties of B. pinnatum against an acetic acid-induced chronic ulcer model and the gastroprotective activity of Bp1 against gastric lesions induced by ethanol and indomethacin. Ultrafast liquid chromatography was used to quantify the main compounds (mg/g of the extract)-quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside (33.12 ± 0.056), kaempferol 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside (3.98 ± 0.049), and quercetin 3-O-α-L-rhamnopyranoside (4.26 ± 0.022) and showed good linearity, specificity, selectivity, precision, robustness, and accuracy. In vivo studies showed that treatment with the extract at 250 and 500 mg/kg stimulated the healing process in the gastric mucosa with significant ulceration index reduction, followed by improvement in the antioxidant defense system [increased glutathione (GSH) levels, decreased superoxide dismutase upregulation, and malondialdehyde (MDA) levels]. Moreover, the extract decreased interleukin-1ß and tumor necrosis factor-a levels and myeloperoxidase (MPO) activity, increased interleukin 10 levels, showed a cytoprotective effect in histological analyzes and also downregulated the expression of cyclooxygenase-2 and NF-κB (p65). The pretreatment with Bp1 at a dose of 5 mg/kg reduced gastric lesions in the ethanol and indomethacin models, increased GSH, and decreased MDA levels. In addition, the pretreatment decreased MPO activity, interleukin-1ß and tumor necrosis factor-α levels, while also showing a cytoprotective effect in histological analyzes. Our study suggests that treatment with B. pinnatum extract showed a higher inhibition percentage than pretreatment with the Bp1. This might in turn suggest that Bp1 has gastroprotective activity, but other compounds can act synergistically, potentiating its effect. We conclude that B. pinnatum leaf extract could be a new source of raw material rich in phenolic compounds to be applied in food or medicine.

Anti-Inflammatory and Chemopreventive Effects of Bryophyllum pinnatum (Lamarck) Leaf Extract in Experimental Colitis Models in Rodents.

Inflammatory bowel diseases, mainly ulcerative colitis and Crohn's disease are characterized by chronic inflammation in the intestine. Currently several therapeutic strategies available to treat inflammatory bowel diseases. Though, most treatments can be associated with serious adverse effects what justifies the search for new treatments. In this sense, we highlight the interest in herbal products rich in bioactive compounds which immunomodulatory and antioxidant properties as is the case of Bryophyllum pinnatum (Crassulaceae). This plant is used in traditional medicine in Brazil for treating inflammatory diseases. We hypothesized that hydroethanolic B. pinnatum leaf extract has intestinal anti-inflammatory effects on two experimental colitis models: 2.4-dinitrobenzene sulfonic acid (DNBS) in rats, and dextran sulfate sodium (DSS) in mice. Ultra-fast liquid chromatography method used for the quantification of the main compounds indicated good linearity, specificity, selectivity, precision, robustness and accuracy. The major flavonoids (mg/g of the extract) quantified were: quercetin 3-O-α-L-arabinopyranosyl-(1→2)-α-L-rhamnopyranoside (35.56 ± 0.086 mg/g), kaempferol 3-O-α-L-arabinopyranosyl-(1→2)-α-L-rhamnopyranoside (4.66 ± 0.076 mg/g) and quercetin-3-O-rhamnopyranoside (4.56 ± 0.026 mg/g). The results obtained in the DNBS and DSS models indicate that extract has both chemopreventive and anti-inflammatory effects, observing a significant reduction in the disease activity index score, and less macroscopic and microscopic damage. The extract promoted downregulation of Toll-like receptor and kappa B p65 nuclear factor gene expression, leading to a reduction in pro-inflammatory and oxidative mediators, chemokines, and cell adhesion molecules. This immunomodulatory property was proposed that one of the possible action mechanisms of extract. An improvement in intestinal damage was also associated with a reduction in oxidative stress and infiltration of leukocytes, as evidenced by the reduction in malonaldialdehyde and myeloperoxidase activity and increase in total glutathione in the colonic tissue. Moreover, the extract improved the cytoarchitecture of the colonic tissue and the integrity of the intestinal epithelial barrier by restoring the expression of the proteins associated with mucosa protection. In view of the beneficial effects showed by the B. pinnatum leaf extract in preclinical rodent models of colitis there is the potential to conduct some future clinical studies to ensure safe and effective development of a phytotherapeutic treatment for human inflammatory bowel diseases.

Intestinal anti-inflammatory activity of xique-xique (Pilosocereus gounellei A. Weber ex K. Schum. Bly. Ex Rowl) juice on acetic acid-induced colitis in rats.

Inflammatory bowel disease (IBD) is characterized by severe mucosal damage in the intestine and a deregulated immune response. Natural products derived from plants that are rich in bioactive compounds are used by many patients with IBD. Xique-xique (Pilosocereus gounellei) is a cactus of the Caatinga family that has been used by the local population for food and medicinal purposes. The intestinal anti-inflammatory effect of xique-xique cladode juice was evaluated in the present study. A dose of 5 mL kg-1 had a protective effect on intestinal inflammation, with an improvement in macroscopic damage, and a decrease in pro-inflammatory markers and oxidative stress, in addition to preserving the colonic tissue. Immunohistochemical analysis revealed the downregulation of IL-17, NF-κB, and iNOS, and upregulation of SOCs-1, ZO-1, and MUC-2. These protective effects could be attributed to the phenolic compounds as well as the fibers present in xique-xique juice. Further studies are needed before suggesting the use of xique-xique juice as a new alternative for treating IBD.

Libidibia ferrea Fruit Crude Extract and Fractions Show Anti-Inflammatory, Antioxidant, and Antinociceptive Effect In Vivo and Increase Cell Viability In Vitro.

BACKGROUND: Libidibia ferrea (L. ferrea) is found throughout the northeastern region of Brazil, where it has been used in folk medicine with beneficial effects on many inflammatory disorders. PURPOSE: This study investigated the phytochemical composition of the crude extract and fractions of L. ferrea fruit and evaluated its anti-inflammatory and antinociceptive activities in vivo and effect on cell viability in vitro. METHODS: Characterization of polyphenols present in crude extract (CE), hydroalcoholic fractions of 20-80% ethanol (CE20, CE40, CE60, and CE80), aqueous fraction (AqF), and ethyl acetate (EAF) fractions of L. ferrea fruit was performed by chromatographic analysis. Anti-inflammatory activity was evaluated by using a carrageenan-induced peritonitis model submitted to a leukocyte migration assay and myeloperoxidase activity (MPO) analysis. Total glutathione and malondialdehyde (MDA) levels were assessed to evaluate the oxidative stress level. Antinociceptive activity was evaluated by acetic acid-induced abdominal writhing and hot plate test. In vitro cell viability was determined by using MTT assay in a mouse embryonic fibroblast cell line (3T3 cells). RESULTS: Chromatography revealed the presence of ellagic acid content in EAF (3.06), CE (2.96), and CE40 (2.89). Gallic acid was found in EAF (12.03), CE 20 (4.43), and CE (3.99). L. ferrea crude extract and all fractions significantly reduced leukocyte migration and MPO activity (p<0.001). L. ferrea antioxidant effect was observed through high levels of total glutathione and reduction of MDA levels (p<0.001). Acetic acid-induced nociception was significantly inhibited after administration of L. ferrea crude extract and all fractions (p<0.001). Crude extract and all fractions significantly increased the viability of the 3T3 cell line (p<0.05). CONCLUSIONS: The appropriate extraction procedure preserves the chemical components of L. ferrea fruit, such as gallic acid and ellargic acid. Crude extract and fractions of L. ferrea fruit exhibited anti-inflammatory, antioxidant, antinociceptive activities in vivo and enhanced cell viability in vitro.

Local anti-inflammatory activity: Topical formulation containing Kalanchoe brasiliensis and Kalanchoe pinnata leaf aqueous extract.

Kalanchoe brasiliensis and Kalanchoe pinnata are used interchangeably in traditional medicine in the treatment of wound healing. In this context, the objective of the present study was to evaluate the local anti-inflammatory activity of a topical formulation containing aqueous extract of both species. The in vivo model used was ear edema induced by croton oil and paw edema induced by carrageenan. The Swiss mice treatments use formulations containing aqueous extract at different concentrations (1.25%, 2.5%, and 5%) or dexamethasone (1 mg/g), all administered topically and immediately after edema induction. The treatment with formulations containing aqueous extract of both species reduced ear and paw edema, besides that, the decrease in edema was evidenced by reduction of myeloperoxidase activity, IL-1ß, and TNF-α levels and increase IL-10 levels. In conclusion, the two species showed local anti-inflammatory activity; however K. brasiliensis showed a better result in both edematogenic models since it had activity in the lowest concentration.

Crude extract from Libidibia ferrea (Mart. ex. Tul.) L.P. Queiroz leaves decreased intra articular inflammation induced by zymosan in rats.

BACKGROUND: Libidibia ferrea (L. ferrea) has been used in folk medicine to treat several conditions and to prevent cancer. This study performed a chromatographic analysis of the crude aqueous extract of Libidibia ferrea (Mart. ex. Tul.) L.P. Queiroz (LfAE) leaves and evaluated its in vivo antioxidant and anti-inflammatory potential. METHODS: Polyphenols present in LfAE were characterized by high performance liquid chromatography (HPLC). Anti-inflammatory activity was studied in an experimental model of zymosan-induced intra-articular inflammation, conducted in Wistar rats treated with LfAE at the doses of 100, 200 and 300 mg/kg by gavage. Synovial fluid was collected for global leukocyte count, for spectrocopical UV/VIS analysis of myeloperoxidase (MPO) activity, total glutathione and malondialdehyde (MDA), and for quantification of inflammatory cytokines IL1-ß and TNF-α by enzyme-linked immunosorbent assay. Synovial membrane was collected for histological analysis. The level of statistical significance was p < 0.05. RESULTS: HPLC detected concentrations of 1.56 (0.77) %m/m for ellagic acid and 1.20 (1.38) %m/m for gallic acid in LfAE leaves. Treatment with LfAE at all doses significantly decreased the leukocyte influx into the synovial fluid (p < 0.001) and myeloperoxidase activity (p < 0.001), an important marker of neutrophils. LfAE at doses of 100 (p < 0.05), 200 and 300 mg/kg (p < 0.001) also reduced the levels of MDA. LfAE at doses of 200 and 300 mg/kg significantly decreased the levels of IL-1ß (p < 0.05) and TNF-α (p < 0.001). All doses of LfAE resulted in increased levels of total glutathione (p < 0.001). Histopathological findings confirmed a reduction of the inflammatory infiltrate in the rats treated with LfAE at a dose of 200 mg/kg (p < 0.05). CONCLUSION: LfAE has an important anti-oxidant and anti-inflammatory effect on intra-articular inflammation.

Intestinal Anti-Inflammatory Activity of the Aqueous Extract from Ipomoea asarifolia in DNBS-Induced Colitis in Rats.

Inflammatory bowel disease is triggered by an uncontrolled immune response associated with genetic, environmental, and intestinal microbiota imbalance. Ipomoea asarifolia (IA), popularly known as "salsa" or "brave salsa", belongs to the Convolvulaceae family. The aim of this approach was to study the preventive effect of IA aqueous extract in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Rats pretreated with IA extract or sulfasalazine (SSZ) received intracolonic instillation of DNBS in 50% ethanol (v/v). IA extract presented a protective effect against intestinal inflammation, with improvement in the disease activity index and macroscopic damage. IA or SSZ significantly reduced myeloperoxidase activity, and also down-regulation of the gene expression of JNK1, NF-κß-p65, STAT3, and decreased levels of TNFα, IL-1ß, and increased IL-10, associated with a significant improvement of oxidative stress, in addition to a reduction in MDA and an increase of glutathione in colonic tissue. The protective effect of the extract was also confirmed in histological evaluation, showing preservation of the colonic cytoarchitecture. Immunohistochemical analysis revealed down-regulation of NF-κß-p65, iNOS, IL-17, and up-regulation of SOCs-1 and MUC-2. IA extract presents antioxidant and anti-inflammatory intestinal properties, and proved to be a potential application for preventing damage induced by DNBS.

Gastroprotective and Antioxidant Activity of Kalanchoe brasiliensis and Kalanchoe pinnata Leaf Juices against Indomethacin and Ethanol-Induced Gastric Lesions in Rats.

Kalanchoe brasiliensis and Kalanchoe pinnata are used interchangeably in traditional medicine for treating peptic ulcers and inflammatory problems. In this context, this study aims to characterize the chemical constituents and evaluate the gastroprotective activity of the leaf juices of the two species in acute gastric lesions models. Thin Layer Chromatography (TLC) and Ultra High Performance Liquid Chromatography coupled to Mass Spectrometer (UHPLC-MS) were performed for chemical characterization. Wistar rats were pre-treated orally with leaf juices (125, 250 and 500 mg/kg) or ranitidine (50 mg/kg). The peaks observed in the chromatogram of K. brasiliensis showed similar mass spectra to flavonoid glycosides derived from patuletin and eupafolin, while K. pinnata showed mass spectra similar to compounds derived from quercetin, patuletin, eupafolin and kaempferol. K. brasiliensis at all doses and K. pinnata at doses of 250 mg/kg and 500 mg/kg significantly reduced the lesions in the ethanol induction model. In the indomethacin induction model, both species showed significant results at doses of 250 and 500 mg/kg. Also, the pre-treatment with leaf juices increased the antioxidant defense system, glutathione (GSH), whereas malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels were significantly decreased. Treatment with leaf juices led to the upregulation of zone occludes-1 (ZO-1) and the downregulation of inducible nitric oxide synthase (iNOS) and factor nuclear-κβ transcription (NF-κB-p65), while also showing a cytoprotective effect and maintaining mucus production. These findings show that the leaf juices of the two species showed gastroprotective effects on ethanol and gastric indomethacin injury which were a consequence of gastric inflammation suppression, antioxidant activity and the maintenance of cytoprotective defenses and mucosal structure architecture.

Crude extract and fractions from Eugenia uniflora Linn leaves showed anti-inflammatory, antioxidant, and antibacterial activities.

BACKGROUND: This study showed phytochemical composition and evaluates the anti-inflammatory, and analgesic activities of crude extract (CE) and fractions from E. uniflora Linn leaves. METHODS: Polyphenols present in crude extract (CE), in aqueous fraction (AqF), and ethyl acetate (EAF) treated fractions from E. uniflora Linn leaves were shown by chromatographic analysis in order to conduct a phytochemical characterization. Antibacterial activity was evaluated based on minimum inhibitory concentrations (MICs) determined using the agar dilution method. Doses of 50, 100, and 200 mg/kg of the CE and fractions were applied for conducting in vivo models (male Swiss mice, 8-10 weeks old). The peritonitis experimental model was induced by carrageenan following of Myeloperoxidase activity (MPO), Total glutathione and malondialdehyde (MDA), IL-1ß and TNF-α levels by spectroscopic UV/VIS analysis. Antinociceptive activity was evaluated based on an abdominal writhing model and hot plate test. The results were statistically evaluated using one-way analysis of variance (ANOVA), followed by Bonferroni's post-hoc test. The level of statistical significance was p < 0.05. RESULTS: High-performance liquid chromatography with photodiode array detection (HPLC-DAD) detected varying concentrations of gallic acid, ellagic acid, and myricitrin in the CE and fractions obtained from E. uniflora Linn leaves (0.05-0.87%w/w, 0.20-0.32%w/w, and 1.71-6.56%w/w, respectively). In general, the CE had lower MIC values than the fractions, including the lowest MIC against the MRSA strain. The CE and AqF also significantly reduced leukocyte migration and MPO activity (p < 0.05). In addition, AqF significantly reduced IL-1ß and TNF-α levels (p < 0.05). Furthermore, the CE and fractions exhibited an antioxidant effect (p < 0.05) and peripheral analgesic activity (p < 0.05). CONCLUSIONS: The CE and fractions from the studied E. uniflora Linn leaves exhibited antibacterial, anti-inflammatory, antioxidant, and analgesic activity in the performed assays.

Low-level laser therapy (780 nm) combined with collagen sponge scaffold promotes repair of rat cranial critical-size defects and increases TGF-ß, FGF-2, OPG/RANK and osteocalcin expression.

The aim of this study was to evaluate the effect of collagen sponge scaffold (CSS) implantation associated with low-level laser therapy (LLLT) on repairing bone defects. A single 5-mm cranial defect was surgically created in forty Wistar rats, which then received one of the following four interventions (n = 10 per group): no treatment (G0); bone defect implanted with collagen sponge scaffold (CSS) alone (G1); defect treated with low-level laser therapy (LLLT) (wavelength 780 nm; total energy density 120 J/cm2 ; power 50 mW) alone (G2); and CSS associated with LLLT treatment (G3). After surgery, animals in each group were euthanized at 21 days and 30 days (n = 5 per euthanasia time group). Bone formation was monitored by X-ray imaging analysis. Biopsies were collected and processed for histological analysis and immunohistochemical evaluation of transforming growth factor-beta (TGF-ß), fibroblast growth factor-2 (FGF-2), osteoprotegerin (OPG) and receptor activator of nuclear factor ƙ (RANK). Osteocalcin (OCN) was detected by immunofluorescence analysis. Compared to the G0 group, defects in the 30-day G3 group exhibited increased bone formation, both by increase in radiopaque areas (P < 0.01) and by histomorphometric analysis (P < 0.001). The histopathological analysis showed a decreased number of inflammatory cells (P < 0.001). The combined CCS + LLLT (G3) treatment also resulted in the most intense immunostaining for OPG, RANK, FGF-2 and TGF-ß, and the most intense and diffuse OCN immunofluorescent labelling at 30 days postsurgery (G3 vs. G0 group, P < 0.05). Therefore, the use of CCS associated with LLLT could offer a synergistic advantage in improving the healing of bone fractures.

Quality of Life, Integrative Community Therapy, Family Support, and Satisfaction with Health Services Among Elderly Adults with and without Symptoms of Depression.

The aim of this cross-sectional study was to analyse quality of life, socio-demographic characteristics, family support, satisfaction with health services, and effect of integrative community therapy among non-institutionalised elderly adults with and without symptoms of depression in the state of Rio Grande do Norte, Brazil. Data from elderly adults with (n = 59) and without (n = 61) depressive symptoms were compared. The instruments used were the Mini-Mental State Examination, the short version of the Geriatric Depression Scale, a clinical socio-demographic questionnaire, the abbreviated version of the World Health Organisation Quality of Life questionnaire, the Family Assessment Device, and the Patient Satisfaction with Mental Health Services Rating Scale. Elderly adults with depressive symptoms had lower quality of life in the social relations domain than did those without depressive symptoms (p = 0.003). In addition, compared with those without depression, fewer elderly adults with depressive symptoms attended integrative community therapy (p = 0.04); they also reported a low degree of family involvement in problem solving (p = 0.04) and showed apathy regarding their satisfaction with health services (p = 0.007). These results have important implications in the decision-making process with regard to strategies for improving the health status of elderly adults with depressive symptoms.

Olmesartan Prevented Intra-articular Inflammation Induced by Zymosan in Rats.

The objective of this study was to study the effect of olmesartan medoxomil (OLM), an antihypertensive drug, on intra-articular inflammation induced by zymosan (Zy) in Wistar rats. Intra-articular inflammation was induced in the right knees of rats by 1 mg Zy dissolved in saline. The animals were divided into the following groups: saline only (oral saline and intra-articular saline); Zy only (intra-articular Zy and oral saline), and intra-articular Zy and oral OLM (5, 15, or 30 mg/kg) or diclofenac sodium (SD; 100 mg/kg). Twenty-four hours after Zy injection, synovial fluid was collected for total leukocyte counts, blood was collected for biochemical measurements, and synovial tissue was collected for histopathology, immunohistochemistry, immunofluorescence and myeloperoxidase (MPO), malonaldehyde (MDA), and non-protein sulphydryl (NPSH) assays. OLM doses of 15 and 30 mg/kg had protective effects, as evidenced by improved histopathological parameters of synovium, reduced total leukocyte counts, reduced MPO and MDA levels, and increased NPSH group levels compared with the Zy group. OLM reduced immunostaining for cyclooxygenase 2, tumour necrosis factor and interleukin 17 and increased immunostaining for superoxide dismutase and glutathione peroxidase. SD produced similar results. The drugs studied caused no change in biochemical parameters of the animals. OLM showed protective effects in this model of Zy-induced intra-articular inflammation.

Spray-dried extract of Phyllanthus niruri†L. reduces mucosal damage in rats with intestinal inflammation.

Phyllanthus niruri L. belongs to the Euphorbiaceae, and is known by the common name of 'stonebreaker' in Brazil. Some species within the Phyllanthus genus are widely used in traditional medicine to counteract different types of anti-inflammatory diseases. OBJECTIVES: In this study, the preventive intestinal anti-inflammatory activity of spray-dried extract of P. niruri (SDEPn) was tested in the model of acetic acid (10%)-induced ulcerative colitis in the rat. METHODS: Colitis animals were given orally at doses 25, 100 and 200 mg/kg. Colons tissue was analysed by macroscopic score, by histopathology score, by the immunohistochemical examination of tumour necrosis factor alpha, p53 and interferon gamma; by spectroscopic ultraviolet-visible spectrophotometry (UV/VIS) analysis of the levels of myeloperoxidase, malonaldehyde and total glutathione. KEY FINDINGS/RESULT: Pretreatment of the extract to colitic rats significantly attenuated colonic macroscopic damage induced by acetic acid (P < 0.01). Spray-dried extract of P. niruri prevented glutathione depletion (P < 0.001) and malondialdehyde levels (P < 0.05) declined. Spray-dried extract of P. niruri significantly reduced microscopic damage to tissues, such as leukocyte infiltration accompanied by a significant reduction in myeloperoxidase activity (P < 0.5). Immunohistochemistry revealed a decline in the TNF-α, IFN-γ and p53 protein (P < 0.05). CONCLUSION: Spray-dried extract of P. niruri has a beneficial effect in the acute phase of acetic acid-induced colitis in the rat, which is probably related to its antioxidant properties.

Quantification of polyphenols and evaluation of antimicrobial, analgesic and anti-inflammatory activities of aqueous and acetone-water extracts of Libidibia ferrea, Parapiptadenia rigida and Psidium guajava.

ETHNOPHARMACOLOGICAL RELEVANCE: Vast numbers of plant species from northeastern Brazil have not yet been phytochemically or biologically evaluated. AIM OF THE STUDY: The goal of this work was to obtain, characterize and show the antimicrobial, analgesic and anti-inflammatory activities of aqueous and acetone-water extracts of Libidibia ferrea, Parapiptadenia rigida and Psidium guajava. MATERIALS AND METHODS: The plant material (100g) was dried, and the crude extracts were obtained by using turbo-extraction (10%; w/v) with water or acetone:water (7:3, v/v) as the extraction solvent. High-performance liquid chromatography (HPLC) methods were used to screen the crude extracts for hydrolysable tannins (gallic acid) and condensed tannins (catechins). The antibacterial activity was evaluated by agar-diffusion and microdilution methods against Gram-positive strains (Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis INCQS 00016, Enterococcus faecalis ATCC 29212 and a clinical isolate of methicillin-resistant Staphylococcus aureus) as well as Gram-negative strains (Escherichia coli ATCC 25922, Salmonella enteritidis INCQS 00258, Shigella flexneri and Klebsiella pneumoniae). To evaluate the anti-inflammatory activity, a leukocyte migration model was used. Analgesic activity was determined by the hot plate test and the acetic acid-induced abdominal writhing test. Data were analyzed by analysis of variance (ANOVA) at a significance level of 5%. RESULTS: Parapiptadenia rigida presented the highest amount of total polyphenols (35.82 ± 0.20%), while the greatest catechin content was found in the acetone-water extract of Psidium guajava (EAWPg; 1.04 µg/g). The largest amounts of catechins were found in the aqueous extract of Libidibia ferrea (EALf; 1.07 µg/g) and the acetone-water extract of Parapiptadenia rigida (EAWPr; 1.0 µg/g). All extracts showed activity against Gram-positive bacteria. The aqueous and acetone-water extracts of Psidium guajava showed the greatest inhibition zones in the agar diffusion tests. In the evaluation of the minimum inhibitory concentration (MIC), the most susceptible Gram-positive bacterium was Staphylococcus epidermidis and the most susceptible Gram-negative bacterium was Shigella flexneri. EAPg and EAWPg showed the greatest MIC values. All extracts were significant inhibitors of leukocyte migration (p<0.05). Using the writhing test, significant analgesic activity was found for EAPr (50 mg/kg), EAWPr (100 mg/kg and 200 mg/kg) and EAWPg (50 mg/kg) (p<0.05). CONCLUSIONS: Thus, the appropriate extraction procedure preserves the chemical components such as gallic acid and catechin, and showed antimicrobial, anti-inflammatory and analgesic properties.

A dry extract of Phyllanthus niruri protects normal cells and induces apoptosis in human liver carcinoma cells.

The ability to induce apoptosis is an important marker for cytotoxic antitumor agents. Some natural compounds have been shown to modulate apoptosis pathways that are frequently blocked in human cancers, and therefore, these compounds provide novel opportunities for cancer drug development. Phyllanthus, a plant genus of the family Euphorbiaceae, exhibits multiple pharmacological actions. Of these, Phyllanthus niruri extracts exhibit significant antitumor activity, which is consistent with the traditional medicinal use of this plant. To examine the apoptotic effects of a spray-dried extract of P. niruri (SDEPN), human hepatocellular carcinoma cells (HepG2, Huh-7), colorectal carcinoma cells (Ht29) and keratinocytes (HaCaT) were exposed to the extract for 4, 8 and 24 h. Flow cytometry and caspase-3 immunostaining were used to detect apoptosis, while analysis of variance was applied to identify significant differences between groups (P < 0.05). At all timepoints, the SDEPN induced significantly different cytotoxic effects for HepG2 and Huh-7 cells compared with control cells (P < 0.001). In contrast, the SDEPN had a protective effect on HaCaT cells compared with control cells at all timepoints (P < 0.001). In caspase-3 assays, activation was detected after cell death was induced in Huh-7 and HepG2 cancer cells by the SDEPN. In combination, these results indicate that the SDEPN is selectively toxic towards cancer cell lines, yet is protective towards normal cells.