In vivo study of anti-inflammatory and antinociceptive activities of Copaifera pubiflora Benth oleoresin.

Copaifera pubiflora Benth oleoresin (CPO) is used as an anti-inflammatory, wound healing, and antimicrobial. This paper reports the cytotoxic, anti-inflammatory, and antinociceptive activities of CPO. CPO (10 mg/kg) did not affect locomotor capacity in the open-field and rotarod tests and was not cytotoxic to CHO-k1, THP-1, and L929 cell lines. It was active in the formalin test at 3 mg/kg by 86 ± 3% and 96 ± 3%, respectively, for the first and second phases. At 10 mg/kg, CPO inhibited 90 ± 7%, the pain in the mechanical hyperalgesia test. In the tail-flick test, CPO at 3 mg/kg affected the tail-flick latencies in mice by 77 ± 20%, which in combination with naloxone was only partially reduced. At 3 mg/kg CPO inhibited 80 ± 12% the carrageenan-induced paw edema, and at 3 mg/kg it reduced by 91 ± 5% the nociception on acetic acid-induced abdominal writhing. Therefore, CPO possesses anti-inflammatory and antinociceptive activities.

Gastric healing effect of p-coumaric acid isolated from Baccharis dracunculifolia DC on animal model.

The p-coumaric acid is a phenolic compound present in large quantities in the extract of Baccharis dracunculifolia DC, a Brazilian medicinal plant used to treat gastric ulcer. Given the necessity for finding new chemical components capable of accelerating gastric healing, in this study, the effects of the p-coumaric acid were evaluated in the acetic acid-induced ulcer model in rats, where histological, inflammatory, and oxidative parameters were analyzed. The healing property was also evaluated in the scratch assay on fibroblast cells (L929) and the cytotoxicity of p-coumaric acid was assessed in both L929 and human gastric adenocarcinoma (AGS) cells by MTT assay. The treatment with p-coumaric acid (10 mg/kg, p.o.) for 7 days, twice a day, decreased by 44.6% the acetic acid-induced gastric ulcer compared with the vehicle-treated group. The vehicle control-treated group showed a larger extension of the ulcer base and an extensive damage into the mucosa and submucosa layers, which were mitigated by the treatment with p-coumaric acid. This beneficial effect was also associated with increased levels of mucin and reduced glutathione, decreased amount of lipid hydroperoxides, and increased superoxide dismutase and catalase activities without interfering with the activity of myeloperoxidase in the gastric tissue. The compound promoted the restructuring of the cell monolayer in the scratch test and did not show toxicity in the L929 cell line, while reduced the viability of the AGS, a lineage of human gastric adenocarcinoma. Thus, p-coumaric acid may be considered a natural source for the treatment of gastric ulcers, by reinforcing protective factors of gastric mucosa and by accelerating gastric healing.

The gastroprotective effect of red propolis extract from Northeastern Brazil and the role of its isolated compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis has been used in folk medicine to treat gastric disorders for centuries. However, although studies have been conducted to validate the gastroprotective and anti-ulcer activity of some types of propolis, red propolis activity remains unknown. AIM OF THE STUDY: The present study aimed to evaluate the gastroprotective effect of the hydroalcoholic extract of red propolis (HERP), its mode of action, and the main compounds involved in its activity, therefore contributing to validate the chemical and pharmacological potential of this product. MATERIAL AND METHODS: The effect of HERP (30, 100 and 300 mg/kg p.o. and 30 mg/kg i.p.), and the isolated compounds vestitol (VS), neovestitol (NV), methylvestitol (MV), medicarpin (MD), and oblongifolin AB (OB) (10 mg/kg p.o.) were evaluated on gastric ulcers induced by 60% ethanol/0.3 M HCl (5 mL/kg, p.o.) in mice. Histological changes and mucin levels were assessed by HE and PAS, respectively. Moreover, oxidative stress parameters and myeloperoxidase activity were analyzed on ulcerated tissue. The effect of HERP on gastric acid secretion was evaluated by pyloric ligature model and the mechanisms involved in its gastroprotective effect were investigated by pretreating mice with L-NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a non-selective cyclooxygenase inhibitor, 10 mg/kg, i.p.). RESULTS: HERP (300 mg/kg p.o. or 30 mg/kg i.p.), MV, and MD (10 mg/kg p.o.) protected gastric mucosa against the damage induced by ethanol/HCl. Histological changes were attenuated by the HERP, MV, and MD. Moreover, HERP and MV increased mucin levels. Besides, oxidative stress and MPO activity were reduced by the three treatments. HERP did not display anti-secretory action, but its effect was abolished by indomethacin treatment. CONCLUSIONS: HERP displays gastroprotective property against ethanol/HCl-induced damage. Its effect is dependent on prostaglandins and mucin production. The compounds MV and MD may have an essential role in the activity of HERP. Our data contribute to validate the traditional use of propolis for gastric disorders.

Antiarthritic and Antihyperalgesic Properties of Ethanolic Extract from Gomphrena celosioides Mart. (Amaranthaceae) Aerial Parts.

Gomphrena celosioides Mart. (Amaranthaceae) is used in folk medicine as a natural analgesic, and in Brazil, the species of genus Gomphrena is used for rheumatism. However, scientific evidence which supports its popular use as an analgesic is scarce. This study assessed the antiarthritic and antihyperalgesic activities of the ethanolic extract obtained from G. celosioides aerial parts on Swiss or C57BL/6 mice. The antiarthritic and antihyperalgesic potential of Gomphrena celosioides was evaluated using paw edema, mechanical hyperalgesia, cold allodynia, carrageenan-induced pleurisy, articular inflammation zymosan-induced, Freund's complete adjuvant-induced inflammation zymosan-induced peritonitis, and carrageenan-induced adhesion and rolling experiment models. All doses of G. celosioides (300, 700, and 1000 mg/kg) significantly reduced edema formation in all the intervals evaluated, whereas the mechanical hyperalgesia was reduced 3 hours after the carrageenan injection. The cold hyperalgesia was significantly decreased 3 (700 mg/kg) and 4 hours (700 and 1000 mg/kg) after the carrageenan injection. Ethanolic extract of G. celosioides at 1000 mg/kg reduced the total leukocyte number, without interfering in the protein extravasation in carrageenan-induced pleurisy model. Ethanolic extract of G. celosioides (300 mg/kg) was also able to reduce significantly the leukocyte migration in zymosan-induced articular edema, while a reduction of the adhesion and migration and leukocyte rolling was induced by the ethanolic extract of G. celosioides (300 mg/kg) in zymosan-induced peritonitis. In Freund's complete adjuvant-induced inflammation model, an edema formation and mechanical hyperalgesia reduction were induced by the ethanolic extract of G. celosioides on day 22, whereas the cold allodynia was reduced on day 6 of treatment with the extract. These results show that ethanolic extract of G. celosioides has antihyperalgesic and antiarthritic potential in different acute and persistent models, explaining, at least in part, the ethnopharmacological relevance of this plant as a natural analgesic agent.

Chemical profile and gastroprotective effect of Jatropha elliptica (Pohl) Oken roots.

Jatropha elliptica (Pohl) Oken (Euphorbiaceae) roots are used in folk medicine to treat gastric ulcers. The purpose of this work was to evaluate the gastroprotective activity of ethanol extract (JER) and hexane fraction (ERH) of J. elliptica roots in mice, as well as to analyze the acute toxicity of the extract and identify the potential active compounds. No signs of toxicity were observed in JER. In both acidified ethanol and indometacin-induced gastric ulcer models, all doses tested of JER and ERH significantly reduced gastric lesions. Dereplication of JER was performed by HPLC-DAD-ESI-MS/MS and resulted in the annotation of compounds fraxetin, propacin, jatrophone and jatropholones A and B. GC-MS analysis of ERH revealed the diterpenes jatrophone, jatropholone A and jatropholone B as the major components. The chemical study of this fraction has led to the isolation of these compounds, in addition to the sequiterpene cyperenoic acid and the diterpene 2ß-hydroxyjatrophone, both reported for the first time in J. elliptica. The isolated compounds were tested against L929 cells and only cyperenoic acid and the mixture of jatropholones A and B did not show toxicity, being then selected as good candidates for bioassays using acidified ethanol-induced gastric ulcer model. Cyperenoic acid significantly decreased gastric lesions and preserved gastric mucus layer. The mixture of jatropholones A and B caused a smaller reduction of gastric lesions, without preservation of the gastric mucus layer. The study showed that J. elliptica roots present gastroprotective activity in mice, without causing acute toxic effects. The activity is related, at least in part, to the occurrence of terpenes, mainly the sesquiterpene cyperenoic acid.

Açaí berries (Euterpe oleracea Mart.) dried extract improves ethanol-induced ulcer in rats.

OBJECTIVES: Açaí (Euterpe oleracea) is widely consumed in Brazil and known for its numerous health-beneficial properties. This study investigated the gastroprotective potential of the dried açaí berries extract (DAE). METHODS: Dried açaí berries extract effect was evaluated against ethanol-induced gastric ulcer in rats. Its ability to regulate antioxidant defenses and reduce inflammatory parameters was evaluated in the ulcerated tissues. The scavenger capability of DAE was assessed by DPPH assay, and phytochemical composition was accessed by UHPLC. KEY FINDINGS: The extract showed radical scavenger activity in vitro (IC50  = 210 µg/ml) and gastroprotective effect in vivo, reducing the ulcerated area by 83%, 67% and 48% at doses of 30 and 100 mg/kg (p.o) and 3 mg/kg (i.p), respectively, compared with vehicle group. Besides, DAE (100 mg/kg, p.o) increased the GSH content and GST activity in ulcerated mucosa. Animals treated with DAE showed normalized levels of SOD activity, elevated CAT activity and decreased MPO activity, as well as reduced TNF-α levels, compared with vehicle group. Peonidin-3-glucoside, peonidin-3-rutinoside, cyanidin-3,5-hexoside-pentoside, cyaniding-3-glucoside, pelargonidin-3-glucoside and pelargonidin-3-rutinoside were identified in DAE. CONCLUSIONS: Our findings suggest that DAE reduces the inflammation and maintains the oxidative balance of gastric mucosa, therefore being a promising natural resource or useful nutraceutical to protect gastric mucosa.

Polymeric films containing pomegranate peel extract based on PVA/starch/PAA blends for use as wound dressing: In vitro analysis and physicochemical evaluation.

Chronic wounds constitute a serious public health problem, and developing pharmaceutical dosage forms to ensure patient comfort and safety, as well as optimizing treatment effectiveness, are of great interest in the pharmaceutical, medical and biomaterial fields. In this work, the preparation of films based on blends of poly(vinyl alcohol), starch and poly(acrylic acid), polymers widely used as pharmaceutical excipients, and pomegranate peel extract (PPE), a bioactive compound with antimicrobial and healing activities relevant to the use as a bioactive wound dressing, was proposed. Initially, the minimum inhibitory concentration (MIC) of the PPE was investigated by an in vitro method. Then, the best concentration of the PPE to be used to prepare the films was researched using an antimicrobial susceptibility test with the disc diffusion method. The microbiological assay was performed in films prepared by the solvent casting method in the presence of two concentrations of PPE: 1.25% w/v and 2.5% w/v. Films containing the lower PPE concentration showed antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis, with a difference that was not considered statistically significant when compared to the higher concentration of the extract. Therefore, the films prepared with the lower proportion of PPE (1.25% w/v) were considered for the other studies. The miscibility and stability of the extract in the films were investigated by thermal analysis. Parameters that determine the barrier properties of the films were also investigated by complementary techniques. Finally, in vitro biological tests were performed for safety evaluation and activity research. Analysis of the results showed that the incorporation of the higher proportion of starch in the blend (15% v/v) (PVA:S:PAA:PPE4) yielded smooth, transparent, and domain-free films without phase separation. Additionally, the PVA:S:PAA:PPE4 film presented barrier properties suitable for use as a cover. These films, when subjected to the in vitro hemolytic activity assay, were nonhemolytic and biocompatible. No toxicity from the extract was observed at the concentrations studied. The results of the wound healing in vitro test showed that films containing 1.25% PPE are efficient in reducing the scratch open area, provoking almost total closure of the scratches within 48 h without cytotoxicity.

Role of the antioxidant properties in the gastroprotective and gastric healing activity promoted by Brazilian green propolis and the healing efficacy of Artepillin C.

Green propolis is a resinous substance used in folk medicine given its anti-inflammatory, antibacterial, and anti-ulcer effects. Our research group has already confirmed the gastroprotective activity of hydroalcoholic extract from green propolis (HEGP), as well as of its main isolated compounds. In continuity, this study evaluated the antioxidant mode of action involved in the preventive effect induced by HEGP, and its therapeutic gastric healing potential on installed ulcers. In addition, the healing effect of its main compound Artepillin C was also investigated. Acute and chronic ulcers were induced in rats by given ethanol or acetic acid, respectively. In acute model, the rats were orally pre-treated with vehicle (water plus 1% Tween, 1 mL/kg), HEGP (30-300 mg/kg), or carbenoxolone (200 mg/kg) 1 h prior the ulcer induction. In the chronic ulcer protocol, the rats received vehicle (water plus 1% Tween, 1 mL/kg), HEGP (300 mg/kg), or omeprazole (20 mg/kg) twice a day by 7 days, whereas groups of mice received vehicle (water plus 1% Tween, 1 mL/kg), Artepillin C (18 mg/kg), or ranitidine (20 mg/kg) twice a day by 4 days. Ulcerated tissue was collected for histological, histochemical, immunostaining, oxidative, and inflammatory analyses. The in vitro scavenger activity of HEGP was also verified using the DPPH assay. The oral pre-treatment with HEGP (100 and 300 mg/kg) prevented the gastric epithelial damage promoted by ethanol. Besides, HEGP (100 and 300 mg/kg) reduced SOD activity about 11% and 26%, respectively, and increased the activity of GST around 20% and CAT in 80%. HEGP (300 mg/kg) also reduced the production of reactive oxygen species, as well as lipoperoxidation levels in the ethanol-ulcerated tissue. In the acetic acid-induced chronic ulcer, the daily treatment with HEGP (300 mg/kg) accelerates the healing process by 71%. In this model, HEGP normalized SOD and CAT activity and increased GST activity by 109% when compared to non-ulcerated rats. In both models, the extract administration increased the mucin PAS staining and reduced the myeloperoxidase activity at the ulcer site. Moreover, the treatment with HEGP enhanced the PCNA immunostaining, but did not alter the concentration of collagen in the acetic acid-ulcerated tissue. The extract had a direct DPPH radical-scavenging ability (LogIC50: 0.56). Besides, as expected, HPLC analysis showed Artepillin C as a major compound and its administration at 18 mg/kg also accelerated the gastric healing ulcer process in mice. Our findings confirm that HEGP displays both gastroprotective and gastric healing properties, contributing to the validation of its popular use as preventive and therapeutic approaches. These actions occur through the increase in mucin production and the reestablishment of the oxidative balance due to a reduction in gastric inflammation.

Gastroprotective activity of hydroalcoholic extract of the leaves of Urera baccifera in rodents.

ETHNOPHARMACOLOGICAL IMPORTANCE: The species Urera baccifera (L.) Gaudich. ex Wedd. (Urticaceae) is native to the Americas and is distributed widely throughout Brazil, where it is known as urtiga-brava, urtiga-vermelha, or urtigão. The leaves are often used as anti-inflammatory and antirheumatic agents and for the treatment of gastric disorders. However, the pharmacological mode of action underlying the gastroprotection induced by this species has not been investigated. AIM OF THE STUDY: To contribute to the knowledge of the gastroprotective mode of action of the hydroalcoholic extract of U. baccifera (HEU) leaves. MATERIALS AND METHODS: Antiulcerogenic effect of HEU against ethanol-induced acute gastric ulcer was evaluated in rats and mice at doses of 3-300 mg/kg. NO-synthase inhibitor (L-NAME), SH blocker (NEM), cyclooxygenase inhibitor (indomethacin) and alpha 2-adrenergic receptor antagonist yohimbine were used to evaluate the participation of cytoprotective factors in HEU gastroprotection. Moreover, the levels of reduced gluthatione (GSH) and cytokines (TNF, IL-6, IL4 and IL-10), as well as the enzymatic activity of gluthatione S-transferase (GST), myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) were measure. Moreover, the samples were analyzed histologically and the antisecretory capability of HEU were quantified using pylorus ligated rats. RESULTS: The phytochemical analysis of HEU (UPLC/ESI-IT-MS) identified the flavonoids diosmetin and apigenin glucuronide. Furthermore, HEU decreased the occurrence of ethanol-induced ulcers at 30 and 300 mg/kg by 57% and 66%, respectively, compared with the vehicle. The gastroprotective effects were accompanied by increased GSH levels and GST and SOD activity as well as by reduced MPO activity in vivo and in vitro, revealing antioxidant effects and inhibition of neutrophil infiltration. The beneficial effects of 30 and 300 mg/kg HEU were also observed upon histological analyses. Regarding the mode of action, the gastroprotective effect of HEU was abolished by the pre-administration of L-NAME, NEM, indomethacin or yohimbine. Moreover, HEU was able to decrease the IL-6, IL-4 and IL-10 in ulcerated tissue, as well as the pepsin activity of the gastric juice in pylorus-ligated rats. CONCLUSION: Together, the results confirmed that the gastroprotection elicited by HEU was due reduction in oxidative damage, neutrophil migration, and peptic activity. This work validates the popular use of U. baccifera to treat gastric disorders and supports important future research for the identification of gastroprotective molecules from this species.

Salvia lachnostachys Benth has antitumor and chemopreventive effects against solid Ehrlich carcinoma.

Salvia lachnostachys is an herbaceous plant with anti-inflammatory, analgesic and cytotoxic properties. This study investigated the antitumor effect of an ethanolic extract of Salvia lachnostachys leaves (EES) in a solid Ehrlich carcinoma model. Ehrlich cells were inoculated subcutaneously in the right pelvic member (2 × 106 cells) in female Swiss mice. The animals were treated with vehicle (10 mL kg-1, p.o.), EES (30 and 100 mg kg-1, p.o.), or methotrexate (2.5 mg kg-1, i.p.) for 21 days (early treatment) or 14 days (late treatment) after tumor inoculation, or 10 days before tumor inoculation and continued for 21 days after tumor inoculation (chemopreventive treatment). The acute toxicity test was performed according OECD guidelines Late treatment with EES had no antitumor effect. Early treatment with 100 mg kg-1 EES prevented tumor development, increased tumor necrosis factor-α (TNF-α) levels and decreased tumor superoxide dismutase (SOD) activity, interleukin-10 (IL-10) levels and Cyclin D1 expression, and tumor cell necrosis was observed. Chemopreventive treatment with EES for 10 and 31 days prevented tumor development in the same manner. EES treatment for 31 days decreased hepatic and tumor SOD activity, tumor IL-10 levels and Cyclin D1 expression, and increased tumor reduced glutathione, N-acetylglucosaminidase, reactive oxygen species, lipid peroxidation, TNF-α levels and Nrf2 expression. No toxicity was observed in the acute toxicity assay. In conclusion, EES had an antitumor effect by inhibiting Cyclin D1 expression and increasing inflammation with early and chemopreventive treatment. Modulation of the antioxidant system also contribute for the antitumor effects of EES.

Hesperidin, a citrus flavanone glycoside, accelerates the gastric healing process of acetic acid-induced ulcer in rats.

The flavonoid hesperidin is abundantly found in citrus fruits and is used to treat vascular diseases. Previous studies described its gastroprotective actions against stress or ethanol-induced ulcer in rodents; however, results from indomethacin-induced ulcer were controversy. Therefore, given its clinical use and contradictory findings in acute models, this study aims to evaluate the effect of hesperidin (1-10 mg/kg, p.o) on chronic gastric ulcer induced by acetic acid in rats, a model that resembles the ulcer in humans. Moreover, the effects of hesperidin on mucin levels and on inflammatory and oxidative parameters at ulcer site were also measured. The treatment with hesperidin at 3 and 10 mg/kg, once a day, by seven days, accelerated by 34 and 62%, respectively, the ulcer healing process when compared to vehicle-treated group (99.1 ±â€¯6.4 mm2). Histological and histochemistry analyses confirmed the healing effect with significant favoring of mucin production. Hesperidin also promoted the preservation of reduced glutathione levels in the gastric mucosa tissue, as well as the normalization of superoxide dismutase and catalase activities at similar levels to those found in the non-ulcerated group. In addition, flavonoid administration increased the enzymatic activity of glutathione-S-transferase by 35%. Tissue lipoperoxides and myeloperoxidase activity were reduced after hesperidin treatment. In conclusion, the flavonoid hesperidin revealed a gastric healing activity in the ulcerated mucosa, an effect that showed to be associated with the reduction of oxidative damage at ulcer site, due to the reduction of the neutrophil migration and the strengthening of the mucus barrier next to the mucosa.

Hydroalcoholic extract of Tagetes erecta L. flowers, rich in the carotenoid lutein, attenuates inflammatory cytokine secretion and improves the oxidative stress in an animal model of ulcerative colitis.

Given the role of oxidative stress in ulcerative colitis (UC) etiology, and the amount of lutein (a carotenoid with antioxidant properties) in the dry hydroalcoholic extract of Tagetes erecta flowers (DHETE), this study investigated the intestinal anti-inflammatory properties of DHETE in an animal model of UC. The amount of lutein in the extract was determined by 1H-nuclear magnetic resonance spectroscopy, and total phenols, radical scavenger capability, cytotoxicity, and effects on reactive oxygen species and nitric oxide production were evaluated in vitro. Experimental UC was established by adding 5% dextran sulfate sodium (DSS) to drinking water, with the effects of DHETE (30-300 mg/kg, once a day for 7 days) on the morphological (colon length and weight), clinical (disease activity index and body weight loss), microscopic (histological score and mucin levels), and biochemical parameters analyzed. The lutein concentration found in DHETE was 8.2%, and DHETE scavenged 2,2-diphenyl-1-picrylhydrazyl radicals at 1000 µg/mL The exposure of intestinal epithelial cells to DHETE did not change its viability but reduced reactive oxygen species and nitric oxide production after lipopolysaccharide stimulation. In vivo, DHETE (300 mg/kg) attenuated weight loss, disease activity index, colon shortening, and histopathological changes promoted by DSS intake. Moreover, DHETE increased mucin colonic staining. The treatment with DHETE decreased myeloperoxidase activity as well as tumor necrosis factor and interleukin-6 levels. The extract also increased reduced glutathione levels and catalase activity and normalized superoxide dismutase and glutathione-S-transferase activities. In conclusion, DHETE reduced colitis severity by attenuating inflammatory cytokine secretion and improved the endogenous antioxidant defense in DSS-induced UC in mice.

Hydroalcoholic extract from Baccharis dracunculifolia recovers the gastric ulcerated tissue, and p-coumaric acid is a pivotal bioactive compound to this action.

Baccharis dracunculifolia is a medicinal plant native to southeastern Brazil and is the main botanical source used by bees (Apis mellifera) in the manufacture of green propolis and display similar gastroprotective action and chemical profile. This article reports the healing gastric ulcer activity of the hydroethanolic extract of B. dracunculifolia (HEBD) in an acetic acid-induced ulcer model. In addition to the extract, the isolated compounds ferulic acid, p-coumaric acid, caffeic acid, baccharin, and aromadendrin-4'-O-methyl ether were also assayed. HEBD at a dose of 300 mg/kg reduced the ulcerated area by 49.4% after treatment for 7 days, twice a day. Histological analyses revealed that the margins and base of the ulcer obtained significant regeneration, and periodic acid Schiff base staining showed a 78.2% increase in the mucin levels. The action on the enzymatic antioxidant system demonstrated an increased activity of superoxide dismutase and glutathione-S-transferase, in addition to raising glutathione reduced levels and myeloperoxidase activity. HEBD did not show cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazole bromine test. In vitro, HEBD inhibited the H+ /K+ -ATPase enzyme and showed antioxidant activity in the 2,2 diphenyl-1-picryllydrazyl test. Regarding the isolated compounds, oral administration of p-coumaric acid (15 mg/kg) reduced the ulcerated area by 66.2%. The results suggest that HEBD recovers the gastric ulcerated tissue, raising mucus and antioxidant enzyme levels, and reducing the H+ /K+ -ATPase activity. In addition, the findings confirm that p-coumaric acid is a pivotal bioactive compound on the gastric healing effects elicited by HEBD. © 2019 BioFactors, 45(3):479-489, 2019.

Chrysophyllum cainito (apple-star): a fruit with gastroprotective activity in experimental ulcer models.

The gastroprotective potential of the methanolic extracts from peels (MEPe), seeds (MESe) and pulp (MEPu) of Chrysophyllum cainito L. (Sapotaceae) fruits was evaluated in mice using ethanol/HCl- and indomethacin-induced ulcer, as well as the antiulcer effect of the juice and flour from this fruit. The lowest oral gastroprotective dose of MEPe, MESe and MEPu against ethanol/HCl was 3, 3 and 10 mg/kg, respectively. Moreover, all extracts increased mucin secretion at 176, 198 and 193%. Intraperitoneal administration of MEPe (0.3 mg/kg), MESe (0.3 mg/kg) and MEPu (1 mg/kg) also promoted gastroprotection against ethanol/HCl. In addition, MEPe (3 mg/kg, p.o), MESe (3 mg/kg, p.o) and MEPu (10 mg/kg, p.o) reduced indomethacin-induced gastric ulcer in mice by 78, 70 and 50%, respectively. Regarding the mode of action, the gastroprotective effect of MEPe was decreased by the pre-administration of N-ethylmaleimide (NEM, a sulfhydryl group chelator, 10 mg/kg, i.p), glibenclamide (a potassium channel blocker, 10 mg/kg, i.p), yohimbine (10 mg/kg, i.p, an alpha-adrenergic receptor antagonist, 10 mg/kg, i.p) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p). The gastroprotective effect of MESe was reduced by the pre-administration of NEM, glibenclamide, N-Nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor, 70 mg/kg, i.p) and yohimbine, while MEPu had the gastroprotective effect decreased in animals pretreated with NEM and L-NAME. However, the extracts did not reduce gastric acid secretion. The supplementation with the flour from C. cainito fruit at 10% by 7 days, but not the juice intake, displayed gastroprotective potential, evidencing the fruit as a promising functional food. Together, the antiulcer effect of extracts of the C. cainito fruit in different experimental models was confirmed by the favoring of mucosal protective mechanisms among different, but complementary, modes of action. In parallel, the gastroprotective effects of the flour from C. cainito fruit were also described.

Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats.

AIM: To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia (HEEP) leaves on gastric ulcer healing. METHODS: In this rat study involving males, intact (cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity. RESULTS: Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males (52.44%), intact females (85.22%), and ovariectomized females (65.47%), confirming that HEEP accelerates the healing of acetic acid-induced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor (intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2 (intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed. CONCLUSION: In gastric ulcers, HEEP-induced healing (modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.

Antineoplastic effect of pectic polysaccharides from green sweet pepper (Capsicum annuum) on mammary tumor cells in vivo and in vitro.

The present study investigated the antineoplastic effects of pectic polysaccharides that were extracted from green sweet pepper (Capsicum annuum [CAP]) in the Ehrlich carcinoma in mice and in human mammary tumor lineages. After the subcutaneous inoculation of 2 × 106 Ehrlich tumor cells, Female Swiss mice received 50, 100, or 150 mg/kg CAP or vehicle orally once daily or methotrexate (2.5 mg/kg, i.p., every 5 days) for 21 days. CAP dose-dependently reduced Ehrlich tumor growth. It also reduced the viability of MCF-7, MDA-MB-231, and MDA-MB-436 human mammary cell lineages. Treatment with CAP reduced the gene expression of vascular endothelial growth factor in vivo and in vitro, reduced vessel areas of the tumors, and induced necrosis in Ehrlich solid tumors. CAP treatment significantly increased Interleukin-6 in tumors. The antineoplastic effect of CAP appears to depend on the regulation of inflammation and angiogenesis. Further studies are encouraged to better understand the CAP potential for the treatment of breast tumors.

The hydroethanolic Litchi chinensis leaf extract alleviate hepatic injury induced by carbon tetrachloride (CCl4) through inhibition of hepatic inflammation.

Various medicinal plants are traditionally used in a hepatoprotective manner, like, for example, the Litchi chinensis leaf infusion that is employed in Chinese medicine as liver tonics to strengthen hepatic functioning. In this context, the present study was designed to evaluate the hepatoprotective and acute toxicological effects of hydroethanolic L. chinensis leaf extract in HepG2 cells and mice. Specifically, the cytotoxicity and hepatoprotective activities of L. chinensis leaf extract were evaluated in HepG2 cells and in vivo against carbon tetrachloride (CCl4)-induced acute liver injury. The administration of CCl4 in mice provokes cell swelling, loss of sinusoid capillary spaces and structural disarrangement of the hepatic lobe, apoptosis and leukocyte infiltration. Further, CCl4 evokes an increase in serum alanine aminotransferase (ALT), tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels in hepatic tissue. However, Silymarin, the positive control, and the L. chinensis extract were able to restore the viability of cells treated with CCl4 at all concentrations evaluated, reduced the inflammatory parameters, TNF and IL-6, reestablished hepatic tissue morphology and did not induce acute toxicological alterations. The data obtained underscore that the extract from L. chinensis leaves features hepatoprotective activity, corroborating with ethnopharmacological use, and does not lead to acute toxicological effects.

Propolis and Its Potential to Treat Gastrointestinal Disorders.

There are a number of disorders that affect the gastrointestinal tract. Such disorders have become a global emerging disease with a high incidence and prevalence rates worldwide. Inflammatory and ulcerative processes of the stomach or intestines, such as gastritis, ulcers, colitis, and mucositis, afflict a significant proportion of people throughout the world. The role of herbal-derived medicines has been extensively explored in order to develop new effective and safe strategies to improve the available gastrointestinal therapies that are currently used in the clinical practice. Studies on the efficacy of propolis (a unique resinous aromatic substance produced by honeybees from different types of species of plants) are promising and propolis has been effective in the treatment of several pathological conditions. This review, therefore, summarizes and critiques the contents of some relevant published scientific papers (including those related to clinical trials) in order to demonstrate the therapeutic value of propolis and its active compounds in the treatment and prevention of gastrointestinal diseases.