Antiulcer mechanisms of the hydroalcoholic extract from Aztec marigolds' medicinal and edible flowers (Tagetes erecta L.).

The antiulcer mechanisms of the dry extract of T. erecta flowers (DETe) were studied here. The acute ulcers induced by acidified ethanol or indomethacin were reproduced in mice pretreated with DETe (3 - 300 mg/kg). The antiulcer activity of DETe was also verified in mice pretreated with NEM, L-NAME, indomethacin, or yohimbine. The antisecretory effect of DETe was verified in rats, and its anti-Helicobacter pylori activity was determined in vitro. DETe (300 mg/kg, p.o) reduced the ethanol- or indomethacin-induced ulcer by 49 and 93%, respectively. The pre-treatment with L-NAME, NEM or yohimbine abolished the gastroprotective effect of DETe. However, DETe did not change the volume, acidity, or peptic activity in rats and did not affect H. pylori. This study expands knowledge about the antiulcerogenic potential of DETe, evidencing the role of nitric oxide, non-protein sulfhydryl groups, α2 adrenergic receptors, and prostaglandins, but not antisecretory or anti-H. pylori properties.

Natural Products as Modulators of Mitochondrial Dysfunctions Associated with Cardiovascular Diseases: Advances and Opportunities.

The mitochondria have an important role in modulating cell cycle progression, cell survival, and apoptosis. In the adult heart, the cardiac mitochondria have a unique spatial arrangement and occupy nearly one-third the volume of a cardiomyocyte, being highly efficient for converting the products of glucose or fatty acid metabolism into adenosine triphosphate (ATP). In cardiomyocytes, the decline of mitochondrial function reduces ATP generation and increases the production of reactive oxygen species, which generates impaired heart function. This is because mitochondria play a key role in maintaining cytosolic calcium concentration and modulation of muscle contraction, as ATP is required to dissociate actin from myosin. Beyond that, mitochondria have a significant role in cardiomyocyte apoptosis because it is evident that patients who have cardiovascular diseases (CVDs) have increased mitochondrial DNA damage to the heart and aorta. Many studies have shown that natural products have mitochondria-modulating effects in cardiac diseases, determining them as potential candidates for new medicines. This review outlines the leading plant secondary metabolites and natural compounds derived from microorganisms as modulators of mitochondrial dysfunctions associated with CVDs.

Gastroprotective effect of Artemisia absinthium L.: A medicinal plant used in the treatment of digestive disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Wormwood (Artemisia absinthium L.) is traditionally used for stomach pain and gastric relief. However, its possible gastroprotective effect has not yet been experimentally evaluated. AIM OF THE STUDY: This study evaluated the gastroprotective effect of aqueous extracts obtained through hot and room temperature maceration of A. absinthium aerial parts in rats. MATERIALS AND METHODS: The gastroprotective effect of hot aqueous extract (HAE) and room temperature aqueous extract (RTAE) from A. absinthium aerial parts were evaluated in rats using a model of acute gastric ulcer induced by ethanol p.a. The stomachs were collected to measure the gastric lesion area and histological and biochemical analysis. UHPLC-HRMS/MS analysis was used to determine the chemical profile of the extracts. RESULTS: Eight main peaks in the UHPLC chromatogram were identified in both HAE and RTAE extracts: tuberonic acid glycoside (1), rupicolin (2), 2-hydroxyeupatolide (3), yangabin (4), sesartemin (5), artemetin (6), isoalantodiene (7), and dehydroartemorin (8). For RTAE, a higher diversity of sesquiterpene lactones was observed. The groups treated with RTAE at 3%, 10%, and 30% presented a gastroprotective effect, reducing the lesion area by 64.68%, 53.71%, and 90.04%, respectively, when compared with the vehicle (VEH)-treated group. On the other hand, the groups treated with HAE at 3%, 10%, and 30% presented values of lesion areas higher than those of the VEH group. Changes in the submucosa layer, inflammatory process with edema, cellular infiltration, and mucin depletion were detected in the gastric mucosa exposed to ethanol, which was fully prevented by RTAE treatment. Neither HAE nor RTAE could increase the reduced glutathione levels in the injured gastric tissue, but RTAE (30%) reduced the formation of lipid hydroperoxides. When the rats were pre-treated with NEM (a chelator of non-protein thiols) or L-NAME (non-selective nitric oxide synthase inhibitor), the RTAE lost the ability to protect the gastric mucosa. CONCLUSIONS: This study corroborates the ethnopharmacological use of this specie to treat gastric disorders revealing the gastroprotective effect of the room-temperature aqueous extract of A. absinthium aerial parts. Its mode of action may involve the ability of the infusion to maintain the gastric mucosal barrier integrity.

Brazilian Red Propolis Accelerates Gastric Healing and Reduces Gastric Submucosal Layer Inflammation in Ultrasound-Monitored Rats.

Propolis has been used for the treatment of gastric disturbances in folk medicine, nevertheless, the gastric healing effects of Brazilian red propolis have not been unveiled. This study aimed to assess the gastric healing effect of the hydroalcoholic extract of red propolis (HERP) in the acetic acid-induced ulcer model. Rats under acetic acid-induced-ulcer were treated with HERP (100 mg/kg, p.o.) twice a day for seven days. Histological changes, oxidative stress, and inflammatory parameters were analyzed in the gastric tissue. Moreover, the gastric wall thickness was measured by ultrasound. The in vitro cytotoxicity of HERP and cellular migration of fibroblasts were evaluated. The treatment with HERP promoted gastric healing, reducing gastric wall thickness, macroscopic lesion area, and histopathological damages compared to the vehicle. Moreover, HERP reduced oxidative stress and inflammation in the gastric tissue but did not change mucin or collagen levels. HERP did not show signs of toxicity either in vivo or in vitro. HERP displayed a healing effect in vivo by reducing oxidative stress and inflammation. These data contribute to validating the popular use of this product in the treatment of gastric disorders and advance scientific knowledge in the search for new drugs for the management of gastric ulcers.

Dimethyl Cardamonin from Fruits of Campomanesia reitziana D. Legrand Promotes Gastroprotection and Gastric Healing Effects in Rodents.

Campomanesia reitziana D. Legrand (Myrtaceae) displays antiulcer properties when given to rodents. The major active chemical components of C. reitziana are chalcones, including 4',6'-dihydroxy-2'-methoxy-3',5'-dimethylchalcone or dimethyl cardamonin (DMC); therefore, we hypothesized that this compound could have antiulcer effects and the present study aimed to evaluate its gastroprotective and gastric healing properties. DMC was isolated from the fruits of C. reitziana, and its gastroprotective effect was evaluated by ethanol and indomethacin-induced gastric ulcer models in mice (0.1 mg/kg, i.p. and 1 and 3 mg/kg, p.o.). Oxidative stress and inflammatory parameters were analyzed in the gastric tissue. Moreover, its gastric healing effect was evaluated in rats. In addition, the compound's mode of action was evaluated in vivo and in vitro by measuring H+ -K+ -ATPase activity. Finally, the cytotoxic potential of DMC was tested in fibroblasts and human gastric adenocarcinoma cells. The DMC reduced the ethanol-induced gastric ulcer in mice by 77 %, increased the adhered mucus, and reduced lipoperoxides levels. The block of nonprotein sulfhydryls (NP-SH) compounds by pretreatment with N-ethylmaleimide (NEM), the inhibition of nitric oxide synthase with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), or the antagonism of α2 receptor using yohimbine reversed the gastroprotective effects of DMC. Furthermore, DMC reduced the acidity of gastric content in pylorus-ligated rats but did not change H+ , K+ -ATPase (isolated from rabbit) activity in vitro. DMC reduced the lesion area in acetic acid-induced ulcers and decreased myeloperoxidase activity. DMC did not change the viability of fibroblast cells (L929) but reduced the viability of human gastric adenocarcinoma cells (AGS). The results confirmed that DMC could significantly enhance the gastric healing process and prevent ulcers due to improving protective factors on the gastric mucosa and reducing gastric acid secretion.

Gastroprotective and gastric healing effects of the aqueous extract of Casearia sylvestris in rodents: Ultrasound, histological and biochemical analyzes.

ETHNOPHARMACOLOGICAL IMPORTANCE: Casearia sylvestris Sw. (Salicaceae) is a native plant from the Americas, where it is also known as "guaçatonga" or "erva-de-bugre." Although its leaves have been commonly used to treat inflammation and gastrointestinal disorders in South America, the antiulcer effects of an aqueous extract from this medicinal plant, similar to popular use, have not to be investigated yet. AIM OF THE STUDY: This study evaluated the hypothesis that the aqueous extract a of C. sylvestris (AEC) prevents the gastric ulcers and accelerates the healing of ulcers already installed, by assessing ultrasound imaging, histological and biochemical analyses. MATERIALS AND METHODS: Rats (females) were treated with AEC (3, 30 or 300 mg/kg) prior to the ethanol or piroxicam-induced gastric ulcers. The healing effect of AEC (300 mg/kg) was examined in 80% acetic acid-induced ulcer in rats, whereas the quality of healing was evaluated in recurrent 10% acetic acid-induced ulcer in mice with recurrence induced by interleukin 1ß. To assess the responses of the lesions, in addition to the classical methods used to analyze gastroprotection (ex vivo), we also measured the gastric wall thickness (in vivo) using ultrasonography. After euthanasia, the extent of ulcer was determined and the levels of reduced glutathione (GSH), lipid hydroperoxides (LOOH), nitrate, and the activities of myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase (NAG), superoxide dismutase (SOD), and glutathione S-transferase (GST) were measured. The antisecretory activity of AEC was also examined based on pylorus ligated rats. Furthermore, gastric tissue samples were analyzed histologically, and phytochemical analyses of the C. sylvestris extract were parallelly performed. RESULTS: The AEC (30 or 300 mg/kg) prevented ulcers in the ethanol- and piroxicam-induced acute. Moreover, the AEC at a dose of 300 mg/kg also accelerated the gastric healing of acetic acid-induced ulcer in rats by 48% and the ultrasonography records shown a decrease in the wall thickness and the extent of edema of ulcerous lesions promoted by the extract. The gastric healing effect of AEC was also accompanied by reduced MPO and NAG activities at acetic acid-induced ulcer in rats; as well as was by the reduction in the nitrate and LOOH levels, the increase in mucin and SOD activity, and by a partial recovery of GSH levels. The AEC (300 mg/kg) minimized the ulcer recurrence in mice exposed to IL-1ß, but the extract administration did not change pH or peptic activity of gastric juice in pylorus ligated rats. CONCLUSION: The results of this study provide convincing evidence for the therapeutic efficacy of C. sylvestris with respect to gastroprotection and indicate that ultrasound examination would be a potentially promising approach for evaluating gastroprotective effects in vivo. Collectively, our findings indicate that the gastric the gastroprotective and healing effects of aqueous extract C. sylvestris involve a reduction in acid secretion, promotion of the antioxidant system, reductions in the migration of neutrophils and mast cells, with a consequent lower inflammatory response, and the preservation of mucin.

Exotic Medicinal Plants Used in Brazil with Diuretic Properties: A Review.

Several exotic plants (non-native) are used in Brazilian traditional medicine and are known worldwide for their possible diuretic actions. Among the wide variety of plants, standing out Achillea millefolium L., Camellia sinensis L. Kuntze, Crocus sativus L., Hibiscus sabdariffa Linn., Petroselinum crispum (Mill.) A.W. Hill, Taraxacum officinale (L.) Weber, and Urtica dioica L., whose effects have already been the subject of some scientific study. In addition, we also discussed other exotic species in Brazil used popularly, but that still lack scientific studies, like the species Arctium lappa L., Carica papaya L., Catharanthus roseus (L.) G. Don, Centella asiatica (L.) Urb, Citrus aurantium L., and Persea americana Mill. However, generally, clinical studies on these plants are scarce. In this context, different plant species can be designated for further comprehensive studies, therefore, promoting support for developing an effective medicine to induce diuresis.

Lupeol Stearate Accelerates Healing and Prevents Recurrence of Gastric Ulcer in Rodents.

Objective: The focus of this study was to evaluate the gastric healing effect of lupeol stearate (LS) and its ability to minimize ulcer recurrence in rodents. Methods: To evaluate the gastric healing properties of LS, rats were subjected to 80% acetic acid-induced ulcer model and treated with vehicle, LS (1 mg/kg, p.o.), or omeprazole (20 mg/kg, p.o.), twice daily by seven days. The gastric ulcers were evaluated macroscopically, histologically, and biochemically. To evaluate the effects of LS in gastric ulcer recurrence, mice were ulcerated with 10% acetic acid and treated with vehicle, LS (1 mg/kg, p.o.), or ranitidine (100 mg/kg, p.o.), twice a day for ten days. Then, ulcer recurrence in these animals was induced by IL-1ß at five days after the treatment period. Results: The oral treatment with LS accelerated gastric healing by 63% in rats compared to the vehicle group, evidenced by histological improvement and increased gastric mucin levels. Moreover, the gastric healing effects of LS in rats were accompanied by an elevation in glutathione S-transferase activity and a reduction in myeloperoxidase activity. Furthermore, the LS treatment reduced the recurred lesions in mice. Conclusions: The oral treatment of LS accelerates gastric healing in rats by favoring mucus production and reducing neutrophil migration, and it also can reduce ulcer recurrence. These data highlighted this compound as promising for developing new pharmacological strategies for the management of gastric ulcer.

Preparations from Campomanesia reitziana reduce the gastrointestinal motility and castor oil-induced diarrhea in a non-opioid and non-dopaminergic pathway in mice and display antimicrobial activity in vitro.

BACKGROUND: This study investigated the antidiarrheal potential of the aqueous extract (AECR) and hydroalcoholic extract of Campomanesia reitziana leaves (HECR), its ethyl acetate (EAF) and dichloromethane fractions (DCMF), and myricitrin isolated from EAF. METHODS: The total phenols and flavonoids were measured, followed by chromatography and myricitrin isolation. The 2,2-diphenyl-1-picryl-hydrazyl scavenger activity, the cytotoxicity, and the effects on LPS-induced nitrite production in intestinal epithelial cells (IEC-6) were quantified. The effect of HECR, EAF, DCMF, and AECR on intestinal motility (IT), gastric emptying (GE), and castor oil-induced diarrhea in mice was determined, as well as its antimicrobial activity. KEY RESULTS: The administration of AECR 10% (10 ml/kg, p.o), but not HECR (300 mg/kg), reduced the GE and IT by 52 and 51%. The EAF and DCMF at 300 mg/kg also reduced IT but did not change GE. Moreover, AECR and EAF, but not DCMF, inhibited the castor oil-induced diarrhea and naloxone or metoclopramide pretreatment did not change these effects. Myricitrin did not change IT and the evacuation index of mice. Finally, the dry residue of AECR inhibited bacterial growth and EAF showed bacteriostatic activity against S. aureus, E. coli, and S. typhimurium and antifungal for C. albicans. However, none of the preparations alter the viability of Giardia spp. trophozoites. CONCLUSIONS: The AECR and EAF can be effective to treat diarrhea acting through opioid- or dopaminergic type 2 receptor-independent mechanisms and by its antimicrobial actions.

Herbal Medicines in the Treatment of Dyspepsia: An Overview.

This review focuses on the efficacy of herbal medicines for managing dyspepsia in humans and animals. Searches were conducted on the PubMed, Science Direct, and Medline databases, for publications in the last 3 years. In each database, the search terms used consisted of the 2 key terms describing the disorder and subtypes plus each of the terms relating to the therapy. The key terms used were "natural product" and "medicinal plant" in a cross-over with "dyspepsia" and "functional dyspepsia" (i.e., gastroprotection, Helicobacter pylori infection, prokinetic). We included all human and animal studies on the effects of herbal medicines reporting the key outcome of dyspepsia symptoms. Preclinical studies using critically validated models showed that most medicinal plants with gastroprotective action had antioxidant, anti-inflammatory, anti-apoptotic, and antisecretory effects. Moreover, several species displayed anti Helicobacter pylori and prokinetic efficacy. The data availability of controlled clinical studies is currently minimal. The use of different methodologies and the minimal number of patients raise doubts about the effects of these preparations. Only adequate clinical trials with scientifically validated methods can determine whether different herbal medicines can be used as viable alternatives to the conventional pharmacological treatments used to control dyspepsia symptoms.

Therapeutic Feasibility of the Natural Products in the Heart Complaints: An Overview.

Heart pain is the most frequent complaint leading patients to seek medical help. Functional heart symptoms, especially chest pain, are prevalent and, according to the International Classification of Diseases (ICD-10), are described as "somatoform autonomous functional disorders of the cardiovascular system." The problem lies in the fact that pain does not always have a somatic background, that is, it may be related to crucial underlying heart disease. The population does not know how to differentiate somatic pain from significant ischemic symptoms, and based on the patient's complaints, traditional medicine ends up treating other underlying cardiac diseases. Many unsuccessful unconventional therapies have been proposed in recent years, including herbal medicines that seek to disrupt the disease's pathogenesis. The present review summarizes research carried out in the last 5 years on natural products' heart complaints, including myocardial ischemia, arrhythmia, and heart failure. Several herbal medicines may be used as a replacement or complementary treatment strategy. A total of 17 medicinal plants have shown promising results in preclinical studies. However, human clinical trials are scarce; only two have been presented. Generally, the data are bland, and many issues have been raised about herbal therapies' safety, efficacy, and mode of action. Besides, relevant clinical trials, future perspectives, and possible clinical applications are discussed.

Tagetes erecta L. flowers, a medicinal plant traditionally used to promote diuresis, induced diuretic and natriuretic effects in normotensive and hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Tagetes erecta L., known as marigold, belongs to the Asteraceae family and is mainly found in South America. Despite reports that T. erecta flowers are used in folk medicine to treat cardiovascular and renal diseases, there is no study regarding its diuretic effect. AIM: This study aimed to evaluate the chemical composition and the diuretic efficacy of the hydroethanolic extract from T. erecta (HETE) in normotensive (NTR) and hypertensive (SHR) rats. MATERIAL AND METHODS: The HETE was analyzed by liquid chromatography coupled to diode array detector and mass spectrometry (LC-DAD-MS). Female and male NTR and SHR received the treatment with vehicle, HETE (0.01 mg/kg, 0.1 mg/kg, and 1 mg/kg) or hydrochlorothiazide (HCTZ; 5 mg/kg) orally. The urinary parameters were measured at the end of the 8-h experiment. RESULTS: From HETE, saccharides and triterpenes were the main annotated compounds, such as erythrodiol and ß-amyrin. The urine volume was significantly increased in the groups treated with HETE, in both male and female NTR and SHR rats, compared to the respective vehicle-treated groups. Regarding electrolytes elimination, the treatment with HETE did not reveal significant changes in the urine levels of K+ or Cl-, but it showed a natriuretic and Ca2+-sparing effects. The HETE beneficial result in reducing Ca2+ excretion was confirmed through the protective effect found in front of the urinary calcium oxalate precipitation and crystallization. The combination with HCTZ, a classic diuretic and saluretic medicine, significantly enhanced HETE-induced diuresis, natriuresis, and the Ca2+-sparing effect. On the other hand, the K+-sparing action was improved in the combination of HETE with amiloride, a standard K+-sparing diuretic. In contrast, the combination of HETE with atropine (a non-selective muscarinic receptor antagonist) and indomethacin (an inhibitor of the cyclooxygenase enzyme), promoted an important reduction in urinary volume, but interestingly the natriuretic effect was maintained. CONCLUSION: This study contributed to the preclinical validation of the diuretic efficacy of T. erecta, highlighting this species as promising for the development of new pharmacological strategies for the management of kidney disorders.

Prolonged Diuretic and Renoprotective Effects of a Xanthone Obtained from Garcinia achachairu Rusby in Normotensive and Hypertensive Rats.

The previous study showed that 1,5,8-trihydroxy-4',5'-dimethyl-2H-pyrano(2,3 : 3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) obtained from Garcinia achachairu Rusby (Clusiaceae) branches induces acute diuresis in normotensive (NTR) and spontaneously hypertensive rats (SHR) after 8 h of the experiment. In complementarity, the present study evaluated the prolonged diuretic and renoprotective effects of TDP in both NTR and SHR. The animals received, once a day, oral treatment with TDP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (VEH; 10 mL/kg). At the end of 7 days, the urine, blood, and kidney samples were collected for biochemical and histological analyzes. The urinary volume of both NTR and SHR after 7 days of treatment with the TDP was significantly increased, associated with augmented urinary electrolyte excretion levels. The treatments did not modify the urinary pH values nor the parameters analyzed in plasma (Na+, K+, Cl-, and Ca2+). Concerning the renal analyzes, when compared with the VEH-treated NTR group, while the activity of the enzymes catalase (CAT) and N-acetyl-ß-D-glucosaminidase (NAG), as well as nitrite levels, were increased, the generation of lipid hydroperoxides and the activity of the enzyme myeloperoxidase (MPO) were unaltered. On the other hand, the activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) and the levels of reduced glutathione (GSH) in kidney homogenates of the SHR group were decreased. However, TDP augmented the levels of GSH and GST activities and reduced the levels of nitrite and the activities of CAT and MPO, when compared with VEH-treated only SHR. Besides, the treatment with TDP alleviated the morphological changes of the renal corpuscle region of SHR. Together, these results revealed the prolonged diuretic effect of TDP and their renal protective effect by improving the antioxidative capacity.

Phytochemistry and Pharmacology of the Genus Equisetum (Equisetaceae): A Narrative Review of the Species with Therapeutic Potential for Kidney Diseases.

The Equisetum genus, Equisetaceae family, is widely distributed worldwide and may be the oldest nonextinct genus on Earth. There are about 30 known species, which are very often used in traditional medicine with diverse applications. This review aimed to compile scientific reports about Equisetum species with relevant pharmacological properties and/or therapeutic potential for kidney diseases. Our bibliographic survey demonstrates that the most widespread traditional use of Equisetum is as a diuretic, followed by the treatment of genitourinary diseases (kidney diseases, urethritis, kidney stones, and others), inflammation, wound healing, rheumatic diseases, prostatitis, and hypertension. The most popular species from the Equisetum genus with medicinal use is E. arvense L., whose diuretic effect was confirmed in animal models and clinical trials. The species E. bogotense Kunth also demonstrated the beneficial effect of inducing diuresis in both experimental and clinical assays. Several other species have also been studied regarding their therapeutic potential, showing different biological actions. Regarding the chemical composition, it contains many active constituents, such as alkaloids, flavonoids, phenol, phytosterols, saponins, sterols, silicic acid, tannin, triterpenoids, and volatile oils. However, despite the widespread traditional use, many species need to be explored in detail for scientific validation of popular use. Indeed, the species of the Equisetum genus have great potential in the management of kidney disorders.

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.

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.

Maytenus robusta Reissek, a medicinal plant popularly used to treat digestive diseases, promotes ameliorative effects in colon and liver of mice exposed to dextran sulfate sodium.

ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus robusta Reissek (Celesteraceae), popularly named as cafezinho do mato or coração de bugre, is employed to treat inflammatory digestive diseases in the south of Brazil. However, despite popular usage, the effects of this species on an experimental model of ulcerative colitis are unknown. AIM OF THE STUDY: To evaluate the effects of M. robusta extract (HEMR) on colon and liver from mice with colitis induced by dextran sulfate sodium (DSS). MATERIALS AND METHODS: Firstly, the cytotoxicity of HEMR and its effects on ROS and nitrite production in IEC-6 cells were evaluated. The experimental colitis was established by adding 3% DSS on drinking water of mice and the effects of HEMR (1-100 mg/kg, p.o, once a day by 7 days) in colonic and hepatic tissues were analyzed. RESULTS: The HEMR (1-100 µg/mL) did not alter the cell viability but reduced nitrite production of IEC-6 stimulated by LPS. Moreover, HEMR (100 mg/Kg) attenuates macro and microscopic alterations in the colon from mice exposed to DSS, as evidenced by a reduction of the colon shortening, attenuation of the epithelial erosion, submucosal edema and preservation of the Goblet cells integrity, as well as the restoration of mucin depletion. The treatment with HEMR increased GSH amount, reduced LOOH levels and normalizes CAT activity in the colon. The group treated with HEMR showed increased GST activity, reduced MPO activity and decreased inflammatory cytokines secretion (TNF and IL-6) in the colonic tissue. In the liver, HEMR increased GST activity, decreased the GPx activity and reduced IL-6 levels. Furthermore, the HEMR treatment reduced AST and ALT serum levels in mice exposed to DSS. Finally, the HEMR was able to reduce intestinal transit. CONCLUSIONS: HEMR treatment minimizes inflammation of the colon and maintaining the antioxidant homeostasis. In addition, HEMR may be a potential tool to prevent hepatic injury secondary to ulcerative colitis.

Gastroprotective effect of the alkaloid boldine: Involvement of non-protein sulfhydryl groups, prostanoids and reduction on oxidative stress.

Boldine is the main alkaloid of Peumus boldus Molina, widely used in the traditional medicine for the treatment of digestive disorders. It is a compound with excellent antioxidant and anti-inflammatory properties already described. Despite the widespread use of P. boldus for digestive disorders treatment, the gastroprotective effect of Boldine remains unknown. Considering the need for new approaches to treat gastric ulcers with fewer side effects than current therapy, this study aimed to investigate the gastroprotective effect of Boldine in mice, as well as the mechanisms underlying this effect. The gastroprotective effect of Boldine was evaluated on gastric ulcer induced by 60% ethanol/0.3 M HCl or indomethacin (100 mg/kg) in mice. Histological analysis and the mucin-like glycoprotein content were evaluated in ethanol-ulcerated tissue, as well as, oxidative stress and inflammatory parameters. The mechanisms involved in the effect of Boldine were evaluated by pretreating mice with NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), l-NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p.). In addition, the in vitro effect of Boldine on H+/K+-ATPase activity was determined. Boldine was able to protect gastric mucosa against the damage induced by ethanol/HCl and indomethacin, as evidenced by reduced lesion area and histological analysis. Moreover, the alkaloid reduced oxidative stress and inflammatory mediators in ethanol-ulcerated tissue, beyond has increased mucin-like glycoprotein amount. Finally, Boldine effect is dependent on non-protein sulfhydryl groups and prostanoids but does not involve the inhibition of H+/K + -ATPase activity, being a promising natural resource for gastric ulcer treatment.

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.