Anthelmintic Drugs as Emerging Immune Modulators in Cancer.

Despite recent advances in treatment approaches, cancer is still one of the leading causes of death worldwide. Restoration of tumor immune surveillance represents a valid strategy to overcome the acquired resistance and cytotoxicity of conventional therapies in oncology and immunotherapeutic drugs, such as immune checkpoint inhibitors and immunogenic cell death inducers, and has substantially progressed the treatment of several malignancies and improved the clinical management of advanced disease. Unfortunately, because of tumor-intrinsic and/or -extrinsic mechanisms for escaping immune surveillance, only a fraction of patients clinically respond to and benefit from cancer immunotherapy. Accumulating evidence derived from studies of drug repositioning, that is, the strategy to identify new uses for approved or investigational drugs that are outside the scope of the original medical indication, has suggested that some anthelmintic drugs, in addition to their antineoplastic effects, exert important immunomodulatory actions on specific subsets of immune cell and related pathways. In this review, we report and discuss current knowledge on the impact of anthelmintic drugs on host immunity and their potential implication in cancer immunotherapy.

TRAIL-Sensitizing Effects of Flavonoids in Cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents a promising anticancer agent, as it selectively induces apoptosis in transformed cells without altering the cellular machinery of healthy cells. Unfortunately, the presence of TRAIL resistance mechanisms in a variety of cancer types represents a major hurdle, thus limiting the use of TRAIL as a single agent. Accumulating studies have shown that TRAIL-mediated apoptosis can be facilitated in resistant tumors by combined treatment with antitumor agents, ranging from synthetic molecules to natural products. Among the latter, flavonoids, the most prevalent polyphenols in plants, have shown remarkable competence in improving TRAIL-driven apoptosis in resistant cell lines as well as tumor-bearing mice with minimal side effects. Here, we summarize the molecular mechanisms, such as the upregulation of death receptor (DR)4 and DR5 and downregulation of key anti-apoptotic proteins [e.g., cellular FLICE-inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), survivin], underlying the TRAIL-sensitizing properties of different classes of flavonoids (e.g., flavones, flavonols, isoflavones, chalcones, prenylflavonoids). Finally, we discuss limitations, mainly related to bioavailability issues, and future perspectives regarding the clinical use of flavonoids as adjuvant agents in TRAIL-based therapies.

Royal Jelly and its dual role in TNBS colitis in mice.

Royal Jelly (RJ) is widely consumed in diets throughout the world due to its beneficial effects: antioxidant, antitumor and anti-inflammatory. We have investigated the role of RJ in the development of TNBS colitis in mice. Colitis was induced by a rectal instillation of TNBS at 0.1 mL per mouse. Intestine samples of the animals orally treated with RJ (100, 150, and 200 mg/kg) were collected for antioxidant assays (GSH and GSH-Px), proinflammatory protein quantification (COX-2 and NF-κB), and histological analyses. RJ 100 mg/kg maintained GSH levels and increased the activity of GSH-Px, downregulated key inflammatory mediators (COX-2 and NF-κB), and decreased the lesions caused by TNBS as shown by the histological analyses. In conclusion, RJ showed anti-inflammatory and antioxidant properties in experimental colitis, resulting in the amelioration of the macroscopic and histological analyses. These results corroborate with the RJ supplementation in diets.

Applications of the hexanic fraction of Agave sisalana Perrine ex Engelm (Asparagaceae): control of inflammation and pain screening.

The present study evaluated the anti-inflammatory and analgesic properties of Agave sisalana Perrine in classic models of inflammation and pain. The hexanic fraction of A. sisalana (HFAS) was obtained by acid hydrolysis followed by hexanic reflux. Anti-inflammatory properties were examined in three acute mouse models (xylene ear oedema, hind paw oedema and pleurisy) and a chronic mouse model (granuloma cotton pellet). The antinociceptive potential was evaluated in chemical (acetic-acid) and thermal (tail-flick and hot-plate test) models of pain. When given orally, HFAS (5, 10, 25 and 50 mg/kg) reduced ear oedema (p < 0.0001; 52%, 71%, 62% and 42%, respectively). HFAS also reduced hind paw oedema at doses of 10 mg/kg and 25 mg/kg (p < 0.05; 42% and 58%, respectively) and pleurisy at doses of 10 mg/kg and 25 mg/kg (41% and 50%, respectively). In a chronic model, HFAS reduced inflammation by 46% and 58% at doses of 10 mg/kg and 25 mg/kg, respectively. Moreover, this fraction showed analgesic properties against the abdominal writhing in an acetic acid model (at doses of 5-25 mg/kg) with inhibitory rates of 24%, 54% and 48%. The HFAS also showed an increased latency time in the hot-plate (23% and 28%) and tail-flick tests (61% and 66%) for the 25 mg/kg and 50 mg/kg doses, respectively. These results suggest that HFAS has anti-inflammatory and analgesic properties.

Special Issue "Drug Treatments for Inflammatory Bowel Diseases".

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic idiopathic, relapsing and remitting inflammatory diseases that affect the gastrointestinal tract, causing significant morbidity and loss of quality of life in affected individuals [...].

Effects of Rhizophora mangle on Experimental Colitis Induced by TNBS in Rats.

Male Unib-WH rats were pretreated for two weeks with butanolic (BuOH) and ethyl acetate (EtOAc) fractions. Colitis was induced by rectal administration of TNBS, the treatment continued, and animals were sacrificed on day 7 after the TNBS administration. Phytochemical studies were performed in order to provide the characterization of the tannins present in the bark of R. mangle. Results showed that EtOAc fraction increased the levels of IL-10 (∗∗P < 0.01) and diminished the levels of TNF-α (∗∗∗P < 0.001) and IL-6 (∗∗P < 0.01). BuOH fraction reduced the MPO activity (∗∗P < 0.01) and levels of TBARS (∗∗∗P < 0.001); it also increased COX-1 expression, diminished the levels of TNF-α (∗∗∗P < 0.001), and increased the levels of IL-12 (∗∗∗P < 0.001). Besides, both treatments augmented the levels of GSH (∗P < 0.05), the activity of GSH-Px (∗∗P < 0.01 for BuOH fraction and ∗∗∗P < 0.001 for EtOAc fraction), and CAT (∗∗P < 0.01). In conclusion, both treatments ameliorated the injury induced by TNBS through different mechanisms, probably by their chemical composition which directed its activity into an antioxidant or anti-inflammatory response, leading to an immune modulation.

Antioxidant action of mangrove polyphenols against gastric damage induced by absolute ethanol and ischemia-reperfusion in the rat.

Rhizophora mangle, the red mangrove, has long been known as a traditional medicine. Its bark has been used as astringent, antiseptic, hemostatic, with antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate the antioxidant properties of a buthanolic fraction of the R. mangle bark extract (RM) against experimental gastric ulcer in rats. Unib-Wh rats received pretreatment of R. mangle after the induction of gastric injury with absolute ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared to the enzymatic assays, the levels of sulfhydril compounds (GSH), lipid peroxides (LPO), and the activities of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The RM protected the gastric mucosa in both methods used, ethanol-induced gastric ulcer and ischemia-reperfusion, probably, by modulating the activities of the enzymes SOD, GPx, and GR and increasing or maintaining the levels of GSH; in addition, LPO levels were reduced. The results suggest that the RM antioxidant activity leads to tissue protection; thus one of the antiulcer mechanisms present on the pharmacological effects of R. mangle is the antioxidant property.

Healing, antioxidant and cytoprotective properties of Indigofera truxillensis in different models of gastric ulcer in rats.

The present study evaluated the antiulcerogenic activity and mechanisms of the aqueous (AqF 100 mg/kg) and ethyl acetate (AcF 50 mg/kg) fractions from Indigofera truxillensis leaves. This dose was selected to assess its activity on ulcer healing and its action on gastric acid and mucus secretion, prostaglandin production and antioxidant enzyme activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd)). Gastric ulcer was induced by absolute ethanol. Antisecretory action, mucus and prostaglandin production, healing and antioxidant enzyme activities were evaluated for both fractions. AqF and AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant at 100 and 50 mg/kg compared with the vehicle. Neither fraction interfered with gastric secretion. AcF increased the PGE(2) production, and both fractions increased mucus production. l-NAME did not alter the gastroprotection exerted by the fractions, but N-ethylmaleimide attenuated only AcF. In the ischemia/reperfusion model both fractions inhibited the mucosal damage. AcF increased SOD, GSH-Px and GSH-Rd activity, but AqF increased only SOD and GSH-Px. In the acetic acid-induced ulcer model AcF only accelerated ulcer healing. These results showed that Indigofera truxillensis acted as a gastroprotective agent, stimulating protective factors and antioxidants enzymes.

Rafoxanide sensitizes colorectal cancer cells to TRAIL-mediated apoptosis.

Colorectal cancer (CRC) remains a leading causes of cancer-related death in the world, mainly due to the lack of effective treatment of advanced disease. TNF-related apoptosis-inducing ligand (TRAIL)-driven cell death, a crucial event in the control of tumor growth, selectively targets malignant rather than non-transformed cells. However, the fact that cancer cells, including CRC cells, are either intrinsically resistant or acquire resistance to TRAIL, represents a major hurdle to the use of TRAIL-based strategies in the clinic. Agents able to overcome CRC cell resistance to TRAIL have thus great therapeutic potential and many researchers are making efforts to identify TRAIL sensitizers. The anthelmintic drug rafoxanide has recently emerged as a potent anti-tumor molecule for different cancer types and we recently reported that rafoxanide restrained the proliferation of CRC cells, but not of normal colonic epithelial cells, both in vitro and in a preclinical model mimicking sporadic CRC. As these findings were linked with the induction of endoplasmic reticulum stress, a phenomenon involved in the regulation of various components of the TRAIL-driven apoptotic pathway, we sought to determine whether rafoxanide could restore the sensitivity of CRC cells to TRAIL. Our data show that rafoxanide acts as a selective TRAIL sensitizer in vitro and in a syngeneic experimental model of CRC, by decreasing the levels of c-FLIP and survivin, two key molecules conferring TRAIL resistance. Collectively, our data suggest that rafoxanide could potentially be deployed as an anti-cancer drug in the combinatorial approaches aimed at overcoming CRC cell resistance to TRAIL-based therapies.

EPIDEMIOLOGIC ASPECTS OF INFLAMMATORY BOWEL DISEASE IN THE WESTERN REGION OF MINAS GERAIS STATE.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC), two of the main inflammatory bowel diseases (IBD), have been increasingly diagnosed in South America. Although IBD have been intensively studied in the last years, epidemiologic data in Brazil are scarce. OBJECTIVE: To study the clinical and epidemiologic profile of IBD patients treated in the Clinical Hospital of the Federal University of Uberlândia from 1999 to 2014. METHODS: We performed a retrospective study of the medical records of patients diagnosed with IBD, according to the international classification of diseases (ICD) - ICD K50 for CD and ICD K51 for UC - confirmed by endoscopic examination in the case of both diseases. We analyzed the following variables: age; sex; ethnicity; smoking habit; primary diagnosis; site of disease manifestation; main clinical manifestations; IBD-related complications; extraintestinal manifestations; and established drug and/or surgical treatment. RESULTS: We evaluated 183 IBD cases (91 UC and 92 CD cases). The estimated prevalence rate of UC was 15.06/100.000 inhabitants and of CD was 15.23/100.000. The CU and CD female to male incidence ratios were 1.7 and 1.8, respectively. The average age of patients diagnosed with UC was 39.4 years and of those diagnosed with CD was 31.1 years. White-skinned people were the most affected by UC (66.0%) and CD (69.0%). Few patients were submitted to surgical procedures as treatment alternative. CONCLUSION: The estimated prevalence of IBD in this population was low compared to that of populations of North America, but high compared to that of other regions considered to present low incidence, such as some Asian and Latin American countries.

Mechanisms of the gastric antiulcerogenic activity of Anacardium humile St. Hil on ethanol-induced acute gastric mucosal injury in rats.

Leaves and bark infusions Anacardium humile St. Hil. (Anacardiaceae), known as in Brazil as "cajuzinho do cerrado", have been used in folk medicine as an alternative treatment for ulcers and gastritis. This study evaluated the gastroprotective activity of an ethyl acetate extract of the leaves of A. humile (AcF) and the mechanism involved in this gastroprotection. Pretreatment concentrations (50, 100, 200 mg x kg⁻¹) were administered by gavage. Following a 60 min. period, all the rats were orally administered 1 mL of absolute ethanol. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated. Prostaglandin PGE2 concentration, gastric adherent mucous, and the participation of nitric oxide (NO) and sulfhydryl compounds in the gastroprotection process were also analyzed using the most effective tested dose (50 mg x kg⁻¹). A histological study of the glandular stomach for the evaluation of the epithelial damage and mucus content was also performed. AcF significantly reduced the gastric damage produced by ethanol. This effect was statistically significant for the 50 mg x kg⁻¹ group compared to control. Also, it significantly increased the PGE2 (by 10-fold) and mucous production, while pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) or N-ethylmaleimide (NEM) completely abolished the gastroprotection. AcF has a protective effect against ethanol, and this effect, might be due to the augmentation of the protective mechanisms of mucosa.

Flavonoids with gastroprotective activity.

Peptic ulcers are a common disorder of the entire gastrointestinal tract that occurs mainly in the stomach and the proximal duodenum. This disease is multifactorial and its treatment faces great difficulties due to the limited effectiveness and severe side effects of the currently available drugs. The use of natural products for the prevention and treatment of different pathologies is continuously expanding throughout the world. This is particularly true with regards to flavonoids, which represent a highly diverse class of secondary metabolites with potentially beneficial human health effects that is widely distributed in the plant kingdom and currently consumed in large amounts in the diet. They display several pharmacological properties in the gastroprotective area, acting as anti-secretory, cytoprotective and antioxidant agents. Besides their action as gastroprotectives, flavonoids also act in healing of gastric ulcers and additionally these polyphenolic compounds can be new alternatives for suppression or modulation of peptic ulcers associated with H. pylori. In this review, we have summarized the literature on ninety-five flavonoids with varying degrees of antiulcerogenic activity, confirming that flavonoids have a therapeutic potential for the more effective treatment of peptic ulcers.

Should Anacardium humile St. Hil be used as an antiulcer agent? A scientific approach to the traditional knowledge.

The crude methanolic extract (ME) obtained from the leaves of Anacardium humile was evaluated orally at doses of 250-500-1000 mg/kg on gastric lesion on ethanol and piroxicam induced gastric lesions in rodents. All the tested doses significantly inhibited gastric lesions by 56 to 100%. These results seems to support the traditional use of this species in the treatment of gastric diseases.

Vernonia polyanthes as a new source of antiulcer drugs.

Methanolic (VPME) and chloroformic (VPCL) extracts, obtained from the aerial parts of Vernonia polyanthes, were investigated for its antiulcerogenic properties. Administration of VPME (250 mg/kg) and VPCL (50 mg/kg) significantly inhibited the gastric mucosa damage (64% and 90%, respectively) caused by absolute ethanol (p.o.). Otherwise, in NSAID-induced gastric damage, their gastroprotective effects have decreased. Since the VPCL extract resulted to be more effective than the VPME we focused our efforts over VPCL action mechanism of action.

Recent Trends in Pharmacological Activity of Alkaloids in Animal Colitis: Potential Use for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and disrupted inflammation of the gastrointestinal tract. IBD have two main conditions, Crohn's disease and ulcerative colitis, and have been extensively investigated in recent years. Antibiotics derived from salicylates, steroids, immunosuppressors, and anti-TNF therapy are part of the therapeutic arsenal for IBD. However, very often patients stop responding to treatments over the time. In this context, searching for alternative agents is crucial for IBD clinical management. Natural products derived from medicinal plants are an interesting therapeutic alternative, since several studies have proven effective treatments in animal models of intestinal inflammation. Several naturally occurring compounds are potent antioxidants, both as free radical scavengers and as modulators of antioxidant enzymes expression and activity. A number of natural compounds have also been proved to inhibit the release of proinflammatory cytokines, decreasing the activation of nuclear factor κB (NF-κB), which is important to the inflammatory response in IBD. The alkaloids are substances of a very diverse class of plant secondary metabolites; an extensive list of biological activities has been attributed to alkaloids, such as being anticholinergic, antitumor, diuretic, antiviral, antihypertensive, antiulcer, analgesic, and anti-inflammatory. In the present work, studies on the pharmacological activity of alkaloids in experimental models of IBD were reviewed.

Anti-inflammatory intestinal activity of Combretum duarteanum Cambess. in trinitrobenzene sulfonic acid colitis model.

AIM: To evaluate the anti-inflammatory intestinal effect of the ethanolic extract (EtOHE) and hexane phase (HexP) obtained from the leaves of Combretum duarteanum (Cd). METHODS: Inflammatory bowel disease was induced using trinitrobenzenesulfonic acid in acute and relapsed ulcerative colitis in rat models. Damage scores, and biochemical, histological and immunohistochemical parameters were evaluated. RESULTS: Both Cd-EtOHE and Cd-HexP caused significant reductions in macroscopic lesion scores and ulcerative lesion areas. The vegetable samples inhibited myeloperoxidase increase, as well as pro-inflammatory cytokines TNF-α and IL-1ß. Anti-inflammatory cytokine IL-10 also increased in animals treated with the tested plant samples. The anti-inflammatory intestinal effect is related to decreased expression of cyclooxygenase-2, proliferating cell nuclear antigen, and an increase in superoxide dismutase. CONCLUSION: The data indicate anti-inflammatory intestinal activity. The effects may also involve participation of the antioxidant system and principal cytokines relating to inflammatory bowel disease.

Gastroprotective effects of hydroethanolic root extract of Arrabidaea brachypoda: Evidences of cytoprotection and isolation of unusual glycosylated polyphenols.

The hydroethanolic root extract of Arrabidaea brachypoda, from Bignoniaceae family, a Brazilian medicinal plant, demonstrated significant in vivo gastroprotective effects using different in vivo assays. The activity was evaluated in several models of experimental gastric ulcer in rats (absolute ethanol, glutathione depletion, nitric oxide depletion, non-steroidal anti-inflammatory drugs, pylorus ligation and acetic acid). Using 300 mg/kg (p.o.) the extract significantly reduced gastric injury in all models. In depth phytochemical investigation of this extract led to the isolation of two previously undescribed phenylethanoid glycosides derivatives and seven unusual glycosylated dimeric flavonoids. The structures were elucidated using UV, NMR and HRMS analysis. Absolute configuration of the dimeric flavonoids was performed by electronic circular dichroism (ECD) spectroscopy.

Aspectos epidemiológicos das doenças intestinais inflamatórias na região oeste do Estado de Minas Gerais / Epidemiologic aspects of inflammatory bowel disease in the western region of minas gerais state

ABSTRACT BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC), two of the main inflammatory bowel diseases (IBD), have been increasingly diagnosed in South America. Although IBD have been intensively studied in the last years, epidemiologic data in Brazil are scarce. OBJECTIVE: To study the clinical and epidemiologic profile of IBD patients treated in the Clinical Hospital of the Federal University of Uberlândia from 1999 to 2014. METHODS: We performed a retrospective study of the medical records of patients diagnosed with IBD, according to the international classification of diseases (ICD) - ICD K50 for CD and ICD K51 for UC - confirmed by endoscopic examination in the case of both diseases. We analyzed the following variables: age; sex; ethnicity; smoking habit; primary diagnosis; site of disease manifestation; main clinical manifestations; IBD-related complications; extraintestinal manifestations; and established drug and/or surgical treatment. RESULTS: We evaluated 183 IBD cases (91 UC and 92 CD cases). The estimated prevalence rate of UC was 15.06/100.000 inhabitants and of CD was 15.23/100.000. The CU and CD female to male incidence ratios were 1.7 and 1.8, respectively. The average age of patients diagnosed with UC was 39.4 years and of those diagnosed with CD was 31.1 years. White-skinned people were the most affected by UC (66.0%) and CD (69.0%). Few patients were submitted to surgical procedures as treatment alternative. CONCLUSION: The estimated prevalence of IBD in this population was low compared to that of populations of North America, but high compared to that of other regions considered to present low incidence, such as some Asian and Latin American countries.

RESUMO CONTEXTO: A doença de Crohn (DC) e a retocolite ulcerativa (RCU), duas das principais doenças inflamatórias intestinais (DIIs), têm sido cada vez mais diagnosticadas na América do Sul. Embora a DII tenha sido intensamente estudada nos últimos anos, os dados epidemiológicos no Brasil são escassos. OBJETIVO: Estudar o perfil clínico e epidemiológico dos pacientes com DII atendidos no Hospital das Clínicas da Universidade Federal de Uberlândia de 1999 a 2014. MÉTODOS: Foi realizado um estudo retrospectivo dos prontuários de pacientes com diagnóstico de DII, de acordo com a classificação internacional de doenças (CID) - CID K50 para DC e CID K51 para RCU - confirmado por exame endoscópico para ambas as doenças. Analisamos as seguintes variáveis: idade; sexo; etnia; hábito tabágico; diagnóstico primário; local de manifestação da doença; principais manifestações clínicas; complicações relacionadas a DII; manifestações extraintestinais; tratamentos medicamentoso e/ou cirúrgico instituídos. RESULTADOS: Foram avaliados 183 casos de DII (91 casos de RCU e 92 casos de DC). A prevalência estimada de RCU foi de 15,06/100.000 habitantes e de DC foi de 15,23/100.000. As taxas de incidência entre pacientes do sexo feminino e masculino foram de 1,7 para RCU e 1,8 para DC. A idade média dos pacientes com diagnóstico de RCU foi de 39,4 anos e daqueles com DC foi de 31,1 anos. A raça branca foi o grupo étnico mais afetado por RCU (66,0%) e DC (69,0%). Poucos pacientes foram submetidos a procedimentos cirúrgicos como alternativas de tratamento. CONCLUSÃO: A prevalência estimada de DII nesta população foi baixa em comparação com populações da América do Norte, mas elevada em comparação com outras regiões consideradas de baixa incidência, como alguns países da Ásia e da América Latina.

Inhibition of tumor necrosis factor-alpha and cyclooxigenase-2 by Isatin: a molecular mechanism of protection against TNBS-induced colitis in rats.

Isatin, an indole alkaloid has been shown to have anti-microbial, anti-tumor and anti-inflammatory effects. Due to its findings, we evaluated whether this alkaloid would have any effect on TNBS-induced colitis. Animals (male Unib:WH rats, aged 8 weeks old) were induced colitis through a rectal administration of 2,4,6-trinitrobenzene sulphonic acid using a catheter inserted 8 cm into the rectum of the animals. The rats were divided into two major groups: non-colitic and colitic. The colitic group was sub-divided into 6 groups (10 animals per group): colitic non-treated, Isatin 3; 6; 12.5; 18.75 and 25 mg/kg. Our main results showed that the oral treatment with Isatin 6 and 25 mg/kg were capable of avoiding the increase in TNF-α, COX-2 and PGE2 levels when compared to the colitic non-treated group. Interestingly, the same doses (6 and 25 mg/kg) were also capable of preventing the decrease in IL-10 levels comparing with the colitic non-treated group. The levels of MPO, (an indirect indicator of neutrophil presence), were also maintained lower than those of the colitic non-treated group. Isatin also prevented the decrease of SOD activity and increase of GSH-Px and GSH-Rd activity as well as the depletion of GSH levels. In conclusion, both pre-treatments (6 and 25 mg/kg) were capable of protecting the gut mucosa against the injury caused by TNBS, through the combination of antioxidant and anti-inflammatory properties, which, together, showed a protective activity of the indole alkaloid Isatin.

Gastroprotective effects (in rodents) of a flavonoid rich fraction obtained from Syngonanthus macrolepsis.

OBJECTIVES: Syngonanthus macrolepis, popularly known in Brazil as 'sempre-vivas', is a plant from the family Eriocaulaceae, it is found in the states of Minas Gerais and Bahia. The species contains a variety of constituents, including flavonoids with gastroprotective effect. In this work, a flavonoid-rich fraction (Sm-FRF) obtained from scapes of S. macrolepis was investigated for preventing gastric ulceration in mice and rats. METHODS: The activity was evaluated in models of induced gastric ulcer (absolute ethanol, stress, non-steroidal anti-inflammatory drugs and pylorus ligation). The cytoprotective mechanisms of the Sm-FRF in relation to sulfhydryl (SH) groups, nitric oxide (NO) and antioxidant enzymes were also evaluated. KEY FINDINGS: The Sm-FRF (100 mg/kg, p.o.) significantly reduced gastric injury in all models, and did not alter gastric juice parameters after pylorus ligation. CONCLUSIONS: The results indicate significant gastroprotective activity for the Sm-FRF, which probably involves the participation of both SH groups and the antioxidant system. Both are integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors.