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

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

Therapeutic Potential of Croton Blanchetianus for the Treatment of Gastric Ulcers: A Brief Review

Natural products are considered one of the main sources that contribute to advances in research in medical science, in such a way that the elucidation of the mechanism of action enables the industry to design new drugs, providing new applications, inputs, and alternatives for the treatment of various pathologies. Studies show the importance of secondary metabolites, presenting pharmacological, microbiological, and food functions. Given the above, this review aims to describe the importance of studies with natural products, emphasizing the gastroprotective activity of the Croton genus. The genus Croton (Euphorbiaceae) is characteristic of the Brazilian biome, especially in the semiarid climate. The species of the genus have anti-inflammatory and curative properties, correlating their gastroprotective effect. Among the plurality of species, one that has therapeutic and economic potential is Croton blanchetianus. The population widely uses the species as it has medicinal properties, used to prepare teas and compresses, helping with inflammatory processes and pain. Thus, it was observed that Croton species have great potential in anti-inflammatory activity and gastroprotection. Therefore, studies with the Croton blanchetianus species should be deepened regarding this activity, providing greater knowledge about this plant.

Antioxidant and gastroprotective effects of the ethyl acetate extract from Stemodia maritima L. in ethanol-induced gastric ulcer model

Stemodia maritima L., is a shrub of the Plantaginaceae family, with some biological activities already described, such as: larvicide, antimicrobial, and anti-inflammatory. Thus, the objective of this work was to evaluate the antioxidant, and gastroprotective activities of the ethyl acetate extract from S. maritima. The phytochemical profile was investigated through the quantification of total phenolic compounds, flavonoids, and CCD analysis. The toxicity of the extract was performed through cell viability using L929 line cell, and acute toxicity by the OECD Guide 423. The antioxidant activity was analyzed by the methods of reduction of the ferric ion (FRAP), total antioxidant activity (TAA), and the gastroprotective activity by the absolute ethanol-induced gastric ulcer model, with analysis of NO, MDA, GSH and MPO levels in the stomach tissues. In the phytochemical profile it was possible to identify the presence of flavonoids, triterpenes, steroids, mono, and sesquiterpenes. The extract was not cytotoxic against L929 lineage, maintaining cell viability above 70% at the doses tested, and in acute toxicity it did not show physiological changes indicative of toxicity compared to the control group. The extract presented antioxidant activity of 157.3 ± 9.7 mg equivalent of Trolox/g of extract in the FRAP method, and 50.0 ± 1.1 % by TAA. The ethyl acetate extract of S. maritima, at the doses tested, reduced the ulcerative lesion index compared to the injured control group, increased the levels of NO and GSH, and was able to decrease the concentrations of MDA and MPO, enhancing their gastroprotective activity.

Macroscopic assessment of protective effect of cryopreserved placenta extract in ibuprofen-induced gastroenterocolonopathy

Background. Over-the-counter use of nonsteroidal anti-inflammatory drugs leads to their uncontrolled consumption among the population, which in some cases makes it impossible to prevent and timely detect adverse drug effects, and their effectiveness does not always satisfy clinicians. The purpose was to characterize the cytoprotective properties of cryopreserved placenta extract according to the condition of the mucous membrane of the proximal (esophagus and stomach) and distal (small and large intestine) parts of the gastrointestinal tract on the model of ibuprofen-induced esophagogastroenterocolonopathy. Mate­rials and methods. In vivo experimental studies were performed on 28 male rats. Subchronic ibuprofen-induced gastrointestinal lesions were reproduced by intragastric administration of ibuprofen to rats at a dose of 310 mg/kg. The condition of the gastrointestinal tract mucous membrane was assessed macroscopically on a scale. Results. The therapeutic and prophylactic efficacy of esomeprazole statistically significantly (р < 0.05) took place in the proximal parts of the gastrointestinal tract but had little effect on the prevalence of ulcerative lesions in the intestine. At the same time, unlike esomeprazole, which is known to have only gastroprotective activity, cryopreserved placenta extract had a cytoprotective effect both in the stomach and in the distal parts of the gastrointestinal tract — small and large intestine. Thus, the prevalence of ibuprofen-induced both entero- and colonopathy on the background of the study of the extract was almost twice lower than in rats that did not receive correction drugs. Conclusions. It is established that the use of cryopreserved placenta extract in the treatment-and-prophylactic mode has comparable to esomeprazole gastroprotective activity. In addition, it was found that the use of the studied cryoextract was accompanied by a decrease in the multiplicity of ulcerative defects in the small and large intestine of rats, by 4.6 and 3.8 times, respectively, compared to the control animals.

Bioactive Compounds of Opuntia spp. Acid Fruits: Micro and Nano-Emulsified Extracts and Applications in Nutraceutical Foods

The acid fruit of the "xoconostle" cactus belongs to the genus Opuntia family of cacti. It is used as a functional food for its bioactive compounds. Several studies reported that xoconostle fruits have a high amount of ascorbic acid, betalains, phenols, tannins, and flavonoids. These compounds confer antioxidant, antibacterial, anti-inflammatory, and hepatoprotective gastroprotective activity. Xoconostle fruit extracts were tested by in vitro assays where the digestion conditions were simulated to measure their stability. At the same time, the extracts were protected by encapsulation (microencapsulation, multiple emulsions, and nanoemulsions). Applications of encapsulated extracts were probed in various food matrices (edible films, meat products, dairy, and fruit coatings). The xoconostle is a natural source of nutraceutical compounds, and the use of this fruit in the new food could help improve consumers’ health.

Propolis and Its Gastroprotective Effects on NSAID-Induced Gastric Ulcer Disease: A Systematic Review

Gastric ulcer disease induced by the consumption of NSAIDs is a major public health problem. The therapy used for its treatment causes adverse effects in the patient. Propolis is a natural product that has been used for the treatments of different diseases around the world. Nevertheless, there is little information about the activity of propolis in gastric ulcers caused by treatment with NSAIDs. Therefore, this review evaluates and compares the gastroprotective potential of propolis and its function against NSAID-induced gastric ulcers, for which a systematic search was carried out in the PubMed and ScienceDirect databases. The main criteria were articles that report the gastroprotective activity of propolis against the damage produced by NSAIDs in the gastric mucosa. Gastroprotection was related to the antioxidant, antisecretory, and cytoprotective effects, as well as the phenolic compounds present in the chemical composition of propolis. However, most of the studies used different doses of NSAIDs and propolis and evaluated different parameters. Propolis has proven to be a good alternative for the treatment of gastric ulcer disease. However, future studies should be carried out to identify the compounds responsible for these effects and to determine their potential use in people.

(-)-Carveol Prevents Gastric Ulcers via Cytoprotective, Antioxidant, Antisecretory and Immunoregulatory Mechanisms in Animal Models

Background: (-)-Carveol (p-Mentha-6,8-dien-2-ol) is a monocyclic monoterpenic alcohol, present in essential oils of plant species such as Cymbopogon giganteus, Illicium pachyphyllum and in spices such as Carum carvi (cumin). Pharmacological studies report its antitumor, antimicrobial, neuroprotective, vasorelaxant, antioxidant and anti-inflammatory activity.Hypothesis/Purpose: The objective of this study was to evaluate the acute non-clinical oral toxicity, gastroprotective activity of monoterpene (-)-Carveol in animal models and the related mechanisms of action.Methods: Acute toxicity was assessed according to OECD guide 423 in mice. Ethanol, stress, NSAIDs and pylorus ligation-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were using the ethanol-gastric lesions protocol.Results: (-)-Carveol has low toxicity, with a lethal dose 50% (LD50) equal to or greater than 2,500 mg/kg according to OECD guide nº 423. In all gastric ulcer induction methods evaluated, (-)-Carveol (25, 50, 100 and 200 mg/kg, p.o.) significantly reduced the ulcerative lesion in comparison with the respective control groups. To investigate the mechanisms involved in the gastroprotective activity, the antisecretory or neutralizing of gastric secretion, cytoprotective, antioxidant and immunoregulatory effects were evaluated. In the experimental protocol of pylorus ligation-induced gastric ulcer, (-)-Carveol (100 mg/kg) reduced (p &lt; 0.001) the volume of gastric secretion in both routes (oral and intraduodenal). The previous administration of blockers NEM (sulfhydryl groups blocker), L-NAME (nitric oxide synthesis inhibitor), glibenclamide (KATP channel blocker) and indomethacin (cyclo-oxygenase inhibitor), significantly reduced the gastroprotection exercised by (-)-Carveol, suggesting the participation of these pathways in its gastroprotective activity. In addition, treatment with (-)-Carveol (100 mg/kg) increased (p &lt; 0.001) mucus adhered to the gastric wall. Treatment also increased (p &lt; 0.001) levels of reduced glutathione (GSH), superoxide dismutase (SOD) and interleukin-10 (IL-10). It also reduced (p &lt; 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels.Conclusion: Thus, it is possible to infer that (-)-Carveol presents gastroprotective activity related to antisecretory, cytoprotective, antioxidant and immunomodulatory mechanisms.