Peptic ulcer disease, the most common gastrointestinal disorder, is currently treated with several types of drugs, but all have severe side effects. The aim of the present study was to evaluate the gastroprotective activity of juanislamin, isolated from Calea urticifolia, in a rat model of ethanol-induced gastric lesions. Thirty minutes after orally administering a given dose of juanislamin (from 1 to 30 mg/kg) or carbenoxolone (the reference drug, at 1–100 mg/kg) to rats, 1 mL of ethanol was applied, and the animals were sacrificed 2 h later. The stomachs were removed and opened to measure the total area of lesions in each. To examine the possible participation of prostaglandins, nitric oxide and/or sulfhydryl groups in the mechanism of action of juanislamin, the rats received indomethacin, NG-Nitro-l-arginine methyl ester hydrochloride (l-NAME) or N-ethylmaleimide pretreatment, respectively, before being given juanislamin and undergoing the rest of the methodology. Juanislamin inhibited gastric lesions produced by ethanol in a non-dose-dependent manner, showing the maximum gastroprotective effect (100%) at 10 mg/kg. The activity of juanislamin was not modified by pretreatment with indomethacin, l-NAME or N-ethylmaleimide. In conclusion, juanislamin protected the gastric mucosa from ethanol-induced damage, and its mechanism of action apparently does not involve prostaglandins, nitric oxide or sulfhydryl groups.

Pain is the most frequent symptom of disease. In treating pain, a lower incidence of adverse effects is found for paracetamol versus other non-steroidal anti-inflammatory drugs. Nevertheless, paracetamol can trigger side effects when taken regularly. Combined therapy is a common way of lowering the dose of a drug and thus of reducing adverse reactions. Since β-caryophyllene oxide (a natural bicyclic sesquiterpene) is known to produce an analgesic effect, this study aimed to determine the anti-nociceptive and gastroprotective activity of administering the combination of paracetamol plus β-caryophyllene oxide to CD1 mice. Anti-nociception was evaluated with the formalin model and gastroprotection with the model of ethanol-induced gastric lesions. According to the isobolographic analysis, the anti-nociceptive interaction of paracetamol and β-caryophyllene oxide was synergistic. Various pain-related pathways were explored for their possible participation in the mechanism of action of the anti-nociceptive effect of β-caryophyllene oxide, finding that NO, opioid receptors, serotonin receptors, and K⁺_ATP channels are not involved. The combined treatment showed gastroprotective activity against ethanol-induced gastric damage. Hence, the synergistic anti-nociceptive effect of combining paracetamol with β-caryophyllene oxide could be advantageous for the management of inflammatory pain, and the gastroprotective activity should help to protect against the adverse effects of chronic use.

Peptic ulcers result from an imbalance between protective factors (e.g., prostaglandins, nitric oxide, and sulfhydryl groups) and aggressive risk factors (e.g., consumption of non-steroidal anti-inflammatory drugs, alcohol, or tobacco) regarding the gastric mucosa. While various existing treatments aim to relieve pain, repair the ulcer, and prevent its recurrence, they often produce undesirable side effects. The Heliotropium indicum (H. indicum) plant has been utilized as a traditional medicine due to its gastroprotective activity. In this study, we identified the compounds responsible for the gastroprotective activity of the hexanic extract of H. indicum in an ethanol-induced damage model, in addition to determination of the activities of prostaglandins, nitric oxide, and non-protein sulfhydryl groups, along with the antisecretory and antioxidant activities (i.e., concentration of malondialdehyde and activities of the enzymes superoxide dismutase, catalase, and glutathione peroxidase). We found at least two groups of compounds that are responsible for this activity, namely 1-acyl-glycerol components and retinyl β-glucuronide derivatives. In conclusion, a mixture of compounds responsible for the gastroprotective activity of H. indicum was isolated from its hexanic extract, and non-protein sulfhydryl groups were implicated in its mechanism of action.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly used, but their adverse effects warrant investigating new therapeutic alternatives. Polyalthic acid, a labdane-type diterpenoid, is known to produce gastroprotection, tracheal smooth muscle relaxation, and antitumoral, antiparasitic and antibacterial activity. This study aimed to evaluate the antinociceptive, antiallodynic, antihyperalgesic and anti-inflammatory effect of polyalthic acid on rats. Moreover, the effectiveness of treating hyperalgesia with a combination of polyalthic acid and naproxen was analyzed, as well as the type of drug–drug interaction involved. Nociception was examined by injecting 1% formalin into the right hind paw and thermal hyperalgesia and inflammation by injecting a 1% carrageenan solution into the left hind paw of rats. Allodynia was assessed on an L5/L6 spinal nerve ligation model. Polyalthic acid generated significant antinociceptive (56–320 mg/kg), antiallodynic (100–562 mg/kg), and antihyperalgesic and anti-inflammatory (10–178 mg/kg) effects. Antinociception mechanisms were explored by pretreating the rats with naltrexone, ODQ and methiothepin, finding the effect blocked by the former two compounds, which indicates the participation of opioid receptors and guanylate cyclase. An isobolographic analysis suggests synergism between polyalthic acid and naproxen in the combined treatment of hyperalgesia.

Schinus molle is a plant traditionally used in Mexico to treat gastric disorders. However, no scientific evidence has been reported on its gastroprotective effect. The aim of the current contribution was to conduct a bioassay-guided study on S. molle to evaluate its gastroprotective activity in a model of Wistar rats given ethanol orally to induce gastric lesions. The hexane and dichloromethane extracts from the tested plant showed over 99% gastroprotection at a dose of 100 mg/kg. From the hexane extract, two of the three fractions (F1 and F2) afforded over 99% gastroprotection. The F1 fraction was subjected to column chromatography, which revealed a white solid. Based on the ESI-MS analysis, the two main compounds in this solid were identified. The predominant compound was probably a triterpene. This mixture of compounds furnished about 67% gastroprotection at a dose of 100 mg/kg. Pretreatment with L-NAME, indomethacin, and NEM was carried out to explore the possible involvement of nitric oxide, prostaglandins, and/or sulfhydryl groups, respectively, in the gastroprotective activity of the white solid. We found evidence for the participation of all three factors. No antisecretory activity was detected (tested by pylorus ligation). In conclusion, evidence is herein provided for the first time of the gastroprotective effect of S. molle.

Traumatic spinal cord injury (SCI) is a serious medical condition that places patients at high risk of developing gastric ulceration and gastrointestinal bleeding. One preventative strategy involves the use of omeprazole; however, its chronic use is associated with adverse effects, highlighting the need for alternative therapies. This study evaluated the protective effects of methyl eugenol (ME) on gastric mucosal damage in a rat model of SCI. ME was administered orally at doses of 30, 100, and 177 mg/kg in SCI induced at the T9 level, alongside diclofenac or ketorolac (30 mg/kg each). The enzymatic activity of superoxide dismutase, catalase, and glutathione peroxidase was assessed, and the levels of total glutathione and malondialdehyde were determined using biochemical kits. Additionally, stomach histological sections were analyzed. ME exhibited dose-dependent gastroprotective effects, with maximal protection observed at 177 mg/kg in the presence of diclofenac (9.78 ± 2.16 mm²) or ketorolac (12.49 ± 2.17 mm²). A histological analysis confirmed these findings. In conclusion, methyl eugenol protects the gastric mucosa from SCI-induced damage, with glutathione peroxidase and catalase playing key roles in its mechanism of gastroprotection.