Gastric ulcer (GU) is a worldwide gastrointestinal disorder associated with NSAID use. Recently, amentoflavone proved to be a potent autophagy modulator, antioxidant, anti-inflammatory, and anti-apoptotic agent. Eight-week-old male Wistar rats received amentoflavone orally for 14 days at 25, 50, or 100 mg/kg/day. On day 14 of treatment, GU was induced by a single oral instillation of 100 mg/kg indomethacin, one hour after the last treatment. Amentoflavone dose-dependently alleviated indomethacin-induced GU, as demonstrated by repression of gastric mucosa pathological manifestations (ulcer index, ulcer surface area, histopathological deviations, and score) and increased ulcer inhibition percentage. These protective effects were due to the enhancement of gastric mucosa autophagy, as demonstrated by increased levels of beclin-1, MAP1LC3B, and CTSD, and reduced expression of p62 (SQSTM1). In addition, amentoflavone modulated the AMPK/mTOR pathway by increasing p-AMPK and reducing mTORC1 levels. Moreover, it hindered the redox aberrations by reducing MDA level and enhancing SOD activity, GSH level, and Nrf2/HO-1 cascade. Furthermore, a decrease in caspase-3 levels, Bax/Bcl-2 ratio and an increase in Bcl-2 expression suggest inhibition of the apoptotic process. Additionally, amentoflavone suppressed gastric mucosal inflammation by decreasing IL-1β, TNF-α, IFN-γ levels, IL-4, IL-6 mRNA expressions and MPO activity, and increasing IL-10 mRNA expresion. Therefore, amentoflavone could consider a promising natural agent protecting against indomethacin-induced GU.

Essential oils (EO) are used as a natural remedy to treat various chronic diseases, although clinical evidence is lacking. In this context, we have endeavored to measure the percentage of chemical composition and biological efficacy of Psidium guajava (guava) leaf essential oil in treating oral infections and oral cancer. The essential oil obtained from hydrodistillation of P. guajava L. leaves was analyzed by gas chromatography–mass spectrometry (GC–MS). The activities of selected oral pathogens Candida albicans (C. albicans) and Streptococcus mutans (S. mutants) were studied in vitro and in silico. MTT assay was used to test for anticancer activity against human oral epidermal carcinoma (KB). GC–MS showed that the main components of PGLEO were limonene (38.01%) and β-caryophyllene (27.98%). Minimum inhibitory concentrations (MICs) of 0.05–0.1% were demonstrated against C. albicans and S. mutans. Antimicrobial activity against C. albicans and S. mutans, as shown by molecular linkage analysis, revealed that the main metabolites, limonene and β-caryophyllene, potentially inhibited the receptors of C. albicans and S. mutans. PGLEO showed significant (p < 0.001) anticancer activity (45.89%) at 200 µg/mL compared to doxorubicin (47.87%) with an IC₅₀ value of 188.98 µg/mL. The outcomes of the present study suggest that PGLEO has promising antimicrobial and anticancer activities and could be a useful source for developing a natural therapeutic agent for oral infections and oral cancer.

Diabetic polyneuropathy is characterized by structural abnormalities, oxidative stress, and neuroinflammation. The current study aimed to determine the antinociceptive effects of isoeugenol and eugenol and their combinations in neuropathic pain resulting from streptozotocin (STZ)-induced diabetes and neuroinflammation. Female SD rats were categorized into normal control, diabetic control, and treatment groups. On the 28th day and 45th day, behavioral studies (allodynia and hyperalgesia) were performed to analyze the development and protection of diabetic polyneuropathy. The levels of inflammatory and oxidative mediators, such as superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), catalase, reduced glutathione, and thiobarbituric acid reactive substances (TBARS), were estimated. In addition, the level of nerve growth factor (NGF) was estimated at the end of the study in different groups. The anti-NGF treatment decreased its upregulation in the dorsal root ganglion significantly. The results showed that isoeugenol, eugenol, and their combination have therapeutic potential against neuronal and oxidative damage induced by diabetes. In particular, both compounds significantly affected behavioral function in treated rats and showed neuroprotection against diabetic neuropathy, and their combination had synergistic effects.