Asiatic acid rescues intestinal tissue by suppressing molecular, biochemical, and histopathological changes associated with the development of ulcerative colitis.

Asiatic acid (AA) is a polyphenolic compound with potent antioxidative and anti-inflammatory activities that make it a potential choice to attenuate inflammation and oxidative insults associated with ulcerative colitis (UC). Hence, the present study aimed to evaluate if AA can attenuate molecular, biochemical, and histological alterations in the acetic acid-induced UC model in rats. To perform the study, five groups were applied, including the control, acetic acid-induced UC, UC-treated with 40 mg/kg aminosalicylate (5-ASA), UC-treated with 20 mg/kg AA, and UC-treated with 40 mg/kg AA. Levels of different markers of inflammation, oxidative stress, and apoptosis were studied along with histological approaches. The induction of UC increased the levels of lipid peroxidation (LPO) and nitric oxide (NO). Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant proteins [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR)] were down-regulated in the colon tissue. Moreover, the inflammatory mediators [myeloperoxidase (MPO), monocyte chemotactic protein 1 (MCP1), prostaglandin E2 (PGE2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß)] were increased in the colon tissue after the induction of UC. Notably, an apoptotic response was developed, as demonstrated by the increased caspase-3 and Bax and decreased Bcl2. Interestingly, AA administration at both doses lessened the molecular, biochemical, and histopathological changes following the induction in the colon tissue of UC. In conclusion, AA could improve the antioxidative status and attenuate the inflammatory and apoptotic challenges associated with UC.

Silver Nanoparticles Enhance Oxidative Stress, Inflammation, and Apoptosis in Liver and Kidney Tissues: Potential Protective Role of Thymoquinone.

Silver nanoparticles (AgNPs) are the most common nanomaterials in consumer products. Therefore, it has been crucial to control AgNPs toxicological effects to improve their safety and increase the outcome of their applications. This work investigated the possible protective effect of thymoquinone (TQ) against AgNPs-induced hepatic and renal cytotoxicity in rats. Serum markers of liver and kidney functions as well as liver and kidney oxidative stress status, pro-inflammatory cytokines, apoptosis markers, and histopathology were assessed. TQ reversed AgNPs-induced elevation in serum liver and kidney function markers, including aspartate transaminase, alanine transaminase, urea, and creatinine. Moreover, TQ co-administration with AgNPs alleviates hepatic and renal oxidative insults by decreasing MDA and NO levels with a significant increase in the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase) compared to AgNPs-treated rats. Besides, TQ upregulated hepatic and renal Nrf2 gene expression in AgNPs-intoxicated rats. Furthermore, TQ co-administration decreased the hepatic and renal pro-inflammatory mediators represented by IL-1ß, TNF-α, TGF-ß, and NF-κB levels. Besides, TQ co-administration decreased apoptotic protein (Bax) levels and increased the anti-apoptotic protein (Bcl-2) levels. These findings were confirmed by the histopathological examination of hepatic and renal tissues. Our data affirmed the protective effect of TQ against AgNPs cytotoxicity and proposed a possible mechanism of TQ antioxidant, anti-inflammatory, and anti-apoptotic effects. Consequently, we could conclude that using TQ might control AgNPs toxicological effects, improve their safety, and increase the outcome of their applications.

Antiulcer activity of proanthocyanidins is mediated via suppression of oxidative, inflammatory, and apoptotic machineries.

Gastric ulcer (GU) is a lesion in the gastric mucosa associated with excessive oxidative damage, inflammatory response, apoptotic events, and irritation which may develop into cancer. However, medications commonly used in GU treatment cannot normalize gastric mucosa, while causing several adverse effects. Proanthocyanidins (PAs) are dietary flavonoids with numerous biological and pharmacological activities. In the current investigation, we studied the potential anti-ulcerative activity of PAs against acidified ethanol (HCl/ethanol)-caused gastric ulceration. Fifty male albino Wistar rats were allocated into five equal groups: control, HCl/ethanol (3 mL/kg), lansoprazole (LPZ, 30 mg/kg) + HCl/ethanol, and PAs (100 and 250 mg/kg) + HCl/ethanol. LPZ and PAs were applied one week before gastric ulcer induction. PAs pretreatment notably reduced gastric mucosal macroscopic and microscopic pathological changes in a dose-dependent manner. Additionally, PAs activated the innate antioxidant molecules including glutathione and its derived antioxidants (glutathione peroxidase and glutathione reductase), along with superoxide dismutase and catalase, while attenuating pro-oxidant formation, including malondialdehyde and nitric oxide. Interestingly, PAs supplementation at a higher dose suppressed gastric inflammatory and apoptotic responses, as demonstrated by the reduced levels of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, high-mobility group box 1, cyclooxygenase 2, prostaglandin E2, nuclear factor kappa-B, Bcl-2-associated X protein, and caspase-3, while B cell lymphoma 2 was elevated. Hence, PAs could exhibit antiulcer activity by protecting gastric tissue from the development of oxidative damage, inflammatory responses, and apoptosis events associated with ulceration. PRACTICAL IMPLICATIONS: Gastric ulcer is a lesion in the gastric mucosal layer associated with excessive inflammatory response, apoptotic events, oxidative damage, and irritation, and may develop into cancer with about 5%-10% morbidity rate. However, medications commonly used in GU treatment cannot normalize gastric mucosa, while causing several adverse effects. Therefore, new therapeutic approaches are needed to treat or prevent gastric ulceration. Proanthocyanidins (PAs, condensed tannins) are dietary flavonoids found in abundance in different plant species, including their fruits, bark, and seeds. Due to their potent antioxidative activity, PAs have been applied to prevent or treat oxidative stress-related diseases, including cancer, as well as metabolic, neurodegenerative, cardiovascular, and inflammatory disorders. Here, we examine the potential therapeutic role of proanthocyanidins (PAs) against acidified ethanol-induced gastric ulcer in rats through evaluating oxidative challenge, inflammatory response, apoptotic events, and histopathological changes in the gastric tissue.

Protocatechuic acid abrogates oxidative insults, inflammation, and apoptosis in liver and kidney associated with monosodium glutamate intoxication in rats.

Monosodium glutamate (MSG), a commonly used flavor enhancer, has been reported to induce hepatic and renal dysfunctions. In this study, the palliative role of protocatechuic acid (PCA) in MSG-administered rats was elucidated. Adult male rats were assigned to four groups, namely control, MSG (4 g/kg), PCA (100 mg/kg), and the last group was co-administered MSG and PCA at aforementioned doses for 7 days. Results showed that MSG augmented the hepatic and renal functions markers as well as glucose, triglycerides, total cholesterol, and low-density lipoprotein levels. Moreover, marked increases in malondialdehyde levels accompanied by declines in glutathione levels and notable decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were observed in MSG-treated group. The MSG-mediated oxidative stress was further confirmed by downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression levels in both tissues. In addition, MSG enhanced the hepatorenal inflammation as witnessed by increased inflammatory cytokines (interleukin-1b and tumor necrosis factor-α) and elevated nuclear factor-κB (NF-κB) levels. Further, significant increases in Bcl-2-associated X protein (Bax) levels together with decreases in B-cell lymphoma 2 (Bcl-2) levels were observed in MSG administration. Histopathological screening supported the biochemical and molecular findings. In contrast, co-treatment of rats with PCA resulted in remarkable enhancement of the antioxidant cellular capacity, suppression of inflammatory mediators, and apoptosis. These effects are possibly endorsed for activation of Nrf-2 and suppression of NF-kB signaling pathways. Collectively, addition of PCA counteracted MSG-induced hepatorenal injuries through modulation of oxidative, inflammatory and apoptotic alterations.