Despite its effectiveness in treating inflammatory diseases and various malignancies, methotrexate (MTX) is well known to cause hepatotoxicity, which involves increased oxidative stress and inflammation, limiting its clinical use. Herein, we looked into the effect of punicalagin (PU), a polyphenolic molecule having a variety of health-promoting attributes, on MTX-induced hepatotoxicity in mice. PU (25 and 50 mg/kg/day) was given orally to the mice for 10 days, while a single dose of MTX (20 mg/kg) was injected intraperitoneally (i.p.) at day 7. The MTX-induced liver damage was demonstrated by remarkably higher transaminases (ALT and AST), ALP, and LDH, as well as significant histological alterations in hepatic tissues. MTX-injected mice also demonstrated increases in hepatic oxidative stress markers, including malondialdehyde (MDA) and nitric oxide (NO), with a concordant drop in glutathione (GSH) content and superoxide dismutase (SOD) and catalase (CAT) activities. PU significantly attenuated the MTX-induced serum transaminases, ALP and LDH elevations, and hepatic oxidative stress measures and boosted antioxidant defenses in the liver. Moreover, the liver of MTX-treated mice showed increases in NF-κB p65 expression, pro-inflammatory cytokine (IL-6 and TNF-α) levels, and pro-apoptotic protein (caspase-3 and Bax) expression, whereas Bcl-2 and Nrf2 expressions were reduced, which were all attenuated by PU treatment. Collectively, PU inhibits oxidative damage, inflammation, and apoptosis and upregulates Nrf2 in the liver of MTX-induced mice. Thus, these findings suggest that PU may have great therapeutic potential for the prevention of MTX-induced hepatotoxicity, pending further exploration in upcoming studies.
Liver injury is among the adverse effects of the chemotherapeutic agent cyclophosphamide (CP). This study investigated the protective role of the flavone apigenin (API) against CP-induced liver damage, pointing to the involvement of Nrf2/HO-1 signaling. Rats were treated with API (20 and 40 mg/kg) for 15 days and received CP (150 mg/kg) on day 16. CP caused liver damage manifested by an elevation of transaminases, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH), and histological alterations, including granular vacuolation, mononuclear cell infiltration, and hydropic changes. Hepatic reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO) were increased and glutathione (GSH) and antioxidant enzymes were decreased in CP-administered rats. CP upregulated the inflammatory markers NF-κB p65, TNF-α, IL-6, and iNOS, along with the pro-apoptotic Bax and caspase-3. Pre-treatment with API ameliorated circulating transaminases, ALP, and LDH, and prevented histopathological changes in CP-intoxicated rats. API suppressed ROS, MDA, NO, NF-κB p65, iNOS, inflammatory cytokines, oxidative DNA damage, Bax, and caspase-3 in CP-intoxicated rats. In addition, API enhanced hepatic antioxidants and Bcl-2 and boosted the Nrf2 and HO-1 mRNA abundance and protein. In conclusion, API is effective in preventing CP hepatotoxicity by attenuating oxidative stress, the inflammatory response, and apoptosis. The hepatoprotective efficacy of API was associated with the upregulation of Nrf2/HO-1 signaling.
Cardiovascular complications are the leading cause of morbidity in diabetes. Oxidative stress and inflammation are implicated in the development and progression of diabetic cardiomyopathy (DCM). This study explored the cardioprotective effect of galangin (Gal), a natural flavonoid with radical-scavenging and anti-inflammatory activities, in diabetic rats. An experimental diabetic rat model was achieved by a single injection of 50 mg/kg streptozotocin. Gal (15 mg/kg) was administered daily for six weeks and the samples were then collected. Diabetic rats exhibited hyperglycemia, increased glycosylated hemoglobin, triglycerides and cholesterol levels and reduced serum insulin. Serum troponin I, CK-MB and LDH were increased in diabetic rats. Furthermore, hearts of diabetic rats were characterized by elevated malondialdehyde, protein carbonyl, NF-κB p65, TNF-α, IL-1β, iNOS, IL-6, Bax, caspase-3 and 8-Oxo-dG, and decreased superoxide dismutase, catalase, reduced GSH, and Bcl-2. Gal ameliorated hyperglycemia, dyslipidemia, and heart function markers, and prevented histopathological alterations in diabetic rats. In addition, Gal attenuated cardiac oxidative injury, inflammation and apoptosis, and boosted antioxidant defenses. In conclusion, Gal has a protective effect on cardiomyopathy by attenuating hyperglycemia, dyslipidemia, oxidative stress and inflammation in diabetic rats.
Diabetes mellitus (DM) induces the production of reactive oxygen species, which may lead to cell injury and death. This study aimed to assess the effects of rosmarinic acid (RA) on testicular damage, oxidative stress, and apoptosis in streptozotocin (STZ)-induced diabetic albino mice. DM in four- to six-week-old BALB/c male albino mice was induced via 50 mg/kg STZ, IP for 5 days. Twelve mice were randomly assigned into each of following groups: a control group, a diabetic (DM) group, RA5 mg/kg and RA15 mg/kg groups, and DM + RA5 mg/kg and DM + RA15 mg/kg groups. RA doses were intraperitoneally injected six times a week for seven weeks. Diabetes increased blood sugar and HbA1c levels and decreased all assessed sperm parameters. Testicular tissues of the diabetic mice showed increased lipid peroxidation, decreased reduced glutathione levels and catalase and superoxide dismutase activities, and increased apoptosis associated with histological abnormalities. Both RA doses had no effects on final body weight, blood sugar, and HbA1c in the diabetic mice. It is concluded that the administration of the potent antioxidant RA to diabetic mice improved the redox status in testicular tissues, protected them from diabetes-induced oxidative damage, and improved the quality of spermatozoa, mostly in a dose-dependent manner, which suggests a potential application value of RA in treating DM-related testicular injury and perhaps other complications.
Cardiovascular complications are considered one of the leading causes of morbidity and mortality among diabetic patients. Diabetic cardiomyopathy (DCM) is a type of cardiovascular damage presents in diabetic patients independent of the coexistence of ischemic heart disease or hypertension. It is characterized by impaired diastolic relaxation time, myocardial dilatation and hypertrophy and reduced systolic and diastolic functions of the left ventricle. Molecular mechanisms underlying these pathological changes in the diabetic heart are most likely multifactorial and include, but not limited to, oxidative/nitrosative stress, increased advanced glycation end products, mitochondrial dysfunction, inflammation and cell death. The aim of this review is to address the major molecular mechanisms implicated in the pathogenesis of DCM. In addition, this review provides studies conducted to determine the pharmacological effects of (−)-epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, focusing on its therapeutic potential against the processes involved in the pathogenesis and progression of DCM. EGCG has been shown to exert several potential therapeutic properties both in vitro and in vivo. Given its therapeutic potential, EGCG might be a promising drug candidate to decrease the morbidity and mortality associated with DCM and other diabetes complications.
Abstract Cancer is a challenging ailment and represents the main reason for death worldwide for humans and animals. Although great developments have hindered cancer progression, several adverse effects are associated with modern chemotherapy. Natural remedies, such as the usage of medicinal plant or their products in cancer treatment, may decrease prejudicial side properties. Recently, the modern research scheme and innovative screening practices for herbs or plants have enabled phytochemical discovery for the prevention and treatment of cancer. This criticism highlights herbs such as acacia, basil, black seeds, cedar, castus, ficus, garlic, ginger, indigo, onion, pomegranate, quince, and thyme, promising anticancer effects. The present review also revealed the mode of action of each herb as anticancer effects at level in vitro and in vivo studies. The item also totalizes the vital mechanisms and signaling molecules involved in preventing cancer diseases. This will fill the investigation gap in the exploration of using natural molecules and encourage researchers in clinical trials of anticancer agents from herbs for humans and animals.