Aging, a complex physiological process affecting all living things, is a major area of research, particularly focused on interventions to slow its progression. This study assessed the antiaging efficacy of dapagliflozin (DAPA) on various aging-related parameters in a mouse model artificially induced to age. Forty male Swiss albino mice were randomly divided into four groups of ten animals each. The control group (Group I) received normal saline. The aging model group (Group II) was administered D-galactose orally at 500mg/kg to induce aging. Following the aging induction, the positive control group received Vitamin C supplementation (Group III), while the DAPA group (Group IV) was treated with dapagliflozin. The inflammatory mediators (TNF-α and IL-1β) showed similar patterns of change. No statistically significant difference was observed between groups III and IV. Both groups had significantly lower values compared to GII, while it was significantly higher compared to GI. Glutathione peroxidase (GSH-Px) showed no statistically significant difference between groups GIII and GIV, but it was higher in GIII compared to GII and significantly lower in GIII compared to GI. The study demonstrated that dapagliflozin exerts a beneficial impact on many indicators of aging in mice. The intervention resulted in a reduction in hypertrophy in cardiomyocytes, an enhancement in skin vitality, a decrease in the presence of inflammatory mediators, and an improvement in the efficacy of antioxidants.

Cardiovascular disease is the most common disease in the world and the first among the causes of human death. Its morbidity and mortality increase annually, but no effective treatment is available. Therefore, new drugs should be developed to treat cardiovascular disease. Gentianella acuta (Michx.) Hulten (G. acuta) is an important Mongolian medicine in China and elicits protective effects on cardiovascular health. In this study, liquid chromatography-mass spectrometry (LC-MS) combined with network pharmacology was used to screen the main active ingredients and confirm that bellidifolin was one of the main components for the treatment of ischemic heart disease. Then, rat myocardial (H9c2) cells injury model induced by hydrogen peroxide (H2O2) in vitro was established to verify the effect of bellidifolin on oxidative stress stimulation, including determination of antioxidant enzyme activity and apoptosis. Transcriptome sequencing, qRT-PCR, and western blot were performed to further verify the antioxidant stress mechanism of bellidifolin. Results showed that bellidifolin pretreatment decreased the rate of apoptosis and the levels of lactate dehydrogenase (LDH), creatine kinase (CK), and alanine aminotransferase (ALT). Conversely, it increased the contents of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in a dose-dependent manner, indicating that bellidifolin caused a protective effect on cardiomyocyte injury. Bellidifolin minimized the H2O2-induced cell injury by activating the PI3K-Akt signal pathway and downregulating glycogen synthase kinase-3β (GSK-3β) and p-Akt1/Akt1. Therefore, this work revealed that G. acuta has a good development prospect as an edible medicinal plant in cardiovascular disease. Its bellidifolin component is a potential therapeutic agent for cardiovascular disease induced by oxidative stress damage.

Gallic acid (GA) is a natural polyphenolic compound with many health benefits. To assess the potential risk of long-term consumption of GA to gut health, healthy dogs were fed a basal diet supplemented with GA (0%, 0.02%, 0.04%, and 0.08%) for 45 d, and fecal microbiota and metabolomics were evaluated. This study demonstrated that GA supplementation regulated serum lipid metabolism by reducing serum triglyceride, fat digestibility, and Bacteroidetes/Firmicutes ratio. In addition, the relative abundance of Parasutterella was significantly lower, and the SCFAs-producing bacteria were increased along with fecal acetate and total SCFAs contents accumulation in the 0.08% GA group. Metabolomics data further elucidated that 0.08% GA significantly affected carbohydrate metabolism by downregulating succinic acid in fece, thereby alleviating inflammation and oxidative stress. Overall, this study confirmed the beneficial effects of long-term consumption of GA on lipid metabolism and gut health, and the optimal level of GA supplementation was 0.08%.

Moringa oleifera Lam. (M. oleifera Lam) is a perennial tropical deciduous tree that belongs to the Moringaceae family. Polysaccharides are one of the major bioactive compounds in M. oleifera Lam and show immunomodulatory, anticancer, antioxidant, intestinal health protection and antidiabetic activities. At present, the structure and functional activities of M. oleifera Lam polysaccharides (MOPs) have been widespread, but the research data are relatively scattered. Moreover, the relationship between the structure and biological activities of MOPs has not been summarized. In this review, the current research on the extraction, purification, structural characteristics and biological activities of polysaccharides from different sources of M. oleifera Lam were summarized, and the structural characteristics of purified polysaccharides were focused on this review. Meanwhile, the biological activities of MOPs were introduced, and some molecular mechanisms were listed. In addition, the relationship between the structure and biological activities of MOPs was discussed. Furthermore, new perspectives and some future research of M. oleifera Lam polysaccharides were proposed in this review.

Hyperuricemia is a common disease caused by a disorder of purine metabolism, which often causes hyperlipidemia and other metabolic diseases. WN1703 was demonstrated to be an effective xanthine oxidoreductase (XOR) inhibitor in our previous study. Here, we evaluated the pharmacodynamic effect of WN1703 on rats suffering from chronic hyperuricemia accompanied by disorders of lipid metabolism. We discovered that WN1703 was an efficacious uric acid (UA)-lowering compound. Simultaneously, it had effect on relieving renal injury, regulating lipid metabolism by reducing levels of triglycerides and low-density lipoprotein-cholesterol, increasing levels of high-density lipoprotein-cholesterol, and improving renal and liver lesions. WN1703 also exhibited anti-inflammatory and antioxidant activity by alleviating the increasing trend of levels of tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1, and malondialdehyde, and improving the activity of superoxide dismutase and glutathione peroxidase. WN1703 appeared to be more effective than febuxostat in inhibiting XOR and had higher antioxidant activity. In general, the pharmacologic action of WN1703 showed a clear dose-effect relationship.

Spinal cord injury (SCI) causes secondary injury, accompanied by pathological changes such as oxidative stress, inflammation and neuronal apoptosis. This leads to permanent disabilities such as paralysis and loss of movement or sensation. Due to the ineffectiveness of drugs passing through the blood spinal cord barrier (BSCB), there is currently no effective treatment for SCI. The aim of this experiment was to design plasma complex component functionalized manganese-doped silica nanoparticles (PMMSN) with a redox response as a targeted drug carrier for resveratrol (RES), which effectively transports insoluble drugs to cross the BSCB. RES was adsorbed into PMMSN with a particle size of approximately 110 ​nm by the adsorption method, and the drug loading reached 32.61 ​± ​3.38%. The RES release results for the loaded sample (PMMSN-RES) showed that the PMMSN-RES exhibited a release slowly effect. In vitro and vivo experiments demonstrated that PMMSN-RES decreased reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, reduced the expression of inflammatory (TNF-α, IL-1β and IL-6) and apoptotic cytokines (cleaved caspase-3) in spinal cord tissue after SCI. In summary, PMMSN-RES may be a potential pharmaceutical preparation for the treatment of SCI by reducing neuronal apoptosis and inhibiting inflammation caused by reducing oxidative stress to promote the recovery of mouse motor function.

Diabetes mellitus is a well-known danger element for the progression of male reproductive dysfunctions. Available evidence supports oxidative stress to be the underlying mechanism for the manifestation of testicular dysfunctions during diabetes, and this relation represents an attractive target to antagonize these complications. Artemisia judaica L. is known to have antidiabetic and antioxidant characteristics. The possible protective effect of Artemisia judaica against diabetes-induced testicular disorders was not explored. In this investigation, we planned to estimate the possible protective effect of Artemisia judaica extract against diabetes-induced testicular disorders in male rats. The blood levels of insulin, glucose, glycosylated hemoglobin, testosterone, luteinizing hormone and follicle stimulating hormone were evaluated in rats after 12 weeks of Artemisia judaica treatment. Further, oxidative stress markers were determined in their testicular tissue. Epididymal fluid and testicular histological changes were also assessed. Expression of proliferating cell nuclear antigen has been evaluated in testis. Testicular mRNA expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 as the significant transcription factors in controlling antioxidant system were evaluated by real-time polymerase chain reaction. Artemisia judaica extracts have the ability to ameliorate the elevation in the serum glucose and blood glycosylated hemoglobin and the reduction in insulin, testosterone, follicle stimulating hormone and luteinizing hormone caused by streptozotocin-induced diabetes. It induced a significant recovery of the testicular oxidative stress markers, sperm characteristics and improved histopathological findings of the testes. Treatment with Artemisia judaica extracts led to an increase in proliferating cell nuclear antigen protein expression. Reduction of testicular oxidative stress potential in streptozotocin-treated groups was confirmed by upregulation of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1.

Allergic rhinitis affects the quality of life of millions of people worldwide. Air pollution not only causes morbidity, but nearly 3 million people per year die from unhealthy indoor air exposure. Furthermore, allergic rhinitis and air pollution interact. This report summarizes the discussion of an International Expert Consensus on the management of allergic rhinitis aggravated by air pollution. The report begins with a review of indoor and outdoor air pollutants followed by epidemiologic evidence showing the impact of air pollution and climate change on the upper airway and allergic rhinitis. Mechanisms, particularly oxidative stress, potentially explaining the interactions between air pollution and allergic rhinitis are discussed. Treatment for the management of allergic rhinitis aggravated by air pollution primarily involves treating allergic rhinitis by guidelines and reducing exposure to pollutants. Fexofenadine a non-sedating oral antihistamine improves AR symptoms aggravated by air pollution. However, more efficacy studies on other pharmacological therapy of coexisting AR and air pollution are currently lacking.

Non-alcoholic steatohepatitis (NASH) is a chronic metabolic syndrome and the CFLAR-JNK pathway can reverse the process of NASH. Although silibinin is used for the treatment of NASH in clinical, its effect on CFLAR-JNK pathway in NASH remains unclear. This study aimed to investigate the effect of silibinin on CFLAR-JNK pathway in NASH models both in vivo and in vitro. The in vivo study was performed using male C57BL/6 mice fed with methionine- choline-deficient diet and simultaneously treated with silibinin for 6 weeks. The in vitro study was performed by using mouse NCTC-1469 cells which were respectively pretreated with oleic acid plus palmitic acid, and adenovirus-down Cflar for 24 h, then treated with silibinin for 24 h. After the drug treatment, the key indicators involved in CFLAR-JNK pathway including hepatic injury, lipid metabolism and oxidative stress were determined. Silibinin significantly activated CFLAR and inhibited the phosphorylation of JNK, up-regulated the mRNA expression of Pparα, Fabp5, Cpt1α, Acox, Scd-1, Gpat and Mttp, reduced the activities of serum ALT and AST and the contents of hepatic TG, TC and MDA, increased the expression of NRF2 and the activities of CAT, GSH-Px and HO-1, and decreased the activities and expression of CYP2E1 and CYP4A in vivo. These effects were confirmed by the in vitro experiments. Silibinin prevented NASH by regulating CFLAR-JNK pathway, and thereby on one hand promoting the β-oxidation and efflux of fatty acids in liver to relieve lipid accumulation, and on the other hand inducing antioxidase activity (CAT, GSH-Px and HO-1) and inhibiting pro-oxidase activity (CYP2E1 and CYP4A) to relieve oxidative stress.

UNASSIGNED: Anti-inflammatory activity of rhein in animal models with potential mechanism of actions.
UNASSIGNED: Rhein was isolated from Cassia fistula L. flowers collected in Chennai, Tamil Nadu, India. Its anti-inflammatory activity was then investigated in Wistar rats and mice using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, cotton pellet-induced granuloma and acetic acid-induced vascular permeability models.
UNASSIGNED: Administration of rhein (10, 20, 40 mg/kg) significantly (p < 0.05) inhibited carrageenan-induced paw oedema in rats and croton oil-induced ear oedema in mice in dose-dependent manners. Continual administration of rhein to rats using implanted cotton pellets significantly (p < 0.05) reduced granuloma formation (20 mg/kg: 17.24%; 40 mg/kg: 36.12%) compared to control group animals. Administration of rhein increased the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and decreased the levels of nitrite, interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA) and vascular endothelial growth factor (VEGF) compared to control animals. Western blotting results revealed that rhein diminished carrageenan-induced cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and increased heme oxygenase (HO)-1, nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR)-γ and heat shock protein (HSP)-72 expression after 6 h in the paw oedema model.
UNASSIGNED: The anti-inflammatory mechanisms of rhein might be related to decrease in the levels of MDA, iNOS and COX-2 and the stimulation of HO-1, PPAR-γ and Nrf2 expression via increases in the activities of CAT, SOD and GSH-px through the suppression of nitrite, TNF-α, IL-6 and IL-1β.