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The regulation of glial cell activation is a critical step for the treatment or prevention of neuroinflammation‐based brain diseases. However, the development of therapeutic drugs that pass the blood–brain barrier (BBB) and inhibit the glia cell activation remains a significant challenge. Herein, an ultrasmall 2D vanadium carbide quantum dots (V2C QDs) that are capable of crossing the BBB are prepared, and the admirable anti‐neuroinflammatory effects are presented. The prepared 2D V2C QDs with an average size of 2.54 nm show good hydrophilicity, physiological stability, and effective BBB‐crossing ability. The biological effect of V2C QDs on inflammatory reactions demonstrates fascinating results in preventing the impairment of learning and memory in BALB/c mice stimulated by lipopolysaccharide. Investigation of molecular mechanism reveals that V2C QDs not only inhibit the toll‐like receptor 4/myeloid differentiation factor 88‐mediated nuclear factor kappa B and mitogen‐activated protein kinase pathways, but also prevent eukaryotic translation initiation factor 2α/activating transcription factor 4/C/EBP homologous protein‐signaling pathway and reduce oxidative stress via activating the NF‐E2‐related factor‐2/heme oxygenase‐1‐signaling pathway, leading to greatly inhibited activation of microglia and astrocytes and weakened production of inflammatory cytokines. In summary, V2C QDs exert potent anti‐inflammatory effects through multiple pathways, thus offer great potential for the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Aging is an irresistible natural law of the progressive decline of body molecules, organs, and overall function with the passage of time, resulting in eventual death. World Health Organization data show that aging is correlated with a wide range of common chronic diseases in the elderly, and is an essential driver of many diseases. Panax Ginseng C.A Meyer is an ancient herbal medicine, which has an effect of "long service, light weight, and longevity" recorded in the ancient Chinese medicine book "Compendium of Materia Medica." Ginsenoside Rg2, the main active ingredient of ginseng, also exerts a marked effect on the treatment of liver injury. However, it remains unclear whether Rg2 has the potential to ameliorate aging-induced liver injury. Hence, exploring the hepatoprotective properties of Rg2 and its possible molecular mechanism by Senescence Accelerate Mouse Prone 8 (SAMP8) and gut microbiota. Our study demonstrated that Rg2 can inhibit pyroptosis and apoptosis through caspase 8, and regulate the gut-liver axis to alleviate liver inflammation by changing the composition of gut microbiota, thus improving aging-induced liver injury. These findings provide theoretical support for the pharmacological effects of ginsenosides in delaying aging-induced liver injury. [ABSTRACT FROM AUTHOR]

Although there have been significant advances in the treatment of heart failure in recent years, chronic heart failure remains a leading cause of cardiovascular disease-related death. Many studies have found that targeted cardiac metabolic remodeling has good potential for the treatment of heart failure. However, most of the drugs that increase cardiac energy are still in the theoretical or testing stage. Some research has found that botanical drugs not only increase myocardial energy metabolism through multiple targets but also have the potential to restore the balance of myocardial substrate metabolism. In this review, we summarized the mechanisms by which botanical drugs (the active ingredients/formulas/Chinese patent medicines) improve substrate utilization and promote myocardial energy metabolism by activating AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs) and other related targets. At the same time, some potential protective effects of botanical drugs on myocardium, such as alleviating oxidative stress and dysbiosis signaling, caused by metabolic disorders, were briefly discussed. [ABSTRACT FROM AUTHOR]

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole‐induced PCOS‐related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p <.01) and relative ovary weight (p <.05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p <.01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p <.01, p <.05), and follicle‐stimulating hormone (FSH) levels were increased (p <.05). SA administration also decreased triglyceride (TG) (p <.01) and total cholesterol (TC) levels (p <.05) and increased high‐density lipoprotein cholesterol (HDL‐C) levels (p <.01), thereby alleviating letrozole‐induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), reduced the activation of transforming growth factor‐β1 (TGF‐β1)/Smads, and decreased collagen I, α‐smooth muscle actin (α‐SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole‐induced PCOS. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the ameliorative effect and molecular mechanism of red ginseng (Panax ginseng C.A. Meyer) extract (RGE) on D-galactose (D-gal)-induced premature ovarian failure (POF) using network pharmacology analysis. Ginsenosides are important active ingredients in ginseng, which also contains some sugar and amino acid derivatives. We aimed to determine the key proteins through which RGE regulates POF. In this work, we retrieved and screened for active ingredients in ginseng and the corresponding POF disease targets in multiple databases. A PPI network of genes was constructed in the STRING database and core targets were screened using topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in R software. Finally, molecular docking was conducted to validate the results. Female ICR mice were used to establish a POF mouse model for in vivo experiments. Serum levels of relevant estrogens were determined using ELISA and expression levels of relevant proteins in ovarian tissues were detected using immunofluorescence and western blot analysis. Network pharmacology analysis predicted that PI3K, Akt, Bax, Bcl-2, p16, and other proteins were highly correlated with POF and RGE. The results clearly showed that RGE could increase estradiol (E2) and lower follicle-stimulating hormone (FSH) levels in D-gal-fed mice. RGE restored the expression levels of related proteins by reducing Nrf2-mediated oxidative stress, PI3K/Akt-mediated apoptosis, and senescence signaling pathways. Overall, RGE has the potential to prevent and treat POF and is likely to be a promising natural protector of the ovaries. [ABSTRACT FROM AUTHOR]

Saponins from the roots of Platycodon grandiflorum, an edible medicinal plant, have shown a wide range of beneficial effects on various biological processes. In this study, an animal model was established by a single intraperitoneal injection of cisplatin (20 mg/kg) for evaluating the protective effects of saponins from the roots of P. grandiflorum (PGS, 15 mg/kg and 30 mg/kg) in mice. The results indicated that PGS treatment for 10 days restored the destroyed intestinal mucosal oxidative system, and the loosened junctions of small intestinal villi was significantly improved. In addition, a significant mitigation of apoptotic effects deteriorated by cisplatin exposure in small intestinal villi was observed by immunohischemical staining. Also, western blot showed that PGS could effectively prevent endoplasmic reticulum (ER) stress-induced apoptosis caused by cisplatin in mice by restoring the activity of PERK (an ER kinase)-eIF2 α -ATF4 signal transduction pathway. Furthermore, molecular docking results of main saponins in PGS suggested a better binding ability with target proteins. In summary, the present work revealed the underlying protective mechanisms of PGS on intestinal injury induced by cisplatin in mice. [ABSTRACT FROM AUTHOR]

Although the protective effect of ginsenoside on cisplatin-induced renal injury has been extensively studied, whether ginsenoside interferes with the antitumor effect of cisplatin has not been confirmed. In this paper, we verified the main molecular mechanism of 20(R)-ginsenoside Rg3 (R-Rg3) antagonizing cisplatin-induced acute kidney injury (AKI) through the combination of in vivo and in vitro models. It is worth mentioning that the two cell models of HK-2 and HepG2 were used simultaneously for the first time to explore the effect of the activation site of tumor-associated protein p53 on apoptosis and tumor suppression. The results showed that a single injection of cisplatin (20 mg/kg) led to weight loss, the kidney index of the mice increased, and creatinine (CRE) and blood urea nitrogen (BUN) levels in mice sharply increased. Continuous administration of R-Rg3 at doses of 10 and 20 mg/kg for 10 days could significantly alleviate this symptom. Similarly, R-Rg3 treatment reduced oxidative stress damage caused by cisplatin. Moreover, R-Rg3 could observably reduce the apoptosis and inflammatory infiltration of renal tubular cells induced by cisplatin. We used western blotting analysis to demonstrate that R-Rg3 restored cisplatin-induced AKI might be related to PI3K/AKT and NF- κ B mediated apoptosis and inflammation pathways. In the meantime, we also verified that R-Rg3 could activate different sites of p53 to control renal cell apoptosis induced by cisplatin without affecting its antitumor effect. [ABSTRACT FROM AUTHOR]

• The study compared the toxicity of TCEP and TCPP on tadpoles and assessed the RQ-based ecological risk. • Tadpoles were more sensitive to TCPP than TCEP as observed by lower LC50 of 70 mg/L for TCPP compared to LC50 of 305 mg/L for TCEP. • Chronic concentration of 300 µg/L for TCEP and TCPP showed similar adverse effects in tadpoles. • Most aquatic environments presented no risk, with TCPP posing higher risks than TCEP across all sources. Tris(2-chloroethyl) phosphate (TCEP) and tris(1‑chloro-2-propyl) phosphate (TCPP) are widely used as chlorinated organophosphate flame retardants (OPFRs) due to their fire-resistance capabilities. However, their extensive use has led to their permeation and pollution in aquatic environments. Using amphibians, which are non-model organisms, to test the toxic effects of OPFRs is relatively uncommon. This study examined the acute and chronic toxicity differences between TCEP and TCPP on Polypedates megacephalus tadpoles and evaluated the potential ecological risks to tadpoles in different aquatic environments using the risk quotient (RQ). In acute toxicity assay, the tadpole survival rates decreased with increased exposure time and concentrations, with TCEP exhibiting higher LC50 values than TCPP, at 305.5 mg/L and 70 mg/L, respectively. In the chronic assay, prolonged exposure to 300 μg/L of both substances resulted in similar adverse effects on tadpole growth, metamorphosis, and hepatic antioxidant function. Based on RQ values, most aquatic environments did not pose an ecological risk to tadpoles. However, the analysis showed that wastewater presented higher risks than rivers and drinking water, and TCPP posed a higher potential risk than TCEP in all examined aquatic environments. These findings provide empirical evidence to comprehend the toxicological effects of OPFRs on aquatic organisms and to assess the safety of aquatic environments. [ABSTRACT FROM AUTHOR]

Cisplatin, a proven effective chemotherapeutic agent, has been used clinically to treat malignant solid tumors, whereas its clinical use is limited by serious side effect including nephrotoxicity. Platycodin D (PD), the major and marked saponin isolated from Platycodon grandiflorum, possesses many pharmacological effects. In this study, we evaluated its protective effect against cisplatin‐induced human embryonic kidney 293 (HEK‐293) cells injury and elucidated the related mechanisms. Our results showed that PD (0.25, 0.5, and 1 μM) can dose‐dependently alleviate oxidative stress by decreasing malondialdehyde and reactive oxygen species, while increasing the levels of glutathione, superoxide dismutase, and catalase. Moreover, the elevation of apoptosis including Bax, Bad, cleaved caspase‐3,‐9, and decreased protein levels of Bcl‐2, Bcl‐XL induced by cisplatin were reversed after PD treatment. Importantly, PD pretreatment can also regulate PI3K/Akt and ERK/JNK/p38 signaling pathways. Furthermore, PD was found to reduce NF‐κB‐mediated inflammatory relative proteins. Our finding indicated that PD exerted significant effects on cisplatin induced oxidative stress, apoptosis and inflammatory, which will provide evidence for the development of PD to attenuate cisplatin‐induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Heat stress (HS) reaction is a stress response caused by adverse conditions. Currently, the incidence of reproductive malignancies particularly in males has been constantly increasing. This work investigated the effects of saponins derived from the stems and leaves of Panax ginseng (GSLS) on testicular injury induced by scrotal hyperthermia in mice. GSLS (150, 300 mg/kg) were administered intragastrically to mice for 14 days, then exposed to a single scrotal heat treatment at 43°C for 18 min on seventh day. HS induced a significant loss of multinucleate giant cells, desquamation of germ cells in destructive seminiferous tubules. Moreover, HS reduced the serum testosterone, testicular tissue superoxide dismutase activity and glutathione (GSH) content, while significantly enhanced the production of malondialdehyde (p <.05). GSLS exhibited the protective potential against HS‐induced injury not only by modulating Bcl‐2 family and caspase protease family, but also by suppressing the protein levels of heme oxygenase‐1 (HO‐1), heat shock protein 70 (HSP70), hypoxia inducible factor‐1α (HIF‐1α) and activation of Mitogen‐activated protein kinase (MAPK) signaling pathways (p <.05). In conclusion, we clearly demonstrated that GSLS exhibited a significant protective effect against HS‐induced testicular dysfunction, mainly the inhibition of oxidative stress associated apoptosis partly via regulation of the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Some researchers have previously shown that RNAi knockdown of arginyl-tRNA synthetase (ArgRS) before or after a hypoxic injury can rescue animals from death, based on the model organism, C. elegans. However, there has been no study on the application of arginyl-tRNA synthetase knockdown in treating mammalian ischemic stroke, and its potential mechanism and effect on ischemic brain damage are still unknown. Here, we focused on the Rars gene, which encodes an arginyl-tRNA synthetase, and examined the effects of Rars knockdown in a permanent middle cerebral artery occlusion model in rats. To achieve this aim, adult male Sprague-Dawley (SD) rats were given right cerebral cortex injections of short hairpin RNA (shRNA) adenovirus (AV) particles to knock down arginyl-tRNA synthetase, and a non-targeting control (NTC) vector or phosphate-buffered solution served as the controls. After 4 days, the rats were exposed to permanent middle cerebral artery occlusion (pMCAO). Then, the right cerebral cortex level of arginyl-tRNA synthetase was examined, and the effects of the Rars knockdown were evaluated by differences in infarction volume, oxidative stress, blood-brain barrier, mitochondrial function, and glucose metabolism at 1 day and 3 days after MCAO. The injection of shRNA adenovirus particles successfully suppressed the expression of arginyl-tRNA synthetase in the cerebral cortex. We observed an improvement in oxidative stress, mitochondrial function, and glucose utilization and a reduction in brain edema compared with the non-targeting control rats with suppressed expression of arginyl-tRNA synthetase mRNA in the ipsilateral ischemic cortex of the brain. Our findings indicate that knockdown of arginyl-tRNA synthetase in the cerebral cortex exerted neuroprotective effects, which were achieved not only by the improvement of oxidative stress and glucose utilization but also by the maintenance of mitochondrial morphological integrity and the preservation of mitochondrial function. Knockdown of ArgRS administration could be a promising approach to protect ischemic stroke. [ABSTRACT FROM AUTHOR]

Aims: To investigate the correlation between thioredoxin-interacting protein (TXNIP) and peripheral nerve conduction velocity (NCV) in patients with type 2 diabetes mellitus. Methods: In total, 338 patients with type 2 diabetes mellitus (T2DM) were included in this study. We collected the clinical data and measured the motor conduction velocities of the bilateral ulnar nerve, median nerve, tibial nerve, and common peroneal nerve, and the sensory conduction velocities of the ulnar nerve, median nerve, sural nerve, and superficial peroneal nerve. According to the results, the patients were divided into two groups: normal peripheral nerve conduction group (NCVN group) and abnormal peripheral nerve conduction group (NCVA group). The two groups were then compared in terms of the conventional biochemical index and the sugar metabolic index as well as the serum levels of TXNIP, reduced glutathione (GSH), total superoxide dismutase (SOD), malondialdehyde (MDA), and tumor necrosis factor alpha (TNF-α). The correlation between TXNIP and NCV was also analyzed. Results: Compared with the NCVN group, the TXNIP and MDA values were significantly increased in the NCVA group (P < 0.05). Among the patients with T2DM, age, fasting glucose, SDBG, and TXNIP were risk factors for NCV abnormality, while vitamin D3 was a protective factor. After adjusting for related confounding factors, TXNIP was significantly correlated with NCV (P < 0.05). Among the patients with T2DM, TXNIP was an independent risk factor for left ulnar motor conduction velocity (MCV), right ulnar MCV, left median MCV, and right median MCV. TNF-α was identified as a positive influencing factor for serum TXNIP, while serum TXNIP was a positive factor for TNF-α and MDA (both P < 0.05). Conclusion: Serum TXNIP is related to NCV in T2DM patients. In combination with oxidative stress and inflammation, TXNIP may affect diabetic peripheral neuropathy (DPN). [ABSTRACT FROM AUTHOR]

Oxidative stress is considered as a major factor in aging and exacerbates aging process through a variety of molecular mechanisms. D-galactose, a normal reducing sugar with high dose can cause the accumulation of reactive oxygen species (ROS) or stimulate free radical production indirectly by the formation of advanced glycation end products in tissues, finally resulting in oxidative stress. 20(R)-ginsenoside Rg3 (20(R)-Rg3), a major and representative component isolated from red ginseng (Panax ginseng C.A Meyer), has been shown to observably have an anti-oxidative effect. We thereby investigated the beneficial effects of 20(R)-Rg3 on D-galactose-induced oxidative stress injury and its underlying mechanisms. Our results showed that continuous injection of D-galactose with 800 mg/kg/day for 8 weeks increased the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). However, such increases were attenuated by the treatment of 20(R)-Rg3 for 4 weeks. Meanwhile, 20(R)-Rg3 markedly inhibited D-galactose-caused oxidative stress in liver and kidney. The anti-oxidants, including catalase (CAT) and superoxide dismutase (SOD), were elevated in the mice from 20(R)-Rg3-treated group compared with that from D-galactose group. In contrast, a significant decrease in levels of cytochrome P450 E1 (CYP2E1) and the lipid peroxidation product malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were observed in the 20(R)-Rg3-treated group. These effects were associated with a significant increase of AGEs. More importantly, 20(R)-Rg3 effectively attenuated D-galactose induced apoptosis in liver and kidney via restoring the upstream PI3K/AKT signaling pathway. Taken together, our study suggests that 20(R)-Rg3 may be a novel and promising anti-oxidative therapeutic agent to prevent aging-related injuries in liver and kidney. [ABSTRACT FROM AUTHOR]

Aim: Caloric restriction (CR), which limits the caloric intake to 60–70% of ad libitum (AL) amounts in various experimental animals, delays aging and extends the lifespan. We previously showed that neuropeptide Y (NPY), an appetite‐stimulating peptide, is essential for the anti‐oxidative and life‐extending effects of CR. Here, we investigated whether a Japanese traditional herbal medicine, rikkunshito (RKT), which induces NPY activation, has CR‐like life‐extending effects. Methods: First, we evaluated the life‐extending activity of RKT by examining the effect of long‐term RKT administration on wild‐type and NPY knockout mice. Furthermore, we tested whether RKT enhances CR‐mediated beneficial effects under AL conditions with a normal diet and under mild CR conditions with a high‐fat diet. We then used 3‐nitropropionic acid or doxorubicin to induce oxidative stress, and analyzed the differences in survival rate, weight loss, gene expression and cellular oxidative damage among groups. Results: RKT administration did not extend the lifespan of wild‐type or NPY knockout mice. In the oxidative stress models, RKT treatment upregulated anti‐oxidative gene expression in the liver. Furthermore, RKT administration reduced the oxidative damage in the liver compared to the CR conditions alone. However, on induction of oxidative stress by 3‐nitropropionic acid or doxorubicin, RKT administration did not affect the survival rate. Conclusions: These results show that RKT administration only partially mimics the effects of CR at the cellular level, but not at the organismal level to increase the lifespan of mice. Geriatr Gerontol Int 2019; ••: ••–••. [ABSTRACT FROM AUTHOR]

Background: Overcoming oxidative stress is a critical step for tumor progression; however, the underlying mechanisms in colorectal cancer (CRC) remain unclear.Methods: We investigated nicotinamide adenine dinucleotide (phosphate) (NAD(P))-dependent enzyme methylene tetrahydrofolate dehydrogenase 2 (MTHFD2) expression, clinical relevance, redox modification, and molecular mechanisms using the CRC cells and tissues (n = 462 paired samples). The antitumor effects of MTHFD2 inhibitor LY345899 on CRC tumorigenesis and metastasis were evaluated in vitro and in vivo. Data analysis used Kaplan-Meier, Pearson's correlation, and Student t test where appropriate. All statistical tests were two-sided.Results: Here, we report that the patients with high expression of MTHFD2 have a shorter overall survival (HR = 1.62, 95% CI = 1.12 to 2.36, P = .01) and disease-free survival (HR = 1.55, 95% CI = 1.07 to 2.27, P = .02) than patients with low MTHFD2 expression. Suppression of MTHFD2 disturbs NADPH and redox homeostasis and accelerates cell death under oxidative stress, such as hypoxia or anchorage independence (P ≤ .01 for all). Also, genetic or pharmacological inhibition of MTHFD2 suppresses CRC cell growth and lung and peritoneal metastasis in cell-based xenografts (n = 5-8 mice per group). Importantly, LY345899 treatment statistically significantly suppresses tumor growth and decreases the tumor weight in CRC patient-derived xenograft models (n = 10 mice per group, mean [SD] tumor weight of the vehicle-treated group was 1.83 [0.19] mg vs 0.74 [0.30] mg for the LY345899-treated group, P < .001).Conclusions: Our study presents evidence that MTHFD2 confers redox homeostasis and promotes CRC cell growth and metastasis. The folate analog LY345899 as MTHFD2 inhibitor displays therapeutic activity against CRC and warrants further clinical investigation for CRC treatment. [ABSTRACT FROM AUTHOR]

Lysosome-associated membrane protein type 2A (LAMP2A) is a key protein in the chaperone-mediated autophagy (CMA) pathway and has been demonstrated to be involved in the pathogenesis of a number of tumors. However, the role of CMA in colorectal cancer cell proliferation, metastasis and cell survival during oxidative stress and oxaliplatin resistance remains to be elucidated. In the present study, elevated expression of LAMP2A was observed in colon cancer tissues. Then, CMA activity was increased in SW480 and HT29 colorectal cancer cells with a LAMP2A overexpression vector and CMA activity was decreased using a LAMP2A short interfering RNA vector. MTT and colony formation assays showed that the colorectal cancer cell proliferation ability and cell viability following treatment with H2O2 or oxaliplatin were decreased significantly after LAMP2A knockdown and increased significantly after LAMP2A overexpression. Wound healing assays and Transwell invasion assays demonstrated that downregulation of LAMP2A expression inhibited the cell migration and invasion abilities of colorectal cancer and that upregulation of LAMP2A expression promoted cell migration and invasion. Extracellular acidification rate (ECAR) assay and lactate determination assay showed that glycolysis in colorectal cancer cells was significantly downregulated after LAMP2A knockdown and significantly upregulated after LAMP2A overexpression. Inhibition of glycolysis by 2-DG markedly attenuated LAMP2A-induced chemoresistance in colorectal cancer cells. Collectively, these data indicated that CMA can promote colorectal cancer cell proliferation, metastasis and cell survival during oxidative stress and oxaliplatin resistance and that the mechanism is related to the glycolytic pathway, which may provide a new therapeutic target for colorectal cancer patients. [ABSTRACT FROM AUTHOR]

The acute exposure of trimethyltin (TMT) develops clinical syndrome characterized by amnesia, aggressive behavior, and complex seizures. This neurotoxicant selectively induces hippocampal neuronal injury and glial activation accompanied with resultant neuroinflammation. Here we report two candidates ginsenosides Rg3 and Rh2 as neuroprotection agents using a mouse model of TMT intoxication via a single injection (2 mg/kg) and primary neuronal culture systems. Four-week administration of Rg3 or Rh2 significantly reduced TMT-induced seizures and behavioral changes. Rg3 and Rh2 significantly attenuated the oxidative stress evidenced by improvement on antioxidant enzymes and neuronal loss and astrocytic activation in mouse brain. In primary cultures, TMT induced significant neuronal death after 24-h intoxication and vigorous secretion of inflammatory cytokines (IL-1α/β, IL-6, TNF-α, and MCP-1) in astrocytes. Pretreatment with Rg3 or Rh2 not only reduced cell death but efficiently suppressed above mentioned inflammatory cytokines confirmed by antibody array test. The underlying protective mechanism by Rg3 and Rh2 was delineated through selective upregulation of PI3K/Akt and suppression of ERK activation. Intriguingly, Rg3 and Rh2 protected oligodendrocyte progenitor cells (O-2A) from TMT intoxication via promoting type 2 astrocytic differentiation without further inflammatory activation. Collectively, Rg3 and Rh2 interventions aimed at reducing oxidative stress and neuroinflammation neurotoxicity therefore are of therapeutic benefit in TMT-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

Acute liver injury (ALI) induced by acetaminophen (APAP) overdose is the most common cause of drug-induced liver injury. Saponins from Platycodon grandiflorum (PGSs) ameliorate alcohol-induced hepatotoxicity and enhance human lung carcinoma cell death via AMPK signaling pathway. However, whether PGS could protect from APAP-induced ALI through AMPK activation and its downstream signals is still poorly elucidated. This work investigated the protective effect and the underlying mechanisms of PGS against APAP-induced liver toxicity in mouse. PGS was administered at 15 or 30 mg/kg i.g./day for 1 week before a single injection of APAP (250 mg/kg, i.p.) 1 hr after last treatment of PGS. Serum alanine/aspartate aminotransferases, liver tumor necrosis factor-α and interleukin-1β levels, liver malondialdehyde formation, liver glutathione depletion, cytochrome P450 E1, and 4-hydroxynonenal levels were measured to demonstrate the protective efficacy of PGS against APAP-induced ALI. Liver histological observation provided further evidence on PGS's protective effects. PGS treatment altered the phosphorylation of AMPK and PI3K/Akt, as well as the downstream signals including Bcl-2 family, caspase, and NF-κB in a dose-dependent manner. In conclusion, we demonstrate that PGS exhibits a significant liver protection against APAP-induced ALI, mainly through NF-κB and AMPK/PI3K/Akt signaling pathways. [ABSTRACT FROM AUTHOR]

Cisplatin is an effective anticancer chemotherapeutic agent, but the use of cisplatin in the clinic is severely limited by side effects. Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy. The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng (GFA) in a murine model of cisplatin-induced acute kidney injury. We observed that pretreatment with GFA attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels and histopathological injury induced by cisplatin. The formation of kidney malondialdehyde, heme oxygenase-1, cytochrome P450 E1 and 4-hydroxynonenal with a concomitant reduction in reduced glutathione was also inhibited by GFA, while the activities of kidney superoxide dismutase and catalase were all increased. GFA also inhibited the increase in serum tumour necrosis factor-α and interleukin-1β induced by cisplatin. In addition, the levels of induced nitric oxide synthase and cyclooxygenase-2 were suppressed by GFA. Furthermore, GFA supplementation inhibited the activation of apoptotic pathways by increasing B cell lymphoma 2 and decreasing Bcl2-associated X protein expression. In conclusion, the findings from the present investigation demonstrate that GFA pre-administration can significantly prevent cisplatin-induced nephrotoxicity, which may be related to its antioxidant, anti-apoptotic and antiinflammatory effects. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Jujuboside A (JuA), as a main effective component of Jujubogenin, has long been known as a sedative-hypnotic drug. The aim of the current study was to investigate the potential effect of JuA on sepsis-induced cardiomyopathy (SIC) induced by lipopolysaccharide (LPS). Wide type C57BL/6 mice and neonatal rat cardiomyocytes (NRCMs) were exposed to LPS to establish myocardial toxicity models. Cardiac function of septic mice was detected by echocardiography. Moreover, the survival rate was calculated for 7 days. ELISA assays were used to analyze inflammatory factors in serum. Furthermore, western blotting, flow cytometry and TUNEL staining were performed to assess cell apoptosis and transmission electron microscopy detect the number of autophagosomes in myocardium. Finally, the expression of proteins related to pyroptosis, autophagy and oxidative stress was analyzed by western blotting and immunohistochemistry staining. Results showed that JuA pretreatment significantly improved the survival rate and cardiac function, and suppressed systemic inflammatory response in septic mice. Further study revealed that JuA could decrease cell apoptosis and pyroptosis; instead, it strengthened autophagy in SIC. Moreover, JuA also significantly decreased oxidative stress and nitrodative stress, as evidenced by suppressing the superoxide production and downregulating iNOS and gp91 expression in vivo. In addition, the autophagy inhibitor 3-MA significantly abolished the effect of JuA on autophagic activity in SIC. In conclusion, the findings indicated that JuA attenuates cardiac function via blocking inflammasome-mediated apoptosis and pyroptosis, at the same time by enhancing autophagy in SIC, heralding JuA as a potential therapy for sepsis. [ABSTRACT FROM AUTHOR]

Objective: To study the prevention effect of salidroside on contrast-induced-nephropathy (CIN) and its underlying mechanism. Methods: A total of 24 Wistar rats were randomly divided into 4 groups with 6 in each group. Rats were firstly administrated with normal saline (control and model groups), N-acetylcysteine (NAC, NAC group) and salidroside (salidroside group) for 7 days before model establishment in each group, respectively. Histopathological analysis was performed by periodic acid-Schiff (PAS) staining. Oxidative stress related parameters including superoxide dismutase (SOD) and methane dicarboxylic aldehyde (MDA), nitric oxide (NO), angiotensin II (Ang II), 8-hydroxy-2′-deoxyguanosine (8-OHdG), mRNA and protein levels of endothelial nitric oxide synthase (eNOS), and nitric oxide synthase (NOS) activity were measured. Results: Compared with the control group, the levels of MDA, Ang II and 8-OHdG were all significantly increased and levels of SOD, NO, and eNOS mRNA and protein were decreased significantly in the model group ( P<0.05). Meanwhile, the NOS activity was also significantly decreased in the model group ( P<0.05). In addition, the levels of these parameters were all improved in the NAC ( P<0.05) and salidroside groups and no significant different was found between these two groups ( P>0.05). Conclusion: Salidroside can be the potential substitute of NAC to prevent CIN. The underlying mechanism may be associated with oxidative stress damage caused by contrast agents. [ABSTRACT FROM AUTHOR]

Changes in temperature are known to cause a variety of physiological stress responses in insects and mites. Thermal stress responses are usually associated with the increased generation of reactive oxygen species (ROS), resulting in oxidative damage. In this study, we examined the time-related effect (durations for 1, 2, 3, and 5 h) of thermal stress conditions-i.e., relatively low (0, 5, 10, and 15 °C) or high (35, 38, 41, and 44 °C) temperatures-on the activities of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), peroxidase (POX), glutathione S-transferases (GSTs), and total antioxidant capacity (T-AOC) of the predatory mite Neoseiulus cucumeris. Also the lipid peroxidation (LPO) levels of the predatory mite were measured under thermal stress conditions. The results confirmed that thermal stress results in a condition of so-called oxidative stress and the four antioxidant enzymes play an important role in combating the accumulation of ROS in N. cucumeris. CAT and POX activity changed significantly when the mites were exposed to cold and heat shock, respectively. The elevated levels of SOD and GSTs activity, expressed in a time-dependent manner, may have an important role in the process of antioxidant response to thermal stress. However, the levels of LPO in N. cucumeris were high, serving as an important signal that these antioxidant enzyme-based defense mechanisms were not always adequate to counteract the surplus ROS. Thus, we hypothesize that thermal stress, especially extreme temperatures, may contribute much to the generation of ROS in N. cucumeris, and eventually to its death. [ABSTRACT FROM AUTHOR]

Ligusticum wallichii has been used to treat renal diseases for thousands of years in China. Ligustrazine (Lig) is the active ingredient of Ligusticum wallichii that possesses a variety of biological activities against kidney disease. The purpose of this review is to further evaluate whether the supplementation with Lig has an effect on improving renal pathology, renal function indexes and blood glucose levels in animal model of diabetic nephropathy (DN). Potential mechanisms of Lig for DN as well as the existing problems regarding the modeling method and limitations in this area of research were also summarized. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist was used to organize the search of eight databases from inception to June 2019. We used Cochrane Collaboration's 10-item checklist and Rev-Man 5.3 software to analyze the data as well as risk of bias. The study quality scores ranged from 2 to 6 points with an average of 4.471. Compared with the control group, Lig significantly improved pathological changes of kidney including glomeruli and tubules, and induced significant decreases in levels of blood urea nitrogen, serum creatinine, 24-h urinary albumin and HbA1c, as well as increasing creatinine clearance rates. In subgroup analysis, the groups of high-dose STZ (≥60 mg/kg) and longer period of Lig treatment (>8 w) showed better results than those of the control group. No difference was seen between the high (>150 mg/kg, QD) and low (≤150 mg/kg, QD) dose of Lig treatment groups. Lig exerts renoprotective functions in an animal model of DN mediated by antioxidant action, inhibition of apoptosis, anti-inflammatory action, reduction of renal fibrosis, reduction of the proliferation of mesangial cells, inhibition of endotheliosis, inhibition of atherosclerosis and promotion of renal autophagy. The positive conclusion should be treated cautiously because of various methodological flaws. Further studies are recommended according to ARRIVE guidelines. The method of modeling with high-dose STZ should be avoided and improved STZ modeling schemes are recommended. Considering the large dosage range of Lig used clinically and in animals, the future studies on the basis of animal renal histology are urgently needed to determine the optimal dosages to delay histological changes. Nevertheless, together, our findings suggest that Lig is a renoprotective candidate drug for treatment of DN. Image 1 [ABSTRACT FROM AUTHOR]

Background: Although kidney injury caused by cisplatin has attracted much attention, cisplatin-induced cardiotoxicity is elusive. Our previous studies have confirmed that saponins (ginsenosides) from Panax quinquefolius can effectively reduce acute renal injuries. Our current study aimed to identify the potential effects of saponins from leaves of P. quinquefolius (PQS) on cisplatin-evoked cardiotoxicity. Methods: Mice were intragastrically with PQS at the doses of 125 and 250 mg/kg daily for 15 days. The mice in cisplatin group and PQS + cisplatin groups received four times intraperitoneal injections of cisplatin (3 mg/kg) two days at a time from the 7th day, respectively. All mice were killed at 48 h following final cisplatin injection. Body weights, blood and organic samples were collected immediately. Results: Our results showed that cisplatin-challenged mice experienced a remarkable cardiac damage with obvious histopathological changes and elevation of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT) concentrations and viabilities in serum. Cisplatin also impaired antioxidative defense system in heart tissues manifested by a remarkable reduction in reduced glutathione (GSH) content and superoxide dismutase (SOD) activity, demonstrating the overproduction of reactive oxygen species (ROS) and oxidative stress. Interestingly, PQS (125 and 250 mg/kg) can attenuate cisplatin-evoked changes in the above-mentioned parameters. Additionally, PQS administration significantly alleviated the oxidation resulted from inflammatory responses and apoptosis in cardiac tissues via inhibition of overexpressions of TNF-α, IL-1β, Bax, and Bad as well as the caspase family members like caspase-3, and 8, respectively. Conclusion: Findings from our present research clearly indicated that PQS exerted significant effects on cisplatin-induced cardiotoxicity in part by inhibition of the NF-κB activity and regulation of PI3K/Akt/apoptosis mediated signaling pathways. [ABSTRACT FROM AUTHOR]

Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (Panax ginseng, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen (APAP)-induced hepatotoxicity and the related molecular mechanisms remain unclear. The purpose of this article was to investigate the protective effect and elucidate the mechanisms of action of maltol on APAP-induced liver injury in vivo. Maltol was administered orally at 50 and 100 mg/kg daily for seven consecutive days, then a single intraperitoneal injection of APAP (250 mg/kg) was performed after the final maltol administration. Liver function, oxidative indices, inflammatory factors—including serum alanine and aspartate aminotransferases (ALT and AST), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), liver glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) were measured. Results demonstrated that maltol possessed a protective effect on APAP-induced liver injury. Liver histological changes and Hoechst 33258 staining also provided strong evidence for the protective effect of maltol. Furthermore, a maltol supplement mitigated APAP-induced inflammatory responses by increasing phosphorylated nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase α/β (IKKα/β), and NF-kappa-B inhibitor alpha (IκBα) in NF-κB signal pathways. Immunoblotting results showed that maltol pretreatment downregulated the protein expression levels of the B-cell-lymphoma-2 (Bcl-2) family and caspase and altered the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in a dose-dependent manner. In conclusion, our findings clearly demonstrate that maltol exerts a significant liver protection effect, which may partly be ascribed to its anti-inflammatory and anti-apoptotic action via regulation of the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives: Based on previous reports that ginsenosides have been shown to exert better preventive effects on cisplatin‐induced kidney injury, the present work aims to evaluate the protective effects of ginsenoside Rb3 (G‐Rb3) on cisplatin‐induced renal damage and underlying mechanisms in vivo and in vitro. Materials and methods: The protective effect of G‐Rb3 on cisplatin‐induced acute renal failure in ICR mouse model and HEK293 cell model was investigated, and the underlying possible mechanisms were also explored. For animal experiment, renal function, kidney histology, inflammation, oxidative stress, relative protein molecules involved in apoptosis and autophagy signalling pathways were assessed. In addition, rapamycin (a specific inhibitor of mTOR), compound C (a specific inhibitor of AMPK) and acetylcysteine (NAC, a specific ROS scavenger) were employed to testify the effects of AMPK/mTOR signal pathway on the protective effects of G‐Rb3 in HEK293 cells. Results: Pre‐treatment with G‐Rb3 at doses of 10 and 20 mg/kg for ten days significantly reversed the increases in serum creatinine (CRE), blood urea nitrogen (BUN) and malondialdehyde (MDA), and decrease in glutathione (GSH) content and superoxide dismutase (SOD) activity. Histopathological examination further revealed that G‐Rb3 inhibited cisplatin‐induced nephrotoxicity. G‐Rb3 diminished cisplatin‐induced increase in protein expression levels of p62, Atg3, Atg5 and Atg7, and decrease in protein expression level of p‐mTOR and the ratio of LC3‐I/LC3‐II, indicating that G‐Rb3 suppressed cisplatin‐induced activation of autophagy. Inhibition of autophagy induced inactivation of apoptosis, which suggested that autophagy played an adverse effect on cisplatin‐evoked renal damage. Further, we found that G‐Rb3 might potentially modulate the expressions of AMPK‐related signal pathways. Conclusions: These findings clearly suggested that G‐Rb3‐mediated alleviation of cisplatin‐induced nephrotoxicity was in part due to regulation of AMPK‐/mTOR‐mediated autophagy and inhibition of apoptosis in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Among antioxidant enzymes, catalases protect microorganisms by degrading hydrogen peroxide under oxidative stress. In this study, the activities of at least four Vibrio parahaemolyticus catalases (Kat1 to Kat4) were differentially detected during different growth stages and under various stress conditions using zymographic analysis. Our results showed that only Kat2 is stable at 55 °C. Kat1 and Kat2 respond to hydrogen peroxide during the early stationary and exponential growth phases, respectively and the response decreases upon entering the stationary phase. Kat3 and Kat4 are bifunctional, exhibiting both catalase and peroxidase activities and are only expressed during the stationary phase, under starvation or under stress at pH 5.5. Our study also shows that expression of Kat3 and Kat4 depends on RpoS. We confirm that both monofunctional and bifunctional catalases are expressed and function differentially under various stresses to contribute total catalase activities for the survival of V. parahaemolyticus . A comparative genomic study among Vibrio species revealed that only V. parahaemolyticus contains two copies of genes that encode monofunctional and bifunctional catalases. We propose that both types of catalases, whether evolved or acquired horizontally through long-term evolution, may play crucial protective roles in V. parahaemolyticus in response to environmental fluctuations. [ABSTRACT FROM AUTHOR]

Xin-Ji-Er-Kang (XJEK) inhibited cardiovascular remodeling in hypertensive mice in our previous studies. We hypothesized that XJEK may prevent isoproterenol (ISO)-induced myocardial hypertrophy (MH) in mice by ameliorating oxidative stress (OS) through a mechanism that may be related to the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) pathways. Forty SPF male Kunming mice were randomized into 5 groups (n = 8 mice per group): control group, MH group, MH + different doses of XJEK (7.5 g/kg/day and 10 g/kg/day), and MH + metoprolol (60 mg/kg/day). On the eighth day after drug treatment, electrocardiogram (ECG) and echocardiography were performed, the mice were sacrificed, and blood and heart tissues were collected for further analysis. XJEK administration markedly ameliorated cardiovascular remodeling (CR), as manifested by a decreased HW/BW ratio and CSA and less collagen deposition after MH. XJEK administration also improved MH, as evidenced by decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) levels. XJEK also suppressed the decreased superoxide dismutase (SOD) and catalase (CAT) activities and increased malondialdehyde (MDA) levels in serum of mice with MH. XJEK-induced oxidative stress may be related to potentiating Nrf2 nuclear translocation and HO-1 expression compared with the MH groups. XJEK ameliorates MH by activating the Nrf2/HO-1 signaling pathway, suggesting that XJEK is a potential treatment for MH. [ABSTRACT FROM AUTHOR]

Oxidative stress is the common mechanism of sensorineural hearing loss (SNHL) caused by many factors, such as noise, drugs and ageing. Here, we used tert-butyl hydroperoxide (t-BHP) to cause oxidative stress damage in HEI-OC1 cells and in an in vitro cochlear explant model. We observed lipid peroxidation, iron accumulation, mitochondrial shrinkage and vanishing of mitochondrial cristae, which caused hair cell ferroptosis, after t-BHP exposure. Moreover, the number of TUNEL-positive cells in cochlear explants and HEI-OC1 cells increased significantly, suggesting that t-BHP caused the apoptosis of hair cells. Administration of deferoxamine (DFOM) significantly attenuated t-BHP-induced hair cell loss and disordered hair cell arrangement in cochlear explants as well as HEI-OC1 cell death, including via apoptosis and ferroptosis. Mechanistically, we found that DFOM treatment reduced t-BHP-induced lipid peroxidation, iron accumulation and mitochondrial pathological changes in hair cells, consequently mitigating apoptosis and ferroptosis. Moreover, DFOM treatment alleviated GSH depletion caused by t-BHP and activated the Nrf2 signalling pathway to exert a protective effect. Furthermore, we confirmed that the protective effect of DFOM mainly depended on its ability to chelate iron by constructing Fth1 knockout (KO), TfR1 KO and Nrf2 KO HEI-OC1 cell lines using CRISPR/Cas9 technology and a Flag-Fth1 (overexpression) HEI-OC1 cell line using the Flp In™ System. Our findings suggest that DFOM is a potential drug for SNHL treatment due to its ability to inhibit apoptosis and ferroptosis by chelating iron and scavenging reactive oxygen species (ROS). [Display omitted] • Deferoxamine is a potential drug for sensorineural hearing loss treatment. • Deferoxamine prevents ototoxicity by inhibiting hair cell apoptosis and ferroptosis. • Gene knocked out or overexpression cells were constructed to explore the mechanism. • Fe2+ plays a key role in the deferoxamine -mediated oto-protection. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Icariin protects human embryonic kidney (HEK) 293 cell from cisplatin-induced damage in concentration dependent manner. • Icariin exerts protective effect on cisplatin-induced cytotoxicity in HEK 293 cells partly through its anti-oxidative stress, anti-inflammatory and anti-apoptosis effect. • ROS-mediated PI3K/Akt signaling pathway is involved in icariin's protective effect on cisplatin-induced cytotoxicity in HEK 293 cells. Abstract Cisplatin, as an effective chemotherapeutic agent, is widely used to treat verious types of cancers. Nephrotoxicity induced by cisplatin seriously limits its clinical application. Icariin, a major and remarkable flavonoid isolated from Epimedium koreanum , has been reported to exert anti-oxidative stress and anti-inflammation actions. The purpose of this study is to explore the protective effect and possible mechanism of icariin on cisplatin-induced nephrotoxicity on HEK-293 cells. In this study, icariin pretreatment for 24 h significantly ameliorated cisplatin-induced oxidative stress by reducing levels of malondialdehyde (MDA) and reactive oxygen species (ROS), while increasing level of glutathione (GSH) in HEK-293 cells. Furthermore, icariin pretreatment reduced NF-κB phosphorylation and nuclear translocation in HEK-293 cells followed by decreased secretion of IL-1β, TNF-α, and iNOS, suggesting a suppression of inflammatory response. Moreover, icariin pretreatment significantly reduced cellular apoptosis via reduced levels of Bax, cleaved caspase-3/9, and increased anti-apoptotic protein Bcl-2 in the cells. Importantly, LY294002, a specific PI3K inhibitor, abrogated the anti-apoptosis effect of icariin, implicating the involvement of PI3K/Akt pathway. In summary, icariin prevents cisplatin-induced HEK-293 cell injury by inhibiting oxidative stress, inflammatory response, and cellular apoptosis partly via regulating NF-κB and PI3K/Akt signaling pathways. Icariin may serve as a potential therapeutic target against cisplatin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Platycodin D (PD) exerts protective effect against APAP-induced hepatotoxicity in C57BL/6J mice. • The liver protection effects of PD is due to association of alterations in MAPK signal pathway in mice. • The inhibition of apoptosis and inflammation response is partly involved in the PD liver protection effects. Abstract The root of Platycodon grandiflorus (Jacq.) A. DC. (P. grandiflorus), Platycodonis Radix, has been commonly applied to prevent and treat human diseases including bronchitis, asthma and excessive phlegm. Platycodin D (PD), one of the most important therapeutic components of P. grandiflorus , has been reported to possess protective effect against alcohol and carbon tetrachloride induced hepatotoxicity. In this study, we examined the protective efficacy of PD on acetaminophen (APAP)-induced liver injury and possible underlying mechanisms in C57BL/6J mice. Administration of PD prior to APAP intoxication significantly ameliorated the increase in serum transferases, interleukin 1β (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), and hepatic malondialdehyde (MDA) and the depletion of glutathione (GSH) in mice. PD pretreatment decreased the expression of heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) in presence of APAP. Moreover, PD treatment noticeably reduced APAP-induced hepatocyte necrosis and apoptosis evidenced by evaluating physiological and histological hepatocyte changes in mice. Finally, PD pretreatment significantly diminished c-Jun NH 2 -terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38 phosphorylation induced by APAP. Collectively, PD pretreatment effectively protects hepatocytes against APAP-induced hepatotoxicity in mice through ameliorating oxidative stress, inflammatory response, and hepatocyte apoptosis. [ABSTRACT FROM AUTHOR]

Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, the in vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20( R )-Ginsenoside Rg3 (20( R )-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20( R )-Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP exposure were also inhibited by 20( R )-Rg3 pretreatment. Moreover, 20( R )-Rg3 pretreatment significantly alleviated APAP-induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20( R )-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20( R )-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Schisandra chinensis (Turcz.) Baill is a frequently used traditional Chinese medicine, and modern pharmacological research has proven that S. chinensis has antioxidant, anti-hepatotoxity, anti-inflammatory, and anti-nephrotoxic effects. Cisplatin is widely used as antineoplastic drug at present, but the clinical application is limited owing to its nephrotoxicity. Aim of the study To demonstrate the renoprotective activity of the extract of the stems of S. chinensis (SCE) in mice established by cisplatin-triggering acute kidney injury (AKI). The possible molecular mechanism of nephroprotection exhibited by SCE was evaluated for the first time. Materials and methods Mice in SCE groups were pre-treated with SCE for 10 consecutive days, and on 7th day 1 h after final administration, following intraperitoneal injection of cisplatin with 20 mg/kg was treated to cisplatin group and SCE groups. On the 10th day, renal function, histopathological change, and oxidative stress markers were investigated. Results Renal oxidative stress level characterized by elevated heme oxygenase 1 (HO-1), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) expression was obviously reduced by SCE pre-treatment. In addition, SCE was found to suppress inflammatory response through the reduction of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-κB) p65 activation. SCE treatment also inhibited activation of apoptotic pathways through down-regulating Bax, cleaved caspase-3, 8, 9 and up-regulating Bcl-2 expression levels. Conclusion These findings illustrated that SCE possessed powerful protective effect on AKI caused by cisplatin via amelioration of oxidative stress, inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Xin-tong-tai Granule (XTTG), a traditional Chinese medicine, has been used to treat atherosclerosis (AS), but its mechanism is poorly understood. Intriguingly, oxidative stress has been recognized as vital factors in the treatment of atherosclerosis. This study aims to explore the potential mechanism of XTTG for treating AS. An in-vivo model of AS was established by feeding ApoE-/- mice with a high-fat diet (HFD), and the Human Aortic Vascular Smooth Muscle Cells (HAVSMCs) were induced by oxidized low-density lipoprotein (ox-LDL) in vitro. After treatment, the blood lipid levels and pathological aortic changes of each group were observed, and the cell proliferation and lipid droplet aggregation in each group were evaluated. The oxidative stress indicators such as malondialdehyde (MDA) and superoxide dismutase (SOD) levels and related NOX/ROS/NF-κB signaling pathway indicators were observed. XTTG improved blood lipid levels and pathological aortic changes of ApoE−/− mice with HFD feeding, inhibited HAVSMCs proliferation and lipid droplet aggregation induced by ox-LDL, reduced MDA content, increased SOD content, inhibited NOX4 and p22phox protein expression, downregulated ROS content, inhibited IKK-α, IKK-β, NF-κB protein and mRNA expression and the phosphorylation of NF-κB. XTTG can inhibit NOX/ROS/NF-κB signaling pathway, reduce damages caused by oxidative stress, and exert anti-AS effects. [Display omitted] • Oxidative stress is one of the major pathophysiological mechanisms of atherosclerosis. • XTTG acted on atherosclerosis via anti-oxidative stress. • XTTG exerted anti-atherosclerosis effects via NOX/ROS/NF-κB signal pathway. [ABSTRACT FROM AUTHOR]

Glaucoma is the second most common blindness in the world, which seriously affects the life quality of patients. Traditional Chinese Medicines (TCM), are important plant materials, widely used for ocular disease all over the world. With the help of modern ophthalmic detection technology, TCM has gradually become an important content in the field of ophthalmology, characterized by more targets and lower toxicity. This review presents an overview of the pathogenesis of glaucoma in both modern and traditional medicines, and summarizes the therapeutic effect of TCM on glaucoma including their formula, crude drugs and active components, and also the application of acupuncture. A collection and collation of relevant scientific articles from different scientific databases was performed regarding TCM and its application on glaucoma. The therapeutic effects of TCM were summarized and analyzed according to the existing experimental and clinical researches, while the GSE26299 database were employed to screen bioinformatics analysis of glaucoma based on the GEO database chip. There were many positive signs showing that TCM could increase the survival rate of retinal ganglion cells, which may be related to its regulation of microcirculation, oxidative stress, and the immune system. Hence, TCM plays an active role in treating glaucoma. In addition, the bioinformatics analysis predicted that the pathogenesis of glaucoma might be related to p53, MAPK, NF-κB signal, as well as other pathways by KEGG analysis, and the results from bioinformatics analysis predicted that PIK3R6, FGF1, and TYRP1 etc. TCM exerts definite effects on preventing and treating ocular disease. It could alleviate and treat glaucoma in various ways. The differentiation syndrome should thus be taken as the basis to propose appropriate treatment options of TCM making their application on glaucoma more popular. [Display omitted] [ABSTRACT FROM AUTHOR]

Cyclocarya paliurus (CP) is a traditional Chinese herb and possesses a variety of biological activities including anti-hyperglycemia, anti-hyperlipidemia, antioxidant and anti-inflammation. Arjunolic acid (AA) is an abundant and bioactive ingredient in CP that shows significant protection against many metabolic diseases such as diabetic complication. Diabetic retinopathy (DR) is a serious complication of diabetes and may lead to vision loss. However, the protective effects and underlying mechanisms of AA against DR is not still understood. We aimed to investigate whether AA activates AMPK/mTOR/HO-1 regulated autophagy pathway to alleviate DR. In the study, the STZ-induced diabetic model of rats was established, and AA with 10 and 30 mg/kg dosages was given orally for ten weeks to investigate their effect on retinal injury of DR. H 2 O 2 -induced ARPE-19 cells were applied to evaluate anti-apoptosis and anti-oxidant effect of AA. The results revealed that AA could prevent STZ-induced weight loss and increase the retinal thickness and nuclei counts. The level of HO-1 protein was upregulated both in vivo and in vitro. In addition, AA prevented retinal damage and cell apoptosis through the AMPK-mTOR-regulated autophagy pathway. Furthermore, anti-apoptosis capacity, as well as the expression of HO-1 and LC3 protein, were effectively locked by AMPK inhibitor dorsomorphin dihydrochloride (compound C). This finding implies that AA may be a promising candidate drug by protecting retinal cells from STZ-induced oxidative stress and inflammation through the AMPK/mTOR/HO-1 regulated autophagy pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a major complication of diabetes. The kidney disease develops in nearly 20%–40% of type 2 diabetes (T2D) patients. Ginseng is the root of Panax ginseng C. A. Meyer and has been used in prevention and treatment of diseases for more than 2000 years as a traditional oriental medicine. The 20(R)-ginsenoside Rg3, an active saponin isolated from ginseng, can prevent and treat many diseases. The object of this research was to explore the alleviative effects of 20(R)-Rg3 on DN in mice. The T2D animal model was induced by continuous access to a high fat diet (HFD) combined with a single injection of 100 mg/kg streptozotocin (STZ) in C57BL/6 mice. The mice were treated by oral gavage of the 20(R)-Rg3 (10, 20 mg/kg) for 8 weeks. Functional and histopathological analyses of the kidneys were then performed. Protein expression levels of MAPKs and NF-κB signal pathways in the kidney were evaluated by western blotting. The expressions of HO-1 and NF-κB in the kidney were measured by fluorescent labeling staining. Other assessments including fasting blood glucose (FBG) levels, blood lipids, oxidative indicators, and inflammatory factors were all performed. Abnormally elevated FBG levels were observed in HFD/STZ mice, contributing significantly to the occurrence of DN. Simultaneously, HFD/STZ mice showed the rise of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, and the decrease in high density lipoprotein cholesterol (HDL-C). DN was evidenced by the overproduction of malondialdehyde (MDA), decreased levels of superoxide dismutase (SOD) and catalase (CAT) enzymatic activities, high levels of serum blood urea nitrogen (BUN) and creatinine (Cr). Simultaneously, the results of the immunofluorescence assay showed an increased expression level in NF-κB p65 while a decrease in antioxidant enzyme HO-1 was observed. Herein, 20(R)-Rg3 treatment for 8 weeks not only attenuated FBG levels and advanced glycation end products (AGEs) levels but also improved insulin (INS) level, blood lipids, oxidative stress, and renal function by regulating MAPKs and NF-κB signal pathways in DN mice. Taken together, the findings from the present study explicitly confirmed that 20(R)-Rg3 exerted ameliorative effects on DN mice via improving anti-oxidative activity and reducing renal inflammation. Image 1 [ABSTRACT FROM AUTHOR]