Vitexin, a fenugreek glycoside, ameliorated obesity-induced diabetic nephropathy via modulation of NF-κB/IkBα and AMPK/ACC pathways in mice.

Obesity is one of the most critical risk factors for diabetes mellitus and plays a significant role in diabetic nephropathy (DN). The present investigation aimed to evaluate the possible mechanism of action of vitexin on obesity-induced DN in a high-fat diet (HFD)-fed experimental C57BL/6 mice model. Obesity was induced in male C57BL/6 mice by chronic administration of HFD, and mice were concomitantly treated with vitexin (15, 30, and 60 mg/kg, p.o.). HFD-induced increased renal oxido-nitrosative stress and proinflammatory cytokine levels were significantly inhibited by vitexin. The Western blot analysis suggested that alteration in renal NF-κB, IκBα, nephrin, AMPK, and ACC phosphorylation levels was effectively restored by vitexin treatment. Histological aberration induced in renal tissue after chronic administration of HFD was also reduced by vitexin. In conclusion, vitexin suppressed the progression of obesity-induced DN via modulation of NF-κB/IkBα and AMPK/ACC pathways in an experimental model of HFD-induced DN in C57BL/6J mice.

Evaluation of Antioxidative Mechanisms In Vitro and Triterpenes Composition of Extracts from Silver Birch (Betula pendula Roth) and Black Birch (Betula obscura Kotula) Barks by FT-IR and HPLC-PDA.

Silver birch, Betula pendula Roth, is one of the most common trees in Europe. Due to its content of many biologically active substances, it has long been used in medicine and cosmetics, unlike the rare black birch, Betula obscura Kotula. The aim of the study was therefore to compare the antioxidant properties of extracts from the inner and outer bark layers of both birch trees towards the L929 line treated with acetaldehyde. Based on the lactate dehydrogenase test and the MTT test, 10 and 25% concentrations of extracts were selected for the antioxidant evaluation. All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells. The chemical composition of bark extracts was accessed by IR and HPLC-PDA methods and surprisingly, revealed a high content of betulin and lupeol in the inner bark extract of B. obscura. Furthermore, IR analysis revealed differences in the chemical composition of the outer bark between black and silver birch extracts, indicating that black birch may be a valuable source of numerous biologically active substances. Further experiments are required to evaluate their potential against neuroinflammation, cancer, viral infections, as well as their usefulness in cosmetology.

Protective effect of N-(p-amylcinnamoyl) anthranilic acid, phospholipase A2 enzyme inhibitor, and transient receptor potential melastatin-2 channel blocker against renal ischemia-reperfusion injury.

The production of reactive oxygen species and inflammatory events are the underlying mechanisms of ischemia-reperfusion injury (IRI). It was determined that transient receptor potential melastatin-2 (TRPM2) channels and phospholipase A2 (PLA 2 ) enzymes were associated with inflammation and cell death. In this study, we investigated the effect of N-( p-amylcinnamoyl) anthranilic acid (ACA), a TRPM2 channel blocker, and PLA 2 enzyme inhibitor on renal IRI. A total of 36 male Sprague-Dawley rats were divided into four groups: control, ischemia-reperfusion (I/R), I/R + ACA 5 mg, I/R + ACA 25 mg. In I/R applied groups, the ischemia for 45 minutes and reperfusion for 24 hours were applied bilaterally to the kidneys. In the I/R group, serum levels of the blood urea nitrogen (BUN), creatinine, cystatin C (CysC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 increased. On histopathological examination of renal tissue in the I/R group, the formation of glomerular and tubular damage was seen, and it was detected that there was an increase in the levels of malondialdehyde (MDA), caspase-3, total oxidant status (TOS), and oxidative stress index (OSI); and there was a decrease in total antioxidant capacity (TAC) and catalase enzyme activity. ACA administration reduced serum levels of BUN, creatinine, CysC, KIM-1, NGAL, interleukin-18. In the renal tissue, ACA administration reduced histopathological damage, levels of caspase-3, MDA, TOS, and OSI; and it increased the level of TAC and catalase enzyme activity. It has been shown with the histological and biochemical results in this study that ACA is protective against renal IRI.

Higenamine protects neuronal cells from oxygen-glucose deprivation/reoxygenation-induced injury.

Higenamine, a plant-based alkaloid, exhibits various properties, such as antiapoptotic and antioxidative effects. Previous studies proved that higenamine possesses potential therapeutic effects for ischemia/reperfusion (I/R) injuries. However, the role of higenamine in cerebral I/R injury has not been fully evaluated. Therefore, we aimed to investigate the effect of higenamine on cerebral I/R injury and the potential mechanism. Our data showed that higenamine ameliorated oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal cells injury. Induction of reactive oxygen species and malonaldehyde production, and the inhibition of superoxide dismutase and glutathione peroxidase activity caused by OGD/R were attenuated by higenamine. In addition, higenamine inhibited the increases in caspase-3 activity and Bax expression, and inhibited the decrease in Bcl-2 expression. Furthermore, higenamine elevated the expression levels of p-Akt, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2). The inhibitor of PI3K/Akt (LY294002) abolished the protective effects of higenamine on OGD/R-induced neuronal cells. These findings indicated that higenamine protects neuronal cells against OGD/R-induced injury by regulating the Akt and Nrf2/HO-1-signaling pathways. Collectively, higenamine might be considered as new strategy for the prevention and treatment of cerebral I/R injury.

Protective effects of dimethyl itaconate in mice acute cardiotoxicity induced by doxorubicin.

Doxorubicin (DOX) is an antitumor drug widely used in hematological tumors and various solid tumors. However, the cardiotoxicity elicited by DOX severely limits its clinical treatment. Dimethyl itaconate (DI), a common form of itaconate, is found many potential targets for prevent heart injury. Here we employed wild type and Nrf2 knockout mice and induced a cardiotoxicity model by administration of DOX to clarify the effects of DI. After treatment with DI, we found that it could effectively alleviate the cardiotoxicity by analyzing morphology, LDH levels and heart weight/body weight ratio changes. Meanwhile we demonstrated that RIP3, a key protein of necrosis, was significantly decreased in DI treated group. Further we observed that treatment with DI could suppress oxidative stress by altering Nrf2/HO-1. Compared with vehicle group, DI could increase the tissue SOD and GSH, and reduce MDA levels, then DHE staining revealed that the level of ROS in DI group reduced by half. Finally, transmission electron microscope (TEM) data showed that treatment with DI obviously decreased the mitochondrial damage. While Nrf2 was ablated in mice, the protective effects of DI were vanished and SOD, GSH, MDA became unchanged related to vehicle group. This report provides the evidence for the protective effects of DI treatment in cardiotoxicity induced by DOX. On mechanisms, DI could reduce the oxidative stress by altering Nrf2/HO-1 pathway and prevent mitochondrial from damage. Taken together, these findings of this paper will afford the new therapeutic targets in DOX related cardiotoxicity.

Synthesis and biological evaluation of thiazolidine-2,4-dione-pyrazole conjugates as antidiabetic, anti-inflammatory and antioxidant agents.

A series of fourteen novel thiazolidine-2,4-dione derivatives clubbed with pyrazole moiety were synthesized via four step reaction procedure. Reactions were monitored by thin layer chromatography and were characterized by physicochemical and spectrophotometric (IR, Mass, 1HNMR and 13CNMR) analysis. The spectral data were in good agreement with their structures. The title compounds were docked against peroxisome proliferated activated receptors (PPAR-γ) and alpha-amylase and further evaluated for in vivo and in vitro antidiabetic, in vitro anti-inflammatory and antioxidant activities. Compound GB14 exhibited significant blood glucose lowering activity and was also found to be active inhibitor of alpha-amylase. Compound GB7 was found to be potent anti-inflammatory agent in terms of reducing inflammatory markers (TNF-α, IL-ß, MDA) and also showed antioxidant activity to good extent. Therefore, these compounds may be considered as promising candidates for the development of new antidiabetic agents.

Echinacoside protects retinal ganglion cells from ischemia/reperfusion-induced injury in the rat retina.

Objective: To investigate whether echinacoside (ECH) protects the retina against ischemia/reperfusion (I/R) injury and the underlying mechanisms. Methods: Adult male Wistar rats were randomly divided into four groups: sham, sham plus ECH, I/R plus vehicle, and I/R plus ECH. Before the retinal I/R injury produced by high intraocular pressure (HOP), ECH was administered (20 mg/kg daily) for 7 days. The level of retinal cell damage was evaluated using Fluoro-Gold (FG) retrograde labeling and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) analysis 7 days after I/R. Optic nerve histology was analyzed with transmission electron microscopy. Levels of retinal malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. The expression of apoptosis-associated factors (Apaf-1, Parp, and Bad) were analyzed with western blotting and quantitative real-time PCR (qPCR). The production of proinflammatory cytokines (tumor necrosis factor-α [TNFα], interleukin-1 beta [IL-1ß], and IL-6) was analyzed with enzyme-linked immunosorbent assay (ELISA) 7 days after the I/R injury as well. Results: The administration of ECH not only preserved retinal morphology but also attenuated retinal inflammation and apoptosis at 7 days after the I/R injury and decreased I/R-induced oxidative stress in the retina statistically significantly. Conclusions: ECH protected against I/R-induced retinal injury, via activation of antioxidant enzymes and suppression of inflammation. Therefore, ECH could be a potential therapeutic candidate for the treatment and management of I/R retinal diseases.

Grape seed extract effects on serum amylase levels and immunohistochemical alterations in Streptozotocin-induced diabetic rats.

In this study, serum amylase activity and structural changes of the pancreatic tissue in rats under the effects of grape seed extract were investigated. Thirty-two female Wistar albino rats were divided into 4 groups. First one was the control group. The second group was the streptozotocin (STZ)-induced diabetes mellitus (DM) group (45 mg/kg), while the third group was the grape seed extract (GSE) group, where the GSE was administrated intragastrically for 20 days (at 0.6 ml/rat). Lastly, the fourth group was the diabetes mellitus+GSE (DM+GSE) group. Blood samples were taken and analyzed for amylase activity. Caspase 3 expressions were inspected with immunohistochemistry. Amylase levels in the diabetic group were found to be the lowest (794.00±44.85 U/L, p<0.001), while the GSE group had the highest value (1623.63±80.04 U/L, p<0.001) Number of apoptotic cells was increased in Langerhans islets of the diabetic group. In the control and GSE groups, the apoptotic cells were found to be almost entirely absent. Increased number of apoptotic cells was found in the DM group, while decreased number of apoptotic cells was found in the DM+GSE group. Furthermore, atrophy in Langerhans islets, hyperemia in capillary veins, hydropic degeneration and necrosis in islet cells were determined in the diabetic group. Only mild hydropic degeneration in islet cells of Langerhans was observed in the DM+GSE group. Histopathologically beneficial changes in the pancreases were detected when grape seed extract was given to diabetic rats. As a conclusion, GSE was determined to have positive effects on the function and structure of the pancreas, improving enzyme activities and the structure of the Langerhans islets.

Fertility enhancing efficacy of Cicer arietinum in male albino mice.

The present study was conducted to investigate the effect of incorporating Cicer arietinum in the diet on the testicular functions of the male mice. Seventy-two mice were divided equally into four groups that were daily fed a diet containing 0, 20, 30 and 50% of C. arietinum seeds, respectively. After 7, 14 and 21 days of starting the experiments, the mice were anesthetized and euthanized to collect the blood, testes, epididymis and seminal vesicles. The present results showed that the increased percentage of C. arietinum in the diet caused significant elevations in the serum levels of testosterone and luteinizing hormone (LH), sperm concentration, sperm motility as well as the testicular levels of antioxidants including glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT), in comparison to the controls. On the other hand, marked reductions in the sperm abnormality, testicular levels of malondialdehyde (MDA), the percentage of DNA damage in tail and tail moment (TM) were observed in the mice that received a diet containing C. arietinum as compared to the controls. Both the sperms and testes of the mice fed a diet containing C. arietinum in the diet showed a normal intact appearance of the electrophoresed genomic DNA on agarose, as those of the controls. In conclusion, C. arietinum is not only a safe ingredient in the fast-food but also an enhancer of the testicular functions.

Effects of plant essential oil supplementation on growth performance, immune function and antioxidant activities in weaned pigs.

BACKGROUND: The aim of this study was to determine the effects of plant essential oil supplementation on growth performance, immune function and antioxidant activities in weaned pigs. METHODS: In the study, 24 weaned pigs were used to explore the effects of plant essential oil (PEO) on growth performance, immune properties and antioxidant activities. Pigs were fed with a basal diet (CON) or basal diet containing different concentrations of PEO (PEO50: 50 ppm; PEO100: 100 ppm; PEO200: 200 ppm). After 3 weeks, all pigs were slaughtered and blood and tissue samples were collected for biochemical analysis. RESULTS: The results showed that PEO supplementation quadratically increased body weight gain (BWG) (P = 0.031), linearly (P <  0.05) and quadratically (P <  0.05) decreased F:G. In addition, IgG increased linearly (P <  0.05) and IgM increased linearly (P <  0.05) and quadratically (P < 0.05) as PEO supplementation. Similarly, MDA in serum, jejunal mucosa and pancreas were linearly decreased (P < 0.05) and GSH in serum (linear and quadratic, P < 0.05), duodenal mucosa (linear and quadratic, P < 0.05) and in ileal mucosa (linear and quadratic, P < 0.05) were notably increased. Futhermore, antioxidant-related genes expression levels of GST in spleen (linear and quadratic, P < 0.05), GPX1 (quadratic, P < 0.05) and SOD1 (linear, P < 0.05) in spleen and GST in liver (quadratic, P < 0.05) were markedly upregulated by PEO supplementation increasing. CONCLUSIONS: These results suggest that PEO improves growth performance, immune function, and antioxidant activities in weaned pigs, and it may also relieve weaning stress if used as a feed additive in the livestock industry. And that supplementation 200 ppm PEO in diet would seem to be economically feasible.

In Vitro and In Vivo Antioxidant Activities of the Flowers and Leaves from Paeonia rockii and Identification of Their Antioxidant Constituents by UHPLC-ESI-HRMSn via Pre-Column DPPH Reaction.

The genus Paeonia, also known as the "King of Flowers" in China, is an important source of traditional Chinese medicine (TCM). Plants of this genus have been used to treat a range of cardiovascular and gynecological diseases. However, the potential pharmacological activity of one particular species, Paeonia rockii, has not been fully investigated. In the first part of the present study, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), reducing power assays, and metal ion chelating assays were used to investigate the in vitro antioxidant activities of Paeonia rockii. In the second portion of the study, a mouse model of d-galactose-induced aging was used to validate the antioxidant effects of the flowers from Paeonia rockii in vivo. Lastly, potential antioxidant constituents were screened and identified by ultra-high pressure liquid chromatography and electrospray ionization coupled with high-resolution mass spectrometry (UHPLC-ESI-HRMSn) combined with the DPPH assay. Results indicated that the flowers and leaves exhibited stronger antioxidant activity than ascorbic acid in vitro. The therapeutic effect of Paeoniarockii was determined in relation to the levels of biochemical indicators, such as 8-iso-prostaglandin F2α (8-iso PGF2α) in the serum, superoxide dismutase (SOD), protein carbonyl, malondialdehyde (MDA), and glutathione (GSH) in the liver and brain, after daily intra-gastric administration of different concentrations of extracts (100, 200 and 400 mg/kg) for three weeks. The levels of 8-iso PGF2α (p < 0.01) and protein carbonyl groups (p < 0.01) were significantly reduced, whereas those of SOD (p < 0.05) had significantly increased, indicating that components of the flowers of Paeonia rockii had favorable antioxidant activities in vivo. Furthermore, UHPLC-ESI-HRMSn, combined with pre-column DPPH reaction, detected 25 potential antioxidant compounds. Of these, 18 compounds were tentatively identified, including 11 flavonoids, four phenolic acids, two tannins, and one monoterpene glycoside. This study concluded that the leaves and flowers from Paeonia rockii possess excellent antioxidant properties, highlighting their candidacy as "new" antioxidants, which can be utilized therapeutically to protect the body from diseases caused by oxidative stress.

Proanthocyanidins Protect Epithelial Cells from Zearalenone-Induced Apoptosis via Inhibition of Endoplasmic Reticulum Stress-Induced Apoptosis Pathways in Mouse Small Intestines.

This study evaluated the protective effect of proanthocyanidins (PCs) on reducing apoptosis in the mouse intestinal epithelial cell model MODE-K exposed to zearalenone (ZEA) through inhibition of the endoplasmic reticulum stress (ERS)-induced apoptosis pathway. Our results showed that PCs could reduce the rate of apoptosis in MODE-K cells exposed to ZEA (p < 0.01). PCs significantly increased the ZEA-induced antioxidant protective effects on the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and on the content of GSH. PCs also significantly decreased the ZEA-induced increase in the content of malondialdehyde (MDA). The analysis indicated that ZEA increased both mRNA and protein expression levels of C/EBP homologous protein (CHOP), GRP78, c-Jun N-terminal kinase (JNK), and cysteinyl aspartate specific proteinase 12 (caspase-12) (p < 0.05), which are related to the ERS-induced apoptosis pathway. ZEA decreased levels of the pro-apoptotic related protein Bcl-2 (p < 0.05) and increased the anti-apoptotic related protein Bax (p < 0.05). Co-treatment with PCs was also shown to significantly reverse the expression levels of these proteins in MODE-K cells. The results demonstrated that PCs could protect MODE-K cells from oxidative stress and apoptosis induced by ZEA. The underlying mechanism may be that PCs can alleviate apoptosis in mouse intestinal epithelial cells by inhibition of the ERS-induced apoptosis pathway.

Evaluation of the Possibility of Correction of Doxorubicin-Induced Chronic Heart Failure in the Experiment with 3-Hydroxypyridine Acetylcysteinate and 3-Hydroxypyridine Succinate.

The possibility of correction of morphological changes in the myocardium and biochemical parameters of the blood with 3-hydroxypyridine acetylcysteinate in a dose of 25 mg/kg was studied in the model of doxorubicin-induced chronic heart failure in rats. It was found that 3-hydroxypyridine acetylcysteinate in a dose of 25 mg/kg produced less pronounced cardio-protective effect in experimental chronic heart failure than 3-hydroxypyridine succinate.

Thymoquinone protects against cobalt chloride-induced neurotoxicity via Nrf2/GCL-regulated glutathione homeostasis.

The prevalence of neurodegenerative diseases worldwide has increased dramatically in the last decades. Hypoxia and oxidative stress play a central role in the pathogenesis of neurodegenerative diseases. Thymoquinone (TQ) is a monoterpenoid hydrocarbon compound that possesses potent antioxidant activity. In the current study, we investigated the neuroprotective effects of TQ against CoCl2, a widely used hypoxia-inducing agent. We found that TQ inhibited CoCl2-indcued cytotoxicity in vitro, as reflected by an increase of cell viability and decrease of apoptosis in CoCl2-treated PC12 cells. TQ exhibited a potent protective effect against CoCl2-induced neurotoxicity in vivo, as evidenced by decreased time spent to find the platform site in the Probe trials, reduced escape latencies, decreased traveling distance and reduction of apoptotic cell death in brains in CoCl2-treated rats. CoCl2-resulted decrease of glutathione (GSH) and increase of malondialdehyde (MDA) levels were significantly inhibited by TQ. Inhibition of GSH synthesis by buthionine sulphoximine (BSO) significantly attenuated TQ-induced neuroprotective effects against CoCl2 in rats and in PC12 cells. TQ could upregulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/glutamate-cysteine ligase catalytic subunit (GCLc) and Nrf2/glutamate-cysteine ligase modifier subunit (GCLm) pathway which contributed to antioxidant and neuroprotective effects of TQ. In summary, we found that TQ exhibited protective effects against neurotoxicity via upregulation of Nrf2/GCL signaling. Upregulation of Nrf2/GCL signaling promoted the synthesis of GSH and contributed to attenuation of oxidative stress, neuronal cell apoptosis and neurotoxicity. These data have appointed a new path toward the understanding of the neuroprotective activities of TQ.

Nullification of aspirin induced gastrotoxicity and hepatotoxicity by prior administration of wheat germ oil in Mus musculus: histopathological, ultrastructural and molecular studies.

Aspirin (acetyl salicylic acid) is used worldwide to treat various inflammatory conditions and prevent cardiovascular disease, along with reducing the risk of cancer. However, administration of aspirin causes toxic effects, especially in the stomach and liver. Thus, our study examined the protective effect of wheat germ oil on aspirin-induced toxicity in the stomach and liver tissues of Swiss albino mice. Administration of wheat germ oil before aspirin has restored normal hepatic and gastric tissue architecture and DNA integrity has become better than that of a negative health control group compared with the aspirin only treated group. The elevated gastric nitric oxide content in the aspirin only treated group was significantly decreased by wheat germ oil prior administration as a result of reduced the expression of inducible nitric synthase and increased the expression of endothelial nitric oxide synthase compared to their expression in the aspirin administered group. Wheat germ oil pre-administration significantly reduced the level of malondialdehyde, increased the level of glutathione and catalase and superoxide dismutase activities compared with those in aspirin only treated group. We conclude that wheat germ oil has a potential protective effect against aspirin induced gastro- and hepato-toxicity because of its free radical scavenging ability.

Complement factor H binds malondialdehyde epitopes and protects from oxidative stress.

Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases.

Klotho ameliorates oxidized low density lipoprotein (ox-LDL)-induced oxidative stress via regulating LOX-1 and PI3K/Akt/eNOS pathways.

BACKGROUND: Atherosclerosis is a common cardiovascular disease that causes myocardial infarction, heart failure, and stroke. Increased oxidized low density lipoprotein (ox-LDL) in the sub-endothelium is the characteristic origin of atherogenesis. Klotho, an anti-aging protein, has been reported to protect against atherosclerosis and ameliorate endothelial dysfunction in vivo. The aim of this study is to investigatethe anti-oxidative activity of Klothoin ox-LDL-treated human umbilical vein endothelial cells (HUVECs). METHODS: After pre-treatment with 200 pMKlotho for 1 h, HUVECs were stimulated with 50 µg/ml ox-LDL for 24 h. Reactive oxygen species (ROS) and superoxide dismutase (SOD) levels were analyzed in the cells. Nitric oxide (NO) concertation was measured in the medium supernatant. Related proteins or genes were detected with Western blot or real time PCR, respectively, in the cell lysates. RESULTS: Initially, oxidative damage in HUVECs was established by adding 50 µg/mL ox-LDL, which resulted in decreased cellular viability, SOD/Cu/Zn-SOD and endothelial NO synthase (eNOS) expression and NO production, as well as increased malondialdehyde (MDA) levels, ROS production, inducible NO synthase (iNOS), phosphatidyl inositol-3 kinase (PI3K), protein kinase B (Akt), gp91 phox, and lectin-like ox-LDL receptor (LOX-1) expression in HUVECs. Pre-incubation with recombinant Klotho (200 pM) significantly prevented all of these alterations. These results suggest that Klotho can attenuate ox-LDL-induced oxidative stress in HUVECs through upregulating oxidative scavengers (SOD and NO) viaactivating the PI3K/Akt/eNOS pathway and depressing LOX-1expression. CONCLUSIONS: These results suggest that Klotho has a potential therapeutic effect on attenuating endothelial dysfunction and ameliorating atherosclerosis.

Anti-Fatigue Effects of the Unique Polysaccharide Marker of Dendrobium officinale on BALB/c Mice.

Dendrobium officinale extract shows potent anti-fatigue effects; however, the active substance responsible for these effects remains undetermined. A glucomannan with a huge molecular size of 730 kDa, called DOP, was identified as the unique authentication marker of this expensive herb. DOP exhibited immunomodulating effects on macrophages and lymphocytes in our previous study. Clinical reports also showed that people with fatigue syndrome have a disturbed immune system. Because DOP is the unique and dominant component of D. officinale, we hypothesize that DOP may also have anti-fatigue activity. The present study aims to evaluate the anti-fatigue activity of DOP on BALB/c mice, with Rhodiola rosea extract as a positive control. DOP and Rhodiola rosea extract were orally administered at doses of 50 mg/kg and 100 mg/kg, respectively, for four weeks, and the anti-fatigue activity of DOP on BALB/c mice was evaluated using the weight-loaded swimming test. The contents of lactic dehydrogenase (LDH), creatine phosphokinase (CK), triglyceride (TG), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA), lactic acid (LD), and glutathione peroxidase (GSH-Px) in serum, glycogen of liver and gastrocnemius muscle were also determined. Their effects on variability of T cells and B cells were determined by using tetrazolium compound (MTS) method. The weight-loaded swimming exercise caused fatigue syndrome, mainly including the decreases of serum SOD/GSH-Px and gastrocnemius glycogen, as well as the increases of LDH, BUN, MDA, CK, TG, and LD in serum. All of these indicators of fatigue were inhibited to a certain extent by both DOP and Rhodiola rosea extract; however, the effects of DOP were much stronger than those of Rhodiola rosea extract. Compared to the positive control, mice dosed with DOP showed increases in endurance, body weight, and food intake. Furthermore, DOP-feeding mice significantly increased the cell variability of T lymphocytes and B lymphocytes, compared with that of mice in control group. This study indicates that the unique and dominant polysaccharide DOP of D. officinale has stronger anti-fatigue activity than Rhodiola rosea extract. As such, DOP has promising potential for pharmaceutical development into health products to reduce fatigue.

Antioxidant and Antiamnestic Effects of Potassium Comenate and Comenic Acid under Conditions of Normobaric Hypoxia with Hypercapnia.

Potassium comenate and comenic acid exhibit manifest and virtually identical antioxidant activity under conditions of hypoxia with hypercapnia. The effects of these drugs on conditioned reflex training with positive reinforcement differ significantly. Potassium comenate promotes retention of the learning capacity and memory in hypoxic rats at the level of intact control, that is, exhibits a pronounced protective antiamnestic effect, while comenic acid only facilitates training of the conditioned reflex with positive reinforcement.

Berberis aristata Ameliorates Adjuvant-Induced Arthritis by Inhibition of NF-κB and Activating Nuclear Factor-E2-related Factor 2/hem Oxygenase (HO)-1 Signaling Pathway.

The present study was carried out to investigate the anti-arthritic activity of Berberis aristata hydroalcoholic extract (BAHE) in formaldehyde-induced arthritis and adjuvant-induced arthritis (AIA) model. Arthritis was induced by administration of either formaldehyde (2% v/v) or CFA into the subplantar surface of the hind paw of the animal. In formaldehyde-induced arthritis and AIA, treatment of BAHE at doses 50, 100 and 200 mg/kg orally significantly decreased joint inflammation as evidenced by decrease in joint diameter and reduced inflammatory cell infiltration in histopathological examination. BAHE treatment demonstrated dose-dependent improvement in the redox status of synovium (decrease in GSH, MDA, and NO levels and increase in SOD and CAT activities). The beneficial effect of BAHE was substantiated with decreased expression of inflammatory markers such as IL-1ß, IL-6, TNF-R1, and VEGF by immunohistochemistry analysis in AIA model. BAHE increased HO-1/Nrf-2 and suppressed NF-κB mRNA and protein expression in adjuvant immunized joint. Additionally, BAHE abrogated degrading enzymes, as there was decreased protein expression of MMP-3 and -9 in AIA. In conclusion, we demonstrated the anti-arthritic activity of Berberis aristata hydroalcoholic extract via the mechanism of inhibition of NF-κB and activation of Nrf-2/HO-1.