Increased Antioxidant Levels Research Articles

The protective effects of topiramate and spirulina against doxorubicin-induced cardiotoxicity in rats.

Doxorubicin (DOX) is a widely used chemotherapy drug that can cause significant cardiotoxicity, limiting its clinical application. This study aimed to investigate the potential protective effects of topiramate (TPM) and spirulina (SP), either alone or in combination, in preventing DOX-induced cardiotoxicity. Adult Sprague Dawley rats were divided into five groups, including a normal control group and groups receiving DOX alone, DOX with TPM, DOX with SP, or DOX with a combination of TPM and SP. Cardiotoxicity was induced by administering DOX intraperitoneally at a cumulative dose of 16 mg/kg over 4weeks. TPM and/or SP administration started 1week before DOX treatment and continued for 35 days. Body weight, serum markers of cardiac damage, oxidative stress and inflammatory parameters were assessed. Histopathological and immunohistochemical examinations were performed on cardiac tissues. Results showed that TPM and SP monotherapy led to significant improvements in serum levels of cardiac markers, decreased oxidative stress, reduced fibrosis-related growth factor levels, increased antioxidant levels, and improved histopathological features. SP demonstrated more prominent effects in comparison to TPM, and the combination of TPM and SP exhibited even more pronounced effects. In conclusion, TPM and SP, either alone or in combination, hold promise as therapeutic interventions for mitigating DOX-induced cardiotoxicity.

The transcription factor MebHLH18 in cassava functions in decreasing low temperature-induced leaf abscission to promote low-temperature tolerance.

The reactive oxygen species (ROS) signal regulates stress-induced leaf abscission in cassava. The relationship between the function of the cassava transcription factor bHLH gene and low temperature-induced leaf abscission is still unclear. Here, we report that MebHLH18, a transcription factor, involved in regulating low temperature-induced leaf abscission in cassava. The expression of the MebHLH18 gene was significantly related to low temperature-induced leaf abscission and POD level. Under low temperatures, the levels of ROS scavengers in different cassava genotypes were significantly different in the low temperature-induced leaf abscission process. Cassava gene transformation showed that MebHLH18 overexpression significantly decreased the low temperature-induced leaf abscission rate. Simultaneously, interference expression increased the rate of leaf abscission under the same conditions. ROS analysis showed a connection between the decrease in the low temperature-induced leaf abscission rate caused by MebHLH18 expression and the increase in antioxidant activity. A Genome-wide association studies analysis showed a relationship between the natural variation of the promoter region of MebHLH18 and low temperature-induced leaf abscission. Furthermore, studies showed that the change in MebHLH18 expression was caused by a single nucleotide polymorphism variation in the promoter region upstream of the gene. The high expression of MebHLH18 led to a significant increase in POD activity. The increased POD activity decreased the accumulation of ROS at low temperatures and the rate of leaf abscission. It indicates that the natural variation in the promoter region of MebHLH18 increases antioxidant levels under low temperatures and slows down low temperature-induced leaf abscission.

Nerolidol Attenuates Cerebral Ischemic Injury in Middle Cerebral Artery Occlusion-Induced Rats via Regulation of Inflammation, Apoptosis, and Oxidative Stress Markers

Background Cerebral ischemia is a syndrome that occurs due to the restricted flow of oxygen-rich blood to the brain, causing damage to the brain cells. Globally, ischemia ranks second in causing mortality and third in causing disability in stroke patients. Nerolidol is a bioactive compound present in the essential oil of plants with a floral odour. It is a natural sesquiterpene alcohol used in cosmetics, perfumes, and as a food flavouring agent. It also possesses antioxidant, antimicrobial, anti-inflammatory, and anticancer properties. Materials and Methods In this study, we assessed the anti-ischemic property of nerolidol in cerebral ischemia-induced mice. Healthy male Wistar rats were induced into cerebral ischemia with middle cerebral artery occlusion (MCAO) and treated with 10 mg and 20 mg nerolidol for 21 days. The brain morphometric, antioxidant, and MMP levels were estimated in the brain tissue of MCAO-performed and nerolidol-treated rats. The cerebral infarct-alleviating potency of nerolidol was analysed by estimating the levels of inflammatory cytokines and apoptotic proteins. It was further confirmed by assessing the levels of COX-2/PGE-2 signalling proteins in brain tissue from MCAO-performed in rats. Results Nerolidol significantly reduced the cerebral infarct volume and brain edema via increased antioxidant levels and decreased MMPs. It also decreased the pro-inflammatory cytokines and proapoptotic proteins in brain tissue. The inflammatory signalling proteins NFκB, COX-2, and PGE-2 were significantly decreased in nerolidol-treated MCAO-performed rats, confirming the antiischemic property of nerolidol. Conclusion Our results prove nerolidol significantly alleviates cerebral ischemia in rats, and it can be subjected to further trials to be formulated as an anti-ischemic drug.

AN EVALUATION OF DIETARY APPROACHES USED IN THE CLINICAL MANAGEMENT OF RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by systemic inflammation, persistent synovitis, and other comorbidities, that affects 0.5-1.0% of the overall population. Long-term active RA causes severe joint damage, disabling pain and diminished life quality. The etiology of RA is not accurately understood, but it is thought to be due to an interaction between the responses of the innate and acquired immune systems. RA is characterized by the presence of Rheumatoid Factor (RF) and anti citrullinated peptide antibodies in the blood circulation. Also the composition of intestinal the gut microbiome is claimed to be critical in immune responses associated with RA. Changes in the microbiota are thought to be related to the risk and severity of the disease. Three regions; primarily the lungs, oral mucosa and gastrointestinal tract have been associated with changes in the microbiota. Commonly, the pharmaceutical treatment of RA includes non-steroidal anti-inflammatory drugs (NSAIDs) that are used to manage the pain and inflammation associated with RA and disease-modifying anti-rheumatic drugs that reduces pain by slowing down the disease. Unfortunately, remission is not likely in many patients. Moreover, side effects related to drugs are commonly reported. Some alterations in the patients’ life and environment are thought to aggravate symptoms, thus influencing severity of RA. For example RA patients, the participants asserted that consumption of red meat, alcoholic and non-alcoholic beverages worsen their symptoms, while nutrients such as fish and blueberries help alleviate the symptoms. To manage the adverse effects of RA, particular dietary alterations are suggested to be effective in reducing inflammation, increasing antioxidant levels, and improving lipid profiles. Antigenic load and food intolerance are thought to play a role in both the onset of Rheumatoid Arthritis. Besides, it has been shown that the intestinal mucosa of the patients would have become more permeable to allergens due to long term NSAIDs use. In this sense, Elimination Diet, Mediterranean Diet, Vegan/Vegetarian Diet approach, Omega-3 Fatty acids, Vitamin D and probiotic supplementation is thought to reduce disease activity. The purpose of this review is to evaluate the efficiency of certain dietary approaches and supplements used for lessening the RA related symptoms, based on the scientific evidence found in the literature.

Yoga as an Integrated Holistic Approach to Oral Health: A Review.

The association between various systemic diseases and periodontitis has been explored extensively. A sedentary lifestyle plays a significant role in systemic and periodontal disease progression. Therefore, lifestyle modification has been considered a component of therapeutic aspects for periodontal disease and systemic disease. This review focuses on how yoga may reduce chronic gingival inflammation by improving the body's defense, which can act more efficiently on periodontal bacteria and help maintain healthy gingiva. A literature search was performed in PubMed/MEDLINE CINAHL, Web of Science, and Google Scholar for all the published articles related to yoga and its systemic benefits and potential role in reducing periodontal breakdown, and the findings were summarized. The practice of yoga therapy has been proven to show several benefits, such as reduced stress levels, anxiety and depression, increased antioxidant levels, reduced insulin resistance, and improved respiratory function. It also helps to improve the immune system. Yoga can be used as a potential treatment modality adjunct to conventional periodontal therapy as it has been shown to have a potential benefit in controlling systemic risk factors.

Hippocampus and Prefrontal Cortex Following the Use of Anti-Retroviral Therapy in Adult Wistar Rats: Therapeutic Role of Epigallocatechin Gallate.

The contribution of prefrontal-hippocampal interactions to brain function of people infected with HIV may be aggravated by toxicities due to long-term use of antiretroviral agents. This study was designed to investigate the curative potential of Epigallotatechin gallate (EGCG) in the treatment of neurodegenerative disorders as a possible consequence of antiretroviral toxicity. Twenty-four adult male Wistar rats, weighing 80~100g, were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (EGCG 2.5mg/kg), D (EGCG 2.5mg/kg) + HAART) Brain histology, immunohistochemistry, and oxidative stress markers such as superoxide dismutase (SOD), glutathione (GSH),catalase (CAT) and malondialdehyde (MDA) were examined. The use of highly active antiretroviral therapy (HAART) showed extensive architectural deformation with pyknotic neuronal cells and obliterated neurons in the hippocampus and prefrontal cortex. Expression of inflammasome cells was also evident in this group. MDA levels increased significantly with a significant reduction in the levels of GSH, as well as antioxidant enzyme (SOD and CAT) activities compared to other treatment groups. Treatment with EGCG resulted in partial neuronal restoration of histopathological alterations, and modulation of NLRP3 inflammasome in the hippocampus and prefrontal cortex. EGCG also showed significant improvements in terms of increased antioxidant levels of SOD, GSH, CAT and a reduced MDA level and well-preserved brain architecture. Epigallocatechin gallate improves brain morphology and function with a reversal of HAART-induced alterations.

Antioxidant Supplementation in Oxidative Stress-Related Diseases: What Have We Learned from Studies on Alpha-Tocopherol?

Oxidative stress has been proposed as a key contributor to lifestyle- and age-related diseases. Because free radicals play an important role in various processes such as immune responses and cellular signaling, the body possesses an arsenal of different enzymatic and non-enzymatic antioxidant defense mechanisms. Oxidative stress is, among others, the result of an imbalance between the production of various reactive oxygen species (ROS) and antioxidant defense mechanisms including vitamin E (α-tocopherol) as a non-enzymatic antioxidant. Dietary vitamins, such as vitamin C and E, can also be taken in as supplements. It has been postulated that increasing antioxidant levels through supplementation may delay and/or ameliorate outcomes of lifestyle- and age-related diseases that have been linked to oxidative stress. Although supported by many animal experiments and observational studies, randomized clinical trials in humans have failed to demonstrate any clinical benefit from antioxidant supplementation. Nevertheless, possible explanations for this discrepancy remain underreported. This review aims to provide an overview of recent developments and novel research techniques used to clarify the existing controversy on the benefits of antioxidant supplementation in health and disease, focusing on α-tocopherol as antioxidant. Based on the currently available literature, we propose that examining the difference between antioxidant activity and capacity, by considering the catabolism of antioxidants, will provide crucial knowledge on the preventative and therapeutical use of antioxidant supplementation in oxidative stress-related diseases.

In vivo attenuation of experimentally-induced oxidative stress by common African vegetable (Corchorus olitorius)

Despite decades of study, the significance of free radicals' function in organ damage remains questionable and is still a significant problem in the diagnosis of many diseases. Therefore, the goal of the current investigation was to determine whether Corchorus olitorius leaves could reduce oxidative stress caused by potassium bromate (KBrO3). Twenty-four rats were put into groups A, B, C, and D. Group A received distilled water as the control. Animals in groups C and D were additionally given 100 and 200 mg/kg body weight of C. olitorius, respectively, in addition to the 100 mg/kg body weight of KBrO3 given to groups B, C, and D on a daily basis for 28 days. The animals were sacrificed while being gently sedated with diethyl ether and the blood, heart, liver, and kidneys were collected. The results showed that KBrO3 decreased plasma, hepatic, renal, and cardiac CAT, SOD, and GPx activities as well as GSH concentrations, but raised MDA levels, as compared to the control group. Rats were given extract from C. olitorius leaves at doses of 100 and 200 mg/kg body weight, with the results of the 200 mg/kg dose being comparable to those observed in the control group. These treatments resulted in significant increases in antioxidant levels (except GPx) and decrease in MDA levels in their plasma and tissues. The study showed that potassium bromate increased the levels of oxidative enzymes leading to oxidative stress. This effect was attenuated by C. Olitorius demonstrating its protective effect on the KBrO3-induced oxidative stress.\

Clinical Investigation of French Maritime Pine Bark Extract on Attention-Deficit Hyperactivity Disorder as compared to Methylphenidate and Placebo: Part 2: Oxidative Stress and Immunological Modulation

To evaluate the effect of French Maritime Pine Bark Extract (PBE; Pycnogenol®) on immune, oxidative stress and neurochemical biomarkers in paediatric Attention-Deficit Hyperactivity Disorder (ADHD) as compared to methylphenidate (MPH) and placebo. Paediatric ADHD patients (n = 88, 70 % male, mean age 10.1 years) were randomised (placebo (n = 30), PBE (n = 32) and MPH (n = 26)) receiving 20 mg/day if < 30 kg or 40 mg/day if ≥ 30 kg PBE, or 20 mg/day if < 30 kg or 30 mg/day if ≥ 30 kg MPH for 10 weeks. In the oxidative stress pathway, catalase (CAT) activity was nominally significant different in the PBE group with a p-value of 0.025 whereas the immunity biomarkers IgA and IgG2 were nominally significant different after MPH treatment with a p-value of 0.028 and 0.017 respectively, compared to baseline. Serum Neuropeptide Y (NPY) levels and weight were significantly lower after 10-weeks MPH. Loss of appetite and weight loss was observed for MPH, whereas no differences in NPY concentrations and a significant weight gain, which is to be an expected physiological process in this age group, was noticed for PBE. Firm evidence that PBE increases antioxidant levels, reduces oxidative damage and improves immune status in general as compared to placebo or MPH could not be obtained.

Isolation and characterization of fucoidan from four brown algae and study of the cardioprotective effect of fucoidan from Sargassum wightii against high glucose-induced oxidative stress in H9c2 cardiomyoblast cells.

Oxidative stress plays a vital role in the initiation and progression of diabetic cardiomyopathy (DCM). Increased cardiac dysfunction and apoptosis in DCM are independent factors associated with hypertension or coronary artery disease. Fucoidan, a class of sulfated polysaccharides, is widely used as food supplements and reported to have various pharmacological properties. However, the pharmacological property of Indian seaweeds remains unexplored. The present study is focused on isolating and characterizing the fucoidan from four brown seaweeds such as Sargassum wightii (SwF), Sargassum swartzii (SsF), Sargassum polycystum (SpF), Turbinaria ornata (ToF), and aimed to investigate cardioprotective effect of fucoidan against High Glucose (HG) induced oxidative stress in H9c2 cells. The mild acid hydrolysis method was used to isolate crude fucoidan from four brown seaweeds purified by the FPLC system. The biochemical composition analysis showed that SwF had a high content of fucoidan and sulfate, followed by SsF, SpF, and ToF. Further, FTIR, XRD, NMR, and SEM analysis confirmed the isolated fucoidan structures. SwF showed higher DPPH activity compared to another isolated fucoidan. In vitro studies with SwF revealed significantly decreased cytotoxicity, prevented the loss of MMP, reduced lipid peroxidation, and increased cellular enzymatic and non-enzymatic activity. qRT-PCR results showed SwF significantly upregulated the Nrf2, HO-1, NQO1, and Bcl2 and down-regulated the Bax and Caspase-3 mRNA expression compared to HG-treated cells. In conclusion, SwF could be used to develop functional foods for diabetic-mediated CVD complications compared to another isolated fucoidan. PRACTICAL APPLICATIONS: Bioactive carbohydrates have gained significant interest among researchers to improve human health. The biomedical field showed great interest in seaweed research in managing various diseases. In particular, seaweeds contain many bioactive compounds because of their chemical and biological diversity. Despite the various beneficial effects of fucoidan in CVD, the therapeutic potential of Indian seaweeds remains largely unexplored. Hence, this study isolated fucoidan from four brown seaweeds and studied their bioactive properties. Results revealed that SwF showed higher free radical scavenging activity compared to another isolated fucoidan. Therefore, SwF was selected for the in vitro study. SwF increased the cytoprotection through increasing antioxidant levels against oxidative stress in H9c2 cells. Staining analysis showed SwF increased cellular protection via inhibiting ROS protection and increasing MMP. Overall, fucoidan from SwF could be developed as a functional food for CVD.

A Lactobacilli diet that confers MRSA resistance causes amino acid depletion and increased antioxidant levels in the C. elegans host.

Probiotic bacteria are increasingly popular as dietary supplements and have the potential as alternatives to traditional antibiotics. We have recently shown that pretreatment with Lactobacillus spp. Lb21 increases the life span of C. elegans and results in resistance toward pathogenic methicillin-resistant Staphylococcus aureus (MRSA). The Lb21-mediated MRSA resistance is dependent on the DBL-1 ligand of the TGF-β signaling pathway. However, the underlying changes at the metabolite level are not understood which limits the application of probiotic bacteria as timely alternatives to traditional antibiotics. In this study, we have performed untargeted nuclear magnetic resonance-based metabolic profiling. We report the metabolomes of Lactobacillus spp. Lb21 and control E. coli OP50 bacteria as well as the nematode-host metabolomes after feeding with these diets. We identify 48 metabolites in the bacteria samples and 51 metabolites in the nematode samples and 63 across all samples. Compared to the control diet, the Lactobacilli pretreatment significantly alters the metabolic profile of the worms. Through sparse Partial Least Squares discriminant analyses, we identify the 20 most important metabolites distinguishing probiotics from the regular OP50 food and worms fed the two different bacterial diets, respectively. Among the changed metabolites, we find lower levels of essential amino acids as well as increased levels of the antioxidants, ascorbate, and glutathione. Since the probiotic diet offers significant protection against MRSA, these metabolites could provide novel ways of combatting MRSA infections.

A Newly Synthesized Derivative and a Natural Parent Molecule: Which Would Be More Beneficial as a Future Antitumor Candidate? Docking and In Vivo Study.

Seeking for new effectual anticancer drugs is of great importance. In this study, a newly synthesized and well-characterized chromene derivative (ethyl 2-amino-4-phenyl-4H-benzo(h)chromene-3-carboxylate) "C" was prepared. Molecular docking studies were done. The new compound "C" in compare to the natural parent Quercetin "Q," as a well-known natural chromene derivative with antioxidant and antitumor activities, were tested for their antitumor activity against Ehrlich ascites carcinoma (EAC)-bearing mice. Both reduced ascites volume, decreased viable EAC cells, and prolonged EAC-bearing mice life span. They normalized troponin, creatine kinase-MB, lactate dehydrogenase, and urea levels, reversed liver enzyme activities towards normal, and increased antioxidant levels while reduced tumor necrosis factor-alpha (TNF-α) levels. Compared to each other, the new synthetic derivative "C" showed stronger antineoplastic effects than the natural parent "Q" may via the anti-inflammatory activities. Therefore, the newly synthesized chromene derivative is more promising as a future antitumor candidate than the natural parent molecule "Quercetin." Finally, our results encourage researchers to pay more attention to developing more novel natural-based derivatives that would be more beneficial as future therapeutics than their natural parents.

A new peptide originated from amphibian skin alleviates the ultravioletB-induced skinphotodamage.

Although amphibian-derived bioactive peptides have attracted increasing attention for their potential use in the treatment of photodamage, research is still in its infancy. In this study, we obtained a new antioxidant peptide, named OA-GI13 (GIWAPWPPRAGLC), from the skin of the odorous frog Odorrana andersonii and determined its effects on ultraviolet B (UVB)-induced skin photodamage as well as its possible molecular mechanisms. Results showed that OA-GI13 directly scavenged free radicals, maintained the viability of hydrogen peroxide-challenged keratinocytes, promoted the release of superoxide dismutase, catalase, and glutathione, and reduced the level of lactate dehydrogenase. Furthermore, topical application of OA-GI13 in mice alleviated dorsal skin erythema and edema and protected the skin against UVB irradiation by increasing antioxidant levels and decreasing peroxide, malondialdehyde, and 8-hydroxydeoxyguanosine levels. OA-GI13 also alleviated oxidative stress injury in vivo and in vitro, possibly by inhibiting p38 protein phosphorylation. Our study confirmed the anti-photodamage effects of this novel amphibian-derived peptide, thus providing a new molecule for the development of drugs and topical agents for the treatment of skin photodamage.

Bergenin alleviates Diabetic Retinopathy in STZ-induced rats.

Diabetic retinopathy (DR) is the key cause of blindness and visual impairment in diabetes patients around the world.The high levels of oxidative stress in diabetes patients cause diabetic retinopathy. In addition to being an antioxidant, Bergenin also works as an immunosuppressant, an anti-inflammatory, and anticarcinogenic against hepatocarcinoma. This study examined the effects of Bergenin on diabetic retinopathy rats, using Streptozotocin (STZ) intraperitoneally to induce diabetes in rats. The animals were divided into four groups (n = 6), including a normal control (Group I), diabetic control (Group II), Bergenin (25mg/kg) (Group III), and metformin (350mg/kg) (Group IV). As previously mentioned, each animal received treatment for 60days. To induce DR, rats were administered STZ (60mg/kg) intraperitoneally for 60days. Standard methods were utilized to measure the body weight of rats, blood glucose levels. We measured lipid profiles (Triglycerides, cholesterol, LDL, and HDL), inflammatory markers, and antioxidant levels with their respective kits. Analysis of retinal tissue morphometry and MMP-9, VEGF, and MCP-1 levels in serum was performed. Our research examined the expression levels of target genes (TNF-α, IL-1β, and IL-6) using RT-PCRanalysis. STZ-induced animals that were treated with Bergenin had less food intake, lower blood glucose, and improved bodyweight. Bergenin significantly suppressed levels of pro-inflammatory cytokines, cholesterol, TG, LDL, AI, MMP-9, VEGF, and MCP-1 and increased the level of HDL and antioxidant enzymes in STZ-induced DR rats. As well as increasing antioxidant levels, reducing retinal thickness, and increasing cell numbers, Bergenin also lessened DR remarkably. The results of this study demonstrated that Bergenin effectivelyinhibited STZ-induced DR in rats.

Effect of different LED light quality combination on the content of vitamin C, soluble sugar, organic acids, amino acids, antioxidant capacity and mineral elements in green onion (Allium fistulosum L.)

The effects of blue-white, green-white, yellow-white, and red-white light combinations on the nutrient composition and antioxidant capacity of pseudo-stems and leaves of ‘Yuanzang’ green onion were investigated using light-emitting diodes (LEDs) with precise modulation of light quality, using white light as the control. The results showed that the leaf pigment, vitamin C, soluble sugar, organic acids, free amino acids, mineral elements, and antioxidant levels were significantly higher in green onion under blue-white combined light treatment, followed by white and red-white combined light, while green-white and yellow-white combined light significantly reduced fruit quality and antioxidant capacity. In conclusion, supplementation with blue LED light was the most effective light condition to improve palatability, nutritional value, and storage resistance of green onion by enhancing various nutrients in the plants, increasing antioxidant levels, and delaying plant aging.

Effects of pepper extract in suckling lamb feed: growth performance, metabolism, and oxidative responses

Abstract Our objective was to determine whether the inclusion of pepper extract would improve health in suckling lambs, stimulating antioxidant activity, and improving performance. We used Lacaune lambs distributed in four treatments, with four repetitions per treatment and three lambs per repetition: control group (T0) and treatments T1, T2, and T3 that received 200, 400, and 800 mg/kg of pepper extract, respectively. Groups T1 and T2 consumed more significant amounts of silage than group T0, and animals from group T1 consumed more concentrate and, consequently, consumed more solids. The addition of pepper extract enhanced growth performance, with the lowest dose (T1) giving rise to the most significant weight gain, average daily gain, and body weight, compared to T0. Regression analysis showed that the optimum point for pepper extract supplementation was 301.5 mg/kg. The levels of total protein and globulins were significantly higher for animals supplemented with pepper extract (day 28) than the control; the concentrations of albumin and urea increased over time but did not differ significantly among treatments. Serum glucose levels decreased significantly over time; however, the groups supplemented with pepper extract showed higher concentrations than group T0. The hematocrit was significantly higher in groups fed pepper extract; hemoglobin concentrations were also more significant, increasing over time in both groups. The groups that consumed the pepper extract had higher leukocyte counts due to greater lymphocytes and neutrophils. Levels of non-protein thiols increased significantly over time, while lipid peroxidation levels decreased significantly in all groups. The concentrations of reactive oxygen species significantly decreased in the serum of group T3 animals, those fed with pepper extract (day 28), compared to the control. In general, the addition of pepper extract in lamb feed can enhance weight gain, increase antioxidant levels, and stimulate the production of leukocytes and globulins in lambs.

CARTILAGE-SPECIFIC SIRT6 LOSS INCREASES CARTILAGE DAMAGE IN A SURGERY-INDUCED OA MOUSE MODEL

Purpose: SIRT6 is a nuclear localized, NAD+ dependent histone deacetylase that regulates many age-associated processes, including longevity. Our recently published data indicates that active SIRT6 is a critical regulator of cartilage redox balance by increasing antioxidant levels (Prx1, Srx, Nrf2) and decreasing the levels of the pro-oxidant, TXNIP. Importantly, our data also demonstrates that SIRT6 activity declines with age. To build on these findings in vivo, this study aimed to define the effect of Sirt6 loss on the development of DMM-induced OA in mice.

Expanding arsenal against diabetes mellitus through nanoformulations loaded with glimepiride and simvastatin: A comparative study

Type 2 diabetes mellitus is one of the most common and life-threatening diseases found across the globe. It occurs due to insulin resistance (IR). Major causes of IR include obesity, sedentary life style and hyperlipidemia. Glimepiride (GLM) is one of the most common oral sulphonyl ureas that is being used to treat diabetes and Simvastatin (SIM) is one of the most common statins that is used to treat hyperlipidaemia. However, both the drugs suffer from dissolution rate limited oral bioavailability. Hence, the aim of present study was to develop two different nanoformulations viz. nanosuspension and self-nanoemulsifying drug delivery systems (SNEDDS) and evaluate their potential in treating type 2 diabetes mellitus on streptozotocin (STZ) induced rats. In the present study two such drugs, GLM and SIM were co-formulated into nanosuspension (NS) as well as self-nanoemulsifying drug delivery systems (L-SNEDDS). Both formulations were spray dried for solidification and evaluated for their antidiabetic potential against high fat diet and streptozotocin induced rat model. The study showed significant (p < 0.05) decrease in lipid/cholesterol and blood glucose levels and significant increase in antioxidant levels in the rats treated with NS and SNEDDS containing the drugs alone as well as their combination as compared to their unprocessed forms. However, the efficacy was more prominent in case of combination possibly due to dual benefits i.e., decrease in IR due to statin and control of blood glucose level. Among NS and SNEDDS, NS was found more efficacious than that of the SNEDDS possibly due to higher enhancement of oral bioavailability in case of NS.

Fertility Potential of Freshly Isolated Adipose Tissue-derived Stromal Cells and Bone Marrow Mesenchymal Stromal Cells in Premature Ovarian Failure

Background: Failure to attain pregnancy or even miscarriage leads to a challenging type of infertility which is premature ovarian failure (POF). Stem cells have the ability to repair ovarian damage; adipose tissue-derived stromal cells (AT-SCs) and bone marrow mesenchymal stromal cells (BM-MSCs) have demonstrated promising regenerative abilities in several diseases, including POF. Methods: Various experiments were performed to prove the ability of AT-SCs and BM-MSCs in restoring ovarian functions; a total of 20 rats were randomly selected and assigned to four experimental groups with 5 rats in each group; 1st untreated, 2nd cyclophosphamide and busulfan, 3rd cyclophosphamide and busulfan + AT-SCs, and 4th cyclophosphamide and busulfan + BM-MSCs treated. Results: Groups 3 and 4 showed a restoration of ovarian functions in the form of an increase in weight (including body weight and ovarian weight), anti-mullerian hormone (AMH) and estradiol (E2) level, a decrease in follicle stimulating hormone (FSH) serum levels and an increase in antioxidant level of glutathione (GSH) and superoxide dismutase (SOD) in comparison with group 2. Histochemistry analysis demonstrated normal tissue distribution in the 3rd and 4th groups compared to 2nd group. Conclusions: We demonstrated the ability of AT-SCs and BM-MSCs to restore ovarian functions in females with POF.

Astrocytic glycogen mobilization participates in salvianolic acid B-mediated neuroprotection against reperfusion injury after ischemic stroke

Astrocytic glycogen serves as an important glucose reserve, and its degradation provides extra support for neighboring neurons during energy deficiency. Salvianolic acid B (SAB) exerts a neuroprotective effect on reperfusion insult after cerebrovascular occlusion, but the effect of SAB on astrocytic glycogen and its relationship with neuroprotection are not completely understood. Here, we knocked down astrocyte-specific glycogen phosphorylase (GP, the rate-limiting enzyme in glycogenolysis) in vitro and in vivo and investigated the changes in key enzymes in glycogen metabolism by performing immunoblotting in vitro and immunofluorescence in vivo. Neurobehavioral and morphological assessments were conducted to uncover the outcomes during brain reperfusion. SAB accelerated astrocytic glycogenolysis by upregulating GP activity but not GP expression after reperfusion. Suppression of astrocytic glycogenolysis weakened SAB-mediated neuroprotection against the reperfusion insult. In addition, activation of glycogenolysis by SAB contributed to the survival of astrocytes and surrounding neurons by increasing antioxidant levels in astrocytes. Our data reveal that astrocytic GP represents an important metabolic target in SAB-induced protection against brain damage after cerebrovascular recanalization.