Increased GSH Levels Research Articles

Relationships between Serum Biomarkers of Oxidative Stress and Tobacco Smoke Exposure in Patients with Mental Disorders.

The role of cigarette smoking as an aggravating factor of systemic oxidative stress in patients with mental disorders has not been extensively investigated, although significantly higher rates of smoking are recorded in these subjects in comparison with the general population. In the present study, we tested the hypothesis that smoking might be an exacerbator of systemic oxidative stress, being directly correlated with the degree of exposure to tobacco smoke. We analyzed, in 76 adult subjects from a public health care unit, the relationships between serum cotinine levels as a marker of tobacco smoke exposure, and three biomarkers of oxidative stress: the serum glutathione (GSH), the advanced oxidation protein products (AOPPs), and the total serum antioxidant status (FRAP). The results indicate that the degree of tobacco smoke exposure was inversely associated with GSH levels in both passive and active smokers, suggesting that smoke particulate components' toxicity is associated with a systemic GSH depletion. Paradoxically, the lowest AOPP levels which were positively associated with GSH, were recorded in active smoking patients whereas in passive smokers individual values of AOPPs decreased along with the increase in GSH levels. Our data suggest that an enhanced inhalation of particulate constituents of cigarette smoke could induce critical changes in systemic redox homeostasis and GSH can no longer exert its antioxidant role.

Evaluation of the immunomodulatory, antioxidant, and histopathological effects of Cymbopogon schoenanthus essential oil extract on kidney and spleen in BALB/C Mice

This study aimed to evaluate the impact of C. schoenanthus essential oil (CSEO) on the immune system, antioxidant balance, and histological changes in the kidney and spleen of female BALB/C mice. The chemical composition of CSEO was analyzed using GC-MS. Twenty-nine compounds were identified, representing 99.04% of the total detected. The main components were Piperitone (47.93%), Elemol (11.91%), 2-Carene (10.69%), β-eudesmol (7.67%), α-eudesmol (5.12%), and γ-eudesmol (4.24%). For bioassay, the mice were divided into three groups: control, 0.5% CSEO (G1), and 1% CSEO (G2). The effects of CSEO on various markers, including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), urea, creatinine, and cytokines (IL-4, TNF-α, and TGF-β1), were evaluated. Additionally, kidney and spleen histopathological examinations were conducted. The treatment groups showed a significant increase in IL-4, TNF-α, and TGF-β1 levels compared to the control group, except for G1, which showed a non-significant decrease in TGF-β1 levels. Group 2 exhibited a significant increase in MDA levels compared to the control group, while group 1 had a nonsignificant increase. Both treatments showed a significant increase in GSH levels, while SOD and CAT levels showed a non-significant increase in G2 and a non-significant decrease in G1. Urea levels showed a non-significant increase, while creatinine levels were significantly decreased in G2 and non-significantly decreased in G1 compared to the control group. The histopathological examinations revealed congested red pulp with activated hematopoiesis and focal fibrosis in spleen sections of both G1 and G2. The study suggests that medicinal herbs such as CSEO need to be used with caution, and their effects should be evaluated carefully, especially in terms of dose-dependent effects. The results indicate that high doses of CSEO may increase the levels of some cytokines and antioxidants and have harmful effects on kidney architecture, congested red pulp, and fibrosis with increased hematopoiesis. Therefore, the random use of medicinal herbs may have harmful effects and needs to be carefully controlled to ensure safe use.

Effect of Melinjo Seed Extract on GSH Levels of Hyperuricemic Wistar Rats

Background: Hyperuricemia is a condition where uric acid levels are above normal. The biosynthesis of uric acid by the enzyme xanthine oxidase (XO) produces free radicals that cause oxidative stress. Oxidative stress lowers cellular GSH levels. Gnetum gnemon L. or melinjo seeds contain stilbenoids and flavonoids that can act as natural XO inhibitors. Objective: To study the effect of melinjo seed extract on GSH levels.Methods: This research was a true experimental with pre and post-test controlled group design. Thirty six male wistar rats were randomly divided into 6 groups consisting of a healthy control (KS), negative control (K1), positive control (K2), treatment 1 (P1) extract 250 mg/kgBW, treatment 2 (P2) extract 500 mg/kgBW, treatment 3 (P3) extract 2000 mg/kgBW. Hyperuricemia was induced by the administration of Maggie® block broth and potassium oxonate. Measurement was carried out on the 21st and 35th day of treatment, then analyzed using Paired-Sample T Test, continued with One-Way Anova test and Post Hoc LSD test. Results: Administration of melinjo seed extract at P1, P2, and P3 significantly increased GSH levels (P<0.05) from 1.23±0.10 to 1.55±0.16; 1.22±0.06 to 1.73±0.16; and 1.21±0.08 to 1.88±0.08. There was significant difference between the three doses with a dose of 250 mg/kgBW melinjo seed extract being more effective than allopurinol 90 mg/kgBW. Conclusion: Melinjo seed extract could increase GSH levels with the most effective dose of 250 mg/kgBB.

Vitexin ameliorated diabetic nephropathy via suppressing GPX4-mediated ferroptosis

Diabetic nephropathy (DN) is common complication of diabetes. Ferroptosis is an atypical form of iron-dependent modulated necrosis and have been proven to contribute to the progress of diabetic nephropathy. Vitexin, a flavonoid monomer derived from medicinal plants that has various biological activities including anti-inflammatory and anticancer effects, has not been investigated in diabetic nephropathy studies. However, whether vitexin has a protective effect on diabetic nephropathy remains unclear. In this study, the roles and mechanism of vitexin on alleviating DN were explored in vivo and in vitro. The protective effect of vitexin in diabetic nephropathy were evaluated by in vitro and in vivo experiment. In this research, we validated that vitexin protect HK-2 against HG-induced damage. Besides, vitexin pretreatment also reduced fibrosis (Collagen type I Col I, TGF-β1). Furthermore, vitexin inhibited ferroptosis induced by HG, accompanied by changes of morphological, decrease of ROS, Fe2+ and MDA, and increased GSH levels. Meanwhile, vitexin up-regulated the protein expression of GPX4 and SLC7A11 in HG-induced HK-2 cells. Moreover, knockdown of GPX4 by shRNA migrated the protective effect of vitexin on HG-challenged HK-2 and reversed the ferroptosis induced by vitexin. Consistent with in vitro, vitexin alleviated renal fibrosis, damage and ferroptosis in DN rat. In conclusion, our findings revealed that vitexin could alleviate diabetic nephropathy by attenuated ferroptosis via activating GPX4.

Knockdown of SHP2 attenuated LPS-induced ferroptosis via downregulating ACSL4 expression in acute lung injury.

Acute lung injury (ALI) is a complex disease with a high mortality. Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) is a protein tyrosine phosphatase that participates in pathogenesis of multiple diseases. Nevertheless, the role of SHP2 in ALI remains unknown. The in vivo and in vitro lipopolysaccharide (LPS)-induced ALI models were successfully established. The histopathological changes were evaluated by hematoxylin and eosin staining. The vascular permeability of lungs was assessed by Evans blue assay. The expression of ACSL4 and SHP2 was detected by western blot and qRT-PCR assay. The lactate dehydrogenase (LDH) activity, malondialdehyde (MDA), iron, and glutathione (GSH) levels were measured by commercial kits. The SHP2 was upregulated in LPS-induced ALI mice and LPS-stimulated MLE-12 cells. In loss-of function experiment, the knockdown of SHP2 attenuated LPS-induced lung injury, microvessels damage, pulmonary edema, and increase of lung vascular permeability in vivo. Mechanically, shSHP2-rescued LPS induced increase in LDH activity, MDA, and iron levels, and decrease in GSH levels, as well as the accumulation of reactive oxygen species in vivo and in vitro, leading to an alleviation of LPS-induced ferroptosis. Notably, shSHP2 reduced the expression of Acyl-CoA synthetase long-chain 4 (ACSL4). In the rescued experiments, overexpression of ACSL4 abolished the shSHP2-induced reduction of LDH activity, MDA, and iron levels, and increase in GSH levels, thereby aggravating the LPS-induced ferroptosis. These findings concluded that the knockdown of SHP2 attenuated LPS-induced ferroptosis via downregulation of ACSL4 expression in ALI, providing a novel sight for ALI treatment.

Protective effect of Anneslea fragrans ethanolic extract against CCl4-induced liver injury by inhibiting inflammatory response, oxidative stress and apoptosis.

Anneslea Fragrans Wall. (AF) is a medicinal and edible plant distributed in China. Its leaves and bark generally used for the treatments of diarrhea, fever, and liver diseases. While its ethnopharmacological application against liver diseases has not been fully studied. This study was aimed to evaluate the hepatoprotective effect of ethanolic extract from A. fragrans (AFE) on CCl4 induced liver injury in mice. The results showed that AFE could effectively reduce plasma activities of ALT and AST, increase antioxidant enzymes activities (SOD and CAT) and GSH level, and decrease MDA content in CCl4 induced mice. AFE effectively decreased the expressions of inflammatory cytokines (IL-1β, IL-6, TNF-α, COX-2 and iNOS), cell apoptosis-related proteins (Bax, caspase-3 and caspase-9) and increased Bcl-2 protein expression via inhibiting MAPK/ERK pathway. Additionally, TUNEL staining, Masson and Sirius red staining, immunohistochemical analyses revealed that AFE could inhibit the CCl4-induced hepatic fibrosis formation via reducing depositions of α-SMA, collagen I and collagen III. Conclusively, the present study demonstrated that AFE had an hepatoprotective effect by MAPK/ERK pathway to inhibit oxidative stress, inflammatory response and apoptosis in CCl4-induced liver injury mice, suggesting that AFE might be served as a hepatoprotective ingredient in the prevention and treatment of liver injury.

Investigation of Oxidative/Antioxidant Effects of Turmeric (Curcuma longa L.) Supplementation on Heart Tissue in Adult Rats

n present study, the effects of curcumin supplementation on oxidative stress and antioxidant defense system in heart tissue in adult rats were investigated. Sixteen rats (8-weeks-old) were selected and divided into two groups. The first group is the experimental group and these rats (n=8) were gavaged with curcumin, dissolved in corn oil, at a dose of 300 mg/kg per day for 28 days. The second group is the control group, rats in this group were given curcumin and equal amount of corn oil to eliminate the porter effect. Euthanasia was performed and total antioxidant capacity (TAS), total oxidant capacity (TOS), malondialdehyde (MDA) and glutathione (GSH) levels were analyzed from heart tissues. Curcumin supplementation resulted in significantly increased GSH levels(P0.05). The total antioxidant capacity (TAS) and total oxidant capacity (TOS) ratios were found to be statistically significant. In the other group supplemented with curcumin, MDA levels tended to decrease compared to the control group, and there was no statistically significant difference between the two groups. Curcumin supplementation protects the heart tissue against oxidative damage and strengthens the antioxidant defense system in adult rats.

Downregulation of Bmal1 Expression in Celiac Ganglia Protects against Hepatic Ischemia-Reperfusion Injury.

Hepatic ischemia-reperfusion injury (HIRI) significantly contributes to liver dysfunction following liver transplantation and hepatectomy. However, the role of the celiac ganglion (CG) in HIRI remains unclear. Adeno-associated virus was used to silence Bmal1 expression in the CG of twelve beagles that were randomly assigned to the Bmal1 knockdown group (KO-Bmal1) and the control group. After four weeks, a canine HIRI model was established, and CG, liver tissue, and serum samples were collected for analysis. The virus significantly downregulated Bmal1 expression in the CG. Immunofluorescence staining confirmed a lower proportion of c-fos+ and NGF+ neurons in TH+ cells in the KO-Bmal1 group than in the control group. The KO-Bmal1 group exhibited lower Suzuki scores and serum ALT and AST levels than the control group. Bmal1 knockdown significantly reduced liver fat reserve, hepatocyte apoptosis, and liver fibrosis, and it increased liver glycogen accumulation. We also observed that Bmal1 downregulation inhibited the hepatic neurotransmitter norepinephrine, neuropeptide Y levels, and sympathetic nerve activity in HIRI. Finally, we confirmed that decreased Bmal1 expression in CG reduces TNF-α, IL-1β, and MDA levels and increases GSH levels in the liver. The downregulation of Bmal1 expression in CG suppresses neural activity and improves hepatocyte injury in the beagle model after HIRI.

Eel Oil Attenuates Acetaminophen-Induced Acute Liver Injury Through Inhibition of Oxidative Stress in Rats

Health practitioners all over the world have studied liver injury caused by drug side effects. Excessive production of free radicals causes cell damage, which has implications for pathological conditions in both humans and animals. Omega-3 fatty acids are a component of fish that can work as hepatoprotective agents. Eel (Anguilla bicolor) is known to contain omega-3 including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This study aimed to evaluate the hepatoprotective activity of eel oil on rats via inhibiting oxidative stress. Methods: Acetaminophen-induced male Wistar rats were used as liver injury experimental models. Rats were divided into 5 groups, namely normal control, negative control, positive control (silymarin, 100 mg/kg), and two groups of eel oil dose (2000 mg/kg and 4000 mg/kg). The study was conducted for 14 days. The levels of serum glutamic pyruvic transaminase (SGPT), serum glutamic pyruvic transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, albumin, Malondialdehyde (MDA), and glutathione (GSH) levels of the liver organ were measured. The data were analyzed using statistics and analysis of variance. Results: The study showed that eel fish oil can reduce SGPT and total bilirubin levels of male Wistar rats induced by acetaminophen. Eel oil at a dose of 4000 mg/kg could significantly reduce SGPT and liver bilirubin levels in male Wistar rats (p<0.05). Eel oil is effective in reducing malondialdehyde (MDA) levels and increasing glutathione (GSH) levels at a dose of 2000 mg/kg. Conclusion: Eel oil has hepatoprotective activity by inhibiting SGPT, total bilirubin, MDA, and increasing GSH levels in rats.

Effect of the Anticancer Drug Doxorubicin (Adriamycin) on Antioxidant Studies and Ultrastructural Investigation in the Liver, Kidney, and Heart Tissues of Male Rats

Doxorubicin is a well-known antineoplastic agent that has proved to be successful in the treatment of various types of cancer. I used rats as the model to evaluate the effect of doxorubicin on antioxidant studies and ultrastructural investigations in the liver, kidney, and heart tissues. Male albino rats were given 1.0 mg/kg body weight of the anticancer drug doxorubicin intraperitoneally three times a week for 52 days. This was for a total of 18 doses. Control animals received 52 doses of 0.5 ml of saline over 52 days. The body weights of rats injected with doxorubicin experienced a significant decrease after the last dose compared to the control group of rats. In this study, the weights of the heart, kidneys, and liver were measured. Except for cardiac tissues, the protein content in the aforementioned tissues in treated rats was significantly different from the control. Glutathione (GSH) levels in the kidneys of experimental rats were not significantly lower (7.946 ± 0.781) compared to controls (8.06 ± 0.74) but there was a non-significant increase in GSH levels in the liver (17.095 ± 1.066) compared to controls (13.8 ± 1.3). In addition, the mean GSH levels in doxorubicin-treated hearts were significantly lower (7.9462 ± 0.781) compared to controls (8.06 ± 0.74). Lipid peroxidation (Lpx) and malondialdehyde content (MDA), a marker of lipid peroxidation, were found in much lower concentrations in the liver organ of the doxorubicin-treated group (0.0162 ± 0.00086) as compared to (0.20 ± 0.02) controls, and MDA content in the kidney was decreased (0.0239 ± 0.0003) compared to control rats (0.31 ± 0.03), as well as heat production (0.0398 ± 0.00097) compared to (47.451 ± 1.708) controls. Glutathione reductase (GR) levels were significantly elevated in the same tissue treatment group. Glutathione-S-Transferase (G-S-T) activity was assessed and significantly increased in all tissues in the doxorubicin model. Glutathione peroxidase (GPx) activity showed a significant decrease in all the above tissues after doxorubicin injection. The catalase (CAT) activity of doxorubicin was greatly increased in one treated rat. In the doxorubicin-treated group, levels of cytochrome p450 (CYTp450) were significantly decreased in liver and kidney tissue and significantly elevated in heart tissue. After doxorubicin treatment, cytochrome b5 (CYTb5) levels in liver tissues increased significantly (837.177± 61.197) compared to controls (615 ± 37.0), and the contents of cytochrome b5 in rats' kidneys increased significantly (447.685 ± 35.215) compared to controls (2605.5± 259.2). and cytochrome b5 in heart tissues was lower (165.352± 8.7) when compared to controls (88± 0.4). The results showed that there were few obvious changes in histological, ultrastructural, and biochemical changes in liver tissue in the doxorubicin model. Long-term doxorubicin treatment in kidney tissue results in no significant changes at the light microscopic level, but the electron microscopic level reveals no change from a histological point of view.

Augmented nephroprotective effect of liraglutide and rabeprazole via inhibition of OCT2 transporter in cisplatin-induced nephrotoxicity in rats

AimsCisplatin, a widely used anticancer treatment, has a marked nephrotoxic effect. This nephrotoxic effect is linked to the triggering of oxidative stress, inflammation, activation of mitogen-activated protein kinase (MAPK) pathway as well as apoptosis. The purpose of the present research was to examine the possible ameliorative effect of liraglutide and/or rabeprazole on cisplatin-induced nephrotoxicity in rats and to underline the potential molecular pathways involved. Main methodsRats were divided into five groups: Control, cisplatin, liraglutide (200 μg/kg/day, i.p), rabeprazole (10 mg/kg/day, orally) and liraglutide + rabeprazole combination groups. All treatments were given for 7 days. Cisplatin was given as a single dose (7 mg/kg, i.p) at day 4 to induce nephrotoxicity in all groups except the control group. Key findingsTreatment with liraglutide and/or rabeprazole prior to cisplatin maintained the function and morphology of kidney via decreasing cisplatin renal uptake by significant inhibition of OCT2. Besides, they showed a significant increase in GLP-1 receptor expression. Liraglutide and/or rabeprazole significantly attenuated the levels of TNF-α. ICAM, NF-κB, and downregulated MAPK pathway proteins such as JNK, and ERK1/2. Moreover, they maintained oxidant antioxidant balance by decreasing MDA level and increasing GSH level and CAT activity. Additionally, liraglutide and/or rabeprazole exhibited antiapoptotic effect evidenced by the decreased caspase-3 level and Bax expression and the increased Bcl-2 expression. SignificanceThe current study showed that both liraglutide and rabeprazole exerted a nephroprotective effect against cisplatin-induced renal toxicity in rats. Interestingly, co-treatment with both drugs showed an augmented effect.

Honokiol reduces oxidative stress by activating the SIRT3-MnSOD2 pathway to alleviate hypertriglyceridemia-induced acute pancreatitis in rats

To determine how honokiol affects the sirtuin-3 (SIRT3)-MnSOD2 pathway and oxidative stress in rats with hypertriglyceridemia-induced acute pancreatitis (HTGP). Thirty 4-week-old male SD rats were randomly divided into two groups for normal feeding and high-fat feeding for 4 weeks, after which the rats with normal feeding were randomized into control group and acute pancreatitis (AP) group (n=6), and those with high-fat feeding were divided into hypertriglyceridemia group, HTGP group, and honokiol treatment group (n=6). In AP, HTGP, and honokiol groups, AP models were established by intraperitoneal injection of cerulean; in honokiol group, the rats received an intraperitoneal injection of 5 mg/kg honokiol 15 min after cerulean injection. Serum TG, IL-6, and TNF-α levels were measured 24 h after the treatments, and pathological changes in the pancreas were observed with HE staining; The levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione peroxidase (GSH) were measured, and SIRT3 and manganese superoxide dismutase (MnSOD2) expressions were detected using Western blotting and immunohistochemistry. Transmission electron microscopy was used to examine the ultrastructure of pancreatic acinar cells and mitochondria. Compared with the those with normal feeding, the rats with high-fat feeding had significantly elevated serum TG level (P < 0.05). The rat models of AP showed significantly increased serum levels of IL-6, TNF-α, and MDA and decreased GSH level and expressions of SIRT3 and MnSOD2, with obvious edema and inflammatory cell infiltration and enhanced ROS fluorescence intensity in the pancreas and ultrastructural damages of the acinar cells and mitochondria. In rats with HTGP, honokiol treatment significantly decreased serum levels of IL-6, TNF-α, and MDA, increased GSH level and SIRT3 and MnSOD2 expressions, reduced ROS production, and alleviated ultrastructural damage of the acinar cells and mitochondria in the pancreas. Honokiol reduce oxidative stress and alleviates pancreatic injuries in HTGP rats possibly by activating the SIRT3-MnSOD2 pathway.

The Emerging Importance of Cirsimaritin in Type 2 Diabetes Treatment.

Cirsimaritin is a dimethoxy flavon that has different biological activities such as antiproliferative, antimicrobial, and antioxidant activities. This study aims to investigate the anti-diabetic effects of cirsimaritin in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with cirsimaritin (50 mg/kg) or metformin (200 mg/kg) for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. Cirsimaritin reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group (p < 0.001). Cirsimaritin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats (p < 0.01). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with cirsimaritin compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 (p < 0.01 and p < 0.05, respectively) and pAMPK-α1 (p < 0.05) were upregulated following treatment with cirsimaritin. Cirsimaritin was able to upregulate GLUT2 and AMPK protein expression in the liver (p < 0.01, <0.05, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with cirsimaritin compared to the vehicle controls (p < 0.001). Cirsimaritin reduced MDA, and IL-6 levels (p < 0.001), increased GSH levels (p < 0.001), and reduced GSSG levels (p < 0.001) in diabetic rats compared to the vehicle control. Cirsimaritin could represent a promising therapeutic agent to treat T2D.

Remote ischemic preconditioning protects against spinal cord ischemia–reperfusion injury in mice by activating NMDAR/AMPK/PGC-1α/SIRT3 signaling

BackgroundTo study the protective effects of delayed remote ischemic preconditioning (RIPC) against spinal cord ischemia–reperfusion injury (SCIRI) in mice and determine whether SIRT3 is involved in this protection and portrayed its upstream regulatory mechanisms.MethodsIn vivo, WT or SIRT3 global knockout (KO) mice were exposed to right upper and lower limbs RIPC or sham ischemia. After 24 h, the abdominal aorta was clamped for 20 min, then re-perfused for 3 days. The motor function of mice, number of Nissl bodies, apoptotic rate of neurons, and related indexes of oxidative stress in the spinal cord were measured to evaluate for neuroprotective effects. The expression and correlation of SIRT3 and NMDAR were detected by WB and immunofluorescence. In vitro, primary neurons were exacted and OGD/R was performed to simulate SCIRI in vivo. Neuronal damage was assessed by observing neuron morphology, detecting LDH release ratio, and flow cytometry to analyze the apoptosis. MnSOD and CAT enzyme activities, GSH and ROS level were also measured to assess neuronal antioxidant capacity. NMDAR-AMPK-PGC-1α signaling was detected by WB to portray upstream regulatory mechanisms of RIPC regulating SIRT3.ResultsCompared to the SCIRI mice without RIPC, mice with RIPC displayed improved motor function recovery, a reduced neuronal loss, and enhanced antioxidant capacity. To the contrary, the KO mice did not exhibit any effect of RIPC-induced neuroprotection. Similar results were observed in vitro. Further analyses with spinal cord tissues or primary neurons detected enhanced MnSOD and CAT activities, as well as increased GSH level but decreased MDA or ROS production in the RIPC + I/R mice or NMDA + OGD/R neurons. However, these changes were completely inhibited by the absence of SIRT3. Additionally, NMDAR-AMPK-PGC-1α signaling was activated to upregulate SIRT3 levels, which is essential for RIPC-mediated neuroprotection.ConclusionsRIPC enhances spinal cord ischemia tolerance in a SIRT3-dependent manner, and its induced elevated SIRT3 levels are mediated by the NMDAR-AMPK-PGC-1α signaling pathway. Combined therapy targeting SIRT3 is a promising direction for treating SCIRI.

Formulation Containing Phytosomes of Carotenoids from Nyctanthes arbor-tristis and Tagetes patula Protect D-galactose Induced Skin Aging in Mice

• Gel containing phytosomes of crocin rich extract(equivalent to crocin 1% w/w) obtained from Nyctanthes arbor-tristis and Lutein rich extract (equivalent to lutein 0.5%w/w) from Tagetes patula indicated • Entrapment of crocin and lutein was found to be (60.20% w/w) and (50.81% w/w) respectively. • Improved stability of crocin and lutein through preparation of Phytosomes • Significant (P<0.01) increase in thickness of dermal and epidermal layer • Significant increase (P<0.05) in glutathione level and decrease (P<0.01) in MDA level • Upregulation of expression of elastin and Collagen gene by 0.26 and 0.03 fold respectively : Carotenoids play important role in delay of aging process. Orange coloured tubular calyx of flowers of Nyctanthes arbor-tristis. contains crocin, an apocarotenoid which forms a major component of stigma of saffron. Due to presence of crocin in orange coloured tubular calyx of Nyctanthes arbor-tristis, it can be used as an economical substitute to saffron for its medicinal and cosmetic utilities. Lutein from flower petals of Tagetes patula L , is another popular carotenoid which has antioxidant effect and many health benefits. The carotenoids are highly unstable when exposed to atmosphere, hence in the present study crocin and lutein rich extracts were entrapped into phytosomes to improve stability and efficacy of topical preparation. : Oxidative stress is considered to be a major contributor to the process of aging. Carotenoids viz, Lutein and crocin, being powerful antioxidants, can delay aging of skin through upregulating col type I gene and elastin gene. The carotenoids have very low oxidation potential, due to which they get oxidized fast and protect oxidation of other compounds which make them highly unstable. One of the ways to improve stability of these phytoconstituents, is their entrapment in phytosomes. Preparation of phytosomes will have dual advantages of improving stability as well as bioavailability of molecule. : The phytosomes of Carotenoid rich extract of tubular calyx of Nyctanthes arbor-tristis L. and the petals of Tagetes patula L. (standardized for crocin and lutein content) were prepared using lipid film hydration technique and these phytosomes were then incorporated into gel base. The gel formulation was evaluated for stability as per ICH guidelines. Efficacy of formulation was evaluated by D-galactose induced aging model. Aging in skin was induced by administration of D-Galactose (100mg/kg b.w.s.c.) to albino mice for 42 days. The gel formulation was applied topically for 42 days. Then the effect of formulation on skin aging was evaluated by estimation of biochemical parameters viz. glutathione and malondialdehyde (MDA) and histopathological studies of treated skin samples. Also expression of COL type I and elastin genes was carried out from the skin samples by RT-PCR method. : Percent entrapment (%w/w) of crocin and lutein in phytosomes were found to be 60.20 and 50.81 respectively. Accelerated stability studies showed improvement in stability of carotenoids viz. crocin and lutein and the content of crocin and lutein in formulation was found in the range of 99.98 % w/w to 99.85%w/w at the end of three months. The formulation containing extract of Phytosomes of carotenoid rich extracts of Nyctanthes arbor-tristis L. and the petals of Tagetes patula L. exhibited potent antiaging activity through significant (p<0.05)increase in dermal and epidermal layers, and increase in GSH levels of skin as compared to the untreated group. The treatment with the gel formulation revealed upregulation of col type I and elastin genes. There was significant reduction in lipid peroxidation as revealed through reduction in MDA levels as compared to untreated group. : Crocin and lutein have potential to prevent skin aging via upregulation of COL type I gene and elastin gene. Upregulation of genes resulted into increase in the thickness of epidermal and dermal layer along with reduction in oxidative stress in skin. Entrapment of carotenoid rich extracts of Nyctanthes arbor-tristis and Tagetes patula in Phytosomes enhanced the stability and efficacy of the formulation.

A Combination of Acetate, Propionate, and Butyrate Increases Glucose Uptake in C2C12 Myotubes

Dietary fibers are subjected to saccharolytic fermentation by the gut microbiota, leading to the production of short chain fatty acids (SCFAs). SCFAs act as signaling molecules to different cells in the human body including skeletal muscle cells. The ability of SCFAs to induce multiple signaling pathways, involving nuclear erythroid 2-related factor 2 (Nrf2), may contribute to the redox balance, and thereby may be involved in glucose homeostasis. The aim of this study is to investigate whether SCFAs increase glucose uptake by upregulating the endogenous antioxidant glutathione (GSH) in C2C12 myotubes. C2C12 myotubes were exposed to 1, 5, or 20 mM of single (acetate, propionate, or butyrate) or mixtures of SCFAs for 24 h. Cytotoxicity, glucose uptake, and intracellular GSH levels were measured. 20 mM of mixture but not separate SCFAs induced cytotoxicity. Exposure to a mixture of SCFAs at 5 mM increased glucose uptake in myotubes, while 20 mM of propionate, butyrate, and mixtures decreased glucose uptake. Exposure to single SCFAs increased GSH levels in myotubes; however, SCFAs did not prevent the menadione-induced decrease in glucose uptake in myotubes. The effect of SCFAs on modulating glucose uptake in myotubes is not associated with the effect on endogenous GSH levels.

Comparative study on the impacts of visnagin and its methoxy derivative khellin on human lymphocyte proliferation and Th1/Th2 balance.

Visnagin is a phenolic and natural compound in turmeric and fenugreek, and its anti-inflammatory effect has been indicated. Therefore, this study aimed to investigate and compare the anti-inflammatory properties of visnagin and its methoxy derivative khellin on human lymphocytes. Human lymphocytes were treated with khellin, visnagin (10, 30, and 100µM), and dexamethasone (0.1mM) in the presence of phytohemagglutinin (PHA). The levels of cell proliferation, nitric oxide (NO), glutathione (GSH), malondialdehyde (MDA), and MDA/GSH ratio were measured using biochemistry methods. Furthermore, the mRNA levels of interferon-γ (IFN-γ), interleukin (IL)-4, and IL-10 were assessed using real-time PCR, while IFN-γ/IL-4(Th1/Th2), IFN-γ/IL-10(Th1/Treg), and IL-4/IL-10(Th2/Treg) ratios were made by dividing their exact values. In the PHA-stimulated group, GSH and IFN-γ/IL-4 levels were markedly diminished, but other variables were significantly elevated compared to the control group. Khellin and visnagin significantly declined the levels of cell proliferation, MDA, MDA/GSH ratio, and NO production. Khellin and visnagin concentration-dependently diminished IFN-γ and IL-4 levels and increased IL-10 levels compared to the PHA-stimulated group. Two higher concentrations of khellin and visnagin (30 and 100μM) considerably diminished the IFN-γ, IFN-γ/IL-10, and IL-4/IL-10 values compared to the PHA-stimulated group. However, 100µM of khellin and visnagin significantly increased GSH level compared to the PHA-stimulated group. In PHA-stimulated lymphocytes, representing Th2 dominant allergic diseases, khellin and visnagin provides more specific anti-oxidant, anti-inflammatory, and immunomodulatory functions than dexamethasone. In addition, the effects of khellin were more prominent than visnagin.

Antioxidant effect of ethanolic extract of Pleurotus Ostreatus on 4-hydroxy-2-nonenal (HNE) and glutathione (GSH) level in lung rats exposed to cigarette smoke

Background: Cigarette smoke can trigger oxidative stress. An alternative to overcome the harmful effects of cigarette smoke is through antioxidants. White oyster mushrooms (Pleurotus Ostreatusostreatus or P. ostreatus) are a source of exogenous antioxidants because many contain active compounds for potential antioxidants such as phenol and flavonoid compounds. The purpose of this study was to analyze the effect of ethanolic extract of Pleurotus P.ostreatus on 4-hydroxy-2-nonenal (HNE) and glutathione (GSH), as well as to analyze their correlation in the lung of Wistar male rats exposed to cigarette smoke. Methods: The study was a preclinical experiment conducted on 24 rats divided into four groups. The treatment was carried out for 42 days and antioxidant effects were assessed through levels of HNE and GSH in rat lungs. Groups were divided as follows: I- normal control, II- negative control, III and IV exposed to cigarette smoke for 60 minutes/day. Group III (treatment group) was treated with ethanolic extract of PleurotusP. ostreatus at 250 mg/kg BW rat/day, and group IV (comparison group) was treated with N-acetyl cysteine 600 mg /day. Data analysis used was one-way ANOVA and Kruskal Wallis test, and Spearmen rank correlation coefficient test. Results: The results showed that the group receiving ethanolic extract of PleurotusP. ostreatus had HNE levels of (44,18 ± 2,09 pg/mL) and GSH (0,04 ± 0,00 pg/mL) protein. This extract significantly increased GSH levels and inhibited the increase of HNE levels. Results of GSH (p≤0.01) showed significant results using one-way ANOVA. Conclusions: The ethanolic extract of P. ostreatus can prevent lipid peroxidation and decrease endogenous antioxidant levels in lung cells exposed to cigarette smoke. Ethanolic extract of PleurotusP. ostreatus has good antioxidant potential.

PHARMACODYNAMIC EVALUATION OF DIETARY SUPPLEMENTATION OF AVERRHOA CARAMBOLA FRUIT EXTRACT AGAINST LEAD ACETATE-INDUCED HEPATOTOXICITY IN RATS

Lead is a toxicant that may induce a wide range of social, biochemical, and physiological changes in humans. This study is undertaken to evaluate the pharmacodynamic effects of dietary supplementation of Averrhoa carambola, fruit extract (ACF) against lead acetate-induced hepatotoxicity in rats. Six groups of rats were used in this study namely, control, lead acetate (20 mg kg-1, ip), lead acetate (20 mg kg-1, ip) + 200 mg kg-1 silymarin orally (reference drug), lead acetate + 100 mg kg-1 ACF orally, lead acetate + 150 mg kg-1 ACF orally and lead acetate + 200 mg kg-1 ACF extract orally. All experimental groups except the control received the lead acetate by intraperitoneal route for 5 days and normal saline or silymarin or ACF by oral route employing an orogastric cannula for seven days. Lead intoxication leads to a significant increase in ALT and AST activities, malondialdehyde (MDA), and a significant decline in liver homogenate, reduced glutathione (GSH) level, and superoxide dismutase (SOD) activity. Different doses of ACF supplement, as well as silymarin, led to improving biochemical parameters of serum and liver and prohibited the lead acetate-induced significant changes in plasma and antioxidant status of the liver. ACF or silymarin supplement exhibited more antioxidant activity. Conclusively, the present work results reveals that the treatment of lead-intoxicated rats with A. carambola fruit extract supplement revealed a significant increase in GSH level, CAT, SOD activity, and a decrease in TBARS levels as compared to lead-intoxicated rats, indicating its antioxidant activity

N-acetylecysteine, a powerful agent in the reinforcement of anti-oxidant profile: A systematic review and dose-response meta-analysis of controlled clinical trials

Several studies have been conducted to evaluate the effect of N-acetylecysteine (NAC) supplementation on antioxidant status, while no dose-response meta-analysis summarized the efficacy of NAC supplementation. The systematic search of literatures was conducted on Scopus, PubMed, Embase, Web of Science electronic databases. Controlled clinical trials investigating the effects of NAC on antioxidant biomarkers were included in the current meta-analysis. Random-effect model was used to perform meta-analysis. Heterogeneity was examined using I2 index. Subgroup analysis was carried out to find the possible sources of heterogeneity. Dose-response analysis was performed to find the non-linear relationships between effect size and independent variables. Overall, 26 eligible studies were included in the review. NAC supplementation significantly increased TAC (SMD=0.77μmol/L; 95% CI: 0.38, 1.16; p<0.001), GSH (SMD=0.80nmol/ml; 95% CI:0.25, 1.34; p=0.004) and CAT (SMD=-0.57 IU/L; 95% CI:-1.13,-0.02; p=0.042) levels. However, no significant improving effect was observed in terms of GR (SMD=0.25 IU/g; 95% CI:-0.14, 0.63; p=0.210), SOD (SMD=0.14 U/ml; 95% CI:-0.20, 0.49; p=0.414) and GPx (SMD=0.19 IU/g; 95% CI:-0.48, 0.86; p=0.576) levels. Furthermore, dose-response analysis show that NAC supplementation in participants with mean age up to 30 years had more robust effect on increasing GSH levels. We found a significant effect of NAC supplementation on TAC, GSH, CAT in adults. Overall, NAC could be considered as a potent agent in enhancing antioxidant capacity.