Berberine attenuates brain aging via stabilizing redox homeostasis and inflammation in an accelerated senescence model of Wistar rats.

Aging is a multifaceted and progressive physiological change of the organism categorized by the accumulation of deteriorating processes, which ultimately compromise the biological functions. The objective of this study was to investigate the anti-aging potential of berberine (BBR) in D-galactose (D-Gal) induced aging in rat models. In this study, male Wistar rats were divided into four groups: The control group was given only vehicle, the BBR group was treated with berberine orally, the D-Gal group was treated with D-galactose subcutaneously and the BBR + D-Gal group was treated with D-galactose and berberine simultaneously. D-galactose exposure elevated the pro-oxidants such as malondialdehyde (MDA) level, protein carbonyl and advanced oxidation protein products (AOPP) in the brain. It decreased the anti-oxidants such as reduced glutathione (GSH) and ferric reducing antioxidant potential (FRAP) in the brain. D-galactose treatment also reduced the mitochondrial complexes (I, II, III and IV) activities and elevated the inflammatory markers such as interleukine-6 (IL-6), tumor necrosis factor- α (TNF-α) and C-reactive protein (CRP). The mRNA expressions of IL-6 and TNF-α in the brain were upregulated following D-galactose exposure. Berberine co-treatment in D-galactose induced aging rat model prevented the alteration of pro-oxidant and anti-oxidant in the brain. Berberine treatment restored the mitochondrial complex activities in the brain and also normalized the inflammatory markers. Based on these findings we conclude that berberine treatment has the potential to mitigate brain aging in rats via stabilizing the redox equilibrium and neuroinflammation.

Hesperidin Supplementation Improves Altered PON -1, LDL Oxidation, Inflammatory Response and Hepatic Function in an Experimental Rat Model of Hyperlipidemia.

In this study, we have examined the effect of hesperidin on rats fed on an experimental high-fat diet. Male Wistar rats were given a high-fat diet orally for one month for developing an HFD (High fat- diet) model. Rats were also supplemented with hesperidin (100 mg/kg body weight) for one month. We determined serum LDL (Low-density lipoprotein) oxidation, Paraoxonase-1 (PON-1) activity, and histopathological profile of the liver. Inflammatory cytokines levels were also measured in serum. HFD induced significant changes in LDL oxidation and PON-1 activity. Liver tissue histopathology and gene expression of inflammatory markers (Il-6(Interleukin-6), TNF- alpha (Tumor necrosis factor alpha), NF-KB (Nuclear factor kappa B) show that significant changes occur in the hyperlipidemic model of rats. We also show that hesperidin can effectively improve plasma antioxidant, LDL oxidation, and inflammatory cytokine expression in rats already subjected to hyperlipidemic stress. We conclude that hesperidin may protect the liver from oxidative stress by improving hepatic function.

Monosodium Glutamate Even at Low Dose May Affect Oxidative Stress, Inflammation and Neurodegeneration in Rats.

Monosodium glutamate (MSG) is a widely used flavour enhancer. A daily intake of MSG at high dosage (2000-4000 mg/kg body weight) is reported to be toxic to humans and experimental animals. The present study aims to investigate the toxic effect of oral administration of MSG at low concentrations (30 and 100 mg/kg body weight) by evaluating biochemical parameters of oxidative stress and inflammation in blood; expression of neuroinflammatory gene and histopathological changes in brain on male Wistar rats. The administration of MSG significantly increases serum level of fasting glucose, insulin, triglycerides, total cholesterol, low-density lipoprotein and decrease level of high-density lipoprotein. Significant low level of FRAP, GSH, SOD, CAT and higher level of MDA, PCO, AOPP, PMRS, NO, CRP, IL-6, TNF-α confirms substantial oxidative stress followed by inflammation after 100 mg MSG treatment. RT-PCR figure shows significant expression of neuroinflammatory gene IL-6 and TNF-α and histopathological examination revealed severe neurodegeneration in hippocampus (CA1 and CA3) and cerebral cortex region of brain at 100 mg MSG treatment. Our result provides evidence that MSG administration at 30 mg does not impose toxicity, however at 100 mg/kg body weight, which is considered a low dose, there is significant toxic effects and may be detrimental to health.

Anti-inflammatory effect of curcumin in an accelerated senescence model of Wistar rat: an in vivo and in-silico study.

Curcumin, a biphenolic substance derived from turmeric (Curcuma longa), offers a number of health-beneficial effects, including anti-inflammatory, cardiovascular protection, anti-cancerous, and anti-angiogenic. By interacting with the PPARγ (Peroxisome Proliferator-Activated Receptor-γ), curcumin inhibits NF-κB. These biological outcomes seem to be the outcome of NF-κB inhibition mediated by curcumin. The current study explores the in vivo impact of curcumin on several inflammatory parameters during aging in Wistar rats. An in-silico docking simulation study using Maestro and Desmond, Schrödinger, was carried out to further validate the experimental findings. According to our observation, rats given curcumin supplementation had a considerably (p ≤ 0.05) reduced level of inflammation. By generating numerous polar and hydrophobic interactions and exhibiting little conformational deviation throughout the simulation, in silico investigations showed that the proposed ligand curcumin had a high affinity for the enzyme COX-2. During simulation, protein-ligand complexes of curcumin with the other targets viz. 5-LOX, TNF-α and IL-6 also demonstrated improved binding and minimal fluctuation. The COX-2 and 5-LOX enzymes and the cytokines (TNF-α and IL-6) implicated in inflammation may have been inhibited by curcumin, highlighting its function as a multi-target inhibitor. Our study provides convincing support for the idea that eating a diet high in curcumin may help to reduce inflammation and help to explain some of its health-beneficial effects.Communicated by Ramaswamy H. Sarma.

Crosstalk Between Aging, Circadian Rhythm, and Melatonin.

Circadian rhythms (CRs) are 24-hour periodic oscillations governed by an endogenous circadian pacemaker located in the suprachiasmatic nucleus (SCN), which organizes the physiology and behavior of organisms. Circadian rhythm disruption (CRD) is also indicative of the aging process. In mammals, melatonin is primarily synthesized in the pineal gland and participates in a variety of multifaceted intracellular signaling networks and has been shown to synchronize CRs. Endogenous melatonin synthesis and its release tend to decrease progressively with advancing age. Older individuals experience frequent CR disruption, which hastens the process of aging. A profound understanding of the relationship between CRs and aging has the potential to improve existing treatments and facilitate development of novel chronotherapies that target age-related disorders. This review article aims to examine the circadian regulatory mechanisms in which melatonin plays a key role in signaling. We describe the basic architecture of the molecular circadian clock and its functional decline with age in detail. Furthermore, we discuss the role of melatonin in regulation of the circadian pacemaker and redox homeostasis during aging. Moreover, we also discuss the protective effect of exogenous melatonin supplementation in age-dependent CR disruption, which sheds light on this pleiotropic molecule and how it can be used as an effective chronotherapeutic medicine.

Vitamin C Improves Inflammatory-related Redox Status in Hyperlipidemic Rats.

Excessive dietary fat is mainly responsible for metabolic diseases including atherosclerosis and cardiovascular disease. We have evaluated the role of Vitamin C in an experimental hyperlipidemic model of rats (male Wistar rat 12-16 months). The hyperlipidemic model of the rat was created by treatment with an atherogenic suspension: cholesterol, cholic acid, and coconut oil, for 30 days once daily, and supplemented with Vitamin C (Ascorbic acid) doses of 0.5 g/kg body weight (orally) for the 30 days once daily. Bodyweight, fasting glucose, triglyceride, cholesterol, ROS (Reactive oxygen species), MDA (Malondialdehyde), FRAP (Ferric reducing the ability of plasma), GSH (Reduced glutathione), PCO (Protein carbonyl), PON-1(Paraoxonase-1), AGE (Advanced glycation end product), PMRS (Plasma membrane reduced system), and inflammatory cytokines (TNF-α and IL-6) were estimated in blood and plasma. Our result shows that oxidative stress, and inflammatory markers, were increased in the HFD-treated group of rats. Vitamin C supplementation protected against lipidemic and, oxidative stress. We conclude that Vitamin C may be useful in maintaining cellular redox balance and protecting against lipidemic stress.

Acarbose Mitigates Age-Dependent Alterations in Erythrocyte Membrane Transporters During Aging in Rats.

Acarbose (ACA), a well-studied and effective inhibitor of α-amylase and α-glucosidase, is a postprandial-acting antidiabetic medicine. The membrane of the erythrocyte is an excellent tool for analyzing different physiological and biochemical activities since it experiences a range of metabolic alterations throughout aging. It is uncertain if ACA modulates erythrocyte membrane activities in an age-dependent manner. As a result, the current study was conducted to explore the influence of ACA on age-dependent deteriorated functions of transporters/exchangers, disrupted levels of various biomarkers such as lipid hydroperoxides (LHs), protein carbonyl (PCO), sialic acid (SA), total thiol (-SH), and erythrocyte membrane osmotic fragility. In addition to a concurrent increase in Na+/H+ exchanger activity and concentration of LH, PCO, and osmotic fragility, we also detected a considerable decrease in membrane-linked activities of Ca2+-ATPase (PMCA) and Na+/K+-ATPase (NKA), as well as concentrations of SA and -SH in old-aged rats. The aging-induced impairment of the activities of membrane-bound ATPases and the changed levels of redox biomarkers were shown to be effectively restored by ACA treatment.

Curcumin displays a potent caloric restriction mimetic effect in an accelerated senescent model of rat.

Curcumin, a strong natural compound with numerous health benefits, is extracted from the Curcuma longa. According to recent research findings, it also acts as a calorie restriction mimetic. We examined established aging biomarkers in erythrocytes and plasma and tested a persistent oral dietary dose of curcumin in young and D-galactose-induced accelerated rat aging models. For four weeks, D-gal (300 mg/kg b.w. subcutaneously) and curcumin (200 mg/kg b.w. oral) were administered simultaneously to test the protective effects of curcumin against D-galactose-induced accelerated aging and oxidative stress. In the accelerated senescent rat model, we discovered a significant rise in protein carbonyl, malonaldehyde (MDA), and advanced oxidation protein products. Increased levels of catalase, superoxide dismutase, ferric-reducing antioxidant potential, and reduced glutathione (GSH) were observed. Our findings reveal that curcumin has characteristics resembling a calorie restriction mimic and can successfully maintain redox equilibrium throughout the aging process in rat erythrocytes and plasma.

Berberine may provide redox homeostasis during aging in rats.

Aging is a natural phenomenon, which is characterised by progressive physiological changes at cellular and organ level. During aging, the defence mechanism of an organism declines over the period of time. The aim of this study was to investigate the biological efficacy of berberine in D-galactose induced aging rat models. For the study, rats were divided into four groups: Control received only vehicle, BBR received berberine orally, D-Gal received D-galactose subcutaneously and BBR + D-Gal received D-galactose and berberine simultaneously. D-galactose treatment increased the pro-oxidants such as malondialdehyde (MDA) level, protein carbonyl, plasma membrane redox system (PMRS) and advanced oxidation protein products (AOPP) in the erythrocytes or plasma. It reduced the anti-oxidant level such as reduced glutathione (GSH), ferric reducing ability of plasma (FRAP), plasma thiols, sialic acid and membrane transporters like Na+/K+ ATPase and Ca2+ ATPase activity in the erythrocyte membrane. Co-treatment of berberine in D-galactose induced aging rat models restored pro-oxidants and anti-oxidants in erythrocytes. Berberine also restored the activity of Na+/K+ ATPase and Ca2+ ATPase in the erythrocyte membrane. On the basis of these findings, we suggest that berberine treatment could attenuate erythrocyte aging in rats through stabilisation of the redox equilibrium.

Acarbose, an α-Glucosidase Inhibitor, Maintains Altered Redox Homeostasis During Aging by Targeting Glucose Metabolism in Rat Erythrocytes.

Increasing age is the single largest risk factor for a variety of chronic illnesses. As a result, improving the capability to target the aging process leads to an increased health span. A lack of appropriate glucoregulatory control is a recurring issue associated with aging and chronic illness, even though many longevity therapies result in the preservation of glucoregulatory control. In this study, we suggest that targeting glucose metabolism to improve regulatory control can help slow the aging process. Male Wistar rats, both young (age 4 months) and old (age 24 months), were given acarbose (ACA) (30 mg/kg b.w.) for 6 weeks. An array of oxidative stress indicators was assessed after the treatment period, including plasma antioxidant capacity as determined by the ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), lipid peroxidation (malondialdehyde [MDA]), reduced glutathione (GSH), total plasma thiol (sulfhydryl [SH]), plasma membrane redox system (PMRS), protein carbonyl (PCO), advanced oxidation protein products (AOPPs), advanced glycation end products (AGEs), and sialic acid (SA) in control and treated groups. When compared with controls, ACA administration increased FRAP, GSH, SH, and PMRS activities in both age groups. The treated groups, on the contrary, showed substantial decreases in ROS, MDA, PCO, AOPP, AGE, and SA levels. The effect of ACA on almost all parameters was more evident in old-age rats. ACA significantly increased PMRS activity in young rats; here the effect was less prominent in old rats. Our data support the restoration of antioxidant levels in older rats after short-term ACA treatment. The findings corroborate the potential role of ACA as a putative calorie restriction mimetic.

Aging, circadian disruption and neurodegeneration: Interesting interplay.

The circadian system is an intricate molecular network of coordinating circadian clocks that organize the internal synchrony of the organism in response to the environment. These rhythms are maintained by genetically programmed positive and negative auto-regulated transcriptional and translational feedback loops that sustain 24-hour oscillations in mRNA and protein components of the endogenous circadian clock. Since inter and intracellular activity of the central pacemaker appears to reduce with aging, the interaction between the circadian clock and aging continues to elude our understanding. In this review article, we discuss circadian clock components at the molecular level and how aging adversely affects circadian clock functioning in rodents and humans. The natural decline in melatonin levels with aging strongly contributes to circadian dysregulation resulting in the development of neurological anomalies. Additionally, inappropriate environmental conditions such as Artificial Light at Night (ALAN) can cause circadian disruption or chronodisruption (CD) which can result in a variety of pathological diseases, including premature aging. Furthermore, we summarize recent evidence suggesting that CD may also be a predisposing factor for the development of age-related neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), although more investigation is required to prove this link. Finally, certain chrono-enhancement approaches have been offered as intervention strategies to prevent, alleviate, or mitigate the impacts of CD. This review thus aims to bring together recent advancements in the chronobiology of the aging process, as well as its role in NDDs.

3-Bromopyruvate elevates ROS and induces hormesis to exert a caloric restriction mimetic effect in young and old rats.

CONTEXT: 3-Bromopyruvate (3-BP) is a glycolytic inhibitor and a putative caloric restriction mimetic. OBJECTIVE: We have examined the effect of low-dose administration of 3-BP to rats and assess the CRM effect by measuring an array of biomarkers of oxidative stress. MATERIALS AND METHODS: Male Wistar young and old rats were administered with a low-dose 3-BP for four weeks. RESULTS: A significant increase in ROS was observed in 3-BP-treated rats (both young and old), an increase in erythrocyte PMRS (plasma membrane redox system), FRAP (Ferric reducing ability of plasma), catalase and superoxide dismutase activities were also observed. Treatment with 3-BP also reduced protein carbonyl, advanced oxidation protein products, plasma sialic acid, and advanced glycation end products. CONCLUSION: Short-term 3-BP treatment can provide protection against oxidant stress. We suggest that 3-BP triggers a hormetic response subsequent to an increase in ROS leading to the induction of a protective defense mechanism.

Therapeutic potential of melatonin and its derivatives in aging and neurodegenerative diseases.

Aging is associated with increasing impairments in brain homeostasis and represents the main risk factor across most neurodegenerative disorders. Melatonin, a neuroendocrine hormone that regulates mammalian chronobiology and endocrine functions is well known for its antioxidant potential, exhibiting both cytoprotective and chronobiotic abilities. Age-related decline of melatonin disrupting mitochondrial homeostasis and cytosolic DNA-mediated inflammatory reactions in neurons is a major contributory factor in the emergence of neurological abnormalities. There is scattered literature on the possible use of melatonin against neurodegenerative mechanisms in the aging process and its associated diseases. We have searched PUBMED with many combinations of key words for available literature spanning two decades. Based on the vast number of experimental papers, we hereby review recent advancements concerning the potential impact of melatonin on cellular redox balance and mitochondrial dynamics in the context of neurodegeneration. Next, we discuss a broader explanation of the involvement of disrupted redox homeostasis in the pathophysiology of age-related diseases and its connection to circadian mechanisms. Our effort may result in the discovery of novel therapeutic approaches. Finally, we summarize the current knowledge on molecular and circadian regulatory mechanisms of melatonin to overcome neurodegenerative diseases (NDDs) such as Alzheimer's, Parkinson's, Huntington's disease, and amyotrophic lateral sclerosis, however, these findings need to be confirmed by larger, well-designed clinical trials. This review is also expected to uncover the associated molecular alterations in the aging brain and explain how melatonin-mediated circadian restoration of neuronal homeodynamics may increase healthy lifespan in age-related NDDs.

Modulatory effect of exogenous Coenzyme Q10 on redox and inflammatory biomarkers during aging in rats.

An impaired redox homeostasis is an important hallmark of biological aging. Coenzyme Q10 is an endogenous lipophilic antioxidant that decreases with age and has been linked to oxidative stress. The purpose of this study was to evaluate the effect of CoQ10 supplementation on redox homeostasis and levels of inflammatory cytokines in young and old rats. Male Wistar rats (young and old) were randomly divided into four groups (n = 6). Group I: young control, Group II: young rats treated with CoQ10, Group III: old control, Group IV: old rats treated with CoQ10. CoQ10 (20 mg/kg) was administered daily to Group II and IV via oral gavage. After 28 days of treatment, rats were sacrificed and biomarkers of oxidative stress and inflammatory cytokines were evaluated. Results demonstrated a significant (p ≤ 0.05) increase in malondialdehyde, protein carbonyl oxidation, advanced oxidation protein products, inflammatory cytokines: CRP, IL-6, TNF-α, and a decline in levels of superoxide dismutase, catalase, reduced glutathione, ferric reducing antioxidant potential in plasma and plasma membrane redox system in old rats when compared to young rats. After treatment with CoQ10 significant decrease in the level of MDA, PCO, AOPP, CRP, IL-6, and TNF-α was observed. Also, significant up-regulation of SOD, CAT, GSH, FRAP, and PMRS was observed. The results show that supplementing rats with CoQ10 aids in the maintenance of redox equilibrium with replenishment of antioxidant reserves and down-regulation of inflammatory biomarkers. Thus CoQ10 supplementation could be a potential anti-aging therapy.

3-Bromopyruvate, a caloric restriction mimetic, exerts a mitohormetic effect to provide neuroprotection through activation of autophagy in rats during aging.

In the present study, attempts have been made to evaluate the potential role of 3 Bromopyruvate (3-BP) a glycolytic inhibitor and a caloric restriction mimetic (CRM), to exert neuroprotection in rats during aging through modulation of autophagy. Young male rats (4 months), and naturally aged (22 months) male rats were supplemented with 3-BP (30 mg/kg b.w., orally) for 28 days. Our results demonstrate a significant increase in the antioxidant biomarkers (ferric reducing antioxidant potential level, total thiol, superoxide dismutase, and catalase activities) and a decrease in the level of pro-oxidant biomarkers such as protein carbonyl after 3-BP supplementation in brain tissues. A significant increase in reactive oxygen species (ROS) was observed due to the mitohormetic effect of 3-BP supplementation in the treated rats. Furthermore, the 3-BP treatment also enhanced the activities of electron transport chain complexes I and IV in aged brain mitochondria thus proving its antioxidant potential at the level of mitochondria. Gene expression analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to assess the expression of autophagy, neuroprotective and aging marker genes. RT-PCR data revealed that 3-BP up-regulated the expression of autophagy markers genes (Beclin-1 and LC3 ß), sirtuin-1, and neuronal marker gene (NSE), respectively in the aging brain. The results suggest that 3-BP induces a mitohormetic effect through the elevation of ROS which reinforces defensive mechanism(s) targeted at regulating autophagy. These findings suggest that consistently low-dose 3-BP may be beneficial for neuroprotection during aging and age-related disorders.

Alternate day fasting and time-restricted feeding may confer similar neuroprotective effects during aging in male rats.

Age associated neurodegenerative changes are acknowledged to play a causative role in a majority of neurological diseases that accompany aging in organisms. To alleviate the deteriorative effects of aging in the brain, we investigated the effects oftwo types of intermittent fasting (IF) methods: alternate day fasting (ADF) and time- restricted feeding (TRF) in young (3 months) and old (24 months) in male Wistar rats comparing the results with age matched controls. The evaluation of biomarkers of oxidative stress showed significant decline in the old (ADF and TRF) groups in addition to up regulation in antioxidant levels. It was observed that ADF and TRF methods helped reduce ROS accumulation in the mitochondria and increased the activity of the electron transport chain complexes especially C-I and III. Gene expression analysis of autophagy genes like beclin and LC3B showed upregulated expression in ADF and TRF group. Sirtuin1 expression too significantly increased during fasting in both young and old groups showing fasting induced protection from aging. Histological analysis of sections of cerebral cortex and CA1 area provide evidence that fasting protected neurons against degeneration with age. Our results prompt us to conclude that the efficacy of these fasting methods ADF and TRF are reliable anti- aging strategies with respect to dietary restriction interventions. Moreover, both these methods compete closely in conferring protection from oxidative stress and inducing neuroprotective changes in brain of aged rats when compared to their young counterparts.

Chitosan reduces inflammation and protects against oxidative stress in a hyperlipidemic rat model: relevance to nonalcoholic fatty liver disease.

BACKGROUND: An altered lipid profile may lead to the development of inflammation and NAFLD (Non-alcoholic fatty liver disease). Although statins have a positive effect on blood lipid levels their long-term use is known to cause adverse effects, in this backdrop there is an interest in natural compounds which may affect lipid metabolism and prevent NAFLD. We have examined the effect of Chitosan on rats subjected to a high-fat diet. METHODS AND RESULTS: Male Wistar middle aged rats (12-16 months) were treated with high-fat diet orally for two months for creating a NAFLD model. Rats were also supplemented with Chitosan (2% chitosan daily) for 2 months. We assessed the activity of antioxidant enzymes, the histopathological profile of the liver. Inflammatory cytokines and adiponectin levels were also measured in serum. HFD induced significant changes in liver tissue and inflammatory markers (Il-6, TNF- alpha, NF-KB). Chitosan treatment protected rats from HFD induced alterations. CONCLUSIONS: The findings suggest that Chitosan can effectively improve liver lipid metabolism by normalizing cholesterol, triglyceride, lowering NF-KB expression, and protecting the liver from oxidative stress by improving hepatic function. Chitosan also regulates genes related to lipidemic stress i,e leptin and adiponectin.

Hormetic Effect of 3-Bromopyruvate on Age-Induced Alterations in Erythrocyte Membrane Transporters and Oxidative Biomarkers in Rats.

3-Bromopyruvate (3-BP) is a glycolytic inhibitor and a potential calorie restriction mimic that shows a variety of beneficial effects in several aging model systems. A chronic low dose of 3-BP was given to male Wistar rats for 4 weeks. The effect of 3-BP on age-dependent alteration on the activities of various transporters/exchangers and redox biomarkers (protein carbonyl [PC], sialic acid [SA], sulfhydryl group [-SH], intracellular calcium ion [Ca2+]i, and osmotic fragility) was studied. In aged rats, 3-BP treatment increases the membrane-bound activities of Na+/K+-ATPase (NKA) and Ca2+-ATPase (PMCA), along with levels of -SH and SA. It also exerts a concomitant decrease in Na+/H+ exchanger (NHE) activity and the levels of [Ca2+]i, PC, and osmotic fragility in aged groups. 3-BP can be considered as a potential antiaging agent that induces a hormetic effect leading to amelioration of age-dependent impairment of membrane-bound ATPases and alterations in the redox biomarker level.

Baicalein May Act as a Caloric Restriction Mimetic Candidate to Improve the Antioxidant Profile in a Natural Rodent Model of Aging.

Caloric restriction (CR) is the most effective intervention for extending the life span of vertebrate and invertebrate aging models. Calorie restriction mimetics (CRMs), which are synthetic or natural chemicals that mimic the biochemical, hormonal, and physiological consequences of calorie restriction, are being researched for antiaging benefits. Baicalein is a plant-derived polyphenol that has the potential of antioxidant, anti-inflammatory, and autophagy inducer. The objective of this study is to evaluate the antiaging, anti-inflammatory, and antioxidant role of Baicalein in erythrocyte membrane and plasma, and evaluate the efficacy of Baicalein to act as a CRM candidate. This study evaluates the effect of Baicalein on aging biomarkers in normal and aged rats. We study various pro- and antioxidant markers, erythrocyte membrane transporters, and eryptosis. Baicalein supplementation in male Wistar rats significantly alleviated pro-oxidant markers and improved antioxidant profile. Improvement was also observed in age-induced alterations in membrane transporters, and eryptosis. Based on the aforementioned observations we conclude that Baicalein has the potential to maintain extracellular reactive oxygen species levels and redox homeostasis during the aging process, an effect that is similar to CR. Thus, Baicalein may be a potent CRM candidate for antiaging interventions.

Metformin ameliorates acetaminophen-induced sub-acute toxicity via antioxidant property.

Acetaminophen or N-acetyl-p-amino-phenol (APAP) is a drug which is available over-the-counter for fever and pain. Its overdosing causes oxidative stress and subsequent acute liver damage. In the present study, we scrutinized the protective effect of metformin co-treatment in APAP induced blood and liver sub-acute toxicity. This is a pre-clinical study in which male Wistar Rats (BW: 300 ± 20 g) were orally co-treated with APAP (1 g/kg/day) and metformin (300 mg/kg/day) for 28-days. Pro- and anti-oxidant markers viz reactive oxygen species, protein carbonyl, malondialdehyde (MDA), the ferric reducing ability of plasma (FRAP), plasma membrane redox system(PMRS) and reduced glutathione (GSH) were evaluated in blood. Additionally, in liver tissue, catalase (CAT), superoxide dismutase (SOD), MDA and GST level were also evaluated. Histological study and estimation of alanine aminotransferase (ALT), and aspartate aminotransferase (AST) level in serum were performed. APAP induces pro-oxidant markers as well as reduces anti-oxidant markers in blood and liver. Hepatic tissues degeneration and vacuolization of hepatocytes were evident after APAP treatment. Metformin treatment reduces pro-oxidant markers as well as increases anti-oxidant markers in both tissues. It also improves liver tissue architecture after treatment. The outcome of this study suggests that metformin has protective capability against APAP-induced blood and liver toxicity. Thus, metformin co-treatment with APAP attenuates oxidative stress and its consequences.