Curcumin protects against aging-related stress and dysfunction through autophagy activation in rat brain.

BACKGROUND: Curcumin (Curcuma longa) is a well-known medicinal plant that induces autophagy in various model species, helping maintain cellular homeostasis. Its role as a caloric restriction mimetic (CRM) is being investigated. This study explores the potential of curcumin (CUR), as a CRM, to provide neuroprotection in D galactose induced accelerated senescence model of rats through modulation of autophagy. For six weeks, male rats received simultaneous supplementation of D-gal (300 mg/kg b.w., subcutaneously) and CUR (200 mg/kg b.w., oral). METHOD AND RESULTS: The oxidative stress indices, antioxidants, and electron transport chain complexes in brain tissues were measured using standard methods. Reverse transcriptase-polymerase chain reaction (RT-PCR) gene expression analysis was used to evaluate the expression of autophagy, neuroprotection, and aging marker genes. Our results show that curcumin significantly (p ≤ 0.05) enhanced the level of antioxidants and considerably lowered the level of oxidative stress markers. Supplementing with CUR also increased the activity of electron transport chain complexes in the mitochondria of aged brain tissue, demonstrating the antioxidant potential of CUR at the mitochondrial level. CUR was found to upregulate the expression of the aging marker gene (SIRT-1) and the genes associated with autophagy (Beclin-1 and ULK-1), as well as neuroprotection (NSE) in the brain. The expression of IL-6 and TNF-α was downregulated. CONCLUSION: Our findings demonstrate that CUR suppresses oxidative damage brought on by aging by modulating autophagy. These findings imply that curcumin might be beneficial for neuroprotection in aging and age-related disorders.

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.

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.

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.

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.

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.

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.

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.

Age-dependent effect of continuous 'artificial light at night' on circadian rhythm in male rats: neuroprotective role of melatonin.

Circadian disruption due to artificial light at night (ALAN) is an alarming threat to modern society. In the present study we evaluated the protective effect of melatonin on age dependent redox insults and neurochemical deficits induced by ALAN in the brain of chronodisrupted rat model. Young (3 months) and old (22 months) male Wistar rats were exposed to ALAN along with melatonin supplementation (10 mg Kg-1, oral) for 10 days. Results demonstrated significant increment in the pro-oxidant biomarkers: reactive oxygen species, lipid hydroperoxidation, protein carbonyl, nitric oxide while suppression in the total thiol, ferric reducing antioxidant potential level, superoxide dismutase and catalase activities in the brain of ALAN exposed groups with higher amplitude in aged rats. Further these oxidative modifications were protected by subsequent administration of melatonin. Mitochondrial complexes (C-I to C-IV) activity was significantly altered in young and old ALAN exposed groups with melatonin showing protective effect. Histopathological analysis show dense cytosolic staining and neuronal degeneration in cerebral cortex and different hippocampus regions with greater extent in old ALAN rats effectively moderated by melatonin supplementation. RT-PCR data analysis revealed melatonin effectively downregulated neuroinflammatory (IL-6, TNF α) and neurodegenerative marker (Ngb) while upregulating the aging (Sirt 1) gene expression in both young and old melatonin supplemented ALAN exposed groups. Our results may help in understanding the degree of ALAN induced photo-oxidative damage in neuronal redox homeostasis during aging. We also show that melatonin supplementation might provide a basis for amelioration of oxidative disturbances to improve circadian entrainment in aged populations.

Spermidine, a caloric restriction mimetic, provides neuroprotection against normal and D-galactose-induced oxidative stress and apoptosis through activation of autophagy in male rats during aging.

Spermidine (SPD) is a natural polyamine present in all living organisms and is involved in the maintenance of cellular homeostasis by inducing autophagy in different model organisms. Its role as a caloric restriction mimetic (CRM) is still being investigated. We have undertaken this study to investigate whether SPD, acting as a CRM, can confer neuroprotection in D-galactose induced accelerated senescence model rat and naturally aged rats through modulation of autophagy and inflammation. Young male rats (4 months), D-gal induced (500 mg/kg b.w., subcutaneously) aging and naturally aged (22 months) male rats were supplemented with SPD (10 mg/kg b.w., orally) for 6 weeks. Standard protocols were employed to measure prooxidants, antioxidants, apoptotic cell death and electron transport chain complexes in brain tissues. Gene expression analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to assess the expression of autophagy and inflammatory marker genes. Our data demonstrate that SPD significantly (p ≤ 0.05) decreased the level of pro-oxidants and increased the level of antioxidants. SPD supplementation also augmented the activities of electron transport chain complexes in aged brain mitochondria thus proving its antioxidant potential at the level of mitochondria. RT-PCR data revealed that SPD up-regulated the expression of autophagy genes (ATG-3, Beclin-1, ULK-1 and LC3B) and down-regulated the expression of the inflammatory gene (IL-6) in aging brain. Our results provide first line of evidence that SPD provides neuroprotection against aging-induced oxidative stress by regulating autophagy, antioxidants level and also reduces neuroinflammation. These results suggest that SPD may be beneficial for neuroprotection during aging and age-related disorders.

Hesperidin attenuates altered redox homeostasis in an experimental hyperlipidaemic model of rat.

Diets rich in saturated fats and cholesterol contribute to the incidence of hyperlipidaemia. An altered lipid profile is a major factor responsible for the development of CVD. Male Wistar rats were fed with a high-fat diet (HFD) (suspension (w/v) of 0.5% cholesterol, 3% coconut oil and 0.25% cholic acid for 30 days) to induce an experimental hyperlipidaemic model. High-fat diet fed rats were also supplemented with hesperidin (100 mg/kg body weight). The present study reports reactive oxygen species (ROS) production, oxidative stress parameters: malondialdehyde (MDA), protein carbonyl (PCO), oxidation of plasma protein (AOPP), and advance glycation end products (AGEs); antioxidant defence parameters: ferric reducing ability of plasma (FRAP), reduced glutathione (GSH), Paraoxonase-1 (PON-1), plasma membrane redox system (PMRS); general biochemical parameters: triglyceride, cholesterol, serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT), fasting insulin, fasting glucose, homeostatic model assessment-insulin resistance (Homa-IR) index, and inflammatory biomarkers: interleukin (IL)-6 and tumour necrosis factor (TNF)-α. Experimental hyperlipidaemia was found to be associated with significantly higher body weight (27.58%), cholesterol (140%), triglyceride (190%), and fasting glucose level (37%). Reactive oxygen species production (67%), MDA (28.9%), AOPP (31.42%), PCO (58.53%), and PMRS (156%), inflammatory markers, cytokines IL-6 and TNF-α, were elevated and GSH (50%), PON 1 (37.07%), and FRAP (26.58%) activity were significantly (P < .05) lower in the high-fat diet group. Hesperidin supplementation protected HFD-fed rats from oxidative damage. Our findings indicate that the supplementation of hesperidin provides protection against redox imbalance induced by hyperlipidaemia in rats.

Fisetin, a potential caloric restriction mimetic, attenuates senescence biomarkers in rat erythrocytes.

An imbalanced redox status is a hallmark of the aging process. Caloric restriction mimetics (CRMs) are compounds that produce caloric restriction benefits at the molecular, cellular, and physiological level, translating into health-promoting effects. Fisetin is the least explored CRM, and its role in modulating oxidative stress during aging is not clearly known. This study investigated the antioxidative and protective potential of fisetin in a rat model of d-galactose (D-gal)-induced accelerated senescence, and in naturally aged rat erythrocytes. Young rats (4 months), aged D-gal-induced rats [24 months; 500 mg/kg body mass (b.m.); subcutaneous injection] and naturally aged D-gal-induced rats [24 months; 500 mg/kg b.m.; subcutaneous injection] were supplemented with fisetin (15 mg/kg b.m.; orally) for 6 weeks. The resulting data indicated that supplementation with fisetin suppresses aging-induced increases in the levels of reactive oxygen species, eryptosis, lipid peroxidation, and protein oxidation. Our data also show that fisetin significantly increases the levels of antioxidants and activates the plasma membrane redox system. Taken together, the findings show that a fisetin-rich diet could be an anti-aging intervention strategy.

Redox homeostasis in a rodent model of circadian disruption: Effect of melatonin supplementation.

Continuous light or dark photoperiods are the leading cause of disruption in the circadian rhythm of day-night cycle. The purpose of this study was to understand the cellular redox balance in a model of circadian disrupted rat model and determine the effect of melatonin supplementation. Young male Wistar rats were randomly divided into five groups (n = 4). Group (I): normal day-night (12 h:12 h) cycle, Group (II): normal rats treated with melatonin, Group (III): rats subjected to continuous light exposure (CLE), Group (IV): CLE rats treated with melatonin, and Group (V) Rats subjected to continuous dark. Melatonin (10 mg/kg) was administered orally at dusk to the Group (II) & (IV). Rats were sacrificed after 10 days of treatment and biomarkers of oxidative stress were evaluated. Results demonstrated significant (p < 0.05) increase of malondialdehyde (MDA), plasma membrane redox system (PMRS), protein carbonyl oxidation (PCO), advanced oxidation protein products (AOPPs), and advanced glycation end products (AGEs) during CLE. A significantly (p < 0.05) decreased level of reduced glutathione (GSH) and ferric reducing antioxidant potential in plasma (FRAP) was also observed during CLE. Treatment with melatonin in CLE rats showed reduced level of MDA, PMRS, PCO, AOPPs and AGEs while GSH and FRAP activity were increased. During continuous dark exposure (CDE) the biomarkers of oxidative stress were attenuated compared to control. Supplementation of melatonin could be a promising strategy to maintain redox homeostasis during prolonged condition of light exposure and other conditions of redox imbalance.

N-acetyl-l-cysteine attenuates oxidative damage and neurodegeneration in rat brain during aging.

N-acetyl-l-cysteine (NAC) is a precursor of cysteine, which is known to increase the level of glutathione (GSH) in the brain. Several neurodegenerative changes linked to oxidative stress take place in the aging brain. This study aimed to assess the neuroprotective effect of NAC supplementation on age-dependent neurodegeneration in the rat brain. Young (4 months) and old (24 months) Wistar rats (n = 6 rats/group) were supplemented with NAC (100 mg/kg b.w. orally) for 14 days. Enzymatic and nonenzymatic antioxidants such as superoxide dismutase and catalase, and GSH and total thiol respectively, prooxidants such as protein carbonyl, advanced oxidation protein products, reactive oxygen species, and malondialdehyde were assessed in the brain homogenates. Furthermore, nitric oxide level, acetylcholinesterase activity, and Na+/K+-ATPase activity were measured and gene expression studies were also performed. The results indicated that NAC augmented the level of enzymatic and nonenzymatic antioxidants with a significant reduction in prooxidant levels in old rats. NAC supplementation also downregulated the expression of inflammatory markers (TNF-α, IL-1ß, IL-6) and upregulated the expression of marker genes associated with aging (sirtuin-1) and neurodegeneration (neuron-specific enolase, neuroglobin, synapsin-I, myelin basic protein 2) in old rats. The present findings support a neuroprotective role of NAC which has therapeutic implication in controlling age-related neurological disorders.

Redox imbalance in a model of rat mimicking Hutchinson-Gilford progeria syndrome.

Although several etiological factors contribute to the complexity of the aging process, the ultimate component of macromolecular damage and consequent cell death involves the altered redox balance inclined towards increased ROS production and/or decreased antioxidant protection. Given that, the chronic dihydrotachysterol (DHT) intoxication in rats induce Hutchinson Gilford progeria like syndrome, the present study provides the evidence for altered redox balance as evidenced by alteration in parameters of oxidative stress in blood plasma and erythrocytes including MDA, GSH, FRAP AOPP PMRS, AGEs, AChE and osmotic fragility which substantiate the suitability of the model for aging studies.

Rapamycin alleviates oxidative stress-induced damage in rat erythrocytes.

An imbalanced cellular redox system promotes the production of reactive oxygen species (ROS) that may lead to oxidative stress-mediated cell death. Erythrocytes are the best-studied model of antioxidant defense mechanism. The present study was undertaken to investigate the effect of the immunosuppressant drug rapamycin, an inducer of autophagy, on redox balance of erythrocytes and blood plasma of oxidatively challenged rats. Male Wistar rats were oxidatively challenged with HgCl2 (5 mg/kg body mass (b.m.)). A significant (p < 0.05) induction in ROS production, plasma membrane redox system (PMRS), intracellular Ca2+ influx, lipid peroxidation (LPO), osmotic fragility, plasma protein carbonyl (PCO) content, and plasma advanced oxidation protein products (AOPP) and simultaneously significant reduction in glutathione (GSH) level and ferric reducing ability of plasma (FRAP) were observed in rats exposed to HgCl2. Furthermore, rapamycin (0.5 mg/kg b.m.) provided significant protection against HgCl2-induced alterations in rat erythrocytes and plasma by reducing ROS production, PMRS activity, intracellular Ca2+ influx, LPO, osmotic fragility, PCO content, and AOPP and also restored the level of antioxidant GSH and FRAP. Our observations provide evidence that rapamycin improves redox status and attenuates oxidative stress in oxidatively challenged rats. Our data also demonstrate that rapamycin is a comparatively safe immunosuppressant drug.

Progress in the Development and Applicability of Potential Medicinal Plant Extract-Conjugated Polymeric Constructs for Wound Healing and Tissue Regeneration.

Wound, burn and tissue related diseases are the most common and devastating forms of trauma worldwide and thousands are still dying each year when they are left untreated. The traditional treatments for wound infection using medicinal plant extracts in hydrogels and ointment formulations have several disadvantages, delicate shape and dry up quickly upon exposure to air. Indeed, there is need for the development of an alternative form of dressing material for wound healing applications. Because the medicinal plant products are economical, researchers have adopted a novel approach of complexing the active components of plants with various groups of polymers to develop biodegradable fabrications. Moreover, fabricated constructs are very extremely useful as scaffold in tissue regeneration with known successes in wound healing/ dressing applications that the fabricated substitutes mimic the extracellular matrix of tissue. In this review, we give an extensive overview on scientifically evaluated bioactive molecules of medicinal plants as well as plant extract blended polymeric constructs for the possible treatment of various skin injuries. In addition, the technological challenges and future trends for recent developments of the treatments of wound infections are extensively summarized. Copyright © 2016 John Wiley & Sons, Ltd.