curcumin and Atrophy

For thousands of years, mankind has been using plant extracts or plants themselves as medicinal herbs. Currently, there is a great deal of public interest in naturally occurring medicinal substances that are virtually non-toxic, readily available, and have an impact on well-being and health. It has been noted that dietary curcumin is one of the regulators that may positively influence changes in the brain after ischemia. Curcumin is a natural polyphenolic compound with pleiotropic biological properties. The observed death of pyramidal neurons in the CA1 region of the hippocampus and its atrophy are considered to be typical changes for post-ischemic brain neurodegeneration and for Alzheimer's disease. Additionally, it has been shown that one of the potential mechanisms of severe neuronal death is the accumulation of neurotoxic amyloid and dysfunctional tau protein after cerebral ischemia. Post-ischemic studies of human and animal brains have shown the presence of amyloid plaques and neurofibrillary tangles. The significant therapeutic feature of curcumin is that it can affect the aging-related cellular proteins, i.e., amyloid and tau protein, preventing their aggregation and insolubility after ischemia. Curcumin also decreases the neurotoxicity of amyloid and tau protein by affecting their structure. Studies in animal models of cerebral ischemia have shown that curcumin reduces infarct volume, brain edema, blood-brain barrier permeability, apoptosis, neuroinflammation, glutamate neurotoxicity, inhibits autophagy and oxidative stress, and improves neurological and behavioral deficits. The available data suggest that curcumin may be a new therapeutic substance in both regenerative medicine and the treatment of neurodegenerative disorders such as post-ischemic neurodegeneration.

Topics: Alzheimer Disease; Amyloid; Animals; Apoptosis; Atrophy; Biological Availability; Blood-Brain Barrier; Brain Edema; Brain Ischemia; Curcumin; Disease Models, Animal; Gastrointestinal Microbiome; Gerbillinae; Hippocampus; Humans; Mice; Neuroinflammatory Diseases; Neuroprotective Agents; Oxidative Stress; Rats; tau Proteins

Cachexia is a multifactorial debilitating syndrome that is responsible for 22% of mortality among cancer patients, and there are no effective therapeutic agents available. Curcumin, a polyphenolic compound derived from the plant turmeric, has been shown to have anti-inflammatory, antioxidant, anti-autophagic, and antitumor activities. However, its function in cancer cachexia remains largely unexplored.. This study aimed to elucidate the mechanisms by which curcumin improves adipose atrophy in cancer cachexia.. C26 tumor-bearing BALB/c mice and β3-adrenoceptor agonist CL316243 stimulated BALB/c mice were used to observe the therapeutic effects of curcumin on the lipid degradation of cancer cachexia in vivo. The effects of curcumin in vitro were examined using mature 3T3-L1 adipocytes treated with a conditioned medium of C26 tumor cells or CL316243.. Mice with C26 tumors and cachexia were protected from weight loss and adipose atrophy by curcumin (50 mg/kg, i.g.). Curcumin significantly reduced serum levels of free fatty acids and increased triglyceride levels. In addition, curcumin significantly inhibited PKA and CREB activation in the adipose tissue of cancer cachectic mice. Curcumin also ameliorated CL316243-induced adipose atrophy and inhibited hormone-mediated PKA and CREB activation in mice. Moreover, the lipid droplet degradation induced by C26 tumor cell conditioned medium in mature 3T3-L1 adipocytes was ameliorated by curcumin (20 µM) treatment. Curcumin also improved the lipid droplet degradation of mature 3T3-L1 adipocytes induced by CL316243.. Curcumin might be expected to be a therapeutic supplement for cancer cachexia patients, primarily through inhibiting adipose tissue loss via the cAMP/PKA/CREB signaling pathway.

Topics: Animals; Atrophy; Cachexia; Culture Media, Conditioned; Curcumin; Lipolysis; Mice; Neoplasms; Obesity; Signal Transduction

Occupational and ecological contacts to lead persist as a universal concern. Lead alters most of the physiological processes via enhancing oxidative stress. Thus, this study was purposed to assess the influence of turmeric (TMRC) and/or vitamin C (VIT-C) on Lead diacetate (Lead diAC)-induced testicular atrophy with an emphasis on oxidative stress, inflammation, BAX/STAR and GRP-78/17β-HSD signalling. Rats were injected with Lead diAC and then treated with TMRC and/or VIT-C orally for 1 week. Lead diAC decreased serum testosterone and testicular glutathione levels. It also decreased superoxide dismutase activity. On the contrary, levels of malondialdehyde, tumour necrosis factor-α, IL-1β and caspase-3 were increased. mRNA levels and protein expressions of GRP-78 and BAX were upregulated, while the expression of both steroidogenic acute regulatory protein and 17β-HSD were downregulated. DNA fragmentation was increased as well. These changes were further confirmed by histopathological findings. Supplementation with TMRC and/or VIT-C ameliorated all of the above parameters. In Conclusion: TMRC or VIT-C specially in combination group prevents Lead diAC testicular damage via reduction of oxidative injury as well as inflammation, downregulation of GRP-78/BAX and upregulation of 17β-HSD and STAR expression as well as improvement in the histological architecture of the testis.

Topics: Animals; Ascorbic Acid; Atrophy; Curcuma; Male; Organometallic Compounds; Oxidative Stress; Rats; Testis; Testosterone

Cerebellar ataxias comprise a group of terminal illnesses with ataxia as the main symptom. Curcumin as a yellow polyphenol was extracted from the rhizome ofCurcuma longa. Owing to its antioxidant, anti-inflammatory, anti-fibrotic and anti-tumor features, curcumin is considered as a potential therapeutic agent.. In this study, we aim to investigate the neuroprotective effects of oral administration of curcumin on a rat model of cerebellar ataxia induced by neurotoxin 3-acetylpyridine.. The animals were randomly separated into three groups (control, 3-acetylpyridine, and curcumin + 3-acetylpyridine). Next, motor performance and muscle electromyography activity were assessed. Then, in the molecular part of the study, the anti-apoptotic role of curcumin in cerebellar ataxia and its relationship to protection of Purkinje cells were investigated.. Curcumin treatment improved motor coordination and muscular activity, reduced cleaved caspase-3, and increased glutathione level in 3-AP-lesioned rats as well as total volumes of cerebellar granular and molecular layers.. the present study implies that curcumin might have neuroprotective effects to counteract neurotoxicity of 3-AP-induced ataxia.

Topics: Animals; Atrophy; Cerebellar Ataxia; Cerebellum; Curcumin; Disease Models, Animal; Electromyography; Male; Motor Activity; Neuroprotective Agents; Purkinje Cells; Pyridines; Rats; Rats, Sprague-Dawley

Malnutrition resulting from protein and calorie deficiency continues to be a major concern worldwide especially in developing countries. Specific deficiencies in the protein intake can adversely influence reproductive performance. The present study aimed to evaluate the effects of curcumin and curcumin nano-emulsion on protein deficient diet (PDD)-induced testicular atrophy, troubled spermatogenesis and decreased reproductive performance in male rats.. PDD induced significant (P < 0.05) reduction in serum testosterone level, sperm motility, testicular GSH, CAT, SOD, testicular cell energy (ATP, ADP and AMP), essential and non-essential amino acids in seminal plasma, an increase in testicular MDA, NOx, GSSG and 8-OHDG. Data was confirmed by histological examination and revealed pathological alteration in the PDD group. Ingestion of curcumin (50 mg/kg) and curcumin nano-emulsion (2.5 and 5 mg/kg) showed significant (P< 0.05) amelioration effects against PDD-induced disrupted reproductive performance as well as biochemical and pathological alterations and the overall results of the nano-emulsion (5 mg/kg) were comparable to curcumin (50 mg/kg).. The present study suggests that administration of curcumin nano-emulsion as a daily supplement would be beneficial in malnutrition- induced troubled male reproductive performance and spermatogenesis cases.

Topics: Animal Feed; Animals; Atrophy; Curcumin; Diet; Dietary Proteins; Dietary Supplements; Drug Delivery Systems; Emulsions; Male; Protective Agents; Rats; Rats, Wistar; Reproduction; Spermatogenesis; Testis

Curcumin, the extract of the rhizome of Curcuma longa, is known for its health-promoting properties in traditional medicine. It has anti-inflammatory, antitumor and antioxidant properties and stimulates appetite. In the present study, we investigated the stability of curcumin and its effect on cytotoxicity, apoptosis and melanin content in melanoma cells and the effect on atrophic C2C12 muscle cells. Cytotoxicity of curcumin was dose-dependent and the EC50 for 24-h incubation was 69 μM. Saturation was reached at 30 μM for a 48-h incubation. The EC50 for 24-h incubation with degraded curcumin solution was 116 μM and that for 48-h was 94 μM. Curcumin induced a strong increase in caspase-3/7 activity at 30-40 μM. Electrical impedance measurements showed that sub-toxic doses of curcumin counteracted atrophy in an in vitro model system. These findings indicate not only the positive effects of curcumin on melanoma cells in vitro, but also that curcumin was able to considerably trigger anti-cachectic effects in vitro. However, the importance of the stability of curcumin and its tumoricidal and anti-cachectic potential might play a pivotal role in its use in the nutrition and health industrie since it degrades rapidly in aqueous solutions.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Atrophy; Cachexia; Caspases; Cell Death; Cell Survival; Curcumin; Enzyme Activation; Glycoproteins; Hypertrophy; Inhibitory Concentration 50; Melanoma, Experimental; Mice; Toxins, Biological

Okadaic acid (OKA) has been observed to cause memory impairment in human subjects having seafood contaminated with dinoflagellate (Helicondria okadai). OKA induces tau hyperphosphorylation and oxidative stress leading to memory impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced memory impairment. Therefore, present study evaluated the effect of curcumin on OKA (100ng, intracerebrally) induced memory impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in memory impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca(2+))i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50mg/kg) for 13 days significantly improved memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca(2+))i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive impairment.

Topics: Acetylcholine; Acetylcholinesterase; Adenosine Triphosphate; Animals; Apoptosis; Atrophy; Avoidance Learning; Brain; Calcium; Curcumin; Energy Metabolism; Glutathione; Male; Malondialdehyde; Maze Learning; Memory; Mice; Microcirculation; Mitochondria; Motor Activity; Neurons; Neuroprotective Agents; Okadaic Acid; Organ Size; Phosphorylation; Reactive Oxygen Species; Transcription, Genetic

Cancer patients often exhibit loss of proper cell-mediated immunity and reduced effector T-cell population in the circulation. Thymus is a major site of T-cell maturation, and tumors induce thymic atrophy to evade cellular immune response. Here, we report severe thymic hypocellularity along with decreased thymic integrity in tumor bearer. In an effort to delineate the mechanisms behind such thymic atrophy, we observed that tumor-induced oxidative stress played a critical role, as it perturbed nuclear factor-kappaB (NF-kappaB) activity. Tumor-induced oxidative stress increased cytosolic IkappaBalpha retention and inhibited NF-kappaB nuclear translocation in thymic T cells. These NF-kappaB-perturbed cells became vulnerable to tumor-secreted tumor necrosis factor (TNF)-alpha (TNF-alpha)-mediated apoptosis through the activation of TNF receptor-associated protein death domain-associated Fas-associated protein death domain and caspase-8. Interestingly, TNF-alpha-depleted tumor supernatants, either by antibody neutralization or by TNF-alpha-small interfering RNA transfection of tumor cells, were unable to kill T cell effectively. When T cells were overexpressed with NF-kappaB, the cells became resistant to tumor-induced apoptosis. In contrast, when degradation-defective IkappaBalpha (IkappaBalpha super-repressor) was introduced into T cells, the cells became more vulnerable, indicating that inhibition of NF-kappaB is the reason behind such tumor/TNF-alpha-mediated apoptosis. Curcumin could prevent tumor-induced thymic atrophy by restoring the activity of NF-kappaB. Further investigations suggest that neutralization of tumor-induced oxidative stress and restoration of NF-kappaB activity along with the reeducation of the TNF-alpha signaling pathway can be the mechanism behind curcumin-mediated thymic protection. Thus, our results suggest that unlike many other anticancer agents, curcumin is not only devoid of immunosuppressive effects but also acts as immunorestorer in tumor-bearing host.

Topics: Animals; Atrophy; Cell Death; Cell Line, Tumor; Curcumin; Humans; Mice; Neoplasms, Experimental; NF-kappa B; Oxidative Stress; Receptors, Tumor Necrosis Factor, Type I; T-Lymphocytes; Thymus Gland; Tumor Necrosis Factor-alpha