curcumin and Alcoholism

Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade free-curcuminoids delivery system (curcumin-galactomannoside complex; CGM) in improving the hepatic function markers (inflammation and oxidative stress) in chronic alcoholics. The double-blinded, placebo-controlled study randomized 48 subjects with elevated serum transaminases and gamma-glutamyl transferase (GGT) levels, who were allocated to two groups (n=24) and to receive either placebo or CGM at (250 mg × 2)/day for 8 weeks. While liver function markers (transaminases and GGT) in the placebo group showed an increase (~ 9.5%), CGM group indicated a significant decrease in transaminases (31%) and GGT (29%) from the baseline levels. The beneficial effect of CGM was also clear from the significant increase (p <0.001) in endogenous antioxidants (GSH, SOD, and GPx) and decrease in inflammatory markers (IL-6 and CRP) levels (p <0.001) as compared to both the baseline and placebo group. To summarize, the nutritional intervention of CGM-curcumin was found to offer a significant hepatoprotective effect to attenuate the alcohol induced alterations to hepatic function markers. The Indian Medical Council and Drug Controller General of India approved Clinical Trial Registry No. CTRI/2018/03/012385.

Topics: Adult; Alcoholism; Biomarkers; Chronic Disease; Curcumin; Double-Blind Method; Drug Delivery Systems; gamma-Glutamyltransferase; Humans; Liver; Male; Middle Aged; Transaminases

Curcumin (CUR) shows great potential in the management of alcohol-use disorders. However, the hydrophobicity and poor oral bioavailability result in the limited therapeutic efficacy of CUR against alcohol-induced tissue injury. Here, self-assembled Soluplus® micelles (Ms) were developed for the enhanced oral delivery of CUR. CUR-loaded Soluplus® micelles (CUR-Ms) were prepared using a thin-film hydration method and these micelles displayed nearly spherical shape with an average size of 62.80 ± 1.29 nm. CUR in micelles showed the greater stability, solubility and dissolution than free CUR. With the increased water solubility of CUR-Ms and P glycoprotein inhibition of Soluplus®, the absorption rate constant (Ka) and apparent permeability coefficient (Papp) of CUR-Ms in intestines was respectively 3.50 and 4.10 times higher than that of free CUR. Pharmacokinetic studies showed that CUR-Ms significantly improved the oral bioavailability of CUR. Specifically, the AUC0-∞ and C

Topics: Administration, Oral; Alcoholism; Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Liver Diseases, Alcoholic; Male; Mice; Mice, Inbred C57BL; Micelles; Rats; Rats, Sprague-Dawley

Curcumin can chelate metal ions, forming metallocomplexes. We compared the effects of Zn(II)-curcumin with curcumin against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism. Oral administration of Zn(II)-curcumin dose-dependently prevented the ethanol-induced elevation of serum malondialdehyde (MDA) content and reductions in glutathione level and superoxide dismutase (SOD) activity. Zn(II)-curcumin also inhibited ethanol-induced liver injury. Additionally, Zn(II)-curcumin dose-dependently inhibited hemorheological abnormalities, including the ethanol-induced elevation of whole blood viscosity, plasma viscosity, blood viscosity at corrected hematocrit (45%), erythrocyte aggregation index, erythrocyte rigidity index and hematocrit. Compared to curcumin at the same dose, Zn(II)-curcumin more effectively elevated SOD activity, ameliorated liver injury and improved hemorheological variables. These results suggest that Zn(II)-curcumin protected the rats from ethanol-induced liver injury and hemorheological abnormalities via the synergistic effect of curcumin and zinc.

Topics: Alcoholism; Animals; Blood Viscosity; Curcumin; Disease Models, Animal; Erythrocyte Aggregation; Ethanol; Female; gamma-Glutamyltransferase; Glutathione; Hematocrit; Liver; Malondialdehyde; Oxidative Stress; Protective Agents; Rats, Sprague-Dawley; Superoxide Dismutase; Zinc

Ethanol consumption induces hepatocellular carcinoma (HCC) cell metastasis by changing the extracellular matrix (ECM). Lysyl oxidase (LOX) catalyzes the cross-linkage of collagen or elastin in the ECM. LOX protein and mRNA overexpression (>21-fold compared with controls, n = 6) was detected in cirrhotic HCC patients with a history of alcoholism. LOX protein expression was induced in HCC cells after long-term treatment with ethanol (10 mM) for 20-40 passages (denoted E20-E40 cells). Pterostilbene (PSB, 1 μM) displayed significant potency to reduce LOX-mediated activity in E40 cells when combined with curcumin and its analogues. The ability of E40 cells to form colonies in soft agar was reduced by both genetic depletion of LOX and by chemical inhibitors of LOX expression. This study suggests that targeting LOX expression with food components such as PSB and curcumin may be a novel strategy to overcome ethanol-induced HCC cell metastasis in liver cancer patients.

Topics: Adult; Aged; Alcoholism; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Movement; Collagen; Curcumin; Elastin; Ethanol; Extracellular Matrix; Female; Gene Expression Regulation; Humans; Laser Capture Microdissection; Liver Neoplasms; Male; Middle Aged; Protein-Lysine 6-Oxidase; Real-Time Polymerase Chain Reaction; RNA, Messenger; Stilbenes

Chronic alcohol drinking has been associated with the development of a number of abnormalities, including neuron-behavioral disorders, liver, pancreas, and heart-related diseases and inflammation and immune disorders. Because diverse mechanisms are involved in the development of these disorders, the commonly used receptor- or enzyme-specific drugs do not provide comprehensive protection against the adverse effects of alcoholism. This study describes possible therapeutic potency of puerarin (PU) from kudzu root, polyenylphosphatidylcholine from soy (SPCh), and curcumin (CU) from turmeric against alcohol's addiction-related and inflammatory-related abnormalities in alcohol-preferring P rats receiving free choice water and 15% ethanol in water. P-rats were fed once daily either the vehicle (for control) or different doses of PU, SPCh, CU, PU + SPCh, or PU + CU. The rats were divided in two groups: one received water alone, and the other free choice water and ethanol. Four rats from each group were fitted with electroencephalogram (EEG) electrodes for EEG recording. After 70 days of alcohol drinking, alcohol was withdrawn for 2 weeks, and the withdrawal symptoms were assessed. This study showed that alcohol drinking for 70 days (1) caused liver inflammation characterized by elevated tumor necrosis factor-alpha, interleukin-1beta, and matrix metalloproteinase-9 expression and (2) dysregulated lipopolysaccharide (LPS)-induced pleurisy. Alcohol withdrawal after 70 days of drinking generated severe withdrawal symptoms including seizure-type EEG activity. PU suppressed the addiction-mediated abnormalities but did not affect the inflammation-related abnormalities, while SPCh or CU suppressed only the inflammation-related abnormalities in alcohol-drinking rats subjected to LPS-induced pleurisy. A combination of PU with SPCh or CU suppressed both the addiction-related and inflammation-related abnormalities of alcohol drinking. Therefore, a mixture consisting of PU and either SPCh or CU may provide alternative therapy for alcohol-related disorders.

Topics: Acetaldehyde; Alcohol-Related Disorders; Alcoholism; Animals; Apoptosis; Curcumin; Electroencephalography; Ethanol; Female; Hepatitis, Alcoholic; Inflammation; Interleukin-1beta; Isoflavones; Liver; Matrix Metalloproteinase 9; Monocytes; Phosphatidylcholines; Phytotherapy; Pleural Effusion; Rats; RNA, Messenger; Tumor Necrosis Factor-alpha