RESUMEN
[This corrects the article DOI: 10.3389/fnut.2023.1200118.].
RESUMEN
Objective: Stress, sleep, and immunity are important interdependent factors that play critical roles in the maintenance of health. It has been established that stress can affect sleep, and the quality and duration of sleep significantly impact immunity. However, single drugs capable of targeting these factors are limited because of their multi-targeting mechanisms. The present study investigated the influence of a proprietary thymoquinone-rich black cumin oil extract (BCO-5) in modulating stress, sleep, and immunity. Methods: A randomized double-blinded placebo-controlled study was carried out on healthy volunteers with self-reported non-refreshing sleep issues (n = 72), followed by supplementation with BCO-5/placebo at 200 mg/day for 90 days. Validated questionnaires, PSQI and PSS, were employed for monitoring sleep and stress respectively, along with the measurement of cortisol and melatonin levels. Immunity markers were analyzed at the end of the study. Results: In the BCO-5 group, 70% of the participants reported satisfaction with their sleep pattern on day 7 and 79% on day 14. Additionally, both inter- and intra- group analyses of the total PSQI scores and component scores (sleep latency, duration, efficiency, quality, and daytime dysfunction) on days 45 and 90 showed the effectiveness of BCO-5 in the improvement of sleep (p < 0.05). PSS-14 analysis revealed a significant reduction in stress, upon both intra (p < 0.001) and inter-group (p < 0.001) comparisons. The observed reduction in stress among the BCO-5 group, with respect to the placebo, was significant with an effect size of 1.19 by the end of the study (p < 0.001). A significant correlation was also observed between improved sleep and reduced stress as evident from PSQI and PSS. Furthermore, there was a significant modulation in melatonin, cortisol, and orexin levels. Hematological/immunological parameters further revealed the immunomodulatory effects of BCO-5. Conclusion: BCO-5 significantly modulated the stress-sleep-immunity axis with no side effects and restored restful sleep.
RESUMEN
Background: Although curcumin is a blood-brain-barrier permeable molecule with the ability to bind and segregate ß-amyloid plaques and neurofibrillary tangles of hyperphosphorylated tau proteins, its poor oral bioavailability, rapid biotransformation to inactive metabolites, fast elimination from the systemic circulation, and hence the poor neuronal uptake has been limiting its clinical efficacy under neurodegenerative conditions. Objective: We hypothesized that the highly bioavailable CurQfen-curcumin (CGM), which has been shown to possess significant blood-brain-barrier permeability and brain bioavailability, would ameliorate dementia in neurodegenerative conditions. Methods: In the present double-blinded placebo-controlled 3-arm 3-sequence comparative study, 48 subjects characterized with moderate dementia due to the onset of Alzheimer's disease were randomized into three groups (N = 16/group) and supplemented with 400 mg × 2/day of either placebo (MCC), unformulated standard curcumin complex with 95% purity (USC), or CGM as a sachet for six months. The relative changes in cognitive and locomotor functions and biochemical markers were compared. Results: Supplementation with CGM produced significant (P < 0.05) improvement in the Mini-Mental State Examination (MMSE) and the Geriatric Locomotive Function Scale (GLFS) scores in both intra- and inter-group comparison by 2 × 2 repeated measures (RM) ANOVA. Further, analysis of the serum levels of specific biomarkers (BDNF, Aß42, tau protein, IL-6, and TNF-α) also revealed a significant (P < 0.05) improvement among CGM subjects as compared to placebo and the USC groups. Conclusion: Supplementation with CGM as sachet was found to offer significant delay in the progress of Alzheimer's disease, as evident from the improvements in locomotive and cognitive functions related to dementia. Clinical trial registration: http://ctri.nic.in, identifier: CTRI/2018/03/012410.
RESUMEN
Black cumin or black seed (Nigella sativa L.) is a popular medicinal herb and culinary spice belonging to Ranunculacea family. Thymoquinone (TQ) is the major active phytoconstituent in black cumin and is abundant in the volatile oil fraction. Though black cumin oil containing low TQ content (less than 1%) has been clinically investigated, clinical efficacy and safety data of TQ-rich oil is limited. A recent study with black cumin oil formulation containing 5% TQ (BCO-5) exhibited significant clinical efficacy to alleviate sleep disorders and stress. So, the present phase 1 randomized, double-blinded, placebo-controlled trial evaluated the safety of BCO-5 at a dose of 200 mg/adult/day for 90 days on healthy subjects (n = 70). Both the biochemical and hematological parameters were analysed along with the adverse events or side effects to establish the clinical safety of BCO-5. The study reported neither serious adverse side effects nor any significant alterations in the hematological parameters. The absence of significant changes in the biochemical parameters related to liver function (ALT, AST, ALP), renal function (serum creatinine and urea) were also observed. However, analysis of lipid profile showed a significant (P < 0.05) reduction in total cholesterol, LDL, VLDL and triglycerides, but within the normal range. In conclusion, BCO-5 is safe at 200 mg/adult/day for human consumption and may be clinically evaluated for various health beneficial pharmacological activities where black cumin oil has been shown to have positive effects.
RESUMEN
OVERVIEW: A novel highly bioavailable curcumin-galactomannan (CGM) formulation was shown to have improved blood-brain-barrier (BBB) permeability of free curcuminoids in animal models; however, this has not been established in humans. The present study was conducted to determine the functional effects of CGM on brain waves in healthy individuals, owing to its BBB permeability. METHODS: A total of 18 healthy volunteers aged 35-65 were randomly assigned to consume 500 mg CGM, Unformulated curcumin (UC) or Placebo capsules twice daily for 30 days. Electroencephalogram (EEG) measurements, audio-visual reaction time tests and a working memory test were conducted at baseline and after 30 days. RESULTS: Supplementation of CGM resulted in a significant increase in α- and ß-waves (p < 0.05) as well as a significant reduction in α/ß ratio in comparison with unformulated curcumin and placebo groups. Furthermore, the CGM showed significant reduction in the audio-reaction time (29.8 %; p < 0.05) in comparison with placebo and 24.6% (p < 0.05) with unformulated curcumin. The choice-based visual-reaction time was also significantly decreased (36%) in CGM as compared to unformulated curcumin and placebo which produced 15.36% and 5.2% respectively. CONCLUSION: The observed increase in α and ß waves and reduction in α/ß ratio in the CGM group suggest that CGM can influence the brain waves in healthy subjects in a manner consistent with penetration of the blood-brain-barrier. The EEG results correlated with improved audio-visual and working memory tests which further support the role of CGM on memory improvements and fatigue reduction.
Asunto(s)
Ondas Encefálicas , Curcumina , Administración Oral , Animales , Encéfalo , Curcumina/farmacología , Método Doble Ciego , Galactosa/análogos & derivados , Humanos , Mananos , Proyectos PilotoRESUMEN
CONTEXT: Molecular pathogenesis of chronic alcoholism is linked to increased endoplasmic reticulum stress. Ethanol is a competitive inhibitor of vitamin A metabolism and vitamin A supplementation aggravates existing liver problems. Hence, we probed into the impact of supplementation of all trans retinoic acid (ATRA), the active metabolite of vitamin A on ethanol-induced endoplasmic reticulcum stress. METHODS: Male Sprague-Dawley rats were divided into four groups - I: Control; II: Ethanol; III: ATRA; IV: ATRA + Ethanol. After 90 days the animals were sacrificed to study markers of lipid peroxidation in hepatic microsomal fraction and expression of ER stress proteins and apoptosis in liver. RESULTS AND CONCLUSION: Ethanol caused hepatic hyperlipidemia, enhanced microsomal lipid peroxidation, upregulated expression of unfolded protein response associated proteins and that of apoptosis. Ethanol also led to downregulation of retinoid receptors. ATRA supplementation reversed all these alterations indicating the decrease in ethanol-induced endoplasmic reticulum stress.
Asunto(s)
Suplementos Dietéticos , Estrés del Retículo Endoplásmico , Hígado Graso Alcohólico/prevención & control , Hígado/metabolismo , Sustancias Protectoras/uso terapéutico , Receptores de Ácido Retinoico/agonistas , Tretinoina/uso terapéutico , Factor de Transcripción Activador 4/agonistas , Factor de Transcripción Activador 4/antagonistas & inhibidores , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Citocromo P-450 CYP2E1/química , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Etanol/toxicidad , Hígado Graso Alcohólico/enzimología , Hígado Graso Alcohólico/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratas Sprague-Dawley , Receptores de Ácido Retinoico/antagonistas & inhibidores , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo , Receptores X Retinoide/agonistas , Receptores X Retinoide/antagonistas & inhibidores , Receptores X Retinoide/genética , Receptores X Retinoide/metabolismo , Factor de Transcripción CHOP/agonistas , Factor de Transcripción CHOP/antagonistas & inhibidores , Factor de Transcripción CHOP/genética , Factor de Transcripción CHOP/metabolismo , Tretinoina/antagonistas & inhibidores , Respuesta de Proteína Desplegada/efectos de los fármacos , Proteína 1 de Unión a la X-Box/agonistas , Proteína 1 de Unión a la X-Box/antagonistas & inhibidores , Proteína 1 de Unión a la X-Box/genética , Proteína 1 de Unión a la X-Box/metabolismoRESUMEN
Nicotine is a parasympathomimetic alkaloid present in tobacco which can induce hyperlipidemia and has a direct effect on neural functions. Statins, competitive inhibitors of 3-hydroxymethyl-3-glutaryl-coenzyme-A reductase, are cholesterol lowering drugs. It has some neuroprotective effects. Hence we analysed the combined effect of nicotine and statin on the learning behaviour of male albino rats. We employed Y-Maze conditional discrimination task. Rats were divided into 4 groups with six rats in each group. (1) Control, (2) Atorvastatin (10mg/kgb.wt), (3) Nicotine (0.6mg/kgb.wt) and (4) Atorvastatin (10mg/kgb.wt)+Nicotine (0.6mg/kgb.wt). After 30days of treatment rats from each group were selected for behavioural study and they were observed for 30days. At the end of the experimental period rats were sacrificed, and brain and liver were dissected out for further biochemical analysis. Nicotine treated group showed least performance in learning in comparison with control, atorvastatin and atorvastatin+nicotine treated groups. Co-administration of atorvastatin and nicotine improved learning behaviour compared to nicotine treated group. Reactive oxygen species level was significantly increased in nicotine group compared to control. The level of neurotransmitter serotonin which has a significant role in learning was found to be decreased in nicotine treated group compared to the control group. Activity of Na(+) K(+) ATPase, Ca(2+) ATPase and glutathione content was significantly reduced in nicotine treated group compared to control. The activity of acetylcholine esterase was significantly increased in the nicotine treated group. Expression studies showed significant decrease in N-methyl D-aspartate receptors and increase in mono amine oxidase-A and mono amine oxidase-B in nicotine treated group and was reversed in atorvastatin + nicotine treated group. It can be concluded that co-administration of nicotine with statin ameliorates the neural functional alterations caused by nicotine to a significant level.
Asunto(s)
Atorvastatina/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Adenosina Trifosfatasas/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/enzimología , Aprendizaje Discriminativo/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Monoaminooxidasa/biosíntesis , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Receptores de N-Metil-D-Aspartato/biosíntesis , Serotonina/metabolismoRESUMEN
OBJECTIVE: To investigate the efficacy of combined administration of alpha-tocopherol (AT) and ascorbic acid (AA) in reducing ethanol-induced hepatotoxicity. METHODS: Rats were maintained for 90 days and grouped as follows: I-control rats, II-ethanol, III-alpha-tocopherol, IV-ethanol+alpha-tocopherol, V-AA, VI-ethanol+ascorbic acid, VII-alpha-tocopherol+ascorbic acid, VIII-ethanol+alpha-tocopherol+ascorbic acid. At the end of the experimental period, markers of hepatic function, oxidative stress, and the expression of markers of inflammation and fibrosis were assayed. RESULTS: The markers of hepatic function, lipid peroxidation products, protein carbonyls, and the expression of nuclear factor kappa B, tumor necrosis factor alpha, transforming growth factor beta 1, cytochrome P4502E1, and collagen Type I were elevated after ethanol administration. All these parameters were reduced in the ethanol group administered AT and AA in combination. The activities of antioxidant enzymes which were reduced by ethanol administration were enhanced on combined administration of AT and AA. The reduction in hepatic fibrosis was almost 20% more in AT and AA co-administered group compared with AT and AA alone treated groups. DISCUSSION: Combined administration of fat soluble AT and water soluble AA was beneficial against ethanol-induced hepatotoxicity. This may be due to their different subcellular localizations.