Corrigendum: Exploring the short-term influence of a proprietary oil extract of black cumin (Nigella sativa) on non-restorative sleep: a randomized, double-blinded, placebo-controlled actigraphy study.

[This corrects the article DOI: 10.3389/fnut.2023.1200118.].

A proprietary black cumin oil extract (Nigella sativa) (BlaQmax®) modulates stress-sleep-immunity axis safely: Randomized double-blind placebo-controlled study.

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.

Attenuation of obesity related inflammation in RAW 264.7 macrophages and 3T3-L1 adipocytes by varanadi kashayam and identification of potential bioactive molecules by UHPLC-Q-Orbitrap HRMS.

Obesity is associated with chronic low-grade inflammation, characterised by the up-regulation of pro-inflammatory cytokines in obese adipose tissue. In this study, 3T3-L1 CM enhanced TNF-α and IL-1ß in RAW 264.7 cells compared with LPS treated cells. However, treatment with Varanadi kashayam suppressed the inflammatory changes associated with RAW 264.7 cells. Subsequently, RAW CM used to stimulate adipocytes, resulting in decreased intracellular lipid content and reduced adipogenic markers after Varanadi kashayam treatment. The chemical profiling of Varanadi kashayam using UHPLC-Q-Orbitrap-HRMS identified 194 compounds by comparing their retention time, the experimentally measured exact mass of precursor, and fragmented ions, and fragmentation pattern with spectral library and reported literature. Collectively, Varanadi kashayam act as a potent anti-inflammatory and anti-adipogenic agent that could disrupt the crosstalk between adipocytes and macrophages. Hence it could be a better candidate for reducing inflammation associated with obese adipose tissue.

Exploring the short-term influence of a proprietary oil extract of black cumin (Nigella sativa) on non-restorative sleep: a randomized, double-blinded, placebo-controlled actigraphy study.

Background: Nigella sativa (black cumin, or black seed) is popularly known as the seed of blessings in the Arab system of medicine. Though not widely recommended for sleep, a unique proprietary black cumin extract (BlaQmax®/ThymoDream™; BCO-5) has been shown to be helpful in the management of stress and sleep issues. Methods: This randomized, double-blind, placebo-controlled trial aimed to investigate the efficacy of BCO-5 on the sleep quality of volunteers characterized with a self-reported non-restorative sleep disorder. Healthy male and female participants (n = 70), aged 18-65 years (BMI 22-28 Kg/m2) were randomized to either placebo or BCO-5 (n = 35/group). Both interventions were supplemented at 200 mg/day for seven days. Actigraphy and a validated restorative sleep questionnaire (RSQ-W) were used to monitor the influence of BCO-5 on sleep. Results: Compared to placebo, BCO-5 significantly improved sleep quality, as evidenced by both intra-group and inter-group analyses of the actigraphy data. The relative improvements observed were sleep efficiency (7.8%, p < 0.001), total sleep time (19.1%, p < 0.001), sleep onset latency (35.4%; p < 0.001), and wake-after-sleep-onset (22.5%; p < 0.001) compared with placebo. BCO-5 also improved sleep by 75.3% compared to baseline (p < 0.001) and by 68.9% compared to placebo (p < 0.001), when monitored by RSQ-W. BCO-5 was well-tolerated with no reports of side effects or toxicity. Conclusion: BCO-5 significantly improved non-restorative sleep in seven days, indicating its potential role as a natural sleep aid.

Protective effect of (+)-catechin against lipopolysaccharide-induced inflammatory response in RAW 264.7 cells through downregulation of NF-κB and p38 MAPK.

Catechin, a flavonol belonging to the flavonoid group of polyphenols is present in many plant foods. The present study was done to evaluate the effect of catechin on various inflammatory mediators using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The effect of catechin on total cyclooxygenase (COX) activity, 5-lipoxygenase (5-LOX), myeloperoxidase, nitrite and inducible nitric oxide synthase (iNOS) level, secretion of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were assessed in LPS-stimulated RAW 264.7 cells. The expression of COX-2, iNOS, TNF-α, nuclear factor-ĸB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) genes were also investigated. The effect was further analyzed using human PBMCs by assessing the level of TNF-α and IL-10. The study demonstrated that the inflammatory mediators such as COX, 5-LOX, nitrite, iNOS, and TNF-α were significantly inhibited by catechin in a concentration-dependent manner whereas IL-10 production was up-regulated in RAW 264.7 cells. Moreover, catechin down-regulated the mRNA level expression of COX-2, iNOS, TNF-α, NF-κB and p38 MAPK. The current study ratifies the beneficial effect of catechin as a dietary component in plant foods to provide protection against inflammatory diseases.

Modulation of proinflammatory cytokines and enzymes by polyherbal formulation Guggulutiktaka ghritam.

BACKGROUND: Guggulutiktaka ghritam is an ayurvedic medicine which has been traditionally used to treat various chronic inflammatory conditions. However, the mechanism of action of the Ayurvedic medication in control of inflammatory conditions has not been clearly evaluated. OBJECTIVE: In the current study, the effect of the Guggulutiktaka ghritam extract (GTG) on the lipoxygenase pathway and in the production of proinflammatory cytokines involved in the pathogenesis of chronic inflammation was studied. MATERIALS AND METHODS: The effect of GTG in the production of leukotriene was determined by enzyme inhibition studies on 12- lipoxygenase. The assay was carried out by ferrous oxidation of xylenol orange (FOX assay) and was compared to a positive control nordihydroguaiaretic acid. The effect of GTG on the production of proinflammatory cytokines TNF-α and IL-1ß in monocytes were studied. For this, the monocytes were pretreated with various concentrations of GTG and subsequently stimulated with lipopolysaccharide. The cytokines TNF-α and IL-1ß produced were quantified by ELISA and the results were compared to positive controls Rolipram and Dexamethasone respectively. The gene expression studies were carried out using qRT-PCR. The IC50 values were calculated and evaluated statistically. RESULTS: The result indicates that GTG in comparison to the positive control Nordihydroguaiaretic acid significantly reduced the activity of 12- lipoxygenase. Also, there was significant inhibition in the production of proinflammatory cytokines in LPS stimulated monocytes pretreated with GTG as compared to positive control Rolipram and Dexamethasone. There was significant downregulation of IL-1ß gene in LPS stimulated monocytes pretreated with GTG as compared to control. These changes are further supported by Raman spectra obtained for GTG treated and untreated cells. CONCLUSION: The study revealed that GTG is a leukotriene and cytokine inhibitor. The inhibition in the production of cytokines may be due to the down-regulation of genes for TNF-α and IL-1ß. The study provides a scientific validation on the possible anti-inflammatory mechanism of action of this traditionally used medicine. Identification of bioactive molecules would aid in developing newer therapeutics for control of chronic inflammation.

Evaluation of anti-inflammatory effect of Varanadi Kashayam (decoction) in THP-1-derived macrophages.

BACKGROUND: Varanadi Kashayam is an Ayurvedic polyherbal decoction containing 16 ingredients, for which the mechanisms of action involved in controlling chronic inflammatory conditions have not been evaluated. The inhibition of release of proinflammatory cytokines by lipopolysaccharide (LPS)-stimulated monocytes/macrophages is an ideal in vitro model for identifying anti-inflammatory molecules. AIM: The aim of the study is to determine the anti-inflammatory effect of Varanadi Kashayam in THP-1-derived macrophages. MATERIALS AND METHODS: The efficacy of Varanadi Kashayam on monocyte cell differentiation was determined by quantitative polymerase chain reaction to assess the expression of differentiation markers MMP-9, CD36, CD11b and CD14. Further Varanadi Kashayam treated THP-1 macrophages were induced with LPS and the production of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß) were measured and corresponding genes expressions were quantified. RESULTS: The results indicate that Varanadi Kashayam reduced the differentiation of THP-1 monocytes to macrophages and downregulated the expression of cell surface markers. Furthermore, it could decrease the release of proinflammatory cytokines from LPS-induced THP-1 macrophages and downregulated the expression of TNF-α and IL-1ß genes. CONCLUSION: The results obtained from this study suggest a possible mechanism of action of the herbal decoction in inflammatory processes and opens up the possibilities of identifying bioactive lead molecules with anti-inflammatory potentials.

Inhibition of proinflammatory pathways by bioactive fraction of Tinospora cordifolia.

Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thomson, a known immunomodulatory agent extensively used in ayurveda, has not been effectively validated for the mechanisms involved in immunomodulation and the identification of the active principles. The bioactive fraction of T. cordifolia (TBF) in methanol was used for nitric oxide (NO) radical scavenging activity, lipoxygenase (LOX) and cyclooxygenase (COX) dual inhibition and cytotoxicity studies. Production of the proinflammatory cytokines, tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in dendritic cell (DC) suspensions treated with lipopolysaccharide (LPS) was also studied. The bioactive principles involved were identified with ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometric (UPLC-Q-ToF MS/MS) system. The results indicate significantly higher potency of TBF as compared to positive standards for LOX/COX inhibition with moderate NO radical scavenging activity and the fraction was also found to be non-cytotoxic to monocyte cells. A significant inhibition was also observed in TNF-α and IL-1ß production in LPS-treated DC suspensions as compared to standards, rolipram and dexamethasone, respectively. 11 compounds were identified from TBF by MS/MS system. The potent inhibition of LOX and COX enzymes with moderate NO scavenging was indicative of a free radical scavenging-independent mechanism of immunomodulation. Further investigations into the active principles identified would result in the development of lead candidates with potent therapeutic implications.

Inhibition of Tumor Necrosis Factor-α and Interleukin-1ß Production in Lipopolysaccharide-Stimulated Monocytes by Methanolic Extract of Elephantopus scaber Linn and Identification of Bioactive Components.

The methanolic extract of E. scaber Linn was evaluated for anti-inflammatory activity by determining its effects on production of pro-inflammatory cytokines like Tumor necrosis factor-α (TNF-α) and Interleukin-1ß (IL-1ß) in Lipopolysaccharide (LPS) stimulated monocytes. The cytotoxicity of the extract was analyzed prior to the cytokine quantification assays. The extract was further subjected to UPLC MS Q-TOF, for the identification of bioactive components present in the crude extract. The extract was found not to be cytotoxic against monocytes, and exhibited significant inhibition in the production of pro-inflammatory cytokines. The presence of 34 components in the methanolic extract was detected through mass spectrum analysis.