Repeated traumatic brain injury has grown in importance as sports-related injuries have increased. Repetitive mild TBI (rmTBI) increases the risk of developing neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, as well as chronic comorbidities like PTSD, depression, substance abuse and neuroendocrine functions. However, no effective therapeutic strategies have been reported for the effective management of TBI. Herein, we examined the effectiveness of co-delivery of the phytonutrients curcumin, trans-resveratrol, and carnosic acid as a bioavailable complex (CGM+) in managing rmTBI in the rodent model. The rats were randomly assigned to sham, rmTBI, and CGM+ (300 mg/kg b.wt.) groups for a total of 21 days. On Days 6 and 7, all animals, except those in the sham group, were subjected to repeated mild traumatic brain injury (rmTBI). The CGM+ group received supplementation throughout the 21 days, while the other groups received a vehicle. Neurological severity score (NSS) was assessed 24 h after the last injury, and behavioral tests were completed within 14 days post-injury. Samples for the biochemical analysis were collected after euthanasia. CGM+ supplementation significantly decreased the sensory-motor deficits associated with rmTBI. Following TBI, the CGM+ group demonstrated enhanced memory and low-stress levels. Furthermore, CGM+ has been shown to modulate neurotransmitter levels and promote neurogenesis. The biochemical and molecular analysis revealed that CGM+ promotes recovery following rmTBI by modulating mitochondrial bioenergetics and BDNF pathways. The findings indicate that CGM+ can be used to manage cognitive and sensory-motor defects caused by rmTBI, such as in the case of sports injuries.

IntroductionAllergic rhinitis (AR) is an IgE-mediated reaction to inhaled allergens, and is a prominent health concern affecting approximately 400 million people worldwide. A comprehensive understanding of AR's pathophysiology is imperative for developing novel therapies, especially considering its frequent co-morbidity with asthma and conjunctivitis. The escalating prevalence of AR is correlated with increased urbanization and environmental pollutants, recognized as prominent contributing factors. Dysregulation in immune networks, Th1/Th2 cytokine imbalance, activation of mast cells and eosinophils are implicated in AR progression. Classic AR symptoms include nasal congestion, nasal itching, rhinorrhea, and sneezing which significantly impact the quality of life, social interactions, and workplace productivity.MethodsThis randomized, double-blind, placebo-controlled, three-arm, three-sequence study was aimed to assess the efficacy of supplementation of a co-delivery form of turmeric extract with ashwagandha extract (CQAB) in comparison with a bioavailable curcumin (CGM) and placebo in alleviating AR symptoms and enhancing the quality of life in individuals with mild AR. Participants received either placebo, CGM, or CQAB twice/day for 28 days, and subjective measures were recorded at the baseline and at the end of study.ResultsCQAB supplementation demonstrated a significant (P < 0.05) improvement in Total Nasal Symptom Score (TNSS) compared to placebo and CGM. Furthermore, CQAB administration resulted in enhanced sleep quality (P < 0.05) as evaluated by the BIS questionnaire, heightened energy levels, and decreased fatigue and overall mood disturbance (POMS-SF) compared to both placebo and CGM.ConclusionThe results suggests that CQAB has the potential to be used as a dietary supplement in alleviating AR discomforts.Clinical Trial Registrationhttps://ctri.nic.in/Clinicaltrials/login.php; Identifier CTRI/2021/01/030355.

BackgroundNigella 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.MethodsThis 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.ResultsCompared 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.ConclusionBCO-5 significantly improved non-restorative sleep in seven days, indicating its potential role as a natural sleep aid.

IntroductionOverweight and obesity are major public health concerns, with a sharp increase in prevalence over the last few decades. The primary cause is an imbalance between calorie intake and expenditure due to a rise in calorie-rich processed food and reduced physical activity. Energy balance in humans involves complex processes including thermogenesis, a crucial factor in regulating energy expenditure.MethodsIn this randomized, double-blinded, placebo-controlled three-arm three-sequence study, we investigated the efficacy of Capsifen® (CapF), a pungency-masked sustained-intestinal release formulation of red chili extract, on energy expenditure, fat oxidation, and endurance using the Quark C-PET system in healthy overweight participants, with and without exercise. In the study, 105 healthy participants were randomized to receive either placebo, CapF 100 mg/day, or CapF 200 mg/day for 28 days.ResultsCapF demonstrated a dose-dependent response to increased energy expenditure and fatty acid oxidation with a concomitant reduction in body weight. Both CapF 100 and CapF 200 also increased the time to exhaustion.DiscussionThese results demonstrate the plausible efficacy of CapF in energy expenditure and physical performance in otherwise healthy adults who have a high body mass index.Clinical trial registrationhttps://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjQzNTg=&Enc=&userName=CTRI/2018/04/013157 dated 04 October 2018.

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

The golden spice turmeric with its main bioactive component curcumin is one of the most popular and extensively studied nutraceuticals. Despite numerous pre-clinical studies reporting positive pharmacodynamics of turmeric extracts and curcumin, the main issues in translating the pharmacological effects to clinical efficacy have been to overcome its poor pharmacokinetics and to deliver significant amounts of the biologically relevant forms of the actives to various tissues. This review is aimed at providing a first critical evaluation of the current published literature with the novel curcumagalactomannoside (CGM) formulation of curcumin using fenugreek galactomannan dietary fibre, specifically designed to address curcumin poor pharmacokinetics. We describe CGM and its technology as a food-grade formulation to deliver ‘free’ unconjugated curcuminoids with enhanced bioavailability and improved pharmacokinetic properties. The therapeutic relevance of improving bioavailability of ‘free’ curcuminoids and some of the technical challenges in the measurement of the ‘free’ form of curcuminoids in plasma and tissues are also discussed. A total of twenty-six manuscripts are reviewed here, including fourteen pre-clinical and twelve clinical studies that have investigated CGM pharmacokinetics, safety and efficacy in various animal models and human conditions. Overall current scientific evidence suggests CGM formulation has improved bioavailability and tissue distribution of the biologically relevant unconjugated forms of turmeric actives called ‘free’ curcuminoids that may be responsible for the superior clinical outcomes reported with CGM treatments in comparison with unformulated standard curcumin across multiple studies.

Background Functional dyspepsia (FD), affecting over 30 % of the global population, manifests with symptoms like fullness, bloating, epigastric pain, early satiety, and gastric motility issues. In the current study, we investigated the efficacy and mechanism of action of a water-soluble powder formulation of Ferula Asafoetida oleo-gum-resin (Asafin) in an animal model of Cisplatin-induced (CP) FD. Methods The animals were divided into four groups: Group I - Normal, Group II - Cisplatin control, Group III - Cisplatin + Standard drug, and Group IV - Cisplatin + Asafin. Various parameters including body weight, food intake, hematological markers, biochemical markers, and histopathology were analyzed during and after a 30-day study period. Results It was observed that CP-treated animals exhibited a marked reduction in food intake and body weight, which significantly improved or reversed when treated with Asafin. Further analysis of gut peptide hormones (Leptin, Ghrelin, GLP-1) and their gene expressions confirmed delayed gastric emptying and impaired gastric motility in CP rats. However, co-administration of Asafin with CP showed a significant improvement in these markers, indicating the normalization of the symptoms. These results were also consistent with the observed gene expressions of appetite-regulating GI peptide hormones CCK, POMC, MTL, NPY, and CART, which returned to normal levels. Histopathology results further supported the significant improvement provided by Asafin in CP rats Conclusions Our findings suggest that Asafin may mitigate FD risk by modulating the gut-brain axis via gut peptide hormones and neurotransmitters.

Background: Despite the beneficial pharmacological effects, poor oral bioavailability limits the nutritional effi-cacy of fisetin, a dietary flavonoid. To this end, herein we report the bioavailability and efficacy of an innovative formulation of fisetin using a fenugreek-galactomannan hydrogel scaffold (FF-20).Methods: In the first phase of the study, female Wistar rats (n = 42) were randomly divided into two groups (n = 21/group) and orally administered with either unformulated (UF) or FF-20 (50 mg/kg b. wt.) and plasma concentration of fisetin was estimated by UPLC-ESI-MS/MS. In the second phase, the relative influence of FF-20 on alcohol-induced neurotoxicity was followed on animals (n = 24) randomized into four groups, Group I - vehicle control, Group II - ethanol treated, Group III - ethanol+ UF, and Group IV - ethanol + FF-20 and treated at 50 mg/kg b. wt. per day for 14 days.Results: Area under plasma concentration verses time curve showed 9.83-fold enhancement in bioavailability for FF-20, with significantly enhanced pharmacokinetic parameters (*** P < 0.001). Behavior studies revealed significant improvement in reference memory errors, working memory errors, and anxiety among fisetin-treated animals and the improvement was significant in FF-20, compared to UF (* P < 0.05). Neurotransmitters and gene expressions of NMDAR, MAO A&B, and KLF-11 were altered by alcohol treatment; but were restored/improved in FF-20 group. Histopathology of brain tissues also indicated the reversal of alcohol-induced necrosis and tissue damage by FF-20.Conclusion: FF-20 enhanced the oral bioavailability and significantly alleviated alcohol-induced neurotoxicity in experimental rats.

Background: Orexins act as a molecular switch for the release of cortisol/corticosterone in response to a stress stimulus and hence to regulate sleep/wake cycle. Orexin agonism during the day promotes wakefulness, and Dual Orexin Receptor Antagonists (DORA) can promote sleep signals by enhancing melatonin, which is an in-hibitor of orexin. It was reported that a proprietary black cumin (Nigella sativa) oil (BCO-5) alleviated stress and improved sleep quality. The present study investigated the mechanism of action of BCO-5 using stress-induced and sleep-deprived model of rats.Methods: Adult Sprague Dawley rats (n = 24) were randomised into 4 groups (Group I - Sham; Group II - Stress -induced group; Group III - BCO-5 treated normal animals; Group IV - Stress + BCO-5 (20 mg/kg b. wt.) for 14 days and monitored the behaviour and biochemical markers.Results: The co-supplementation of BCO-5 significantly decreased the body weight, locomotor activity, rearing and grooming frequencies among Group IV animals significantly compared to Group II. The observed behaviour was also correlated with the significant decrease in orexin, corticosterone and c-fos expression levels, while an increase was observed in melatonin concentration. Conclusion: Our results support the plausible role of BCO-5 as a DORA to manage stress and improve sleep.

Background Although curcumin is a blood-brain-barrier permeable molecule with the ability to bind and segregate β-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, Aβ42, 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.

Nutraceutical-based interventions hold promise to reduce blood pressure (BP) and arterial stiffness, which are two cardiovascular disease (CVD) risk factors. However, the effects of coconut sap powder (CSP), an Asian sweetener and novel nutraceutical, on BP and arterial stiffness in middle-aged and older adults (MA/O, ≥45 yr) has yet to be established. We hypothesized CSP will decrease BP and arterial stiffness in MA/O adults. In a double-blind, randomized, placebo-controlled study design, 19 (age 55.3 ± 2.1 yr) MA/O adults completed measures of brachial and carotid BP, and arterial stiffness [carotid-femoral pulse wave velocity (cfPWV), common carotid artery (CCA) β-stiffness, compliance, distensibility, and Young's and Peterson's Elastic moduli] before and after 8 wk of CSP (1.5 g/day) or placebo (1.5 g/day). A two-way repeated-measures analysis of variance was used to compare group mean differences. Compared with placebo, CSP lowered brachial systolic BP (SBP) (CSP pre: 117.4 ± 2.9 vs. post: 109.0 ± 2.4 mmHg, P < 0.05), but not carotid SBP (P = 0.12). CSP also lowered Young's (CSP pre: 5,514.4 ± 1,115.4 vs. post: 3,690.6 ± 430.9 kPa) and Peterson's elastic moduli (CSP pre: 22.2 ± 4.4 vs. post: 19.2 ± 4.5 kPa) (P < 0.05, both). A trend for CSP to lower CCA β-stiffness (P = 0.06) and increase CCA compliance (P = 0.07) was also observed. Arterial stiffness assessed by cfPWV did not change (P > 0.05). No inflammatory or antioxidant biomarkers were affected by CSP. In summary, 8 wk of CSP lowers brachial SBP and CCA mechanical stiffness indicating a potential cardioprotective effect in MA/O adults.NEW & NOTEWORTHY Blood pressure (BP) and arterial stiffness are important predictors of cardiovascular health with aging. Nutraceuticals are an easy-to-implement lifestyle strategy demonstrating promise to effectively lower BP and arterial stiffness with aging and ultimately cardiovascular disease risk. We demonstrate that coconut sap powder (CSP), a traditional Asian sweetener, lowers brachial systolic BP and carotid artery mechanical stiffness in middle-aged and older (MA/O) adults. These findings provide initial evidence for the CSP-related cardioprotective effects in MA/O adults.

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.

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 alpha- and beta-waves (p < 0.05) as well as a significant reduction in alpha/beta 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 alpha and beta waves and reduction in alpha/beta 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.

Introduction: Insomnia, the inability to get sleep or sleep well at night, is a universal health problem. In the present single-arm, open-label, pilot study, the safety and efficacy of a thymoquinone-rich (5% w/w) black cumin oil (Nigella sativa) (BCO) was investigated for the first time, among healthy subjects characterized with significant sleep problems.Methods: Fifteen subjects were selected for the study and were provided with softgel capsules of BCO (200 mg x 1/day, after dinner) for 28 days. Polysomnographic analysis was performed to assess sleep quality, sleep efficiency and sleep latency (primary outcomes) at the beginning (visit 2) and after 7 days of supplementation (visit 3). Sleep quality index, anxiety and stress (secondary outcomes) were also measured at the beginning and at the end of the study period (28 days) using the validated questionnaires Pittsburgh Sleep Quality Index (PSQI), Depression Anxiety Stress Scale-21 (DASS-21) and Hamilton Anxiety Rating Scale-A (HAM-A), along with the measurements of cortisol and safety parameters.Results: The results suggested a significant improvement in primary outcomes such as total sleep time, sleep latency and sleep efficiency with an increase of 82.49 % in Non-Rapid Eye Movement (NREM 3) and 29.38 % increase in Rapid Eye Movement sleep (REM sleep). The secondary outcome measurements also showed a significant reduction (P < 0.05) in anxiety and stress as evident from DASS-21 and HAM-A scales, with significant reduction in Cortisol. Haematological and biochemical analysis demonstrated the safety of BCO during the study period.Conclusion: Supplementation of BCO was safe and found to significantly improve the sleep quality and ameliorate stress and anxiety. [Clinical Trial Reg No: CTRI/2018/03/012,391 dated 07/03/2018]

Objective Though a number of bioavailable formulations of curcuminoids have been reported and available commercially as nutraceuticals for brain health, systematic informations on their blood-brain-barrier permeability and brain tissue distribution have not been reported. The present study was aimed to investigate the brain regional pharmacokinetics of curcuminoids following both single dose and repeated dose oral administration of a self-emulsifying food-grade formulation of curcuminoids using fenugreek galactomannan hydrogel scaffold as 'curcumagalactomannosides' (CGM), and its influence on cognitive functions in comparison with unformulated natural curcuminoids (NC) in Wistar rats. Methods CGM was given to animals in single dose (100 mg curcuminoids/kg b. wt.) and repeated dose (100 mg curcuminoids/kg b. wt. for 28 days) and the concentration of total curcuminoids at various parts of brain was evaluated at different time points using Ultra-performance liquid chromatography/electrospray ionization triple quadruple tandem mass spectroscopy (UPLC-ESI-MS/MS) system. Another set of animals were also fed with CGM at single dose (100 mg curcuminoids/kg b. wt.) and repeated dose (100 mg curcuminoids/kg b. wt. for 28 days) and the behavioural studies were conducted using open field test and radial arm maze. Results UPLC-ESI-MS/MS analyses of plasma revealed significant absorption of unconjugated (free) curcuminoids upon both single and repeated dose administration of CGM with maximum concentrations of 173.34 +/- 27.12 ng/mL and 223.22 +/- 32.73 ng/mL, respectively. Further analysis of brain tissues demonstrated significant blood-brain-barrier permeability. Brain regional pharmacokinetics (AUC, C (max) and t (1/2)) indicated a relative distribution order of hippocampus > striatum > cerebellum > cerebral cortex > brain stem. Supplementation of CGM for 28 days also offered significant (p < 0.05) improvement in locomotor activity and reduction in spatial memory errors as compared to NC. The NC treatment also improved the behaviour better than the vehicle-treated group. Conclusion CGM could distribute significant amount of free curcuminoids, in brain especially in the hippocampus at both single and repeated dose administration with an elimination half-life of 2.6 h. CGM also showed a positive impact in behaviour of animals in comparison with normal unformulated curcuminoids.

Despite the vast array of health beneficial pharmacological effects, the bioavailability of the dietary flavonoid quercetin was found to be poor due to insolubility, incompatibility, and rapid biotransformation. Herein, we investigated the solubility, morphology, particle size, stability, in vitro release, and human pharmacokinetics of a hybrid-hydrogel formulation of quercetin (FQ-35) using fenugreek galactomannans as the hydrogel scaffold. Physicochemical characterization revealed that the crystalline quercetin was well encapsulated in the hydrogel matrix to form translucent microgel particles of FQ-35 with enhanced solubility (96-fold). The mean particle size was found to be 183.6 ± 42.7 nm with a zeta potential of 35.1 ± 3.8 mV. Pharmacokinetic investigation on healthy volunteers (N = 16) employing tandem mass spectrometric (ultra-performance liquid chromatography-electrospray tandem mass spectrometry) measurements of the concentration of free (unconjugated) and conjugated quercetin metabolites revealed an 18.6-fold improvement in free (unconjugated) quercetin bioavailability and 62-fold improvement in total quercetin (sum of free and conjugated) bioavailability, compared to the unformulated quercetin extracted from Sophora japonica. In summary, the natural self-emulsifying reversible hybrid-hydrogel delivery system was found to offer significant solubility, stability, and bioavailability of quercetin upon single-dose oral administration.

Background Fenugreek ( Trigonella foenum-graecum ) seed is a popular kitchen spice and medicinal herb with wide applications in Indian folklore. Earlier studies have shown that the hydro-ethanolic extracts of fenugreek are efficient in the management of a number of hormone related disorders in women, including post and peri-menopausal discomforts, sexual dysfunctions, lactation and even in amenorrhea. However, systematic informations on their safety and influence on hormonal balance are limited. Results Forty-eight healthy menstruating women aged 20 to 48 were randomized either to FHE ( n = 24) or placebo ( n = 24) and supplemented with 250 mg × 2/day for 42 days. FHE did not produce any side effects or adverse events. It offered significant ( P < 0.05) beneficial effects to sexual problems (41.6%) and irritability (40%) among the participants who had higher sexual dysfunctions scores (> 1) when monitored by the validated Menopausal Rating Scale (MRS) scale. Further, hormone analysis indicated an enhancement in estradiol ( P = 0.040), free testosterone ( P = 0.025), and total testosterone ( P = 0.012) in FHE group in comparison to placebo. There were no significant changes in progesterone ( P = 0.174) and FSH ( P = 0.879) upon FHE supplementation. The hematological and biochemical safety parameters were also at par with the safety of the extract. Conclusion Thus, the supplementation of FHE may be considered as a natural alternative for sexual issues in women. Trial registration CTRI/2018/09/015614 dated 05/09/2018.

Rheumatoid Arthritis (RA) is a complex autoimmune disorder involving chronic and persistent inflammation, principally influencing the synovial joints which further prompting the obliteration of articular cartilage. Although black cumin (Nigella sativa) oil has already studied for its anti-arthritic properties, the current study was focused on the comparative evaluation of the antioxidant and anti-inflammatory properties of a thymoquinone (TQ)-rich (5% w/v) black cumin oil (BQ) with the commonly available standard black cumin oil (BM) containing 0.4% (w/v) TQ, and subsequent investigation on the potential application of BQ in the management of RA. Adjuvant-induced arthritis (AA) was instigated by a single intradermal infusion of 0.1 mL of Complete Freund's adjuvant (CFA) on the paw of adult Wistar rats. Based on the primary dose-response study using the carrageenan-induced paw edema model, 50 mg/kg b.wt. of BQ was employed for the treatment. The endogenous antioxidants (SOD, Catalase, GPx, and GSH), pro-inflammatory cytokines (COX-2, Nitrate, iNOS, TNF-α, IL-6), lipid peroxidation, and histopathology were evaluated to monitor the influence of BQ in AA rats. Adjuvant-induced animals showed a critical downregulation in antioxidant status with elevated levels of pro-inflammatory cytokines and lipid peroxidation. But, the treatment with BQ significantly reversed the antioxidant and inflammatory markers with downregulation of the pro-inflammatory gene expressions. Histopathology showed a significant reduction in the massive cell infiltration and epidermal edema of the paw tissue in AA rats when administered with BQ and indicated its potential effect to alleviate RA conditions in experimental rats.

BACKGROUND:Cervical cancer is the most common cancer and has the highest morbidity rate of gynaecological malignancies in women worldwide. So, the development of effective anti-cancer agents to treat this condition is vital. Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade, free-curcuminoids (curcumin-galactomannoside complex; CGM) on cervical cancer cells (HeLa) of human origin. In this study, we examined the anticancer potential of CGM as well as its effects on the cell cycle and the apoptosis of HeLa cancer cell. METHODS:Determination of anti-proliferative and apoptosis validation of CGM on HeLa cells was performed by 3-(4,5-Dimethylthiazol-2-yl)-2, 5,-diphenyltetrazolium bromide (MTT), acridine orange/propidium iodide and annexin-V-fluorescein isothiocyanate assays. Measurement of Reactive Oxygen Species (ROS) production, Caspase activities and protein expression experiments were performed to investigate the potential mechanisms of action in the apoptotic process. RESULTS:The cytotoxic assays revealed that the CGM showed inhibition of cell survival and exhibited high cytotoxic activity against HeLa cells at 25 μg/mL. Further studies on morphological changes were done in CGM-treated cervical cancer cells contributing to apoptosis. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that CGM induced apoptosis in HeLa cell lines at 25 μg/mL. By the supplementation of CGM showed an increase in Bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure. CONCLUSION:The evidence obtained from this study suggests that CGM is a potent and promising natural formulation against cervical cancer cells via induction of apoptosis through ROS mediated mitochondrial damage in HeLa cells. Hence, CGM could be further explored as a potential lead in treating cancer..