Curcumin-Galactomannoside Complex inhibits the Proliferation of Human Cervical Cancer Cells: Possible Role in Cell Cycle Arrest and Apoptosis.

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.
.

Surface-engineered liposomal particles of calcium ascorbate with fenugreek galactomannan enhanced the oral bioavailability of ascorbic acid: a randomized, double-blinded, 3-sequence, crossover study.

The antioxidant, anti-inflammatory, immunomodulating, anti-thrombotic, and antiviral effects along with its protective effects against respiratory infections have generated a great interest in vitamin C (vitC) as an attractive functional/nutraceutical ingredient for the management of COVID-19. However, the oral bioavailability and pharmacokinetics of vitC have been shown to be complex and exhibit dose-dependent non-linear kinetics. Though sustained-release forms and liquid liposomal formulations have been developed, only marginal enhancement was observed in bioavailability. Here we report a novel surface-engineered liposomal formulation of calcium ascorbate (CAAS), using fenugreek galactomannan hydrogel in powder form, and its pharmacokinetics following a randomized, double-blinded, single-dose, 3-way crossover study on healthy human volunteers (n = 14). The physicochemical characterization and in vitro release studies revealed the uniform impregnation of CAAS liposomes within the pockets created by the sterically hindered galactomannan network as multilaminar liposomal vesicles with good encapsulation efficiency (>90%) and their stability and sustained-release under gastrointestinal pH conditions. Further human studies demonstrated >7-fold enhancement in the oral bioavailability of ascorbate with a significant improvement in pharmacokinetic properties (C max, T max, T 1/2, and AUC), compared to the unformulated counterpart (UF-CAAS) when supplemented at an equivalent dose of 400 mg of CAAS as tablets and capsules.

Amelioration of Radiation-Induced Damages in Mice by Curcuminoids: The Role of Bioavailability.

PURPOSE: The present study investigated the role of free curcuminoids bioavailability on the relative radioprotective efficacy of natural unformulated curcuminoids. MATERIALS AND METHODS: A food-grade bioavailable formulation of curcuminoids as curcumagalactomannosides (CGM) and unformulated curcuminoids (UC) were employed for the study. Swiss albino mice were randomized into Normal control, Radiation control, Radiation + UC, and Radiation + CGM groups and irradiated with γ-radiation of 6, 8, 10 and 12 Gy. Survival rate, hematological and biochemical parameters, bone marrow cellularity, chromosomal aberrations and histopathology of intestine were followed as a measure of the relative efficacy.Results and Discussion: Oral administration with both UC and CGM at 100 mg/kg. b.wt. produced significant radioprotective effect over the untreated control group of animals. However, CGM treatment was found to provide better clastogenic and genotoxic potential as compared to UC. Further, the histopathology analysis of intestine confirmed the better protective effect of CGM over UC-treated animals. CONCLUSION: The present study demonstrated the positive role of the bioavailability of curcuminoids in the amelioration of radiation-induced damages in mice since CGM treatment exerted better survival rate and radioprotective effect as compared with UC, despite the relatively low concentrations of curcuminoids in CGM (39% w/w).

Efficacy of a novel extract of fenugreek seeds in alleviating vasomotor symptoms and depression in perimenopausal women: A randomized, double-blinded, placebo-controlled study.

The present randomized, double-blinded, placebo-controlled study investigated the effect of a standardized fenugreek extract (FHE) on perimenopausal discomforts and its influence on hormonal balance and safety. Healthy women characterized with perimenopausal symptoms (n = 48), as assessed by MRS questionnaire, were randomized either to FHE (n = 24) or placebo (n = 24) and supplemented with 250 mg × 2/day for 42 days. Both inter and intra-group comparison revealed a significant improvement in somatic, psychological, and urogenital scores in FHE group, especially for hot flashes (25.9%), night sweats (26.5%), depression (31.8%), and insomnia (21.6%). Further hormone analysis revealed an enhancement in serum estradiol (18.9%), free testosterone (38.2%), and progesterone (19.9%) concentrations and a significant decrease in FSH (38.2%) and SHBG (21.1%) concentrations toward establishing a hormonal balance among FHE-group; without significant changes in other clinical safety parameters. Thus, FHE supplementation offered a significant reduction in vasomotor effects and depression in perimenopausal women, without any adverse effects PRACTICAL APPLICATIONS: Fenugreek is a popular kitchen spice and Ayurvedic medicine for a variety of health conditions including diabetes, hypercholesterolemia, hepatotoxicity, gastritis, and also for a variety of hormone-related health conditions such as sexual functions, lactation, osteoporosis, PCOS, and post/perimenopausal discomforts. Fenugreek is rich in alkaloids, steroidal saponins, flavonoids and 4-hydroxyisoleucine. The present randomized-controlled study investigated the plausible application of a standardized hydro-ethanolic extract of fenugreek seeds (FHE) having a unique 3:1 ratio for protodioscin to trigonelline in the management of perimenopausal discomforts. It was observed that FHE at a dosage of 250 mg × 2/day for 42 days significantly reduced the discomforts, especially vasomotor symptoms and depression, and helped to attain a hormonal balance without any adverse effects or deviations in clinical safety parameters. Thus, FHE could be a potential natural agent for the management of post and perimenopausal discomforts and has to be explored in future studies.

Safety assessment of a fenugreek dietary fiber-based formulation of capsaicinoids-rich red chili (Capsicum annum) extract (Capsifen®): Acute and sub-chronic studies.

Despite the promising health beneficial effects (thermogenic, lipolytic, hypotriglyceridemic, hypocholesterolemic, anti-inflammatory and anticancer) of capsaicinoids-rich red chili pepper, commonly known as cayenne pepper (Capsicum annum or Capsicum frutescence), its consumption at physiologically relevant dosage is always hampered by the pungency and stomach discomforts. The present study examined the safety of a pungency-masked and sustained release food-grade formulation of capsaicinoids-rich red chili pepper extract using fenugreek derived galactomannan soluble dietary fiber (Capsifen®). The safety was assessed by oral acute (300, 2000, 5000 mg/kg b. wt. for 14 days) and subchronic (250, 500 and 1000 mg/kg b. wt.) toxicity studies in Wistar rats. None of the group of animals belonging to both acute and subchronic treatments did produce any adverse events in feeding behavior, urine analysis, and in hematology/biochemical parameters when compared to the control. However, a decrease in body weight was observed among 500 and 1000 mg/kg b. wt. treated groups. The terminal autopsy did not reveal any alterations in relative organ weight except for the high dose treated group, where an increase in liver and kidney weight was observed. Histopathology of all the animals was normal. Thus, the Low-observed-adverse-effect level (LOAEL) of Capsifen was determined for 500 mg/kg b. wt. /day.

Dietary addition of a standardized extract of turmeric (TurmaFEEDTM) improves growth performance and carcass quality of broilers.

BACKGROUND: Indiscriminate use of antibiotics in livestock and poultry farming has caused emergence of new pathogenic strains. The situation has warrented the development of safe and alternative growth promoters and immunity enhancers in livestock. Herbal additives in animal and bird feed is a centuries-old practice. Thus, the present study investigated the efficacy of a standardized formulation of lipophilic turmeric extract containing curcumin and turmerones, (TF-36), as a natural growth promoter poultry feed additive. METHODS: The study was designed on 180 one-day old chicks, assigned into three groups. Control group (T0) kept on basal diet and supplemented groups T0.5 and T1 fed with 0.5% and 1% TF-36 fortified basal diet for 42 days. Each dietary group consisted of six replicates of ten birds. Body weight, food intake, food conversion ratio, skin colour, blood biochemical analysis and antioxidant status of serum were investigated. RESULTS: Body weight improved significantly in T1 with a 10% decrease in FCR as compared to the control. TF-36 supplementation in T1 enhanced the antioxidant enzyme activity significantly (p < 0.05) with a decrease (p < 0.05) in lipid peroxidation. It also caused a slight yellow skin pigmentation without any change in meat color, indicating the bioavailability of curcumin from TF-36. However, no significant change in the concentration of serum creatinine, total protein and liver enzyme activities were observed, indicating the safety. CONCLUSION: In summary, we concluded that TF-36 can be a natural feed additive to improve growth performance in poultry, probably due to the better antioxidant activity and antimicrobial effects contributed by the better bioavailability of curcuminoids and turmerones. Besides, curcuminoids and turmerones were also known to be gastroprotective and anti-inflammatory agents.

Nephro-protective effect of a novel formulation of unopened coconut inflorescence sap powder on gentamicin induced renal damage by modulating oxidative stress and inflammatory markers.

Fresh oyster white translucent sap obtained from the tender unopened inflorescence of coconut trees (Cocos nucifera) is identified to have great health benefits. Drug induced Nephrotoxicity is one of the major causes of renal damage in present generation. As a therapeutic agent, gentamicin imparts direct toxicity to kidney, resulting in acute tubular necrosis, glomerular and tubulointerstitial injury, haemodynamically mediated damage and obstructive nephropathy.There exists an increasing demand for safe and natural agents for the treatment and/or preventionofchronic nephrotoxicity and pathogenesis of kidney diseases. Our study shows the nephro protective/curing effect of a novel powder formulation of micronutrient enriched, unfermented coconut flower sap (CSP). The study was performed on adult male Wistar rats. The animals were grouped into three and treated separately with vehicle, gentamicin and gentamicin+CSP for 16days. Initially, gentamicin treatment significantly (p<0.05)reduced thelevels of antioxidant enzymes (SOD, CAT, GPx) and GSH and increased (p<0.05) the levels of creatinine, uric acid, urea, inflammatory markers (nitrite, IL-6, TNF- α, iNOS) and lipid peroxidation. Supplementation of coconut flower sap powder showed significant (p<0.05) reversal of all these biochemical parameters indicating an effective inhibition of the pathogenesis of nephrotoxicity and kidney disease.

Safety, Tolerance, and Enhanced Efficacy of a Bioavailable Formulation of Curcumin With Fenugreek Dietary Fiber on Occupational Stress: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

Drug delivery systems capable of delivering free (unconjugated) curcuminoids is of great therapeutic significance, since the absorption of bioactive and permeable form plays a key factor in mediating the efficacy of a substance which undergoes rapid biotransformation. Considering the recent understanding on the relatively high bioactivities and blood-brain-barrier permeability of free curcuminoids over their conjugated metabolites, the present human study investigated the safety, antioxidant efficacy, and bioavailability of CurQfen (curcumagalactomannoside [CGM]), a food-grade formulation of natural curcumin with fenugreek dietary fiber that has shown to possess improved blood-brain-barrier permeability and tissue distribution in rats. In this randomized double-blinded and placebo-controlled trial, 60 subjects experiencing occupational stress-related anxiety and fatigue were randomized to receive CGM, standard curcumin, and placebo for 30 days (500 mg twice daily). The study demonstrated the safety, tolerance, and enhanced efficacy of CGM in comparison with unformulated standard curcumin. A significant improvement in the quality of life (P < 0.05) with considerable reduction in stress (P < 0.001), anxiety (P < 0.001), and fatigue (P < 0.001) was observed among CGM-treated subjects as compared with the standard curcumin group, when monitored by SF-36, Perceived Stress Scale with 14 items, and Beck Anxiety Inventory scores. Improvement in the quality of life was further correlated with the significant enhancement in endogenous antioxidant markers (P < 0.01) and reduction in lipid peroxidation (P < 0.001). Further comparison of the free curcuminoids bioavailability after a single-dose (500 mg once per day) and repeated-dose (500 mg twice daily for 30 days) oral administration revealed enhanced absorption and improved pharmacokinetics of CGM upon both single- (30.7-fold) and repeated-dose (39.1-fold) administrations.

Beyond the flavour: a de-flavoured polyphenol rich extract of clove buds (Syzygium aromaticum L) as a novel dietary antioxidant ingredient.

Though kitchen spices constitute an important source of dietary antioxidants, their consumption at a physiologically relevant dose is very often hampered by their unpleasant flavour characteristics. The present paper describes a novel approach to derive stable de-flavoured spice extracts with minimised taste and odour profiles which are suitable for impregnation into a variety of food and beverage matrices at physiologically relevant doses. A popular kitchen spice, clove bud (Syzygium aromaticum L), having strong flavour and pungency characteristics was selected in the present study to derive a de-flavoured extract with a standardised polyphenolic profile (Clovinol) and was incorporated into various foods. The antioxidant efficacy of Clovinol on healthy human volunteers who check and answer official emails involving responsibility was investigated by analysing their endogenous antioxidant enzymes and the extent of lipid peroxidation upon consumption of Clovinol either as capsules or in a different food/beverage at 250 mg per serving per day for 30 days. It was observed that Clovinol can be conveniently incorporated in various food matrices without flavour issues and the consumption of such food/beverage items may support an effective detoxification process with an average elevation of 33 ± 3% in catalase, 66 ± 8% in SOD, 56 ± 5% in GPx and 167 ± 21% in GSH levels, and 81 ± 11% attenuation in membrane lipid peroxidation level.

Effects of the polyphenol content on the anti-diabetic activity of Cinnamomum zeylanicum extracts.

Cinnamomum zeylanicum is a popular kitchen spice widely investigated for insulin potentiating effects. Though a group of water soluble polyphenols belonging to the oligomeric procyanidins has been identified as the bioactive principle, the lack of systematic information on the effect of the polyphenol content on safety and anti-diabetic efficacy remains as a major limitation for the development of optimized and standardized cinnamon extracts for functional use. In the present paper, water soluble extracts of Cinnamomum zeylanicum containing 45 and 75% gallic acid equivalents (GAE) of polyphenol content were prepared by a novel process and characterized by tandem mass spectrometry. The polyphenol enhanced extracts were shown to be safe and offered better antioxidant potential, hypoglycemic effect, hypolipidimic effect, and significant decrease in other biochemical parameters as compared to the standard aqueous extract containing 15% GAE, when administered to streptozotocin-induced diabetic rats at 200 mg per kg b.w. for 30 days. The efficacy of polyphenol extracts in lowering blood glucose levels and ameliorating oxidative stress was further demonstrated in humans by administrating 'procynZ-45' containing 45% GAE polyphenols at a relatively low dosage of (125 mg × 2) per day for 30 days to 15 volunteers who had elevated fasting blood glucose levels; but not involved in any medication.