Two-Stage Supramolecular Self-Assembly-Directed Collagen-Peptide-Decorated Liposomal Complexes of Curcumin Microspheres with Enhanced Solubility and Bioavailability.

Green formulations of phytonutrients with enhanced solubility and bioavailability are of great significance in nutrition therapy. In the present contribution, we hypothesized that the collagen peptides could be a safe, natural, food-grade, and cost-effective functional agent for the surface decoration and stabilization of liposomes in powder form and hence a "green" solution for the oral delivery of phytonutrients. The present study reports a two-stage supramolecular self-assembly-directed process for the preparation of collagen peptide-decorated liposomal complexes of curcumin (CCL) [10% (w/w)] as microspheres (125 ± 25 µm) with improved solubility (1.46 × 105-fold) and sustained-release properties under gastrointestinal pH conditions. The molecular self-assembly of collagen peptides around the lipid bilayers and the various noncovalent interactions and conformational changes leading to the supramolecular assembly to act as a matrix for the encapsulation of lipid vesicles of curcumin were clear from the spectroscopic studies (UV-vis, fluorescence, FTIR, and circular dichroism). Further investigation of pharmacokinetics following a randomized double-blinded controlled trial on healthy volunteers (n = 15) demonstrated that the oral administration of 2.5 g of CCL sachet (250 mg of curcumin) enhanced the plasma concentration (Cmax: 118 vs. 4.3 ng/mL), the elimination half-life (4.2 vs. 0.7 h), and bioavailability as per the area under the curve over 12 h [AUC0-12h (CCL) = 506·8 vs. AUC0-12h (C95) = 9.47 (53-fold)], when the plasma concentration of curcumin was estimated with triple quadruple tandem mass spectrometry (UPLC-ESI-MS/MS).

Enhanced Bioavailability and Pharmacokinetics of a Natural Self-Emulsifying Reversible Hybrid-Hydrogel System of Quercetin: A Randomized Double-Blinded Comparative Crossover Study.

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.

A phase I clinical trial to evaluate the safety of thymoquinone-rich black cumin oil (BlaQmax®) on healthy subjects: Randomized, double-blinded, placebo-controlled prospective study.

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.

Micelle/Hydrogel Composite as a "Natural Self-Emulsifying Reversible Hybrid Hydrogel (N'SERH)" Enhances the Oral Bioavailability of Free (Unconjugated) Resveratrol.

The poor oral bioavailability, rapid biotransformation to less active metabolites, and fast elimination from systemic circulation have been identified as the major limitations responsible for the clinical insignificance of many drug candidates and phytonutrients. Despite the technological advancements in the nanoformulations of synthetic drugs, there exist many challenges for nutritional therapy, due to the regulatory issues, use of high levels of synthetic emulsifiers and polymers, low stability, low loading levels, mainly liquid state, etc. Herein, we report the characterization and human pharmacokinetics of a natural self-emulsifying hybrid-hydrogel formulation of trans-resveratrol prepared by uniformly impregnating resveratrol micelles into the fenugreek galactomannan hydrogel scaffold to form a water-soluble micelle/hydrogel composite in powder form (RF-20). Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), particle size analysis by dynamic light scattering (DLS), and transmission electron microscopy (TEM) demonstrated the uniform impregnation of resveratrol micelles within the galactomannan hydrogel matrix to form a soluble (average particle size of 172.0 ± 10.4 nm and -21.0 ± 2.5 mV zeta potential) and amorphous powder form with smooth and translucent surface morphology for RF-20, with no chemical alterations. Upon pharmacokinetic studies on healthy human subjects (n = 16) following a randomized, double-blinded, placebo-controlled, 2-arm, 4-sequence crossover design and tandem mass spectrometry (UPLC-ESI-MS/MS), 80 mg of trans-resveratrol from RF-20 provided enhanced free resveratrol bioavailability and pharmacokinetic properties compared to the unformulated resveratrol with 98% purity. The enhancement in bioavailability was more when supplemented in sachet (12.98-fold) form than the capsule (10.48-fold) with improved absorption (C max = 50.97 ± 15.82 ng/mL), circulation half-life (t 1/2 = 7.01 ± 1.44 h), and sustained delivery (T max = 4.71 ± 0.73 h), as compared to the unformulated form (C max = 15.07 ± 5.10 ng/mL; t 1/2 = 1.58 ± 0.65 h; T max = 1.21 ± 0.42 h).

The effects of oral administration of curcumin-galactomannan complex on brain waves are consistent with brain penetration: a randomized, double-blinded, placebo-controlled pilot study.

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.

Safety assessment of a highly bioavailable curcumin-galactomannoside complex (CurQfen) in healthy volunteers, with a special reference to the recent hepatotoxic reports of curcumin supplements: A 90-days prospective study.

Recently, there is a growing concern about the use of curcumin supplements owing to a few reported hepatotoxicity related adverse events among some of the long-term consumers. Even though no clear evidence was elucidated for the suspected toxicity, the addition of adjuvants that inhibits body's essential detoxification pathways, adulteration with synthetic curcumin, and presence of contaminants including heavy metals, chromate, illegal dyes, non-steroidal anti-inflammatory agents, and pyrrole alkaloids were suggested as plausible reasons. Considering these incidences and speculations, there is a need to critically evaluate the safety of curcumin supplements for prolonged intake. The present study is an evaluation of the safety of curcumin-galactomannoside complex (CGM), a highly bioavailable curcumin formulation with demonstrated high free curcuminoids delivery. Twenty healthy human volunteers were evaluated for toxic manifestations of CGM when supplemented with 1000 mg per day (∼380 mg curcuminoids) for 90-days. CGM supplementation did not cause any adverse effects or clinically significant variations in the vital signs, hematological parameters, lipid profile and renal function markers of the volunteers, indicating its safety. Liver function enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and bilirubin were in the normal range after 90-day supplementation of CGM. In summary, no adverse effects were observed under the conditions of the study. CGM can be considered as a safe curcumin supplement for regular consumption and is devoid of any adulterants or contaminants.

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).

Influence of a low-dose supplementation of curcumagalactomannoside complex (CurQfen) in knee osteoarthritis: A randomized, open-labeled, active-controlled clinical trial.

A 6-week, randomized, open-label, active-controlled clinical trial was conducted to evaluate the influence of a low-dose curcumagalactomannosides (CGM) (400 mg once daily) in OA subjects. The treatment was compared with a standard combination of 500 mg glucosamine hydrochloride (GLN) and 415 mg chondroitin sulphate (CHN), supplied as a single oral dose twice a day. Out of 84 subjects randomized, 72 subjects who have completed the study were evaluated for the safety and efficacy of the treatments at baseline and subsequent visits (day 28 and 42), by measuring walking performance, VAS, KPS, and WOMAC scores. CGM exhibited 47.02, 21.43, and 206% improvement in VAS, KPS, and walking performance, respectively, compared to the baseline. Similarly, there was 31.17, 32.93, 36.44, and 35% improvement in the pain, stiffness, physical function, and total WOMAC scores. CGM also caused a substantial reduction in the serum inflammatory marker levels. The results indicate that a short-term supplementation of a low dosage CGM exerted superior beneficial effects than a high-dosage CHN-GLN combination in alleviating the pain and symptoms of OA subjects. Further clinical trials of extended duration in a larger population is required to substantiate the efficacy of CGM in the long-term management of OA.

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.

Curcumagalactomannoside/Glucosamine Combination Improved Joint Health Among Osteoarthritic Subjects as Compared to Chondroitin Sulfate/Glucosamine: Double-Blinded, Randomized Controlled Study.

Objective: A combination of curcumagalactomannosides (CGM) (400 mg) with glucosamine hydrochloride (GLN) (500 mg) was evaluated against a standard dietary supplement combination chondroitin sulfate (CHN) (415 mg)/GLN (500 mg) for their effectiveness in alleviating the pain and symptoms among osteoarthritic subjects. Design: Randomized, double-blinded and active-controlled study. Settings/Location: The study was conducted in a hospital-based research center in Vadodara, Gujarat, India. Subjects: Eighty subjects (38 males and 42 females), with confirmed osteoarthritis (OA) (Class I-III), were randomized into two parallel groups designated as Group I (CGM-GLN) and Group II (CHN-GLN). Interventions: All the study subjects were supplemented with their corresponding intervention capsules (ether CGM along with GLN or CHN along with GLN), as a single oral dose twice a day, once in the morning 10-15 min before breakfast and again in the evening before dinner, for 84 days. Outcome measures: A validated treadmill uphill walking protocol was used for the study, and the efficiency of supplementation was evaluated using visual analogue scale (VAS) score, Karnofsky Performance Scale (KPS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire at the baseline, 28th, and 84th day following the treatment. Mechanism of action of CGM-GLN combination was analyzed by measuring the levels of serum inflammatory markers interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and soluble vascular cell adhesion molecule-1 (sVCAM) at the baseline and 84th day. Results: CGM-GLN was found to offer significant beneficial effects to pain, stiffness, and physical function of OA subjects compared with CHN-GLN, which was evident from the improvement in walking performance, VAS score, KPS score, and WOMAC score. The efficiency of CGM-GLN was almost double compared with the CHN-GLN by the end of the study (84th day). A significant reduction of inflammatory serum marker levels was observed among CGM-GLN subjects compared with CHN-GLN subjects. Compared with the baseline, CGM-GLN produced 54.52%, 59.08%, and 22.03% reduction in IL-1ß, IL-6, and sVCAM levels, respectively. Whereas CHN-GLN group of subjects expressed only 23.17%, 21.38%, and 6.82% reduction in IL-1ß, IL-6, and sVCAM levels, respectively. Conclusions: In conclusion, the present study demonstrated the potential benefits of CGM-GLN supplements in alleviating the symptoms and function of OA subjects compared with the standard CHN-GLN treatment. The augmented efficacy of CGM-GLN combination could be attributed to the enhanced anti-inflammatory effect of CGM.

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.

Comparative neuroprotective effects of native curcumin and its galactomannoside formulation in carbofuran-induced neurotoxicity model.

Toxicity of the pesticide carbofuran (CF) can be alleviated by curcumin, if not for its poor bioavailability. Hence, we investigated the effect of a bioavailable curcumin-galactomannan complex (CGM) on CF-induced neurotoxicity in rats in comparison to that of unformulated standard curcumin (CS). The CF (5 mg/kg b.wt/day) treatment for 90 days produced chronicity model which were treated with either CS or CGM (100 mg/kg b.wt and 250 mg/kg b.wt/day) for another 30 days. Improvement in CF-induced behaviour was evident in endurance, motor co-ordination and pain response on both CS (p < 0.01) and CGM (p < 0.001) supplementation. Amelioration of CF-induced toxicity parameters, oxidative stress, and mitochondrial dysfunction on CS (p < 0.01) and CGM (p < 0.001) supplementation was further confirmed by histopathology of brain and liver tissues. But, CGM was more effective in mitigating CF toxicity, with results comparable to that of normal. Hence, CGM might be superior in toxicity management against CF.

Corrigendum to "A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study".

[This corrects the article DOI: 10.1155/2018/9159281.].

Toxicological evaluation of a saponin-rich standardized extract of fenugreek seeds (FenuSMART®): Acute, sub-chronic and genotoxicity studies.

The present study investigated the safety of a saponin-rich standardized extract of fenugreek seeds (FenuSMART®; FHE), that has been clinically shown to be effective in ameliorating the postmenopausal discomforts and establishing hormonal balance. The safety was assessed by oral acute (2500 mg/kg b. wt. for 14 days) and subchronic (250, 500 and 1000 mg/kg b. wt. for 90 days) toxicity studies on Wistar rats and mutagenicity studies employing Salmonella typhimurium strains. Administration of FHE did not produce any toxicologically significant changes in clinical/behavioral observations, ophthalmic examinations, body weight, organ weight, feed consumption, urinalysis, hematology and clinical biochemistry parameters when compared to the untreated control group of animals. Highest dose recovery group (1000 mg/kg b. wt.) of animals also showed no mortality or adverse events; with hematological and biochemical parameters at par with those of controls. Terminal autopsy revealed no alterations in relative organ weight or any treatment-related histopathology changes. FHE also showed no mutagenicity upon Ames test employing TA-98, TA-100 and TA-102 Salmonella typhimurium strains with or without metabolic activation. Based on the results of the study, the no observed-adverse-effect level (NOAEL) of FHE was determined as 1000 mg/kg b. wt./day, the highest dose tested.

A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study.

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.

Clove Bud Polyphenols Alleviate Alterations in Inflammation and Oxidative Stress Markers Associated with Binge Drinking: A Randomized Double-Blinded Placebo-Controlled Crossover Study.

Acetaldehyde, the major cytotoxin formed by the metabolism of alcohol, is responsible for liver injury, extracellular matrix alterations, inflammation, and hangover in heavy drinkers. This study aimed to demonstrate the efficacy of a standardized polyphenolic extract of clove buds (Clovinol) in ameliorating the oxidative stress and inflammation caused by the accumulation of acetaldehyde after binge drinking. We used a randomized, double-blinded crossover study with 16 male social drinkers. The subjects were randomized into two groups of eight subjects and received either placebo or Clovinol in a single hard shell gelatin capsule (250 mg × 1) per day. The dosage of alcohol was 1 g/kg body weight/day. After 2 weeks of washout period, the treatment regime was reversed. Blood samples were drawn at 0, 0.5, 2, 4, and 12 h after treatment with either placebo or Clovinol, and biochemical parameters were analyzed. Hangover severity score was determined by using a validated questionnaire as reported earlier. Results showed faster elimination of blood acetaldehyde with significant decreases in oxidative stress, lipid peroxidation, C-reactive protein, interleukin-6, and significant enhancement in glutathione and superoxide dismutase as compared with placebo along with an overall reduction of 55.34% in hangover severity in Clovinol-treated subjects. This study demonstrated the efficacy of clove bud polyphenols for alleviating alcohol-related side effects among social drinkers at the studied dose.

Safety and Efficacy of Ferula asafoetida in Functional Dyspepsia: A Randomized, Double-Blinded, Placebo-Controlled Study.

Despite the availability of various synthetic drugs for the treatment of functional dyspepsia (FD), the side effects and their cost have always created a great interest in the search for novel natural alternatives for the management of gut disorders. The present contribution reports the safety and efficacy of the kitchen spice asafoetida (Ferula asafoetida) in FD for the first time. In the double-blinded, placebo-controlled study, 43 subjects diagnosed to have moderate to severe discomforts of nonulcer FD were randomized to receive hard-shell capsules (250 mg × 2/day) of either placebo (n=22) or a food-grade formulation of asafoetida (Asafin) (n=21) for 30 days. When evaluated by a set of validated indexing tools (GSRS, GDSS, and NDI), almost 81% in the Asafin group showed significant (p < 0.01) improvement in the overall score and quality of life as compared to the placebo. At the end of the study, 66% of subjects in the Asafin group remained symptoms-free. Although the symptoms score improved significantly in both the groups (from -5.67 to -25.29 in Asafin group versus -1.55 to -6.0 in the placebo; p ≤ 0.001), the relative percentage of subjects in the Asafin group with more than 80% reduction in various symptoms were: bloating (58%), appetite (69%), postprandial fullness (74%) motion sickness (75%), and digestion (77%) as compared to less than 10% nonspecific improvement in the placebo group. All the subjects remained safe with no adverse events or variations in haematological and biochemical parameters. The study was registered at http://ctri.nic.in/ (CTRI/2018/ 01/011149).

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.