RESUMO
Hepatic lipid metabolism is modulated by the circadian rhythm; therefore, circadian disruption may promote obesity and hepatic lipid accumulation. This study aims to investigate dietary pterostilbene (PSB) 's protective effect against high-fat-diet (HFD)-induced lipid accumulation exacerbated by chronic jet lag and the potential role of gut microbiota therein. Mice were treated with a HFD and chronic jet lag for 14 weeks. The experimental group was supplemented with 0.25% (w/w) PSB in its diet to evaluate whether PSB had a beneficial effect. Our study found that chronic jet lag exacerbates HFD-induced obesity and hepatic lipid accumulation, but these adverse effects were significantly mitigated by PSB supplementation. Specifically, PSB promoted hepatic lipolysis and ß-oxidation by upregulating SIRT1 expression, which indirectly reduced oxidative stress caused by lipid accumulation. Additionally, the PSB-induced elevation of SIRT1 and SIRT3 expression helped prevent excessive autophagy and mitochondrial fission by activating Nrf2-mediated antioxidant enzymes. The result was evidenced by the use of SIRT1 and SIRT3 inhibitors in in vitro studies, which demonstrated that activation of SIRT1 and SIRT3 by PSB is crucial for the translocation of PGC-1α and Nrf2, respectively. Moreover, the analysis of gut microbiota suggested that PSB's beneficial effects were partly due to its positive modulation of gut microbial composition and functionality. The findings of this study suggest the potential of dietary PSB as a candidate to improve hepatic lipid metabolism via several mechanisms. It may be developed as a treatment adjuvant in the future.
Assuntos
Dieta Hiperlipídica , Síndrome do Jet Lag , Metabolismo dos Lipídeos , Fígado , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Sirtuína 1 , Sirtuína 3 , Estilbenos , Animais , Sirtuína 1/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos , Masculino , Metabolismo dos Lipídeos/efeitos dos fármacos , Estilbenos/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Sirtuína 3/metabolismo , Síndrome do Jet Lag/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade , Suplementos NutricionaisRESUMO
Hexahydrocurcumin (HHC) and octahydrocurcumin (OHC) were synthesized, and their enantiomers were separated using supercritical fluid chromatography. The absolute configurations (ACs) of HHC and OHC were independently determined using experimental measurements and quantum theoretical predictions of vibrational circular dichroism, electronic circular dichroism, and optical rotatory dispersion. These studies lead to AC assignments of (-)-(R)-HHC and (+)-(R,R)-OHC. The AC of OHC is further confirmed by its structure determined from single crystal x-ray diffraction.
Assuntos
Estereoisomerismo , Dispersão Óptica Rotatória , Dicroísmo CircularRESUMO
The SARS-CoV-2 infection is a highly contagious viral infection, which has claimed millions of lives in the last two years. The infection can cause acute respiratory distress, myocarditis, and systemic inflammatory response in severe cases. The interaction of the viral spike protein with the angiotensin-converting enzyme in various tissues causes damage to vital organs and tissues, leading to complications in the post-infection period. Vaccines and antiviral drugs have improved patient response to the infection, but the long-term effect on vital organs is still unknown. Investigations are now focused on supportive nutrient therapies, which can mitigate the susceptibility as well as the long-term complications of COVID-19. Selenium is one such micronutrient that plays a vital role in preventing oxidative stress induced by the virus. Further, selenium is important for effective immune response, controlling systemic inflammation, and maintain overall health of humans. We examine the role of selenium in various aspects of SARS-CoV-2 infection and address the importance of selenium supplementation in reducing the susceptibility and severity of infection in this review.
Assuntos
Tratamento Farmacológico da COVID-19 , Selênio , Antivirais/uso terapêutico , Humanos , Micronutrientes , SARS-CoV-2 , Selênio/uso terapêuticoRESUMO
Feruloylacetone (FER) is a natural degradant of curcumin after heating, which structurally reserves some functional groups of curcumin. It is not as widely discussed as its original counterpart has been previously; and in this study, its anticancer efficacy is investigated. This study focuses on the suppressive effect of FER on colon cancer, as the efficacious effect of curcumin on this typical cancer type has been well evidenced. In addition, demethoxy-feruloylacetone (DFER) was applied to compare the effect that might be brought on by the structural differences of the methoxy group. It was revealed that both FER and DFER inhibited the proliferation of HCT116 cells, possibly via suppression of the phosphorylated mTOR/STAT3 pathway. Notably, FER could significantly repress both the STAT3 phosphorylation and protein levels. Furthermore, both samples showed capability of arresting HCT116 cells at the G2/M phase via the activation of p53/p21 and the upregulation of cyclin-B. In addition, ROS elevation and changes in mitochondrial membrane potential were revealed, as indicated by p-atm elevation. The apoptotic rate rose to 36.9 and 32.2% after being treated by FER and DFER, respectively. In summary, both compounds exhibited an anticancer effect, and FER showed a greater proapoptotic effect, possibly due to the presence of the methoxy group on the aromatic ring.
Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Curcumina/farmacologia , Mitocôndrias/efeitos dos fármacos , Estirenos/farmacologia , Antineoplásicos/química , Antioxidantes/química , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Curcumina/química , Curcumina/metabolismo , Ciclina B1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/agonistas , Fase G2/efeitos dos fármacos , Células HCT116 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Fenol/química , Fenol/farmacologia , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Estirenos/química , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/agonistasRESUMO
BACKGROUND: Emblica officinalis, known as amla in Ayurveda, has been used as a folk medicine to treat numerous pathological conditions, including diabetes. However, the novel extract of E. officinalis fruit extract (amla fruit extract, AFE, Saberry®) containing 100 g kg-1 ß-glucogallin along with hydrolyzable tannins has not yet been extensively studied for its antidiabetic potential. OBJECTIVE: The aim of this study was to investigate the antidiabetic and antioxidant activities of AFE and its stability during gastric stress as well as its thermostability. METHODS: The effect of AFE on the inhibition of pancreatic α-amylase and salivary α-amylase enzymes was studied using starch and yeast α-glucosidase enzyme using 4-nitrophenyl α-d-glucopyranoside as substrate. Further, 2,2-diphenyl-1-picrylhydrazyl radical scavenging and reactive oxygen species inhibition assay was performed against AFE. RESULTS: AFE potently inhibited the activities of α-amylase and α-glucosidase in a concentration-dependent manner with half maximal inhibitory concentration (IC50 ) values of 135.70 µg mL-1 and 106.70 µg mL-1 respectively. Furthermore, it also showed inhibition of α-glucosidase (IC50 562.9 µg mL-1 ) and dipeptidyl peptidase-4 (DPP-4; IC50 3770 µg mL-1 ) enzyme activities. AFE is a potent antioxidant showing a free radical scavenging activity (IC50 2.37 µg mL-1 ) and protecting against cellular reactive oxygen species (IC50 1.77 µg mL-1 ), and the effects elicited could be attributed to its phytoconstituents. CONCLUSION: AFE showed significant gastric acid resistance and was also found to be thermostable against wet heat. Excellent α-amylase, α-glucosidase, and DPP-4 inhibitory activities of AFE, as well as antioxidant activities, strongly recommend its use for the management of type 2 diabetes mellitus. © 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Assuntos
Antioxidantes/química , Inibidores da Dipeptidil Peptidase IV/química , Frutas/química , Inibidores de Glicosídeo Hidrolases/química , Phyllanthus emblica/química , Extratos Vegetais/química , Antioxidantes/isolamento & purificação , Diabetes Mellitus Tipo 2/enzimologia , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Extratos Vegetais/isolamento & purificação , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , alfa-Glucosidases/químicaRESUMO
A double-blind, placebo-controlled human trial was conducted to evaluate the safety and efficacy of a standardized oral supplementation of Boswellin®, a novel extract of Boswellia serrata extract (BSE) containing 3-acetyl-11-keto-ß-boswellic acid (AKBBA) with ß-boswellic acid (BBA). A total of 48 patients with osteoarthritis (OA) of the knee were randomized and allocated to the BSE and placebo groups for intervention. Patients were administered BSE or placebo for a period of 120 days. The trial results revealed that BSE treatment significantly improved the physical function of the patients by reducing pain and stiffness compared with placebo. Radiographic assessments showed improved knee joint gap and reduced osteophytes (spur) confirming the efficacy of BSE treatment. BSE also significantly reduced the serum levels of high-sensitive C-reactive protein, a potential inflammatory marker associated with OA of the knee. No serious adverse events were reported. This is the first study with BSE conducted for a period of 120 days, longer than any other previous clinical trial on patients with OA of the knee. The findings provide evidence that biologically active constituents of BSE, namely, AKBBA and BBA, act synergistically to exert anti-inflammatory/anti-arthritic activity showing improvement in physical and functional ability and reducing the pain and stiffness.
Assuntos
Boswellia/química , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Projetos Piloto , Extratos Vegetais/efeitos adversos , Triterpenos/administração & dosagemRESUMO
Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,40-trihydroxystilbene) is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects of gnetol (trans-3,5,20,60-tetrahydroxystilbene) and pterostilbene (trans-3,5-dimethoxy-40-hydroxystilbene) on cardiac hypertrophy. In vitro, gnetol and pterostilbene prevented endothelin-1-induced indicators of cardiomyocyte hypertrophy including cell enlargement and protein synthesis. Gnetol and pterostilbene stimulated AMP-activated protein kinase (AMPK), and inhibition of AMPK, using compound C or shRNA knockdown,abolished these anti-hypertrophiceffects. In contrast,resveratrol, gnetol, nor pterostilbene reduced blood pressure or hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat. In fact, AMPK levels were similar between Sprague-Dawley and SHHF rats whether treated by stilbenoids or not. These data suggest that the anti-hypertrophic actions of resveratrol (and other stilbenoids?) do not extend to the SHHF rat, which models heart failure superimposed on hypertension. Notably, SHHF rat hearts exhibited prolonged isovolumic relaxationtime(an indicator of diastolicdys function),and this was improved by stilbenoid treatment.In conclusion, stilbenoid-based treatment as a viable strategy to prevent pathological cardiac hypertrophy,a major risk factor for heart failure,may be context-dependent and requires furtherstudy.
Assuntos
Cardiomegalia/metabolismo , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Polifenóis/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/tratamento farmacológico , Cardiomegalia/patologia , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/patologia , Testes de Função Cardíaca , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Polifenóis/química , Ratos , Ratos Endogâmicos SHR , Resveratrol , Estilbenos/química , Estilbenos/farmacologiaRESUMO
BACKGROUND: Bacillus coagulans MTCC 5856 has been marketed as a dietary ingredient, but its efficacy in diarrhea predominant irritable bowel syndrome (IBS) condition has not been clinically elucidated till date. Thus, a double blind placebo controlled multi-centered trial was planned to evaluate the safety and efficacy of B. coagulans MTCC 5856 in diarrhea predominant IBS patients. METHODS: Thirty six newly diagnosed diarrhea predominant IBS patients were enrolled in three clinical centres. Along with standard care of treatment, 18 patients in group one received placebo while in group two 18 patients received B. coagulans MTCC 5856 tablet containing 2 × 10(9) cfu/day as active for 90 days. Clinical symptoms of IBS were considered as primary end point measures and were evaluated through questionnaires. The visual analog scale (VAS) was used for abdominal pain. Physician's global assessment and IBS quality of life were considered as secondary efficacy measures and were monitored through questionnaires. RESULTS: Laboratory parameters, anthropometric and vital signs were within the normal clinical range during the 90 days of supplementation in placebo and B. coagulans MTCC 5856 group. There was a significant decrease in the clinical symptoms like bloating, vomiting, diarrhea, abdominal pain and stool frequency in a patient group receiving B. coagulans MTCC 5856 when compared to placebo group (p < 0.01). Similarly, disease severity also decreased and the quality of life increased in the patient group receiving B. coagulans MTCC 5856 when compared to placebo group. CONCLUSIONS: The study concluded that the B. coagulans MTCC 5856 at a dose of 2 × 10(9) cfu/day along with standard care of treatment was found to be safe and effective in diarrhea predominant IBS patients for 90 days of supplementation. Hence, B. coagulans MTCC 5856 could be a potential agent in the management of diarrhea predominant IBS patients.
Assuntos
Bacillus , Diarreia/terapia , Microbioma Gastrointestinal , Síndrome do Intestino Irritável/terapia , Probióticos/administração & dosagem , Dor Abdominal/terapia , Adolescente , Adulto , Gerenciamento Clínico , Método Duplo-Cego , Feminino , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Projetos Piloto , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
Commercial probiotics preparation containing Bacillus coagulans have been sold in the market for several decades. Due to its high intra-species genomic diversity, it is very likely that B. coagulans strain may alter in different ways over multiple years of production. Therefore, the present study focuses to evaluate the genetic consistency and probiotic potential of B. coagulans MTCC 5856. Phenotypic and genotypic techniques including biochemical profiling, 16S rRNA sequencing, GTG 5â³, BOX PCR fingerprinting, and Multi-Locus-Sequence typing (MLST) were carried out to evaluate the identity and consistency of the B. coagulans MTCC 5856. Further, in vitro probiotic potential, safety and stability at ambient temperature conditions of B. coagulans MTCC 5856 were evaluated. All the samples were identified as B. coagulans by biochemical profiling and 16S rRNA sequencing. GTG 5â³, BOX PCR fingerprints and MLST studies revealed that the same strain was present over 3 years of commercial production. B. coagulans MTCC 5856 showed resistance to gastric acid, bile salt and exhibited antimicrobial activity in in-vitro studies. Additionally, B. coagulans MTCC 5856 was found to be non-mutagenic, non-cytotoxic, negative for enterotoxin genes and stable at ambient temperature (25 ± 2 °C) for 36 months. The data of the study verified that the same strain of B. coagulans MTCC 5856 was present in commercial preparation over multiple years of production.
Assuntos
Bacillus/classificação , Bacillus/fisiologia , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana/métodos , Bacillus/genética , Impressões Digitais de DNA , DNA Bacteriano/genética , DNA Ribossômico/genética , Tipagem de Sequências Multilocus , Fenótipo , Probióticos , RNA Ribossômico 16S/genéticaRESUMO
Abstract: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is far from over as new strains are emerging all over the world. Selenium as a micronutrient is important for immunity and also has anti-viral activity. Objective: The study evaluated the activity of a Selenium enriched garlic powder (SeGP or SelenoForce®) against SARS-CoV-2 viral replication in vitro and explored its possible mechanism of action. Methods: The anti-SARS-CoV-2 activity assay was carried out in Vero E6 cells in vitro. Human lung carcinoma A549 cells were used to study the antioxidant activity, expression of angiotensin converting enzyme (ACE), transmembrane protease, serine 2 (TMPRSS2) and the activity of proprotein convertase, and furin. Anti-inflammatory activity was evaluated in lipopolysaccharide-activated RAW 264.7 cells. Results: SeGP inhibited the replication of SARS-CoV-2 in Vero E6 cells with an IC50 of 19.59 µg/ml. It exhibited significant antioxidant activity in vitro with IC50 value determined as 43.45 µg/ml. The Selenium enriched product inhibited the expression of ACE and TMPRSS2 and also showed inhibition of furin protease activity. In the presence of SeGP, the secretion of nitric oxide, interleukin -6 and TNF-α were reduced in activated RAW 264.7 macrophages. Conclusion: The results of the study suggest that Selenium enriched garlic powder could inhibit SARS-CoV-2 multiplication in vitro, reduce oxidative stress and inflammatory mediators suggesting that it could be developed as an effective supplement or adjunct therapy to combat viral infections.
RESUMO
SCOPE: Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with higher interleukin-6 (IL-6) levels, and suppression of the Janus kinase 2/Signal transducer and activator of transription 3 (JAK2/STAT3) pathway may contribute to the suppression of this cancer. This study aims to compare the anti-cancer effect of pterostilbene (PSB) and 2'- and 3'-hydroxypterostilbene (2HPSB and 3HPSB, respectively) on the JAK2/STAT3 pathway. METHODS AND RESULTS: In vitro experiments with the OCCC cell line TOV21G and a xenograft nude mouse model are used to achieve the study aims. The results showed that 3HPSB has the greatest anti-proliferative and pro-apoptotic effects of the three compounds studied. Activation of the JAK2/STAT3 pathway and the nuclear translocation of STAT3 are effectively inhibited by 3HPSB and PSB. Both 3HPSB and PSB can effectively suppress tumor growth, which is mediated by the inhibition of JAK2/STAT3 phosphorylation. CONCLUSION: This is the first study to compare the efficacy of PSB, 3HPSB, and the newly identified compound 2HPSB regarding ovarian cancer. Moreover, targeting JAK2/STAT3 is shown to be a potentially effective strategy for OCCC treatment. This study is expected to provide new insights into the potential of the abovementioned phytochemicals for development as adjuvants for cancer treatment in the future.
Assuntos
Carcinoma , Neoplasias Ovarianas , Feminino , Animais , Camundongos , Humanos , Janus Quinase 2/metabolismo , Janus Quinase 2/farmacologia , Linhagem Celular Tumoral , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Fator de Transcrição STAT3/metabolismo , Proliferação de CélulasRESUMO
Some thermal degradants of curcuminoids have demonstrated moderate health benefits in previous studies. Feruloyl acetone (FER), recently identified as a thermal degradant of curcumin, has been previously associated with anticancer and antioxidative effects, yet its other capabilities remain unexplored. Moreover, earlier reports suggest that methoxy groups on the aromatic ring may influence the functionality of the curcuminoids. To address these gaps, an animal study was conducted to investigate the antiobesity effects of both FER and its demethoxy counterpart (DFER) on mice subjected to a high-fat diet. The results demonstrated the significant prevention of weight gain and enlargement of the liver and various adipose tissues by both samples. Furthermore, these supplements exhibited a lipid regulatory effect in the liver through the adiponectin/AMPK/SIRT1 pathway, promoted thermogenesis via AMPK/PGC-1α activation, and positively influenced gut-microbial-produced short-chain fatty acid (SCFA) levels. Notably, DFER demonstrated superior overall efficacy in combating obesity, while FER displayed a significant effect in modulating inflammatory responses. It is considered that SCFA may be responsible for the distinct effects of FER and DFER in the animal study. Future studies are anticipated to delve into the efficacy of curcuminoid degradants, encompassing toxicity and pharmacokinetic evaluations.
Assuntos
Fármacos Antiobesidade , Curcumina , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Obesidade , Animais , Curcumina/química , Curcumina/farmacologia , Curcumina/metabolismo , Camundongos , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Masculino , Fármacos Antiobesidade/química , Fármacos Antiobesidade/administração & dosagem , Humanos , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/química , Termogênese/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/químicaRESUMO
BACKGROUND: z-Guggulsterone (z-Gug) and Gugulipid (GL) have been used to treat a variety of ailments. We now report their anti-cancer effect and mechanism against human breast cancer. METHODS: Using the human estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells as well as the normal human mammary epithelial cell line (HMEC), we evaluated the anti-breast-cancer efficacy and apoptosis inducing activity of GL. We determined the cellular and molecular mechanism of GL-inhibited breast cancer cell growth. RESULTS: GL significantly inhibited growth of MCF-7 and MDA-MB-231 cells with an IC50~2 µM at pharmacologically relevant concentrations standardized to its major active constituent z-Gug. The GL-induced growth inhibition correlated with apoptosis induction as evidenced by an increase in cytoplasmic histone-associated DNA fragmentation and caspase 3 activity. The GL-induced apoptosis was associated with down-regulation of the ß-Catenin signaling pathway. The decreased expression of Wnt/ß-Catenin targeting genes, such as cyclin D1, C-myc and survivin, and the inhibition of the activity of the transcription factor (T-cell factor 4, TCF-4) were observed in GL-treated breast cancer cells. The GL treatment resulted in a significant reduction of ß-Catenin /TCF-4 complex in both of the cancer cells. The GL-induced apoptotic cell death was significantly enhanced by RNA Interference of ß-Catenin and TCF-4. On the other hand, the normal human mammary epithelial cell HMEC, compared with the human breast cancer cells, is significantly more resistant to growth inhibition and apoptosis induction by GL. CONCLUSION: The present study indicates that the ß-Catenin signaling pathway is the target for GL-induced growth inhibition and apoptosis in human breast cancer.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Commiphora/química , Extratos Vegetais/farmacologia , Gomas Vegetais/farmacologia , Pregnenodionas/farmacologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Ayurveda , Ligação Proteica , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição 4 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , beta Catenina/metabolismoRESUMO
BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has resulted in a surge in stress, anxiety, and depression worldwide. Ashwagandha, an ayurvedic adaptogen has been traditionally used to manage stress, anxiety, and general well-being. OBJECTIVE: We assessed the effect of Ashwagandha root extract (ARE-500 mg) standardized for 2.5% withanolides as per USP protocol with piperine (5 mg of 95% piperine) once daily for 60 days (12.5 mg withanolides/day) to alleviate stress and anxiety in healthy individuals with mild to moderate symptoms. METHODS: A randomized, double-blind, placebo-controlled study was conducted for 60 days using ARE (nâ =â 27) and placebo (nâ =â 27) once daily at night at Narayana Institute of Cardiac Sciences, Bangalore, and Vijaya Super Specialty Hospital, Nellore, in India. The objectives of this study were to assess an improvement in perceived stress scale (PSS), generalized anxiety disorder (GAD-7), quality of life (QOL), cognitive scores in the Cambridge Neuropsychological Test Automated Battery (CANTAB), changes in salivary cortisol, urinary serotonin, dopamine, serum levels of nitric oxide (NO), glutathione (GSH) and malondialdehyde (MDA) from baseline to end of the study. Safety was evaluated by laboratory parameters, and by monitoring any incidence of adverse events. RESULTS: 54 individuals were randomized and 50 of them completed the study. The PSS, GAD-7, and QOL scores improved significantly in all the participants taking ARE compared to the placebo. The CANTAB analysis revealed a significant improvement in multitasking, concentration, and decision taking time in ARE compared to placebo. ARE was also associated with a greater reduction in the morning salivary cortisol and an increase in urinary serotonin compared to placebo. Serum levels of NO, GSH, and MDA were not significantly different. Biochemical and hematological parameters remained in the normal range in all participants and ARE was well tolerated during the study. CONCLUSION: The results of the study suggest that ARE with 2.5% withanolides can effectively improve stress and anxiety by reducing cortisol and increasing serotonin in healthy individuals with mild to moderate symptoms.
Assuntos
COVID-19 , Vitanolídeos , Humanos , Adulto , Qualidade de Vida , Hidrocortisona , Serotonina , Vitanolídeos/uso terapêutico , Índia , Transtornos de Ansiedade/tratamento farmacológico , Ansiedade/tratamento farmacológico , Método Duplo-CegoRESUMO
Background: Pterostilbene is an active molecule from the bark of the Pterocarpus marsupium tree with antioxidant and anti-inflammatory properties. Objective: This study aimed to evaluate the clinical safety of a standardized P. marsupium extract (PME) containing 90% pterostilbene (200â mg per day) in healthy adults. Methods: In a randomized, double-blind, placebo-controlled study, 60 healthy adult participants (27 males and 33 females) were randomized to receive PME-100 mg or placebo capsule twice a day for two months. The primary objectives of the study were to assess any changes in laboratory parameters, vital signs, and the occurrence of adverse events from screening to the final visit. Serum antioxidant enzyme levels were evaluated as a secondary outcome. Results: The hematological, lipid, glycemic, thyroid profiles and liver and renal functions remained within the normal range in all participants, with no difference between PME and placebo. Vital signs, including blood pressure, pulse rate, body weight, body mass index and electrocardiogram, did not reveal any significant differences between the PME and placebo groups at the beginning and end of the study. No serious adverse events were observed in any participant throughout the study period. The serum antioxidant profile was not significantly different between the treatment groups, although the glutathione levels were relatively higher in the PME group. Conclusions: Scientific evaluation of clinical safety of standardized extract is mandatory for its use as a supplement for various health benefits. The results of this study convincingly establish the safety of PME (>90% Pterostilbene) at 200â mg/day (100â mg bid) for human use. The study was approved by the Institutional Ethics Committee of BGS Global Institute of Medical Sciences & Hospital, Bangalore with the registration number CTRI/2019/08/020736.
Assuntos
Antioxidantes , Extratos Vegetais , Masculino , Feminino , Humanos , Adulto , Antioxidantes/efeitos adversos , ÍndiaRESUMO
BACKGROUND: Gut microbiome dysbiosis is a major cause of abdominal gas, bloating, and distension. Bacillus coagulans MTCC 5856 (LactoSpore) is a spore-forming, thermostable, lactic acid-producing probiotic that has numerous health benefits. We evaluated the effect of Lacto Spore on improving the clinical symptoms of functional gas and bloating in healthy adults. METHODS: Multicenter, randomized, double-blind, placebo-controlled study at hospitals in southern India. Seventy adults with functional gas and bloating with a gastrointestinal symptom rating scale (GSRS) indigestion score ≥ 5 were randomized to receive B coagulans MTCC 5856 (2 billion spores/day, N = 35) or placebo (N = 35) for 4 weeks. Changes in the GSRS-Indigestion subscale score for gas and bloating and global evaluation of patient's scores from screening to the final visit were the primary outcomes. The secondary outcomes were Bristol stool analysis, brain fog questionnaire, changes in other GSRS subscales, and safety. RESULTS: Two participants from each group withdrew from the study and 66 participants (n = 33 in each group) completed the study. The GSRS indigestion scores changed significantly (P < .001) in the probiotic group (8.91-3.06; P < .001) compared to the placebo (9.42-8.43; P = .11). The median global evaluation of patient's scores was significantly better (P < .001) in the probiotic group (3.0-9.0) than in the placebo group (3.0-4.0) at the end of the study. The cumulative GSRS score, excluding the indigestion subscale, decreased from 27.82 to 4.42% (P < .001) in the probiotic group and 29.12 to 19.33% (P < .001) in the placebo group. The Bristol stool type improved to normal in both the groups. No adverse events or significant changes were observed in clinical parameters throughout the trial period. CONCLUSIONS: Bacillus coagulans MTCC 5856 may be a potential supplement to reduce gastrointestinal symptoms in adults with abdominal gas and distension.
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Bacillus coagulans , Dispepsia , Adulto , Humanos , Flatulência/terapia , Método Duplo-Cego , Suplementos NutricionaisRESUMO
Purpose: There has been a growing interest in the use of probiotics and their products for skin care, over the last decade. LactoSporin is the extracellular metabolite of a spore-forming probiotic Bacillus coagulans (Weizmannia coagulans) MTCC 5856, with antimicrobial and skin protecting activity. Patients and Methods: The anti-skin-aging potential of LactoSporin was evaluated in a randomized, double-blinded, placebo-controlled study in healthy female participants (70 screened and 56 randomized). The participants applied either LactoSporin or matched placebo formulation (N=28 in each group) for 10 weeks, and the effects were assessed by dermatological, and non-invasive instrument-based evaluation using Antera, Cutometer, Corneometer, and Tewameter. All the 56 participants completed the study and were included for the analysis. Results: The regular use of LactoSporin cream for 10 weeks showed a significant reduction in visibility of wrinkles around crow's feet, nasolabial folds, frown lines, and facial fine lines compared to baseline and placebo by dermatological and Antera assessments. LactoSporin showed improvement in skin elasticity and hydration by dermatological assessments, but the effect was not significantly different from placebo when assessed by Cutometer, Corneometer, and Tewameter. No adverse events or skin irritation was observed in any participants during the study. Conclusion: These results suggest that LactoSporin could be a safe natural ingredient to reduce wrinkles and fine lines in cosmetic formulations.
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Inflammatory bowel disease has become a significant health concern across the globe, causing frequent and long-term harm to the digestive system. This study evaluated the effect of piceatannol (PIC) and 3'-hydroxypterostilbene (HPSB) on dextran sulfate sodium (DSS)-induced colitis in mice and investigated whether their effects are exerted through the amelioration of gut barrier dysfunction to reduce the severity of colitis. The findings showed that both PIC and HPSB attenuated inflammation by inhibiting the TNF-α/NF-κB/MLC pathway and reducing NLRP3 inflammasome activation. However, PIC was comparably effective in modulating tight junctions. The results may be attributed to the effect of PIC on reducing cell apoptosis-associated protein expression, including Bax/Bcl-2 and caspase-3 activation. Furthermore, microbiota analysis revealed that both PIC and HPSB increased representative probiotic species, including Akkermansiaceae and Lactobacillus intestinalis, and exhibited inhibitory effects on several bacterial species (Spiroplasmataceae and Acholeplasmataceae). Based on linear discriminant analysis effect size, butyrate-producing bacteria were identified as a biomarker in the PIC group. Overall, the results demonstrated that PIC repressed inflammation, inhibited cell apoptosis, and regulated microbiota composition. Consequently, PIC is more effective in maintaining gut barrier integrity than HPSB, and it is a promising ingredient in the development of functional food for colitis prevention.
Assuntos
Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Inflamação , Doenças Inflamatórias Intestinais/tratamento farmacológico , Camundongos Endogâmicos C57BLRESUMO
Background: Withania somnifera (Linn) or Ashwagandha is used in Ayurveda and other traditional medicine systems as an adaptogen and a neuroprotective supplement. Objective: The effect of Ashwagandha root extract (ARE) standardized for 2.5% full-spectrum withanolides as per The United States Pharmacopeia (USP) protocol with piperine (500 mg with 5 mg of 95% piperine) once a day (12.5 mg withanolides/day) was evaluated in individuals with mild to moderate depression and anxiety. Methods: In a randomized, double-blind placebo-controlled study, for 90 days, 70 participants were randomized to ARE (n = 34) or placebo (n = 36) once daily at night. Mean change in the Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), Groningen Sleep Quality Scale (GSQS), and quality of life (QOL) from screening to days 30, 60, and 90 were evaluated. Safety was evaluated by monitoring any incidence of adverse events and laboratory parameters. Two-way analysis of variance (ANOVA) and repeated-measure ANOVA were used to compare ARE and placebo, and the changes within the group at different time points. Results: Seventy individuals were randomized and all of them completed the study. The HARS, HDRS, GSQS, and QOL scores improved significantly (p < 0.001) in all the participants taking ARE compared to placebo on days 30, 60, and 90. Anxiety and depression improved from baseline to end of the study in both groups, but the quantum of improvement was significantly higher in ARE. Serum levels of serotonin increased in ARE, but showed a decrease in placebo, the difference being statically significant (p < 0.001). Biochemical and hematological parameters remained in the normal range in all participants and ARE was well tolerated during the study. Conclusion: The results of the study suggest that 500 mg of ARE standardized for 2.5% withanolides with 5 mg piperine is beneficial in improving depression, and anxiety, by increasing serum serotonin levels. The trial was registered prospectively with the Clinical Trial Registry of India (CTRI) with the registration number CTRI/2022/05/042640, on May 18, 2022.
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Results: Our findings suggest that antioxidants and PMF may alleviate impaired protein synthesis and degradation pathways in skeletal muscle atrophy. PTS showed a positive effect on the anabolic pathway, while RSV and PMF demonstrated potential for ameliorating the catabolic pathway. Notably, the combination therapy of antioxidants and PMF exhibited a stronger ameliorative effect on skeletal muscle atrophy than either intervention alone. Conclusion: The present results highlight the benefits of employing a multimodal approach, involving both antioxidant and PMF therapy, for the management of muscle-wasting conditions. These treatments may have potential therapeutic implications for skeletal muscle atrophy.