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1.
Front Microbiol ; 15: 1418556, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946910

RESUMO

Introduction: This study aimed to explore the anti-oxidative and anti-inflammatory properties of Lactococcus lactis subsp. lactis HFY14 (LLSLHFY14) and investigate its effects on the intestinal barrier, cranial nerve, and motor function in mice treated with antibiotics. Methods: Mice were administered an antibiotic mixture (neomycin 5 mg/mL, vancomycin 25 mg/mL, amphotericin B 0.1 mg/mL, ampicillin 10 mg/mL, metronidazole file 5 mg/mL, and lipopolysaccharide 1.5 µg/mL) intraperitoneally, and oxidative stress and inflammatory markers in the serum and brain tissues, and liver index were measured. H&E staining was performed to detect pathological alterations in brain tissues. The expression of intestinal-barrier-related genes and that of genes involved in inflammatory pathways in the brain were detected using polymerase chain reaction (PCR). Results: LLSLHFY14 administration extended the weight-loaded swimming and running times of mice and decreased the liver index. Moreover, the levels of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the serum and brain tissue were reduced, whereas those of superoxide dismutase (SOD), glutathione (GSH), and interleukin-10 (IL-10) were elevated. Elevated brain expression of the protein kinase B (AKT)/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/extracellular signal-regulated kinase 1 (ERK1) pathway, decreased brain expression of the IL-6 gene, and elevated cecum expression of zonula occludens-1 (ZO-1), occludin-1, and claudin-1 genes were noted. LLSLHFY14 supplementation significantly increased Bacteroidetes expression but decreased Firmicutes expression, thus increasing the Bacteroidetes/Firmicutes ratio. Discussion: Overall, LLSLHFY14 supplementation ameliorated antibiotic-induced oxidative stress and inflammation in the mouse central nervous system, intestinal barrier dysfunction, and increased motor function, thus confirming its potential application as probiotics.

3.
Heliyon ; 10(3): e24780, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38318056

RESUMO

Nutritional supplements have been used to improve immune function. Condensed fuzheng extract (CFE) is a well-known traditional Chinese medicine (TCM) formula that is predominantly made from sheep placenta, Astragalus mongholicus Bunge, and Polygonatum kingianum Collett & Hemsl. However, the toxicological profile of CFE has not been determined. In this study, we investigated the acute (14 days) and sub-chronic (90 days) oral toxicities of CFE in mice and rats and the phytochemical composition of CFE. Materials and methods: For the assessment of acute toxicity, 80 ICR mice of both sexes were randomly divided into four groups. Three groups were treated with 4500, 2250 and 1125 mg/kg/d bw CFE daily (n = 10/group per sex) for 14 days; a separate group was used as control. To test the sub-chronic toxicity, male and female Sprague Dawley rats were orally administered 8150, 4075 or 2037 mg/kg bw of CFE for 90 days; a control group was included. Hematological, biochemical, and histopathological markers were tested at the end of the experiment. The chemical composition of CFE was determined by UPLC-HRMS method. Results: In both acute and sub-chronic toxicity studies, no mortalities, indications of abnormality, or treatment-related adverse effects were observed. The LD50 of CFE was higher than 4500 mg/kg. There were no significant changes in the hematological and biochemical data in the treatment group compared with the control group (p > 0.05). Histopathological analyses of the heart, liver, spleen, lungs, kidneys, thymus, testes (male rats) and ovaries (female rats) revealed no anatomical changes of each organ. Phytochemical analysis of CFE revealed the presence of flavonoids (highest abundance), phenols and alkaloids. In conclusion, our results showed that CFE is a safe and non-toxic formula. We also reported phytochemicals in CFE that may possess important pharmacological effects.

4.
Nutrients ; 15(15)2023 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-37571326

RESUMO

This study investigated the potential therapeutic properties of fermented ginseng berry extract (GBE) for Alzheimer's disease (AD). Fermented GBE was examined for its ginsenoside content and physiological properties, which have been suggested to have neuroprotective effects and improve cognitive function. The results showed that fermented GBE contains high levels of major active ginsenosides and exhibits antioxidant and acetylcholinesterase inhibitory activities. Post-fermented GBE demonstrated therapeutic potential in AF64A-induced damaged neural stem cells and an animal model of AD. These findings suggest that fermented GBE may hold promise as a candidate for developing new therapeutic interventions for memory deficits and cognitive disorders associated with AD and other neurodegenerative conditions. However, further studies are needed to evaluate the safety, tolerability, and efficacy of fermented GBE in human subjects and to determine its clinical applications. In conclusion, our study provides evidence that fermented GBE has potential as a natural product for the prevention and treatment of AD. The high levels of active ginsenosides and antioxidant and acetylcholinesterase inhibitory activities of fermented GBE suggest that it may be a promising therapeutic agent for improving cognitive function and reducing neurodegeneration.


Assuntos
Ginsenosídeos , Panax , Animais , Humanos , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Extratos Vegetais/efeitos adversos , Antioxidantes/efeitos adversos , Frutas , Acetilcolinesterase , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/prevenção & controle , Transtornos da Memória/induzido quimicamente , Cognição
5.
Microbiol Res ; 275: 127462, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37473669

RESUMO

Gut microbiota play vital roles in the maintenance of human health and in various diseases. We aimed to investigate the association of gut microbiota with aging and sarcopenia. This study contained two experimental designs using the ICR mouse model for 1) determining the association between aging and gut microbiota (by analyzing murine fecal samples) and 2) determining the association between sarcopenia and gut microbiota in mice treated with microorganisms or dexamethasone. The composition of the gut microbiota was determined by next-generation sequencing. Marginally significant differences were observed in taxon composition of the gut microbiota depending on age; particularly, the abundance of the genusAlistipes increased with increasing age. In addition, the abundance of the class Bacteroidia decreased with increasing age, whereas that of the genus Oscillibacter increased. The microbiome composition differed between young mice and aging mice with sarcopenia. Moreover, the gut microbiota in aging and sarcopenia showed altered abundances of Alistipes, Lachnospiraceae, and Bacteroides. Although the sample size was small, these results point to similarities in the gut microbiota between aging and sarcopenia and to differences between young and old individuals. The results on gut microbiota obtained in this study form a basis for studying the development of sarcopenia in geriatric animal models in the future.


Assuntos
Microbioma Gastrointestinal , Sarcopenia , Humanos , Camundongos , Animais , Idoso , Camundongos Endogâmicos ICR , Envelhecimento , Modelos Animais de Doenças
6.
Arch Med Sci ; 19(3): 792-799, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37313183

RESUMO

Introduction: Hyperlipidemia refers to a group of lipid metabolism disorders characterized by increased levels of total cholesterol, triglyceride, and/or low-density lipoprotein cholesterol and/or decreased levels of high-density lipoprotein cholesterol. This study aims to investigate the effects of Lactobacillus on lipid metabolism and hepatic steatosis in male mice fed with a high-fat diet by measuring blood lipid, hepatic function and hepatocyte morphology. Material and methods: Eighty male Institute of Cancer Research (ICR) mice were fed with a high-fat diet for 6 weeks to establish hyperlipidemic models. Then, mice were treated with a high or low concentration of Lactobacillus of human source, mouse source, or plant source, respectively. Results: After 3 weeks of therapy, except for the human Lactobacillus treatment group, the blood cholesterol, triglyceride and low-density lipoprotein cholesterol in mice treated with Lactobacillus of mouse and plant source were lower than those in the hyperlipidemic model group. After 4 weeks of treatment, the levels of blood biochemical indexes in mice in all treatment groups were significantly different, when compared to those in the hyperlipidemic model group. Conclusions: Lactobacillus may regulate blood lipid in mice fed with a high-fat diet. Lactobacillus can improve the high cholesterol, high blood lipid, and injury of hepatic function, and prevent further development of atherosclerosis caused by a high-fat diet to some extent. Correct dietary structure is the basis for the treatment of dietary hyperlipidemia and its complications.

7.
Front Pain Res (Lausanne) ; 4: 1150236, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37139343

RESUMO

This study evaluated climbing in mice as a tool to assess the expression and treatment of pain-related behavioral depression in male and female ICR mice. Mice were videotaped during 10-min sessions in a vertical plexiglass cylinder with wire mesh walls, and "Time Climbing" was scored by observers blind to treatments. Initial validation studies demonstrated that baseline climbing was stable across repeated days of testing and depressed by intraperitoneal injection of dilute lactic acid (IP acid) as an acute pain stimulus. Additionally, IP acid-induced depression of climbing was blocked by the positive-control non-steroidal anti-inflammatory drug (NSAID) ketoprofen but not by the negative control kappa opioid receptor agonist U69593. Subsequent studies examined effects of single-molecule opioids (fentanyl, buprenorphine, naltrexone) and of fixed-proportion fentanyl/naltrexone mixtures (10:1, 3.2:1, and 1:1) that vary in their efficacy at the mu opioid receptor (MOR). Opioids administered alone produced a dose- and efficacy-dependent decrease in climbing, and fentanyl/naltrexone-mixture data indicated that climbing in mice is especially sensitive to disruption by even low-efficacy MOR activation. Opioids administered as a pretreatment to IP acid failed to block IP acid-induced depression of climbing. Taken together, these findings support the utility of climbing in mice as an endpoint to evaluate candidate-analgesic effectiveness both to (a) produce undesirable behavioral disruption when the test drug is administered alone, and (b) produce a therapeutic blockade of pain-related behavioral depression. The failure of MOR agonists to block IP acid-induced depression of climbing likely reflects the high sensitivity of climbing to disruption by MOR agonists.

8.
Environ Sci Pollut Res Int ; 30(21): 60976-60993, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37042914

RESUMO

In the recent past, phytomolecules are exponentially applied in discovering the antidiabetic drug due to less adverse effects. This work screened the active solvent fraction of Lespedeza cuneata based on the phytochemical, enzyme inhibition, and antioxidant properties. The antioxidant efficacy of the different fractions of the L. cuneata was assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing power, hydrogen peroxide, and hydroxyl radical scavenging assays. The digestive enzyme (α-amylase and α-glucosidase) inhibitory activity was also evaluated. The phytochemical composition of ethyl acetate fraction of L. cuneata (Lc-EAF) was studied by UHPLC-QTOF-MS/MS. The effect of Lc-EAF treatments on glucose uptake was studied in insulin resistance HepG2 cells (IR-HepG2). Further, the antidiabetic effect of Lc-EAF in streptozotocin (STZ)-induced diabetic mice were demonstrated. Ethyl acetate, hexane, and methanol fractions of the L. cuneata showed notable antioxidant, α-amylase, and α-glucosidase inhibitory properties. Among the fractions, Lc-EAF was found to be the most potent. The Lc-EAF exhibited an IC50 of 205.32 ± 23.47 µg/mL and 105.32 ± 13.93 µg/mL for α-amylase and α-glucosidase inhibition, respectively. In addition, 75 µg/mL of Lc-EAF exposure enhanced glucose uptake (68.23%) in IR-HepG2 cells. In vivo study indicated that treatment of Lc-EAF (100 mg/kg b.wt) maintained the blood glucose level through reduced insulin level while improving the lipid profile, hepatic, and renal markers. These findings suggest that Lc-EAF could be considered a prominent source for antidiabetic, anti-hyperlipidemic, and anti-ROS potentials.


Assuntos
Diabetes Mellitus Experimental , Lespedeza , Ratos , Camundongos , Animais , Hipoglicemiantes/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Diabetes Mellitus Experimental/tratamento farmacológico , Estreptozocina , alfa-Glucosidases , Espectrometria de Massas em Tandem , Extratos Vegetais/química , alfa-Amilases , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Glucose
9.
J Hazard Mater ; 445: 130547, 2023 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-37055962

RESUMO

Polychlorinated biphenyls (PCBs) are environmental organic pollutants widely used in industry that can bioaccumulate and affect the reproductive systems of male animals of different species. 2,3',4,4',5-Pentachlorobiphenyl (PCB118) is a representative of the 209 toxic PCB congeners. In this study, male mice were exposed to PCB118 at 0, 50, and 500 µg/kg/day for 35 days beginning 3-4 weeks after birth. The results of the study showed that PCB118 exposure during puberty reduced testicular quality, caused tissue damage, decreased sperm motility and sperm count, and increased malformation and testicular cell apoptosis in mice. Moreover, PCB118 increased the oxidative stress levels in sperm and testicular tissue and the expression of aryl hydrocarbon receptor (AhR) and Cyp1a1 and siginificantly decreased the level of nuclear factor-erythroid 2-related factor 2 (Nrf2). The results indicate that PCB118 can activate the AhR/Cyp1a1 pathway and inhibit Nrf2 expression to aggravate testicular oxidative stress and induce cell apoptosis, resulting in testicular and sperm quality damage.


Assuntos
Poluentes Ambientais , Bifenilos Policlorados , Masculino , Camundongos , Animais , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Sêmen , Motilidade dos Espermatozoides , Bifenilos Policlorados/toxicidade , Bifenilos Policlorados/metabolismo , Poluentes Ambientais/toxicidade , Poluentes Ambientais/metabolismo , Apoptose , Mitocôndrias/metabolismo , Células Germinativas/metabolismo
10.
Front Physiol ; 13: 1026884, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36523549

RESUMO

Transverse aortic constriction (TAC) is a frequently used model to investigate pressure overload-induced progressive heart failure (HF); however, there is considerable phenotypic variation among different mouse strains and even sub-strains. Moreover, less is known about the TAC model in ICR mice. Therefore, to determine the suitability of the ICR strain for TAC-induced HF research, we compared the effects of TAC on ICR and C57BL/6J mice at one, two and four weeks post-TAC via echocardiography, organ index, morphology, and histology. At the end of the study, behavior and gene expression patterns were assessed, and overall survival was monitored. Compared to the sham-operated mice, ICR and C57BL/6J mice displayed hypertrophic phenotypes with a significant increase in ventricle wall thickness, heart weight and ratio, and cross-sectional area of cardiomyocytes after a 2-week TAC exposure. In addition, ICR mice developed reduced systolic function and severe lung congestion 4 weeks post-TAC, whereas C57BL/6J did not. Besides, ICR mice demonstrated comparable survival, similar gene expression alteration but severer fibrotic remodeling and poor behavioral performance compared to the C57BL/6J mice. Our data demonstrated that ICR was quite sensitive to TAC-induced heart failure and can be an ideal research tool to investigate mechanisms and drug intervention for pressure overload-induced HF.

11.
Molecules ; 27(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36558137

RESUMO

The variety of stressful conditions in daily human activity requires nutritional support with safe, specialized food products containing functional food ingredients (FFIs) enriched with biologically active plant substances with proven adaptogenic properties. In this in vivo study, by evaluating a set of physiological parameters and biochemical markers, we investigated the effectiveness of the developed FFIs from Chenopodium quinoa grains in stress conditions induced by daily episodes of immobilization for 36 days. The results of the evaluation of the anxiety-like functions, locomotor, and search activity of rats in the "open field" and "elevated plus maze" tests demonstrated the ability of FFIs to reduce stressful behavior induced by immobilization. The improvement in the long-term memory of animals treated with FFIs was noted in the passive avoidance test. Together with the hypolipidemic effect and compensation of transaminase levels, FFIs normalized the excretion of catecholamines in the urine and reduced the levels of malondialdehyde to values of the control group. According to the results of the assessment of FFI acute oral toxicity, the LD50 value exceeded 5000 mg/kg of body weight, which categorizes the FFIs under hazard class 5-substances with low hazard. The conducted experiment demonstrated the effectiveness of nutritional support with FFIs on the selected stress model. The positive safety profile of FFIs makes them reasonable to study on other stress models and to conduct clinical testing as part of specialized food products in various categories of people exposed to chronic stress.


Assuntos
Ansiolíticos , Chenopodium quinoa , Humanos , Ratos , Animais , Antioxidantes/farmacologia , Ansiolíticos/farmacologia , Polifenóis , Ansiedade/tratamento farmacológico
12.
Molecules ; 27(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36432032

RESUMO

Globally, plastics are used in various products. Concerns regarding the human body's exposure to plastics and environmental pollution have increased with increased plastic use. Microplastics can be detected in the atmosphere, leading to potential human health risks through inhalation; however, the toxic effects of microplastic inhalation are poorly understood. In this study, we examined the pulmonary toxicity of polystyrene (PS), polypropylene (PP), and polyvinyl chloride (PVC) in C57BL/6, BALB/c, and ICR mice strains. Mice were intratracheally instilled with 5 mg/kg of PS, PP, or PVC daily for two weeks. PS stimulation increased inflammatory cells in the bronchoalveolar lavage fluid (BALF) of C57BL/6 and ICR mice. Histopathological analysis of PS-instilled C57BL/6 and PP-instilled ICR mice showed inflammatory cell infiltration. PS increased the NLR family pyrin domain containing 3 (NLRP3) inflammasome components in the lung tissue of C57BL/6 and ICR mice, while PS-instilled BALB/c mice remained unchanged. PS stimulation increased inflammatory cytokines, including IL-1ß and IL-6, in BALF of C57BL/6 mice. PP-instilled ICR mice showed increased NLRP3, ASC, and Caspase-1 in the lung tissue compared to the control groups and increased IL-1ß levels in BALF. These results could provide baseline data for understanding the pulmonary toxicity of microplastic inhalation.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Microplásticos , Camundongos , Humanos , Animais , Cloreto de Polivinila/toxicidade , Poliestirenos/toxicidade , Plásticos , Polipropilenos/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos Endogâmicos ICR , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos BALB C
13.
Artigo em Inglês | MEDLINE | ID: mdl-35243111

RESUMO

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) in Asian countries is increasing at concerning level. Currently, no specific treatment available to prevent its oxidative stress and progression except for diet and lifestyle changes. Vitamin E such as tocotrienol-rich fraction (TRF) has a promising potential in preventing NAFLD progression. TRF is a potent antioxidant but has low bioavailability due to the use of long-chain triglycerides (LCT) as its carrier. Testing of potential therapeutic agents such as TRF are commonly carried out using animal models. These animal models are often costly due to limited access to the supply especially Asian countries and predisposed to high transportation cost. Lower expenditure of NAFLD model should be investigated without forfeiting the outcome of study. Therefore, this study addresses the gap by utilizing the ICR mice as NAFLD model through dietary modification and testing on the newly formulated TRF with combination of palm kernel oil (PKO) as a medium-chain triglycerides (MCT) carrier. METHODS: Fifteen ICR strain mice were randomly group into two control and one treatment group. Control groups received high-fat diet (HFD) only and standard diet while treatment group was given HFD with TRF (200 mg/kg/day). Study was carried out for 10 weeks. Weights were recorded twice a week. At the end of study, all mice were euthanized and data such weights, waist circumference and random blood glucose were recorded. Liver from each mouse were prepared for histology assessment. RESULTS: Mice mean weights and random blood sugar showed no difference between group (P>0.05) while significance waist circumference was larger in HFD and TRF groups compared to SD (P<0.05). Histology assessment showed steatosis in TRF group had lower severity compared to HFD group. NAFLD activity score (NAS) was lower in treatment group compared to HFD group. CONCLUSIONS: TRF showed promising potential as an agent to reduce NAFLD progression in ICR mice. Further study at gene and protein levels are required to fully elucidate the mechanism of this new TRF formulation in reducing NAFLD progression.

14.
Curr Mol Pharmacol ; 15(7): 969-979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35176991

RESUMO

BACKGROUND: Fangchinoline is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra S. Moore that is conventionally used as an analgesic, antirheumatic, and antihypertensive drug in China. However, the application of Fanchinoline in Sjögren syndrome (SS) remains unreported. OBJECTIVE: This study aimed to identify the potential role of Fangchinoline in the treatment of SS via altering Akt/mTOR signaling. METHODS: First, we examined levels of p-Akt and p-mTOR in infiltrating lymphocytes of labial glands from SS patients by immunohistochemistry. Then, the effects of Fangchinoline on Raji cells and Daudi cells were investigated using the CCK-8 assay, propidium iodide (PI)/RNase, and Annexin V/PI staining. Western blotting was used to identify the levels of Akt, p-Akt(ser473), mTOR, and p-mTOR. For in vivo analyses, NOD/Ltj and wild-type ICR mice were treated with a Fangchinoline solution, an LY294002 solution (an inhibitor of the PI3K/Akt/mTOR pathway), or their solvent for 28 days. Then, salivary flow assays and hematoxylin and eosin staining of submandibular glands were performed to determine the severity of SS-like responses in the mice. RESULTS: Immunohistochemical staining of labial glands from SS patients showed that activation of p-Akt and p-mTOR in infiltrating lymphocytes might be correlated with SS development. In vitro, Fangchinoline and LY294002 inhibited proliferation, induced cell cycle arrest, and promoted apoptosis in Raji and Daudi cells by altering Akt/mTOR signaling. In vivo, Fangchinoline and LY294002 significantly improved the salivary secretion by NOD/Ltj mice and reduced the number of lymphocytic foci in the submandibular glands. CONCLUSION: These results indicated that Fangchinoline could effectively inhibit the proliferation of neoplastic B-lymphoid cells and reduce SS-like responses in NOD/Ltj mice. Our study highlights the potential value of the clinical application of Fangchinoline for SS treatment.


Assuntos
Benzilisoquinolinas , Síndrome de Sjogren , Animais , Linfócitos B , Benzilisoquinolinas/farmacologia , Benzilisoquinolinas/uso terapêutico , Proliferação de Células , Leucemia Linfoide , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Camundongos Endogâmicos NOD , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/metabolismo , Serina-Treonina Quinases TOR
15.
Plants (Basel) ; 10(12)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34961026

RESUMO

Increasing the ability of the human body to adapt in conditions of physical or emotional stress is promising from the standpoint of the use of preventive nutrition containing functional food ingredients (FFI) with proven effectiveness in complex physiological in vivo studies. In this work, we developed FFI from spinach leaves (Spinacia oleracea L.) with a high content of polyphenols and adaptogens-phytoecdysteroids. Using in vivo models of increased physical activity and immobilization-induced emotional stress, we evaluated the nonspecific resistance of rats in response to the addition of the developed FFI to the diet. In the acute toxicity experiment, we found no signs of FFI toxicity up to 5000 mg/kg body weight. As a result of the daily 26-day consumption of FFI, we observed an anxiolytic effect in physiological studies. FFI prevented an increase in the content of biogenic amines in the blood, the main markers of the stress system, and had a positive effect on the lipid metabolism of the rats. The obtained results demonstrate a "smoothing" effect on the body's reaction in response to induced stress conditions.

16.
Biophys Chem ; 278: 106664, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34438243

RESUMO

Colorectal cancer is the third most commonly occurring cancer with very less treatment options in case surgery fails to cure the disease. The emergence of drug resistant colon cancer poses a new threat and calls for better drugs for treatment of colon cancer patients. Novel substituted benzo[d]thiazol-2-yl)-5-(pyridin-2-yl) penta-1,4-dien-3-one trihybrid molecules were synthesized following appropriate synthetic route. These compounds were tested for their efficacy in colon cancer and drug resistant colon cancer cell lines. Their toxicity was studied on the ICR mice model and the selectivity study was performed in calorimetric assay and xenograft mice model. An attempt was also made to chalk out the feasible mechanism of action based on molecular docking and molecular dynamics simulation studies. Compounds 4f, 4h and 4i were found to be highly effective and selective towards the inhibition of the colon cancer and drug resistant colon cancer cell lines and in the xenograft method. Selective compounds from this study can be developed into potential drug candidates for the possible treatment of drug resistant colorectal cancer.


Assuntos
Antineoplásicos , Animais , Antineoplásicos/química , Benzotiazóis/química , Benzotiazóis/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Desenho de Fármacos , Humanos , Camundongos , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
17.
Eur J Pharmacol ; 906: 174204, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34051220

RESUMO

Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease which seriously threatens young children's health and lives. However, there is no effective therapy currently available for treating these infections. Therefore, effective drugs to prevent and treat EV-A71 infections are urgently needed. Here, we identified Mulberroside C potently against the proliferation of EV-A71. The in-vitro anti-EV-A71 activity of Mulberroside C was assessed by cytopathic effect inhibition and viral plaque reduction assays, and the results showed that Mulberroside C significantly inhibited EV-A71 infection. The downstream assays affirmed that Mulberroside C inhibited viral protein and RNA synthesis. Furthermore, Mulberroside C effectively reduced clinical symptoms in EV-A71 infected mice and reduced mortality at higher concentrations. The mechanism study indicated that Mulberroside C bound to the hydrophobic pocket of viral capsid protein VP1, thereby preventing viral uncoating and genome release. Taken together, our study indicated that Mulberroside C could be a promising EV-A71 inhibitor and worth extensive preclinical investigation as a lead compound.


Assuntos
Antivirais/farmacologia , Benzopiranos/farmacologia , Enterovirus Humano A/efeitos dos fármacos , Doença de Mão, Pé e Boca/tratamento farmacológico , Animais , Animais Recém-Nascidos , Antivirais/uso terapêutico , Benzopiranos/uso terapêutico , Proteínas do Capsídeo/antagonistas & inibidores , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Linhagem Celular Tumoral , Chlorocebus aethiops , Modelos Animais de Doenças , Enterovirus Humano A/metabolismo , Doença de Mão, Pé e Boca/virologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Morus/química , Organismos Livres de Patógenos Específicos , Células Vero , Replicação Viral/efeitos dos fármacos
18.
Antiviral Res ; 195: 105091, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34044060

RESUMO

Enterovirus A71 (EV-A71) is one of the main causative agents of hand-foot-mouth disease (HFMD) and causes serious neurological complications. However, no effective therapy is currently available for treating these infections. Therefore, effective drugs to prevent and treat EV-A71 infections are urgently needed. Here, we demonstrated that treatment with Licochalcone A (LCA) significantly inhibited EV-A71 replication in a dose-dependent manner, with an EC50 of 9.30 µM in RD cells and 5.73 µM in Vero cells. The preliminary results on the inhibition mechanism showed that LCA exerted antiviral effects by interfering with the early step of viral replication. We further demonstrated that LCA showed potent antiviral activity against many enteroviruses, including EV-A71 (strain C4), EV-A71 (strain H), and coxsackievirus A16 (CV-A16). Furthermore, LCA could effectively prevent the clinical symptoms and death of virus infected mice and decreased viral load in EV-A71-infected mice. Taken together, our studies showed for the first time, that LCA is a promising EV-A71 inhibitor and provide important information for the clinical development of LCA as a potential new anti-EV-A71 agent.


Assuntos
Antivirais/farmacologia , Chalconas/farmacologia , Enterovirus Humano A/efeitos dos fármacos , Infecções por Enterovirus/tratamento farmacológico , Animais , Animais Recém-Nascidos , Linhagem Celular Tumoral , Chlorocebus aethiops , Enterovirus Humano A/crescimento & desenvolvimento , Doença de Mão, Pé e Boca/tratamento farmacológico , Doença de Mão, Pé e Boca/virologia , Humanos , Camundongos , Células Vero , Carga Viral/efeitos dos fármacos , Replicação Viral
19.
J Parasitol ; 107(3): 381-387, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33971011

RESUMO

Co-infections of mammalian hosts with intestinal helminths and bacterial pathogens are common, especially in areas with inadequate sanitation. Interactions between co-infecting species and host microbiota can cause significant changes in host immunity, disease severity, and pathogen transmission, requiring unique treatment for each case. A greater understanding of the influences of parasite-bacteria co-infections will improve diagnosis and therapeutic approaches to control infectious diseases. To study the influence of the trematode parasite Echinostoma caproni on commensal and pathogenic bacteria in the mouse gut, we examined the abundance of intestinal lactic acid bacteria and Salmonella enterica serovar Typhimurium in control mice not exposed to E. caproni (P-) or S. Typhimurium (S-), E. caproni-infected (P+S-), S. Typhimurium-infected (P-S+), and E. caproni-S. Typhimurium co-infected (P+S+) mice, and determined bacterial burdens in the livers and spleens of the P-S+ and P+S+ mice. We also examined a subset of P+S- and P+S+ mice for survival and the relative location of E. caproni in the small intestine. The numbers of presumptive lactic acid bacteria were significantly higher in the P+S+ and P-S+ mice compared to the uninfected mice, and S. Typhimurium colonization in the liver and spleen was significantly reduced in the P+S+ mice compared to the P-S+ mice. Echinostoma caproni were located anteriorly in the intestine of P+S- mice, while in the P+S+ mice, the parasites were distributed more posteriorly. Survival of E. caproni was unaffected in either group. The results of our study suggest that E. caproni facilitates a higher abundance of presumptive lactic acid bacteria in the mouse intestine and reduces colonization of S. Typhimurium in the liver and spleen of the co-infected host.


Assuntos
Echinostoma/fisiologia , Intestino Delgado/microbiologia , Intestino Delgado/parasitologia , Lactobacillales/crescimento & desenvolvimento , Salmonella typhimurium/crescimento & desenvolvimento , Animais , Biomphalaria/parasitologia , Echinostoma/isolamento & purificação , Fezes/microbiologia , Fezes/parasitologia , Feminino , Lactobacillales/isolamento & purificação , Fígado/microbiologia , Fígado/parasitologia , Metacercárias/isolamento & purificação , Metacercárias/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Método de Monte Carlo , Salmonella typhimurium/isolamento & purificação , Baço/microbiologia , Baço/parasitologia
20.
Curr Res Food Sci ; 4: 295-300, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33997796

RESUMO

For patients with inflammatory bowel disease, cow's milk allergy, and lactose intolerance, soymilk is a potential alternative to cow's milk. In this study, we aimed to identify the effects of a soy protein-based low-protein diet on the body and organ weights and the gut microbiome of six-week-old mice fed a diet containing 20% (SP) or 5% (LP) soy protein for 14 days via 16S rRNA (V4) amplicon sequencing. Body weight gain (growth) and liver, spleen, and fat tissue weight were significantly suppressed by the LP diet. Operational taxonomic unit numbers and α-diversity were lower in the LP group than in the SP group. A principal coordinate analysis revealed differences in the gut microbiome compositions of SP and LP mice. The abundances of caecal Roseburia sp., Alistipes sp., and bacteria from the family Muribaculaceae were lower in the LP group than in the SP group. In contrast, the abundance of Desulfovibrionaceae, which is positively correlated with inflammation, was higher in the LP group than in the SP group. These results differed from the effects of a milk casein-based low-protein diet (reported previously). Based on these findings, we conclude that the undesirable effects of a low-protein diet and/or protein deficiency are related to changes in the gut microbiome composition and may differ depending on the kind of proteins used.

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