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1.
Nutrients ; 16(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38892601

ABSTRACT

Type 2 diabetes mellitus (T2DM) is a major global public health concern, prompting the ongoing search for new treatment options. Medicinal plants have emerged as one such alternative. Our objective was to evaluate the antidiabetic effect of an extract from the leaves of Passiflora ligularis (P. ligularis). For this purpose, T2DM was first induced in mice using a high-fat diet and low doses of streptozotocin. Subsequently, an aqueous extract or an ethanolic extract of P. ligularis leaves was administered for 21 days. The following relevant results were found: fasting blood glucose levels were reduced by up to 41%, and by 29% after an oral glucose overload. The homeostasis model assessment of insulin resistance (HOMA-IR) was reduced by 59%. Histopathologically, better preservation of pancreatic tissue was observed. Regarding oxidative stress parameters, there was an increase of up to 48% in superoxide dismutase (SOD), an increase in catalase (CAT) activity by 35% to 80%, and a decrease in lipid peroxidation (MDA) by 35% to 80% in the liver, kidney, or pancreas. Lastly, regarding the lipid profile, triglycerides (TG) were reduced by up to 30%, total cholesterol (TC) by 35%, and low-density lipoproteins (LDL) by up to 32%, while treatments increased high-density lipoproteins (HDL) by up to 35%. With all the above, we can conclude that P. ligularis leaves showed antihyperglycemic, hypolipidemic, and antioxidant effects, making this species promising for the treatment of T2DM.


Subject(s)
Blood Glucose , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Diet, High-Fat , Hypoglycemic Agents , Passiflora , Plant Extracts , Plant Leaves , Animals , Plant Leaves/chemistry , Diabetes Mellitus, Experimental/drug therapy , Plant Extracts/pharmacology , Hypoglycemic Agents/pharmacology , Diet, High-Fat/adverse effects , Passiflora/chemistry , Mice , Male , Blood Glucose/drug effects , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Oxidative Stress/drug effects , Streptozocin , Insulin Resistance , Pancreas/drug effects , Pancreas/pathology , Pancreas/metabolism , Antioxidants/pharmacology , Liver/drug effects , Liver/metabolism , Lipids/blood , Phytotherapy
2.
Nutrients ; 16(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38892612

ABSTRACT

Pharmacotherapy is the therapeutic mainstay in epilepsy; however, in about 30% of patients, epileptic seizures are drug-resistant. A ketogenic diet (KD) is an alternative therapeutic option. The mechanisms underlying the anti-seizure effect of a KD are not fully understood. Epileptic seizures lead to an increased energy demand of neurons. An improvement in energy provisions may have a protective effect. C8 and C10 fatty acids have been previously shown to activate mitochondrial function in vitro. This could involve sirtuins (SIRTs) as regulatory elements of energy metabolism. The aim of the present study was to investigate whether ß-hydroxybutyrate (ßHB), C8 fatty acids, C10 fatty acids, or a combination of C8 and C10 (250/250 µM) fatty acids, which all increase under a KD, could up-regulate SIRT1, -3, -4, and -5 in HT22 hippocampal murine neurons in vitro. Cells were incubated for 1 week in the presence of these metabolites. The sirtuins were measured at the enzyme (fluorometrically), protein (Western blot), and gene expression (PCR) levels. In hippocampal cells, the C8, C10, and C8 and C10 incubations led to increases in the sirtuin levels, which were not inferior to a ßHB incubation as the 'gold standard'. This may indicate that both C8 and C10 fatty acids are important for the antiepileptic effect of a KD. A KD may be replaced by nutritional supplements of C8 and C10 fatty acids, which could facilitate the diet.


Subject(s)
3-Hydroxybutyric Acid , Diet, Ketogenic , Drug Resistant Epilepsy , Fatty Acids , Hippocampus , Neurons , Sirtuins , Animals , Neurons/drug effects , Neurons/metabolism , Diet, Ketogenic/methods , Mice , Sirtuins/metabolism , Fatty Acids/metabolism , Drug Resistant Epilepsy/diet therapy , Drug Resistant Epilepsy/drug therapy , Hippocampus/metabolism , Hippocampus/drug effects , 3-Hydroxybutyric Acid/pharmacology , Cell Line
3.
Nutrients ; 16(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38892616

ABSTRACT

(1) Background: Irritable bowel syndrome (IBS) is a common disease in the gastrointestinal (GI) tract. Atractylodes macrocephala Koidz (AMK) is known as one of the traditional medicines that shows a good efficacy in the GI tract. (2) Methods: We investigated the effect of AMK in a network pharmacology and zymosan-induced IBS animal model. In addition, we performed electrophysiological experiments to confirm the regulatory mechanisms related to IBS. (3) Results: Various characteristics of AMK were investigated using TCMSP data and various analysis systems. AMK restored the macroscopic changes and weight to normal. Colonic mucosa and inflammatory factors were reduced. These effects were similar to those of amitriptyline and sulfasalazine. In addition, transient receptor potential (TRP) V1, voltage-gated Na+ (NaV) 1.5, and NaV1.7 channels were inhibited. (4) Conclusion: These results suggest that AMK may be a promising therapeutic candidate for IBS management through the regulation of ion channels.


Subject(s)
Atractylodes , Disease Models, Animal , Irritable Bowel Syndrome , TRPV Cation Channels , Zymosan , Animals , Irritable Bowel Syndrome/drug therapy , Irritable Bowel Syndrome/chemically induced , TRPV Cation Channels/metabolism , Mice , Atractylodes/chemistry , Male , Plant Extracts/pharmacology , NAV1.7 Voltage-Gated Sodium Channel/metabolism , Colon/drug effects , Colon/metabolism , Colon/pathology , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects
4.
Nutrients ; 16(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38892624

ABSTRACT

Probiotics have garnered increasing attention as a potential therapeutic approach for type 2 diabetes mellitus (T2DM). Previous studies have confirmed that Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) could stimulate the secretion of glucagon-like peptide-1 (GLP-1) in NCI-H716 cells, but whether MN-Gup has a hypoglycemic effect on T2DM in vivo remains unclear. In this study, a T2DM mouse model was constructed, with a high-fat diet and streptozotocin in mice, to investigate the effect of MN-Gup on diabetes. Then, different doses of MN-Gup (2 × 109 CFU/kg, 1 × 1010 CFU/kg) were gavaged for 6 weeks to investigate the effect of MN-Gup on glucose metabolism and its potential mechanisms. The results showed that a high-dose of MN-Gup significantly reduced the fasting blood glucose (FBG) levels and homeostasis model assessment-insulin resistance (HOMA-IR) of T2DM mice compared to the other groups. In addition, there were significant increases in the short-chain fatty acids (SCFAs), especially acetate, and GLP-1 levels in the MN-Gup group. MN-Gup increased the relative abundance of Bifidobacterium and decreased the number of Escherichia-Shigella and Staphylococcus. Moreover, the correlation analysis revealed that Bifidobacterium demonstrated a significant positive correlation with GLP-1 and a negative correlation with the incremental AUC. In summary, this study demonstrates that Bifidobacterium animalis subsp. lactis MN-Gup has significant hypoglycemic effects in T2DM mice and can modulate the gut microbiota, promoting the secretion of SCFAs and GLP-1.


Subject(s)
Bifidobacterium animalis , Blood Glucose , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Glucagon-Like Peptide 1 , Probiotics , Animals , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/microbiology , Probiotics/pharmacology , Blood Glucose/metabolism , Mice , Male , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide 1/blood , Fatty Acids, Volatile/metabolism , Insulin Resistance , Diet, High-Fat , Mice, Inbred C57BL , Streptozocin , Bifidobacterium
5.
Nutrients ; 16(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38892626

ABSTRACT

In this study, we prepared fermented products of isoflavone-enriched soybean leaves (IESLs) and analyzed their nutrients, isoflavones, anti-obesity efficacy, and effects on gut microbiota. Fermented IESLs (FIESLs) were found to be rich in nutrients, especially lauric acid, oleic acid, and linoleic acid. In addition, the concentrations of most essential free amino acids were increased compared to those of IESLs. The contents of bioactive compounds, such as total phenolic, total flavonoid, daidzein, and genistein, significantly increased as well. In addition, FIESLs administration in a high-fat diet (HFD) animal model improved the final body weight, epididymal fat, total lipid, triglyceride, total cholesterol, blood glucose, and leptin levels, as well as reverting microbiota dysbiosis. In conclusion, these findings indicate that FIESLs have the potential to inhibit obesity caused by HFDs and serve as a modulator of gut microbiota, offering the prevention of diet-induced gut dysbiosis and metabolite diseases associated with obesity.


Subject(s)
Anti-Obesity Agents , Diet, High-Fat , Fermentation , Gastrointestinal Microbiome , Glycine max , Isoflavones , Lactic Acid , Obesity , Plant Leaves , Gastrointestinal Microbiome/drug effects , Animals , Isoflavones/pharmacology , Obesity/metabolism , Obesity/microbiology , Male , Diet, High-Fat/adverse effects , Anti-Obesity Agents/pharmacology , Lactic Acid/metabolism , Mice, Inbred C57BL , Mice , Dysbiosis
6.
Nutrients ; 16(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38892635

ABSTRACT

Dendritic cells (DCs) can initiate immune response through the presenting antigens to naïve T lymphocytes. Esculeoside A (EsA), a spirosolane glycoside, is reported as a major component in the ripe fruit of tomato. Little is known about the effect of tomato saponin on mice bone marrow-derived DCs. This study revealed that EsA and its aglycon, esculeogenin A (Esg-A), attenuated the phenotypic and functional maturation of murine DCs stimulated by lipopolysaccharide (LPS). We found that EsA/Esg-A down-regulated the expression of major histocompatibility complex type II molecules and costimulatory molecule CD86 after LPS stimulation. It was also determined that EsA-/Esg-A-treated DCs were poor stimulators of allogeneic T-cell proliferation and exhibited impaired interleukin-12 and TNF-α production. Additionally, EsA/Esg-A was able to inhibit TLR4-related and p-NFκB signaling pathways. This study shows new insights into the immunopharmacology of EsA/Esg-A, and represents a novel approach to controlling DCs for therapeutic application.


Subject(s)
Dendritic Cells , Saponins , Signal Transduction , Solanum lycopersicum , Toll-Like Receptor 4 , Animals , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Dendritic Cells/immunology , Toll-Like Receptor 4/metabolism , Signal Transduction/drug effects , Saponins/pharmacology , Mice , NF-kappa B/metabolism , Lipopolysaccharides/pharmacology , Mice, Inbred C57BL , Interleukin-12/metabolism , Cell Proliferation/drug effects , Mice, Inbred BALB C , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , T-Lymphocytes/immunology , Tumor Necrosis Factor-alpha/metabolism , Fruit/chemistry , B7-2 Antigen/metabolism , Sapogenins
7.
Nutrients ; 16(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38892639

ABSTRACT

Compared to the general population, patients with inflammatory bowel disease (IBD) are less likely to be vaccinated, putting them at an increased risk of vaccine-preventable illnesses. This risk is further compounded by the immunosuppressive therapies commonly used in IBD management. Therefore, developing new treatments for IBD that maintain immune function is crucial, as successful management can lead to better vaccination outcomes and overall health for these patients. Here, we investigate the potential of recombinant banana lectin (rBanLec) as a supporting therapeutic measure to improve IBD control and possibly increase vaccination rates among IBD patients. By examining the therapeutic efficacy of rBanLec in a murine model of experimental colitis, we aim to lay the foundation for its application in improving vaccination outcomes. After inducing experimental colitis in C57BL/6 and BALB/c mice with 2,4,6-trinitrobenzene sulfonic acid, we treated animals orally with varying doses of rBanLec 0.1-10 µg/mL (0.01-1 µg/dose) during the course of the disease. We assessed the severity of colitis and rBanLec's modulation of the immune response compared to control groups. rBanLec administration resulted in an inverse dose-response reduction in colitis severity (less pronounced weight loss, less shortening of the colon) and an improved recovery profile, highlighting its therapeutic potential. Notably, rBanLec-treated mice exhibited significant modulation of the immune response, favoring anti-inflammatory pathways (primarily reduction in a local [TNFα]/[IL-10]) crucial for effective vaccination. Our findings suggest that rBanLec could mitigate the adverse effects of immunosuppressive therapy on vaccine responsiveness in IBD patients. By improving the underlying immune response, rBanLec may increase the efficacy of vaccinations, offering a dual benefit of disease management and prevention of vaccine-preventable illnesses. Further studies are required to translate these findings into clinical practice.


Subject(s)
Colitis , Disease Models, Animal , Inflammatory Bowel Diseases , Mice, Inbred BALB C , Mice, Inbred C57BL , Musa , Animals , Inflammatory Bowel Diseases/drug therapy , Mice , Musa/chemistry , Colitis/drug therapy , Colitis/immunology , Colitis/prevention & control , Plant Lectins/pharmacology , Trinitrobenzenesulfonic Acid , Immunomodulating Agents/pharmacology , Female , Colon/drug effects , Colon/immunology , Colon/pathology , Male
8.
Nutrients ; 16(11)2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38892715

ABSTRACT

NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of Gynostemma pentaphyllum extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3-V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as Akkerrmansia and decreased the abundance of opportunistic pathogens such as Klebsiella. Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-α (TNF-α), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation.


Subject(s)
Gastrointestinal Microbiome , Gynostemma , Non-alcoholic Fatty Liver Disease , Plant Extracts , Animals , Gastrointestinal Microbiome/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Mice , Gynostemma/chemistry , Plant Extracts/pharmacology , Male , Inflammation/drug therapy , Liver/drug effects , Liver/metabolism , Mice, Inbred C57BL , Disease Models, Animal , Signal Transduction/drug effects , Anti-Inflammatory Agents/pharmacology
9.
Molecules ; 29(11)2024 May 21.
Article in English | MEDLINE | ID: mdl-38893287

ABSTRACT

Psoriasis is a common chronic immune-mediated inflammatory skin disorder. Sophora flavescens Alt. (S. flavescens) has been widely acknowledged in the prevention and treatment of psoriasis. Kushenol F (KSCF) is a natural isopentenyl flavonoid extracted from the root of S. flavescens. We aimed to investigate the effect and mechanism of KSCF on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. A mouse model of psoriasis was induced with 5% IMQ for 5 days, and the mice were given KSCF dermally for 5 days. Changes in skin morphology, the psoriasis area, the severity index (PASI), and inflammatory factors of psoriasis-like skin lesions were evaluated. Metabolites in the psoriasis-like skin lesions were analyzed with ultra-high-performance liquid chromatography/mass spectrometry followed by a multivariate statistical analysis to identify the differential metabolites and metabolic pathway. The results of the present study confirmed that KSCF significantly reduced PASI scores, epidermal thickening, and epidermal cell proliferation and differentiation. KSCF also reduced the levels of interleukin (IL)-1ß, IL-6, IL-8, IL-17A, IL-22, IL-23, and tumor necrosis factor (TNF)-α in the injured skin tissues while increasing IL-10 content. KSCF significantly regulated metabolites in the skin samples, and a total of 161 significant metabolites were identified. These differential metabolites involved sphingolipid and linoleic acid metabolism and steroid hormone biosynthesis. Collectively, KSCF inhibited the inflammatory response to prevent IMQ-induced psoriasis-like skin lesions in mice by call-backing the levels of 161 endogenous metabolites and affecting their related metabolic pathways. KSCF has the potential to be developed as a topical drug for treating psoriasis symptoms.


Subject(s)
Disease Models, Animal , Imiquimod , Metabolomics , Psoriasis , Psoriasis/chemically induced , Psoriasis/drug therapy , Psoriasis/metabolism , Psoriasis/pathology , Animals , Imiquimod/toxicity , Mice , Chromatography, High Pressure Liquid , Metabolomics/methods , Metabolome/drug effects , Cytokines/metabolism , Flavonoids/pharmacology , Mass Spectrometry , Skin/metabolism , Skin/drug effects , Skin/pathology , Male
10.
Molecules ; 29(11)2024 May 22.
Article in English | MEDLINE | ID: mdl-38893313

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) are recognized as major immune suppressor cells in the tumor microenvironment that may inhibit immune checkpoint blockade (ICB) therapy. Here, we developed a Stattic-loaded mesoporous silica nanoparticle (PEG-MSN-Stattic) delivery system to tumor sites to reduce the number of MDSCs in tumors. This approach is able to significantly deplete intratumoral MSDCs and thereby increase the infiltration of T lymphocytes in tumors to enhance ICB therapy. Our approach may provide a drug delivery strategy for regulating the tumor microenvironment and enhancing cancer immunotherapy efficacy.


Subject(s)
Immunotherapy , Myeloid-Derived Suppressor Cells , Nanoparticles , Silicon Dioxide , Tumor Microenvironment , Silicon Dioxide/chemistry , Nanoparticles/chemistry , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/drug effects , Immunotherapy/methods , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Animals , Mice , Porosity , Humans , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/drug therapy , Cell Line, Tumor , Drug Carriers/chemistry , Drug Delivery Systems , Polyethylene Glycols/chemistry
11.
Molecules ; 29(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38893335

ABSTRACT

Depression is a chronic, severe, and often life-threatening neurological disorder. It not only causes depression in patients and affects daily life but, in severe cases, may lead to suicidal behavior and have adverse effects on families and society. In recent years, it has been found that sub-anesthetic doses of ketamine have a rapid antidepressant effect on patients with treatment-resistant depression and can significantly reduce the suicidal tendencies of patients with major depressive disorder. Current studies suggest that ketamine may exert antidepressant effects by blocking NMDAR ion channels, but its anesthetic and psychotomimetic side effects limit its application. Here, we report efforts to design and synthesize a novel series of ketamine derivatives of NMDAR antagonists, among which compounds 23 and 24 have improved activity compared with ketamine, introducing a new direction for the development of rapid-acting antidepressant drugs.


Subject(s)
Antidepressive Agents , Drug Design , Ketamine , Receptors, N-Methyl-D-Aspartate , Ketamine/chemistry , Ketamine/pharmacology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/metabolism , Antidepressive Agents/pharmacology , Antidepressive Agents/chemical synthesis , Antidepressive Agents/chemistry , Humans , Animals , Structure-Activity Relationship , Mice
12.
Molecules ; 29(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38893339

ABSTRACT

Six ionone glycosides (1-3 and 5-7), including three new ones, named capitsesqsides A-C (1-3), together with an eudesmane sesquiterpenoid glycoside (4) and three known triterpenoid saponins (8-10) were isolated from Rhododendron capitatum. The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.


Subject(s)
Glycosides , Rhododendron , Rhododendron/chemistry , Mice , Glycosides/chemistry , Glycosides/pharmacology , Glycosides/isolation & purification , RAW 264.7 Cells , Animals , Molecular Docking Simulation , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Norisoprenoids/chemistry , Norisoprenoids/pharmacology , Norisoprenoids/isolation & purification , Molecular Structure , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology
13.
Molecules ; 29(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38893341

ABSTRACT

Perilla frutescens var. acuta (Lamiaceae) is widely used not only as an oil or a spice, but also as a traditional medicine to treat colds, coughs, fever, and indigestion. As an ongoing effort, luteolin-7-O-diglucuronide (1), apigenin-7-O-diglucuronide (2), and rosmarinic acid (3) isolated from P. frutescens var. acuta were investigated for their anti-adipogenic and thermogenic activities in 3T3-L1 cells. Compound 1 exhibited a strong inhibition against adipocyte differentiation by suppressing the expression of Pparg and Cebpa over 52.0% and 45.0%, respectively. Moreover, 2 inhibited the expression of those genes in a dose-dependent manner [Pparg: 41.7% (5 µM), 62.0% (10 µM), and 81.6% (50 µM); Cebpa: 13.8% (5 µM), 18.4% (10 µM), and 37.2% (50 µM)]. On the other hand, the P. frutescens var. acuta water extract showed moderate thermogenic activities. Compounds 1 and 3 also induced thermogenesis in a dose-dependent manner by stimulating the mRNA expressions of Ucp1, Pgc1a, and Prdm16. Moreover, an LC-MS/MS chromatogram of the extract was acquired using UHPLC-MS2 and it was analyzed by feature-based molecular networking (FBMN) and the Progenesis QI software (version 3.0). The chemical profiling of the extract demonstrated that flavonoids and their glycoside derivatives, including those isolated earlier as well as rosmarinic acid, are present in P. frutescens var. acuta.


Subject(s)
3T3-L1 Cells , Anti-Obesity Agents , Cinnamates , Depsides , Perilla frutescens , Plant Extracts , Rosmarinic Acid , Mice , Perilla frutescens/chemistry , Animals , Plant Extracts/pharmacology , Plant Extracts/chemistry , Depsides/pharmacology , Depsides/chemistry , Depsides/isolation & purification , Anti-Obesity Agents/pharmacology , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/isolation & purification , Cinnamates/pharmacology , Cinnamates/chemistry , Cinnamates/isolation & purification , Adipogenesis/drug effects , Adipocytes/drug effects , Adipocytes/metabolism , Cell Differentiation/drug effects , Obesity/drug therapy , Obesity/metabolism , Thermogenesis/drug effects
14.
Molecules ; 29(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38893349

ABSTRACT

This study aimed to isolate and purify resveratrol and oxyresveratrol from the heartwoods of Maclura cochinchinensis, and to evaluate their inhibitory effects on melanogenesis in B16F10 murine melanoma cells. A methanol maceration process yielded a crude extract comprising 24.86% of the initial mass, which was subsequently analyzed through HPTLC, HPLC, and LC-MS/MS. These analyses revealed the presence of resveratrol and oxyresveratrol at concentrations of 4.32 mg/g and 33.6 mg/g in the extract, respectively. Initial purification employing food-grade silica gel column chromatography separated the extract into two fractions: FA, exhibiting potent inhibition of both tyrosinase activity and melanogenesis, and FM, showing no such inhibitory activity. Further purification processes led to the isolation of fractions Y11 and Gn12 with enhanced concentrations of resveratrol (94.9 and 110.21 mg/g, respectively) and fractions Gn15 and Gn16 with elevated levels of oxyresveratrol (321.93 and 274.59 mg/g, respectively), all of which significantly reduced melanin synthesis. These outcomes affirm the substantial presence of resveratrol and oxyresveratrol in the heartwood of M. cochinchinensis, indicating their promising role as natural agents for skin lightening.


Subject(s)
Melanins , Melanoma, Experimental , Plant Extracts , Resveratrol , Stilbenes , Resveratrol/pharmacology , Resveratrol/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Animals , Mice , Melanins/biosynthesis , Stilbenes/pharmacology , Stilbenes/chemistry , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Cell Line, Tumor , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry , Melanogenesis
15.
Molecules ; 29(11)2024 May 27.
Article in English | MEDLINE | ID: mdl-38893406

ABSTRACT

A Cucurbita phloem exudate lectin (CPL) from summer squash (Cucurbita pepo) fruits was isolated and its sugar-binding properties and biological activities were studied. The lectin was purified by affinity chromatography and the hemagglutination assay method was used to determine its pH, heat stability, metal-dependency and sugar specificity. Antimicrobial and anticancer activities were also studied by disc diffusion assays and in vivo and in vitro methods. The molecular weight of CPL was 30 ± 1 KDa and it was stable at different pH (5.0 to 9.0) and temperatures (30 to 60 °C). CPL recovered its hemagglutination activity in the presence of Ca2+. 4-nitrophenyl-α-D-glucopyranoside, lactose, rhamnose and N-acetyl-D-glucosamine strongly inhibited the activity. With an LC50 value of 265 µg/mL, CPL was moderately toxic and exhibited bacteriostatic, bactericidal and antibiofilm activities against different pathogenic bacteria. It also exhibited marked antifungal activity against Aspergillus niger and agglutinated A. flavus spores. In vivo antiproliferative activity against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice was observed when CPL exerted 36.44% and 66.66% growth inhibition at doses of 3.0 mg/kg/day and 6.0 mg/kg/day, respectively. A 12-day treatment by CPL could reverse their RBC and WBC counts as well as restore the hemoglobin percentage to normal levels. The MTT assay of CPL performed against human breast (MCF-7) and lung (A-549) cancer cell lines showed 29.53% and 18.30% of inhibitory activity at concentrations of 128 and 256 µg/mL, respectively.


Subject(s)
Anti-Infective Agents , Cucurbita , Plant Lectins , Cucurbita/chemistry , Animals , Plant Lectins/pharmacology , Plant Lectins/chemistry , Plant Lectins/isolation & purification , Mice , Humans , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/pathology
16.
Molecules ; 29(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38893431

ABSTRACT

BACKGROUND: With the changes in lifestyle and diet structure, the incidence of obesity has increased year by year, and obesity is one of the inducements of many chronic metabolic diseases. Epigallocatechin gallate (EGCG), which is the most abundant component of tea polyphenols, has been used for many years to improve obesity and its complications. Though it has been reported that EGCG can improve obesity through many molecular mechanisms, EGCG may have many mechanisms yet to be explored. In this study, we explored other possible mechanisms through molecular docking and in vitro experiments. METHODS: AutoDock Vina was selected for conducting the molecular docking analysis to elucidate the interaction between EGCG and Notch1, while molecular dynamics simulations were employed to validate this interaction. Then, the new regulation mechanism of EGCG on obesity was verified with in vitro experiments, including a Western blot experiment, immunofluorescence experiment, oil red O staining, and other experiments in 3T3-L1 adipocytes. RESULTS: The molecular docking results showed that EGCG could bind to Notch1 protein through hydrogen bonding. In vitro cell experiments demonstrated that EGCG can significantly reduce the sizes of lipid droplets of 3T3-L1 adipocytes and promote UCP-1 expression by inhibiting the expression of Notch1 in 3T3-L1 adipocytes, thus promoting mitochondrial biogenesis. CONCLUSIONS: In this study, molecular docking and in vitro cell experiments were used to explore the possible mechanism of EGCG to improve obesity by inhibiting Notch1.


Subject(s)
3T3-L1 Cells , Adipogenesis , Catechin , Molecular Docking Simulation , Receptor, Notch1 , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/chemistry , Animals , Mice , Receptor, Notch1/metabolism , Adipogenesis/drug effects , Molecular Dynamics Simulation , Gene Expression Regulation/drug effects , Uncoupling Protein 1/metabolism , Obesity/drug therapy , Obesity/metabolism
17.
Molecules ; 29(11)2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38893493

ABSTRACT

GSK-3ß, IKK-ß, and ROCK-1 kinases are implicated in the pathomechanism of Alzheimer's disease due to their involvement in the misfolding and accumulation of amyloid ß (Aß) and tau proteins, as well as inflammatory processes. Among these kinases, GSK-3ß plays the most crucial role. In this study, we present compound 62, a novel, remarkably potent, competitive GSK-3ß inhibitor (IC50 = 8 nM, Ki = 2 nM) that also exhibits additional ROCK-1 inhibitory activity (IC50 = 2.3 µM) and demonstrates anti-inflammatory and neuroprotective properties. Compound 62 effectively suppresses the production of nitric oxide (NO) and pro-inflammatory cytokines in the lipopolysaccharide-induced model of inflammation in the microglial BV-2 cell line. Furthermore, it shows neuroprotective effects in an okadaic-acid-induced tau hyperphosphorylation cell model of neurodegeneration. The compound also demonstrates the potential for further development, characterized by its chemical and metabolic stability in mouse microsomes and fair solubility.


Subject(s)
Alzheimer Disease , Glycogen Synthase Kinase 3 beta , I-kappa B Kinase , Thiazoles , rho-Associated Kinases , tau Proteins , tau Proteins/metabolism , Glycogen Synthase Kinase 3 beta/antagonists & inhibitors , Glycogen Synthase Kinase 3 beta/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Animals , Thiazoles/pharmacology , Thiazoles/chemistry , Humans , rho-Associated Kinases/antagonists & inhibitors , rho-Associated Kinases/metabolism , Mice , I-kappa B Kinase/metabolism , I-kappa B Kinase/antagonists & inhibitors , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Cell Line , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Microglia/drug effects , Microglia/metabolism , Nitric Oxide/metabolism , Lipopolysaccharides , Protein Aggregates/drug effects , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism
18.
Molecules ; 29(11)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38893506

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a significant hepatic condition that has gained worldwide attention. Kaempferol (Kae), renowned for its diverse biological activities, including anti-inflammatory, antioxidant, anti-aging, and cardio-protective properties, has emerged as a potential therapeutic candidate for non-alcoholic steatohepatitis (NASH). Despite its promising therapeutic potential, the precise underlying mechanism of Kae's beneficial effects in NASH remains unclear. Therefore, this study aims to clarify the mechanism by conducting comprehensive in vivo and in vitro experiments. RESULTS: In this study, a murine model of non-alcoholic steatohepatitis (NASH) was established by feeding C57BL/6 female mice a high-fat diet for 12 weeks. Kaempferol (Kae) was investigated for its ability to modulate systemic inflammatory responses and lipid metabolism in this model (20 mg/kg per day). Notably, Kae significantly reduced the expression of NLRP3-ASC/TMS1-Caspase 3, a crucial mediator of liver tissue inflammation. Additionally, in a HepG2 cell model induced with palmitic acid/oleic acid (PA/OA) to mimic NASH conditions, Kae demonstrated the capacity to decrease lipid droplet accumulation and downregulate the expression of NLRP3-ASC/TMS1-Caspase 3 (20 µM and the final concentration to 20 nM). These findings suggest that Kae may hold therapeutic potential in the treatment of NASH by targeting inflammatory and metabolic pathways. CONCLUSIONS: These findings suggest that kaempferol holds potential as a promising therapeutic intervention for ameliorating non-alcoholic fatty liver disease (NAFLD).


Subject(s)
Caspase 3 , Kaempferols , NLR Family, Pyrin Domain-Containing 3 Protein , Neutrophils , Non-alcoholic Fatty Liver Disease , Signal Transduction , Kaempferols/pharmacology , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/pathology , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Mice , Humans , Signal Transduction/drug effects , Caspase 3/metabolism , Female , Neutrophils/drug effects , Neutrophils/metabolism , Disease Models, Animal , Mice, Inbred C57BL , Liver/drug effects , Liver/metabolism , Liver/pathology , Hep G2 Cells , Diet, High-Fat/adverse effects
19.
Molecules ; 29(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38893549

ABSTRACT

The Omicron BA.5 variant of SARS-CoV-2 is known for its high transmissibility and its capacity to evade immunity provided by vaccine protection against the (original) Wuhan strain. In our prior research, we successfully produced the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in an E. coli expression system. Extensive biophysical characterization indicated that, even without glycosylation, the RBD maintained native-like conformational and biophysical properties. The current study explores the immunogenicity and neutralization capacity of the E. coli-expressed Omicron BA.5 RBD using a mouse model. Administration of three doses of the RBD without any adjuvant elicited high titer antisera of up to 7.3 × 105 and up to 1.6 × 106 after a booster shot. Immunization with RBD notably enhanced the population of CD44+CD62L+ T cells, indicating the generation of T cell memory. The in vitro assays demonstrated the antisera's protective efficacy through significant inhibition of the interaction between SARS-CoV-2 and its human receptor, ACE2, and through potent neutralization of a pseudovirus. These findings underscore the potential of our E. coli-expressed RBD as a viable vaccine candidate against the Omicron variant of SARS-CoV-2.


Subject(s)
Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Animals , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Mice , Antibodies, Neutralizing/immunology , COVID-19/prevention & control , COVID-19/immunology , Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme 2/immunology , Angiotensin-Converting Enzyme 2/chemistry , Humans , COVID-19 Vaccines/immunology , COVID-19 Vaccines/chemistry , Antibodies, Viral/immunology , Disease Models, Animal , Protein Domains , Glycosylation , Protein Binding , Female , Escherichia coli/metabolism , T-Lymphocytes/immunology
20.
Molecules ; 29(11)2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38893558

ABSTRACT

Polysaccharides have been assessed as a potential natural active component in Chinese herbal medicine with anti-inflammatory properties. However, the complex and indefinite structures of polysaccharides limit their applications. This study explains the structures and anti-inflammatory potentials of three neutral polysaccharides, RIP-A1 (Mw 1.8 × 104 Da), RIP-B1 (Mw 7.4 × 104 Da) and RIP-B2 (Mw 9.3 × 104 Da), which were isolated from the roots of Isatis indigotica Fort. with sequenced ultrafiltration membrane columns, DEAE-52 and Sephadex G-100. The planar structures and microstructures of RIP-A1, RIP-B1 and RIP-B2 were further determined by HPGPC, GC-MS, methylation analysis, FT-IR, SEM and AFM, in which the structure of RIP-A1 was elucidated in detail using 1D/2D NMR. The Raw 264.7 cells were used for the anti-inflammatory activity in vitro. The results showed that RIP-A1, RIP-B1 and RIP-B2 are all neutral polysaccharides, with RIP-A1 having the smallest Mw and the simplest monosaccharide composition of the three. RIP-A1 is mainly composed of Ara and Gal, except for a small quantity of Rha. Its main structure is covered with glycosidic linkages of T-α-Araf, 1,2-α-Rhap, 1,5-α-Araf, T-ß-Galp, 1,2,4-α-Rhap, 1,3,5-α-Araf and 1,6-ß-Galp with 0.33:0.12:1.02:0.09:0.45:11.41:10.23. RIP-A1 significantly inhibited pro-inflammatory cytokines (NO, TNF-α, IL-6 and IL-1ß) and increased anti-inflammatory cytokines (IL-4) in LPS-stimulated RAW 264.7 cells. Moreover, RIP-A1 could significantly inhibit the mRNA expression of TNF-α, IL-6 and L-1ß. It could also activate IKK, p65 and IκBα (the components of the NF-κB signaling pathway). In conclusion, the above results show the structural characterization and anti-inflammatory potentials of RIP-A1 as an effective natural anti-inflammatory drug.


Subject(s)
Anti-Inflammatory Agents , Isatis , Plant Roots , Polysaccharides , Mice , Animals , Plant Roots/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Isatis/chemistry , RAW 264.7 Cells , NF-kappa B/metabolism , Macrophages/drug effects , Macrophages/metabolism , Cytokines/metabolism
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