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1.
Crit Rev Immunol ; 44(1): 1-16, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37947068

RESUMO

Qufeng Zhitong capsule (QFZTC) is a traditional Chinese herbal formula with potential therapeutic efficacy in rheumatoid arthritis (RA). This study seeks to clarify the potential effects and mechanisms of QFZTC against RA. Active compounds and targets of QFZTC were retrieved from the Herbal Ingredients' Targets (HIT), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and Traditional Chinese Medicine Integrated Database (TCMID) databases. RA-related targets were searched on GeneCards and DisGeNET databases. Protein-protein interaction (PPI) network was established using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analyses were performed on hub targets. Molecular docking was conducted on hub targets and active compounds. High-performance liquid chromatography (HPLC) was applied to characterize the active compounds in QFZTC. RA-fibroblast like synoviocytes (RA-FLSs) were cultured and treated by QFZTC-containing serum, in which proinflammatory cytokines and hub targets were detected. Cell viability was determined by cell counting kit-8 (CCK-8) assay. A total of 360 active compounds and 445 potential targets are identified for QFZTC against RA. Protein-protein interaction (PPI) network determined five hub targets, interleukin 6 (IL6), IL1B, VEGFA, JUN, and tumor necrosis factor (TNF). GO and KEGG analyses revealed that the MAPK pathway may be a critical signaling in QFZTC treating RA. Molecular docking showed that luteolin, kaempferol, and myricetin has good affinity with TNF, and they were identified by HPLC. In vitro experiments confirmed that QFZTC restrained the cell viability and inflammation in RA. This study revealed the active compounds and molecular targets for QFZTC treating RA. QFZTC is a promising drug and ameliorates RA by inhibiting inflammatory response.


Assuntos
Artrite Reumatoide , Farmacologia em Rede , Humanos , Simulação de Acoplamento Molecular , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa
2.
J Ethnopharmacol ; 318(Pt A): 116855, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37390878

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sargentodoxa cuneata and Patrinia villosa (S&P) are two natural herbal medicine widely used for treatment of various inflammatory diseases in Traditional Chinese Medicine, whereas the mode of action needs to be further investigated. AIM OF THE STUDY: This study aimed to explore the anti-inflammatory effects and unravel the involved mechanism of S&P extract. MATERIALS AND METHODS: The components of S&P extract were first detected using the liquid chromatography-tandem mass spectrometry (LC-MS/MS). The effects of S&P extract on the viability and migration ability of macrophages were detected using CCK8, LDH, adhesion and transwell assays. Cytokine release and macrophage phenotype transition were measured using a cytometric bead array and flow cytometry. The potential mechanism was uncovered using an integrative approach combining RNA sequencing and LC-MS/MS-based metabolic analysis. The expression of related proteins was further validated using western blotting. RESULTS: S&P extract inhibited the proliferation and migration of LPS-induced macrophages, changed the morphology of macrophages, and inhibited the production of NO and the expression of iNOS. Furthermore, the extract inhibited tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production and the expression of the M1 phenotype markers CD11c and CD16/32, whereas it promoted interleukin-10 (IL-10) production and the expression of the M2 phenotype markers CD206 and arginase 1 (Arg1). RNA sequencing analysis demonstrated that the upregulated genes by S&P extract treatment were involved in M2 macrophages: Il10, Ccl17, Ccl22, Cd68. The downregulated genes were involved in M1 macrophages and glycolysis processes: Stat1, Il18, Cd80, Cd86, Nos2, Il6, Pik3ap1, Raf1, Pdhb, etc. Metabolomics results showed that the S&P extract strongly ameliorated lipopolysaccharide (LPS)-induced metabolic disturbances. KEGG analysis indicated that most of these metabolites were involved in glucose metabolism, which is involved in the tumor necrosis factor (TNF), phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt), Glycolysis, and mitogen-activated protein kinase (MAPK) pathways. In vitro experiments further confirmed that the extract significantly inhibited the phosphorylation of focal adhesion kinase (FAK), PI3K and Akt, and the expression of glucose metabolism-related proteins. Adding a FAK inhibitor (defactinib) further inhibited the expression of M1/M2 phenotypic markers and the phosphorylation of FAK, PI3K, and Akt. CONCLUSIONS: S&P extract can induce M2 polarization and shift macrophages from M1 to M2 tissue repair in LPS-induced inflammation by regulating glucose metabolism and the FAK/PI3K/Akt pathway.


Assuntos
Patrinia , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-akt/metabolismo , Lipopolissacarídeos/farmacologia , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Macrófagos , Fator de Necrose Tumoral alfa/metabolismo , Glucose/metabolismo
3.
J Ethnopharmacol ; 318(Pt A): 116843, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37414197

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, the causes of diabetic retinopathy (DR) are blood stasis and heat. Curcuma wenyujin Y. H. Chen & C. Ling and its extracts have the effects of promoting blood circulation to remove blood stasis, clearing the heart, and cooling the blood, and have been used in the treatment of DR. Elema-1,3,7 (11),8-tetraen-8,12-lactam (Ele), an N-containing sesquiterpene isolated from this plant. However, the anti-inflammatory and anti-angiogenic effects of Ele and its therapeutic potential in DR are still unknown. AIM OF THE STUDY: To evaluate the anti-inflammatory and anti-angiogenic effects of Ele and its therapeutic potential in DR. MATERIALS AND METHODS: In vitro, anti-inflammatory and anti-angiogenic effects were assessed using TNF-α or VEGF-stimulated HUVECs. Protein expression was analyzed using Western blotting. ICAM-1 and TNF-α mRNA expressions were analyzed using real-time quantitative RT-PCR. The therapeutic potential in DR was assessed using both animal models of STZ-induced diabetes and oxygen-induced retinopathy. The retinal vascular permeability was measured using Evans blue, and the quantitation of retinal leukostasis using FITC-coupled Con A. The retinal neovascular tufts were analyzed using fluorescein angiography and counting pre-retinal vascular lumens. RESULTS: Ele inhibited NF-κB pathway, and ICAM-1, TNF-α mRNA expression in TNF-α- stimulated HUVECs. It also inhibits the multistep process of angiogenesis by inhibiting the phosphorylation of VEGFR2 and its downstream signaling kinases Src, Erk1/2, Akt, and mTOR in VEGF-stimulated HUVECs. Intravitreal injection of Ele can significantly reduce retinal microvascular leakage, leukostasis, and expression of ICAM-1, TNF-α in diabetic rats and inhibits oxygen-induced retinal neovascularization and VEGFR2 phosphorylation in OIR mice. CONCLUSIONS: Ele has anti-inflammatory and anti-angiogenic effects through inhibiting NF-κB and VEGFR2 signaling pathways, and it may be a potential drug candidate for DR.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Leucostasia , Ratos , Camundongos , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , NF-kappa B/metabolismo , Curcuma , Molécula 1 de Adesão Intercelular/genética , Diabetes Mellitus Experimental/tratamento farmacológico , Leucostasia/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Necrose Tumoral alfa , Oxigênio , Anti-Inflamatórios/efeitos adversos , RNA Mensageiro
4.
J Ethnopharmacol ; 318(Pt A): 116870, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37423517

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Shaoyao San (DSS) has effective in treating hepatic ascites and liver disease. AIM OF THE STUDY: To explore the chemical characterization of DSS and protective effect on CCl4-induced hepatic fibrosis and its mechanism, especially its anti-oxidative stress and anti-inflammation. MATERIALS AND METHODS: The chemical characterization of DSS was determined by HPLC-Q-Exactive Orbitrap MS. And the antioxidant activity of DSS in vitro was determined. The hepatic fibrosis model was established using intragastric administration of 40% CCl4/soybean oil (v/v) twice weekly for 13 weeks. From 6th week, the DSS group and the positive control group were given DSS (2, 4, 8 g/kg/d) and silymarin (50 mg/kg/d), respectively. The livers of rats were examined histologically by H&E. The ALT, AST, ALB and TBIL were determined, and hepatic fibrosis markers (HA, LN, CIV, PIIINP), oxidative stress (SOD, MDA, GST, GSH) and inflammatory factor (IL-6, TNF-α) were tested using ELISA kits. In addition, the levels of TAC, TOS, LOOH and AOPP in the liver were also determined. RESULTS: The chemical characterization of DSS was determined by HPLC-Q-Exactive Orbitrap MS. The results show that DSS mainly includes triterpenoids, monoterpenes, phenols, sesquiterpenes, butyl phthalide, etc., and DSS has good antioxidant activity in vitro. In addition, the ALT, AST and TBIL of rats were remarkably reduced after treatment with DSS at three doses. Liver histopathological analysis showed that DSS alleviated the inflammatory infiltration, hepatocyte swelling, necrosis and hepatic fibrosis induced by CCl4. DSS significantly decreased HA, IV-C, PIIINP and LN. Further determination showed that DSS significantly increased TAC, OSI and decreased TOC, LOOH and MDA, indicating that DSS could regulate redox balance and reduce lipid peroxidation in vivo. DSS also increased the activity of GST, SOD and GSH concentration. In addition, DSS also reduced IL-6 and TNF-α. CONCLUSIONS: In this study, we described the chemical characterization of DSS and found that it has good antioxidant activity. We proved that DSS has the functions of reducing oxidative stress, anti-inflammatory, protecting liver cells and reducing hepatic fibrosis.


Assuntos
Antioxidantes , Fator de Necrose Tumoral alfa , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Estresse Oxidativo , Fígado , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/efeitos adversos , Superóxido Dismutase/metabolismo , Tetracloreto de Carbono/farmacologia
5.
J Ethnopharmacol ; 318(Pt A): 116900, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37442489

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sharbat-e-bazoori Motadil (SBM) is a polyherbal formulation that have been used for centuries as a part of the Unani system of medicine for renal disease. AIM OF THE STUDY: The objective of this study was to explore and validate the nephroprotective potential of sugar-free SBM (SF-SBM) and its mechanisms of action against sodium fluoride (NaF)-induced nephrotoxicity in HEK-293 cells. Additionally, the study aimed to assess the quality control of SF-SBM and investigate its effects using an in vivo rat model with pattern recognition following oral administration of SF-SBM. MATERIALS AND METHODS: The nephroprotective effect of SF-SBM was investigated using both an HEK-293 cell line and Wistar rats. Nephrotoxicity was induced in these models by administering NaF at a concentration of 600 ppm (parts per million) for a duration of seven days. The SF-SBM formulation was standardized using high-performance thin-layer chromatography (HPTLC) to assess the presence of marker compounds, namely gallic acid, quercetin, and ferulic acid. Metabolite characterization of SF-SBM was carried out using ultra-high-performance liquid chromatography mass spectrometry (UPLC-MS) with a monolithic capillary silica-based C18 column. This analytical technique allowed for the identification of bioactive substances and verification of the identified markers. Acute toxicity of SF-SBM was evaluated in Wistar rats by administering a single oral dose of 2000 mg/kg of SF-SBM. The nephroprotective efficacy of SF-SBM was further assessed at low (LD), medium (MD) and high (HD) doses of 32.1, 64.2, and 128.4 mg/kg, respectively, administered orally. Nephrotoxicity was induced in Wistar rats by adding NaF to their drinking water for seven days. Biochemical and urine markers were analyzed to evaluate the antioxidant, inflammatory, and apoptotic potential of SF-SBM. Additionally, histopathological analysis and immunohistochemical alterations in the expression of caspase-3 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4 (NOX-4) in kidney tissue were performed to confirm the findings of the in vivo experiments. Furthermore, in vivo pattern recognition of SF-SBM metabolites, identified through GC-MS metabolomics, and in-silico docking analysis of major metabolites in plasma were conducted to gain further insights. RESULT: Phytochemical analysis using HPTLC, TLC-bioautography, and UPLC-MS revealed the presence of several bioactive constituents in SF-SBM, including ferulic acid, gallic acid (GA), ellagic acid, quercetin, and apigenin. These compounds exhibit diverse pharmacological properties. In vitro studies demonstrated the protective effect of SF-SBM on HEK-293 cell line against nephrotoxicity. The acute toxicity study of SF-SBM at a dose of 2000 mg/kg showed no mortality or signs of toxicity throughout the 14-day observation period. In the in vivo studies, administration of NaF resulted in significant elevation (P < 0.001) of biochemical and urine parameters, indicating oxidative, inflammatory, and apoptotic stress. Histopathological examination revealed severe depletion of Bowman's capsule, and immunohistochemistry demonstrated negative immunostaining for caspase-3 and reduced NOX-4 reactions. Pre-treatment with SF-SBM significantly attenuated the elevated biochemical and urine markers, restored the antioxidant enzyme levels (such as SOD, CAT, GSH, GPx and NO), and regulated the expression of inflammatory cytokines (TNF-α, IL-1ß, CASP-3) in kidney tissue at doses of SF-SBM-MD (64.2 mg/kg) and SF-SBM-HD (128.4 mg/kg), showing comparable results to those of α-Ketoanalogue. Histopathological assessment demonstrated improvements in tissue damage. Pattern recognition analysis of SF-SBM identified the presence of 56 metabolites at different time intervals. Additionally, in-silico studies revealed strong interactions of SF-SBM with a binding energy of -6.5 and -5.6 kcal for 4C2N. CONCLUSION: The phytoconstituents present in SF-SBM play a crucial role in its nephroprotective action by acting as potent antioxidants and reducing proinflammatory and apoptotic damage in rat cells. This indicates that SF-SBM has promising potential for the treatment of nephrotoxicity.


Assuntos
Antioxidantes , Fluoreto de Sódio , Ratos , Humanos , Animais , Antioxidantes/uso terapêutico , Ratos Wistar , Fluoreto de Sódio/toxicidade , Fluoreto de Sódio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Quercetina/farmacologia , Caspase 3/metabolismo , Cromatografia Líquida , Células HEK293 , Espectrometria de Massas em Tandem , Estresse Oxidativo , Rim , Ácido Gálico/farmacologia
6.
J Ethnopharmacol ; 318(Pt A): 116911, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37451488

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional system of medicine, Piper species, or its components are widely used to treat many diseases including memory improvement. One of the wild species Piper trioicum Roxb. (Piperaceae) is found in South Asian countries. The whole plant is used as folk medicine to improve memory. AIM OF THE STUDY: To our knowledge, no previous research has investigated the neuroprotective activities of P. trioicum. So, we studied the ameliorative effect of P. trioicum in attenuating cognitive deficit in scopolamine induced neurotoxicity in experimental rats. MATERIALS AND METHODS: Wistar rats were exposed to scopolamine (3 mg/kg, i. p.) for 14 consecutive days, and the effect of P. trioicum (HAPT; oral, 300, 400 mg/kg) on scopolamine-invoked neurotoxicity in brain were studied. During the experimental period, behaviour analyses of rats were observed 30 min post-drug administration. The role of antioxidants of HAPT in scavenging cellular oxygen/peroxyl radicals were studied. Acetylcholinesterase and butyrylcholinesterase inhibitions, and mode of inhibition kinetics of HAPT were studied. Pathogenic cellular oxidative (MDA, GSH, SOD, and CAT), DNA damage (8-oxodG), neurochemical (acetyl- and, butyryl-cholinesterase), ß-secretase (BACE-1 and 2), MAPτ, and neuroinflammation (IL-6, TNF-α) biomarkers in extension to the histopathological observation of brain cortex were studied. GC-MS/MS analysis was carried out to investigate the presence of bioactive constituents in HAPT. RESULTS: HAPT, a rich source of phenol and flavonoid type antioxidants were responsible in quenching oxygen/peroxyl radicals and protected the cellular membrane, and lipoproteins against ROS in DPPH, ORAC, and CAPe tests. HAPT inhibited acetylcholinesterase and butyrylcholinesterase activities, and showed competitive-inhibition (reversible) towards cholinesterase activities. HAPT-400 significantly improved the learning and memory-impairment by restoring oxidative MDA, GSH, SOD, CAT, and DNA damage (8-oxodG) markers of serum, and cortex. It also improved acetyl- and, butyryl-cholinesterase, ß-secretase, and MAPτ level in brain by restoring proinflammatory cytokines IL-6, and TNF-α indicators in neurotoxic rats. GC-MS/MS reported therapeutic significance active compounds were molecular-docked towards target proteins, found that proscillaridin showed the highest affinity towards AChE, BuChE, BACE1, and BACE2 with binding energy of ΔGb -9.1, ΔGb -10.2, ΔGb -11.4 and ΔGb -11.5 Kcal/mol, respectively. Cymarin and morphine-3-glucuronide showed the second highest binding affinity towards AChE (ΔGb -8.8) and BuChE (ΔGb -10.0), respectively. In BACE-1, betulin showed the second highest binding affinity ΔGb -10.7 Kcal/mol and in BACE-2, morphine-3-glucuronide showed the second highest binding affinity ΔGb -9.8 Kcal/mol. CONCLUSIONS: Synergistic impact of proscillaridin, Cymarin, morphine-3-glucuronide, betulin like compounds in HAPT improved memory impairment, healing of tissue architecture of cortex with the restoration of neurochemical, neuroinflammation, and oxidative indicators in neurotoxic rats.


Assuntos
Piper , Proscilaridina , Ratos , Animais , Escopolamina/farmacologia , Secretases da Proteína Precursora do Amiloide , Butirilcolinesterase/metabolismo , Acetilcolinesterase/metabolismo , Antioxidantes/farmacologia , Ratos Wistar , Piper/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Cimarina , Interleucina-6 , Doenças Neuroinflamatórias , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ácido Aspártico Endopeptidases/metabolismo , Superóxido Dismutase , Cognição , Oxigênio , Inibidores da Colinesterase/farmacologia
7.
J Ethnopharmacol ; 318(Pt A): 116940, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37479067

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pingchong Jiangni recipe (PJR) is often used in the treatment of endometriosis (EM). This formula has been clinically validated by the State Administration of Traditional Chinese Medicine Key Specialties Collaborative Group for its therapeutic efficacy. Recently, our research team also confirmed that PJR has a shrinking effect on ovarian chocolate cysts. Additionally, PJR was also found to have a shrinking effect on EM lesions; however, the mechanism by which this effect occurs remains unclear. AIM OF THE STUDY: To explore the mechanisms by which PJR relieves pain in patients with EM. MATERIALS AND METHODS: A rat model of EM was established by autologous transplantation. PJR (3.78 g/kg, 7.56 g/kg, and 15.12 g/kg) was orally administered for 21 days. The rat grimace scale (RGS) score and paw withdrawal threshold (PWT) were measured at a fixed time during the experiment. Hematoxylin and eosin staining was performed to observe histopathological changes in EM rats after administration, enzyme-linked immunosorbent assay to evaluate the plasma expression of tumor necrosis factor-α (TNF-α) and nerve growth factor (NGF), and immunohistochemistry and western blotting to identify differences in the expression of pain-related factors in EM rats. RESULTS: The medium-dose group of PJR (7.56 g/kg) had the best effect on relieving pain in EM rats by reducing RGS, increasing PWT, reducing the ectopic endometrium, improving the cellular structure of the lesion, and reducing TNF-α and NGF levels. However, PJR significantly decreased the expression of transient receptor potential vanilloid 1 (TRPV1), phosphorylated TRPV1 (p-TRPV1), protein kinase C (PKC), and NGF. CONCLUSION: The mechanism by which PJR relieves EM pain may be through the downregulation of NGF, PKC, and TRPV1 expression.


Assuntos
Endometriose , Humanos , Feminino , Ratos , Animais , Endometriose/tratamento farmacológico , Endometriose/metabolismo , Fator de Crescimento Neural/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Canais de Cátion TRPV/metabolismo , Dor , Transdução de Sinais
8.
J Ethnopharmacol ; 318(Pt B): 116929, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37480965

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. (M. oleifera) is a perennial deciduous tree with considerable agricultural and pharmacological value. Nearly all parts of the tree are edible, and nearly all parts are used in traditional medicine. Leaves of M. oleifera have the functions of hypoglycemic (antidiabetic), anti-cancer and anti-oxidant stress, but less research pay attention to the anti-inflammatory effect of M. oleifera leaves. AIM OF THE STUDY: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut with no ideal medication. Here, we investigated the anti-inflammatory effects of aqueous extract of M. oleifera leaves. MATERIALS AND METHODS: Intestinal organoids and mice as in vitro and in vivo models to investigate the effects of aqueous extract of M. oleifera leaves on inflammation induced by TNF-α and dextran sulfate sodium (DSS) respectively. The expression of inflammatory cytokines and proliferation-related genes were evaluated by RT-qPCR, respectively. The compounds in the leaf extract were determined by LC/MS, and network pharmacology approach was employed to predict 54 anti-IBD potential targets of quercetin-3-galactoside (QG) and isoquercitrin (IS). RESULTS: We found that the extract protected against damage to intestinal organoids caused by tumor necrosis factor (TNF-α), and significantly down-regulated the expression of inflammatory cytokines. The extract also suppressed the TNF-α-induced expression of Pcna, c-Myc, and c-Jun. Additionally, oral administration of the extract also ameliorated DSS-induced colon damage (colonic shortening, loss of goblet cells and overall abnormal cellularity), and inhibited the expression of inflammatory cytokines and proliferation-related genes in colitis. By LC/MS we identified nearly 2000 of the compounds in the leaf extract, of the flavonoids identified, QG and IS made up the largest percentage; both have been shown to have anti-inflammatory properties. Moreover, network pharmacology approach was employed to predict 54 anti-IBD potential targets of QG and IS. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the overlapping targets participated in response to oxidative stress and PI3K-Akt signaling pathway respectively. CONCLUSIONS: The present study demonstrated the anti-inflammatory capability, in vitro and in vivo, of the aqueous extract of M. oleifera leaves and suggests its potential phytotherapeutic treatment for IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Camundongos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Colo , Anti-Inflamatórios/efeitos adversos , Citocinas/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL
9.
J Ethnopharmacol ; 318(Pt A): 116934, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37480967

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Wuweiganlu (WGL) is a well-known formulation described in the "Four Medical Scriptures of Tibetan medicine", which is mainly used for the treatment of Rheumatoid Arthritis (RA) and other chronic ailments prescribed by Tibetan medicine. Nonetheless, the active constituents present in the water extracts of Wuweiganlu (WGLWE) specifically targeting arthritis treatment are largely unknown. AIM OF THE STUDY: The aim of this study is to explore the effects and underlying mechanisms of the active components in WGLWE on RA. MATERIALS AND METHODS: We utilized ultra-performance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC-Q-TOF-MS) to identify the main chemical compositions of WGLWE. The polarization effect of WGLWE on bone marrow-derived macrophages (BMDM) was determined. A rat model of collagen-induced arthritis (CIA) was established by injecting an emulsion of bovine type II collagen mixed with an equal volume of incomplete Freund's adjuvant into the tail, paw and back of rats. A WGLWE-based ointment was topically applied to the legs and paws of the rats for 30 days. The rats' ankles were photographed to measure the degree of swelling. Micro-CT was used to image the knee joint and paw of rats, and the bone mineral density (BMD) and bone volume fraction (BV/TV) of knee joint in rats were analyzed. High-frequency ultrasound imaging of the rat knee joint was performed to observe knee joint effusion. Further, the serum levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), IL-10, and arginine (Arg-1) in CIA rats were detected by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) and immunofluorescence (IF) co-staining were employed to detect the expression levels of inflammatory factors in synovium. RESULTS: A total of 28 main components were identified in WGLWE, and these compounds can directly bind to the inflammatory pathway proteins such as JAK2, NFκB and STAT3. In vitro experiments demonstrated that WGLWE promoted the transformation of M1 macrophages into M2 macrophages and suppressed the release of proinflammatory cytokines TNF-α and IL-6. In vivo studies showed that WGLWE effectively reduced ankle swelling, alleviated knee joint effusion, and improved BV/TV while also reducing synovial inflammation levels. Furthermore, WGLWE compounds induced the transition of M1-type macrophages to M2-type macrophages in synovial tissue, resulting in decreased secretion of inflammatory factors TNF-α, WGLWE improved the synovial inflammatory state. CONCLUSION: Our results indicated that WGLWE alleviated joint inflammation in CIA rats and the underlying mechanism may be related to inducing the transformation of bone marrow-derived M1 macrophages to M2 macrophages, leading to an increase in the secretion of anti-inflammatory factors and a decrease in pro-inflammatory factors. Therefore, WGLWE may be used as a potential herbal preparation for the treatment of RA.


Assuntos
Artrite Experimental , Artrite Reumatoide , Ratos , Animais , Bovinos , Artrite Experimental/patologia , Fator de Necrose Tumoral alfa , Medicina Tradicional Tibetana , Interleucina-6 , Ratos Wistar , Artrite Reumatoide/tratamento farmacológico , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Macrófagos/metabolismo
10.
J Ethnopharmacol ; 318(Pt A): 116966, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37499845

RESUMO

BACKGROUND: Hosta plantaginea (Lam.) Aschers flower is a famous Mongolian folk medicine in China and has a therapeutic effect on acute pharyngitis (AP). However, the effect and potential mechanism of H. plantaginea flower on AP have not been fully elucidated. AIM OF THE STUDY: The present work aimed to evaluate the effects and mechanisms of the crude extract of H. plantaginea flowers (HP) and its four fractions of petroleum ether fraction (HPA), ethyl acetate fraction (HPB), n-butanol fraction (HPC), and water residue (HPD) against AP in rats. MATERIALS AND METHODS: A 15% ammonia-induced AP rat model in rats was established. Therapeutic effects of HP and HPA∼D in model rats were evaluated based on body weight, histopathological analysis, and inflammatory parameters, including tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), interleukin 1ß (IL-1ß), and IL-6. The protein expression of nuclear factor kappa-B p65 (NF-κB p65), inhibitor of NF-κB alpha (IκBα), c-Jun N-terminal kinases (JNK), mitogen-activated protein kinase (MAPK) p38, extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) were detected by a Western blotting assay. RESULTS: HP, HPB, and HPC treatments markedly alleviated AP in rats by increasing body weight and improving pathological damages in pharyngeal tissues. In addition, HP, HPB, and HPC treatments significantly inhibited inflammation, including decreasing the levels of TNF-α, PGE2, IL-1ß, and IL-6, and suppressing phosphorylated protein expression of p65, IκBα, JNK, p38, Erk, JAK1, STAT3, PI3K, and Akt in pharyngeal tissues of rats. CONCLUSION: Collectively, HP, HPB, and HPC can attenuate pharynx injury in rats by suppressing inflammation via inhibition of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt pathways, which supports the traditional use of H. plantaginea flowers.


Assuntos
Hosta , Faringite , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Inibidor de NF-kappaB alfa/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Hosta/metabolismo , Interleucina-6 , Inflamação/tratamento farmacológico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Flores/metabolismo
11.
J Ethnopharmacol ; 318(Pt A): 116962, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37499844

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dry mature fruits of Hippophae rhamnoides L. (HRL), Elaeagnaceae, have traditional functions of invigorating spleen and improving spleen insufficiency. Traditional Chinese medicine (TCM) clinics have been proved that HRL is in favor of diabetes treatment. Modern pharmacological studies demonstrated that total flavones of Hippophae rhamnoides (TFH) are the main substance for HRL to develop anti-inflammation and anti-diabetes functions. However, chemical features, active ingredients and anti-diabetes pharmacological mechanism of HRL still remain unclear. AIM OF THE STUDY: Key targets and metabolites in anti-type-II diabetes mellitus (T2DM) of TFH have been explored based on AGE-RAGE signaling pathway in diabetic complications. The anti-T2DM mechanism of TFH has been elaborated from comprehensive perspectives, including target prediction, metabolites, potential metabolic pathways, and so on. MATERIALS AND METHODS: In this study, a qualitative test of chemical composition of HRL was carried out based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The anti-T2DM targets and pathways of HRL were predicted through network pharmacological approach. The T2DM rat model was induced by high-fat and high-glucose diet combined with streptozotocin (STZ). The T2DM model was evaluated through fasting blood glucose level, body weight, serum biochemical indicators, insulin levels and homeostatic model assessment of insulin resistance. The key metabolic pathways were screened through the correlation between metabolites and key targets. Finally, the quantitative analysis of key targets and metabolites was verified through experiments. RESULTS: After TFH intervention, the fasting blood-glucose level of T2DM rats induced by high-fat and high-glucose diet combined with streptozotocin (STZ) was downregulated significantly, while body weight, serum liquid level, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) were improved. According to ELISA, Western blotting (WB) and reverse transcriptase polymerase chain reaction (RT-PCR), TFH significantly downregulates expression levels of diglyceride (DAG)-activated protein kinase C (PRKCA), mitogen activated protein kinase 10 (MAPK10), human nuclear factor κB subunit p65 (NF-κB p65) and tumor necrosis factor-α (TNF-α) in pancreas of STZ-induced rats. CONCLUSIONS: TFH downregulates expressions of PRKCA, MAPK10 and p65 TNF-α as well as level of the key metabolite DA in the DAG/PRKCA/MAPK10/TNF-α/p65 pathways, improves lipid metabolism disorder, inhibits inflammatory response and thereby relieves symptoms of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Hippophae , Resistência à Insulina , Insulinas , Humanos , Ratos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Flavonoides/farmacologia , Fator de Necrose Tumoral alfa , Hippophae/química , Proteína Quinase 10 Ativada por Mitógeno/metabolismo , Estreptozocina , Transdução de Sinais , Glucose/metabolismo , Peso Corporal , Insulinas/uso terapêutico , Proteína Quinase C-alfa/metabolismo
12.
J Ethnopharmacol ; 318(Pt B): 117000, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37544345

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Eriocephalus africanus infusion is used as a diuretic and a diaphoretic and is also used in the treatment of gastrointestinal disorders and gynaecological conditions, inflammation and dermal disorders, asthma, coughs, fevers, and painful ailments. The plant has been used traditionally as a medication to cure inflammation and skin problems. AIM OF THE STUDY: Studying E. africanus essential oil (EAEO) as a potential hepatoprotective measure against concanavalin (Con) A-induced hepatitis in mice and investigating its underlying mechanism. MATERIALS AND METHODS: Hydro-distilled oil of the fresh plant aerial shoots is subjected to GC/MS analysis. Autoimmune hepatitis (AIH) was induced in mice by intravenous injection of Con A (15 mg/kg). EAEO was administered orally before Con A injection to test its hepatoprotective activity. RESULTS: GC/MS analysis revealed the presence of 22 compounds representing 99.43% of the oil components. The monoterpene artemisia ketone (41.02%) and the sesquiterpene juniper camphor (14.17%) are the major components. The in vivo study showed that the oil suppressed Con A-induced neutrophil and CD4+T cell infiltration into the liver, restored hepatic redox balance, inhibited Con A-induced elevation of tumor necrosis factor-alpha (TNF-α), interleukin (IL-6), and interferon-gamma (IFN-γ) hepatic levels which were correlated with its ability to suppress nuclear factor kappa B (NF-κB) and Signal Transducer and Activator of Transcription (STAT1) activation in the liver. CONCLUSION: EAEO showed hepatoprotective potential against Con A-induced hepatitis in mice collectively through selective anti-oxidant, anti-inflammatory, and anti-necrotic effects.


Assuntos
Hepatite , Óleos Voláteis , Animais , Camundongos , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Concanavalina A/metabolismo , Concanavalina A/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Óleos Voláteis/metabolismo , Transdução de Sinais , Hepatite/metabolismo , Fígado , Inflamação/patologia , Citocinas/metabolismo
13.
J Ethnopharmacol ; 318(Pt B): 117020, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37567428

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chi006Eese herbal medicine Weifuchun Tablets (WFC) approved by the State Food and Drug Administration in 1982 has been widely used in treating a variety of chronic stomach disorders including Chronic atrophic gastritis (CAG) and Gastric precancerous lesions in China clinically. This study aimed to investigate the efficacy and potential mechanism of WFC in treating Gastric intestinal metaplasia (GIM) and Gastric dysplasia (GDys). MATERIALS AND METHODS: Rat GIM and GDys established by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) combined with hot paste, ethanol injury, and intermittent fasting were intervened by WFC. Body weight, histopathology, pH of gastric acid, pepsin activity, intestinal metaplasia index and inflammation were detected. Rat bone marrow derived macrophages (BMDMs) pretreated with WFC were stimulated by LPS. Inflammatory factors and the nuclear factor-kappa B (NF-κB) pathway were assessed. GES-1 cells pretreated by WFC were stimulated by MNNG and TNF-α, intestinal metaplasia index, the NF-κB pathway and interaction between P65 and CDX2 were detected. RESULTS: WFC improved rat body weight, histopathology, pH value of gastric acid, activity of gastric pepsin, intestinal metaplasia (CDX2), inflammation (IL-1ß, IL-6 and TNF-α), macrophage aggregation (CD68) in gastric mucosa in rat GIM and GDys. WFC inhibited inflammation (IL-1ß and TNF-α) by inactivating the NF-κB pathway. WFC reduced the expression of CDX2 by inhibiting the binding of CDX2 promoter TSS upstream region with p65. CONCLUSION: WFC blocked GIM and GDys associated with inflammation by regulating the NF-κB pathway.


Assuntos
Lesões Pré-Cancerosas , Neoplasias Gástricas , Ratos , Animais , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Metilnitronitrosoguanidina , Pepsina A/metabolismo , Inflamação/patologia , Lesões Pré-Cancerosas/tratamento farmacológico , Hiperplasia/patologia , Neoplasias Gástricas/patologia , Metaplasia/metabolismo , Metaplasia/patologia , Mucosa Gástrica/patologia
14.
J Ethnopharmacol ; 318(Pt B): 117039, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37579922

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Herb couple Rehmannia glutinosa Libosch and Cornus officinalis Sieb (RC), originated from "Liuwei Dihuang Pill" which recorded in Key to Therapeutics of Children's Diseases. Traditionally, they have been used widely for their ability to nourish yin and energize the kidneys. Our previous study indicated that the RC could protect against adenine induced Chronic kidney disease (CKD) rats. Nevertheless, there is still no clear explanation of the mechanisms by which RC affects renal interstitial fibrosis in CKD rats. AIM OF THE STUDY: Current Work aims to explore the amelioration and potential mechanism of RC on renal interstitial fibrosis in CKD rats. MATERIALS AND METHODS: CKD rats were induced by adenine. Two weeks after administration, blood, urine, and kidney tissue were collected for biochemical analysis. Observing the physiological state of rats through the changes of rat body weight and renal index. The pro-inflammatory cytokines were measured by enzyme linked immunosorbent assay (ELISA), while renal tissue damage and fibrosis were assessed with Hematoxylin-eosin staining (H&E) and Masson's trichrome staining. In order to determine the levels of indicators and proteins associated with fibrosis signaling pathways, real time PCR (Rt-PCR), Western blot (WB), and immunofluorescence were employed. RESULTS: The renal interstitial fibrosis led to impaired cellular functions with increased the levels of Blood Urea Nitrogen (BUN), Urine protein (UP), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), and Tumor Necrosis Factor alpha (TNF-α). and simultaneous up-regulated collagenⅠ(COL-1), fibronection (FN), α-smooth muscle actin (a-SMA), transforming growth factor-ß1 (TGF-ß1), c-Jun N-terminal kinase (JNK), p38 and extracellular regulated protein kinases (ERK), down-regulated the expression of the E-cadherin proteins. RC notably improved renal dysfunction in CKD rats as indicated by decreases in BUN, UP, and renal index. In addition, consistent with the morphological changes of renal tissue, renal interstitial fibrosis in CKD rats after RC intervention was significantly improved, mainly manifested by a decrease in the positive expression of COL-1, FN, and a-SMA, and increased levels of E-cadherin protein. Meanwhile, RC reduced the classical pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α in adenine-induced CKD rats. Additionally, RC administration also down-regulated TGF-ß1, JNK, p38 and ERK. CONCLUSION: In conclusion, RC may reduce inflammation in adenine induced CKD rats, improve extracellular matrix (ECM) components deposition, and diminish epithelial-mesenchymal transition (EMT) marker protein levels. Furthermore, RC intervention significantly reduces the release of inflammatory cytokines and inhibits the TGF-ß1/MAPK signaling pathway. Based on the results, RC might be useful in the treatment of adenine induced renal fibrosis.


Assuntos
Cornus , Rehmannia , Insuficiência Renal Crônica , Ratos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Rim/patologia , Transdução de Sinais , Insuficiência Renal Crônica/metabolismo , Citocinas/metabolismo , Fibrose , Caderinas/metabolismo
15.
J Ethnopharmacol ; 318(Pt B): 117058, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37597675

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge (Danshen) and Ligusticum chuanxiong Hort. (Chuanxiong) is the core herb pair in traditional Chinese medicines (TCMs) formulae for treating ischemic stroke. However, the synergistic effect of Danshen-Chuanxiong against anti-ischemic stroke and its compatibility mechanism remains unclear. AIM OF THE STUDY: This study aimed to uncover the compatibility mechanism of Danshen-Chuanxiong against ischemic stroke through chemical profiling, pharmacodynamics evaluation, network pharmacology and experimental validation. MATERIALS AND METHODS: Ultra-high performance liquid chromatography (UHPLC) combined with quadrupole time-of-flight tandem mass spectrometry (QTOF-MS) and UHPLC connected with tandem triple quadrupole mass spectrometry (QQQ-MS) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of Danshen-Chuanxiong against ischemic stroke were comprehensively evaluated by the middle cerebral artery occlusion reperfusion (MCAO/R) mice model, zebrafish ischemic stroke model and glutamic acid-induced PC12 cells injury model. Afterwards, network pharmacology and molecular docking were applied to dissect the significant active compounds and potential mechanisms. Finally, the key target proteins were experimentally validated by Western blot. RESULTS: 83 compounds were characterized in Danshen-Chuanxiong by UHPLC-QTOF-MS analysis, and 4 compounds were tentatively identified for the first time. The quantification results (24 accurately identified compounds) in 13 proportions of Danshen-Chuanxiong revealed that Danshen significantly increased the dissolution of most phthalides (from Chuanxiong), while Chuanxiong facilitated the dissolution of most phenolic acids (from Danshen) in solution. The anti-ischemic stroke effects of Danshen-Chuanxiong were significantly better than Danshen or Chuanxiong in attenuating infarct size, reducing brain edema and neurological scores in MCAO/R mice. Also, compared with single herbs, this herb pair exerted better effects of suppressing the incidence of cerebral thrombosis in zebrafish, and increasing the cell viability of glutamic acid-induced PC12 cells. In network pharmacology, 7 effective compounds (rosmarinic acid, chlorogenic acid, salvianolic acid B, (Z)-ligustilide, ferulic acid, caffeic acid, tanshinone IIA) and 5 hub targets (AKT, TNF-α, IL-1ß, CASP3 and BCL2) as well as 4 key pathways were predicted. Western blot results showed that Danshen-Chuanxiong exert therapeutic effects mainly through decreasing the protein expressions of TNF-α, IL-1ß and Cleaved-CASP3, elevating the levels of p-AKT and BCL2. CONCLUSIONS: This work provided an integration strategy for uncovering the synergistic effects and compatibility mechanism of Danshen-Chuanxiong herb pair for treating ischemic stroke, and laid foundation for the further development and utilization of this herb pair.


Assuntos
AVC Isquêmico , Salvia miltiorrhiza , Ratos , Animais , Camundongos , Caspase 3 , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-akt , Fator de Necrose Tumoral alfa , Peixe-Zebra , Cromatografia Gasosa-Espectrometria de Massas , Glutamatos , Proteínas Proto-Oncogênicas c-bcl-2
16.
J Ethnopharmacol ; 318(Pt B): 117064, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37598770

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Arnica montana L. has been shown to alleviate inflammation, pain and swelling associated with trauma, and post-operative clinical conditions, yet the mechanism of action is not well understood. AIM OF THE STUDY: The study was designed to investigate the effect of Arnica montana (A. montana) mother tincture and homeopathic dilutions on inflammation markers, oxidative stress and cell migration in diverse cell culture models. MATERIALS AND METHODS: We tested A. montana mother tincture and a range of homeopathic dilutions in different human and murine cell culture models to demonstrate their anti-inflammatory properties by measuring the inflammatory markers: tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule (ICAM-1), reactive oxygen species (ROS) and cell migration. The inflammatory markers were measured by ELISA assays. The intracellular oxidative stress (ROS) in microglial cells was measured using Deep Red CellROX probe. The cell migration was examined by wound healing using the Oris Cell migration assay. RESULTS: These data showed the ability of A. montana (mother tincture and mainly 1C dilution) to significantly reduce TNFα production in inflamed macrophages compared with vehicle (control). They significantly reduced both IL-6 and MCP-1 in inflamed human microglial cells and significantly decreased COX-2 expression in inflamed murine fibroblasts. Moreover, A. montana mother tincture reduced the cell migration whereas 9C dilution significantly enhanced the migration of fibroblast cells compared with vehicle. The expression of ICAM-1 was significantly reduced with A. montana mother tincture and 1C, 3C, 5C, and 9C dilutions in inflamed human endothelial cells compared with vehicle. A. montana mother tincture and 1C, 3C, 5C and 9C dilutions induced a significant and consistent effect on ROS production in inflamed murine microglial cells. A. montana 1C had the largest impact on ROS production. CONCLUSIONS: Mother tincture and 1C dilution of A. montana showed anti-inflammatory properties assessed by measurement of several markers (pro-inflammatory cytokines, adhesion molecule, ROS) in various human and murine cell models. In addition, A. montana 3C, 5C, 9C dilutions have anti-inflammatory and antioxidant effects as highlighted on both primary endothelial cells and murine microglial cells.


Assuntos
Arnica , Produtos Biológicos , Humanos , Feminino , Animais , Camundongos , Ciclo-Oxigenase 2 , Células Endoteliais , Molécula 1 de Adesão Intercelular , Interleucina-6 , Mães , Espécies Reativas de Oxigênio , Fator de Necrose Tumoral alfa , Extratos Vegetais/farmacologia , Inflamação/tratamento farmacológico
17.
J Ethnopharmacol ; 318(Pt B): 117051, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37598765

RESUMO

ETHNO-PHARMACOLOGICAL RELEVANCE: The Andean Schkuhria pinnata species commonly known as 'Canchalagua' is used as an infusion in Andean countries to treat various anti-inflammatory and skin-related pathologies. AIM OF THE STUDY: This study determined the anti-inflammatory activity of the aqueous extract from Schkuhria pinnata, identified compounds with high biological activity and performed a structure-activity relationship analysis to determine their binding mechanism. MATERIALS AND METHODS: A bio-guided isolation of the active compounds of Schkuhria pinnata was carried out by selecting the most active sub-extracts and fractions to test their anti-inflammatory activity against the ASK1 and TNF-α cytokines. RESULTS: Three compounds were obtained, and their structures were elucidated by nuclear magnetic resonance. The compounds were (3R,4R)-4-(3,4-dimethoxybenzyl)-3-(4-hydroxy-3-methoxybenzyl) dihydrofuran-2(3H)-one (1), N-[2,3-dihydro-1,3-dimethyl-6-[(2R)-2-methyl-1-piperazinyl]-2-oxo-1H-benzimidazol-5-yl]-2-methoxybenzamide (2), and N-hydroxy-1-cyclopentene-1-carboxamide (3). Regarding their anti-inflammatory activity, the three compounds inhibited the TNF-α and ASK1 cytokines, however, compound 2 was the most active, with an IC50 of 19.08 and 8.94 nM, respectively. CONCLUSION: The anti-inflammatory activity of the aqueous extract of Schkuhria pinnata was evaluated, followed by the isolation of three compounds and the study of their pharmacological activity. The three compounds have been shown as promising treatment against dermatitis, confirming at the same time their traditional use.


Assuntos
Asteraceae , Dermatite , Fator de Necrose Tumoral alfa , Citocinas , Ciclopentanos
18.
Talanta ; 267: 125232, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37806108

RESUMO

A simultaneous detection method for two cardiac disease protein biomarkers present in serum samples on a single planar gold chip using surface plasmon resonance (SPR) is described. The detection of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tumor necrosis factor α (TNF-α), which are known as acute myocardial infarction (AMI) biomarkers, with predetermined clinically relevant concentrations was performed using mixed aptamers specific to each protein tethered on a single gold surface. After the binding of NT-proBNP and/or TNF-α to the mixed aptamers, an antibody specific to each target protein was injected to form a surface sandwich complex to improve selectivity. In order to adjust the dynamic ranges in the known clinically relevant concentration significantly different for NT-proBNP (0.13-0.24 nM) and TNF-α (0.5-3 pM), the surface density ratios of the corresponding pair of aptamer and antibody were first systematically determined, which were the 1:1 mixed aptamer chip with 40 nM anti-NT-proBNP and 100 nM anti-TNF-α. This allowed to establish the distinct dynamic ranges of 0.05-0.5 nM for NT-proBNP and 0.1-5 pM for TNF-α in a buffer, along with detection and quantification limits of 0.03 and 0.19 nM for NT-proBNP and 0.06 and 0.21 pM for TNF-α, respectively. The changes in refractive unit (RU) values observed when exposing both proteins at different concentrations alongside the corresponding fixed concentration of antibodies onto the 1:1 mixed aptamer chip were then correlated to the sum of RU values measured when using the injection of individual protein for evaluating each protein concentration. With a complete characterization of the simultaneous quantification of two protein concentrations in the buffer, the mixed aptamer chip was finally employed for direct measurements of NT-proBNP and TNF-α concentrations in undiluted serum samples from healthy controls and AMI patients. The results of simultaneous SPR measurements for the two proteins in the serum samples were further compared to the individual protein concentration results using an enzyme-linked immunosorbent assay.


Assuntos
Aptâmeros de Nucleotídeos , Infarto do Miocárdio , Humanos , Ressonância de Plasmônio de Superfície , Fator de Necrose Tumoral alfa , Inibidores do Fator de Necrose Tumoral , Infarto do Miocárdio/diagnóstico , Anticorpos/química , Ouro/química , Aptâmeros de Nucleotídeos/química , Biomarcadores , Fragmentos de Peptídeos
19.
J Ethnopharmacol ; 319(Pt 1): 117133, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37690476

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Alangium chinense has been used as traditional folk medicine for centuries to treat rheumatoid arthritis (RA) by Guizhou Miao nationality with remarkable clinical effect. But the mechanism of its anti-RA is not fully clarified. AIM OF THE STUDY: To explore the effect and underlying mechanism of A. chinense against RA. MATERIAL AND METHODS: RA rats were induced by CII/IFA, and oral administrated with or without ethyl acetate extracts of Alangium chinense (ACEE) and tripterygium glycosides (GTW). Then arthritis scores, inflammatory factors in serum and histological evaluation were evaluated to assess the degree of joints disease. Proteomics were conducted via LC-MS/MS to clarify the mechanism of ACEE preliminarily, and further examined by immunohistochemistry, immunofluorescence, western botting, and molecular docking. RESULTS: ACEE decreased joints swelling, cell abscission and necrosis of joint tissues arthropathy of RA rats, and attenuated expression of TNF-α, IL-1ß, IL-6, PGE2, TGF-ß. Meanwhile, differentially expressed proteins in the ACEE treated groups were observed, which were involved in RA, spliceosome, cell adhesion molecules, phagosome and lysosome signaling pathways. Moreover, ACEE significantly ameliorated arthropathy, suppressed JAK-STAT pathway (JAK3, p-JAK3, STAT3, iNOS, RANKL), COX-2 pathway (COX-2, TNF-α, IL-6I, L-1ß, 5-LOX), and autophagic signaling pathway (LC3-Ⅰ, LC3-Ⅱ, p62, mTOR). But it showed little effect on the expression of COX-1, JAK1, JAK2, TyK2. CONCLUSION: It is the first evidence that A. chinense significantly ameliorates RA, and the underlying immune mechanism involves reducing autophagy with targeting regulate JAK3-STAT3 and COX-2 pathways.


Assuntos
Alangiaceae , Artrite Experimental , Artrite Reumatoide , Ratos , Animais , Ciclo-Oxigenase 2/metabolismo , Alangiaceae/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Janus Quinases/metabolismo , Simulação de Acoplamento Molecular , Cromatografia Líquida , Fatores de Transcrição STAT/metabolismo , Espectrometria de Massas em Tandem , Artrite Reumatoide/patologia , Artrite Experimental/patologia , Citocinas/metabolismo
20.
Curr Mol Pharmacol ; 17(1): e060923220758, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37691196

RESUMO

Tumor necrosis factor-alpha (TNFα) is a pleiotropic pro-inflammatory cytokine of the TNF superfamily. It regulates key cellular processes such as death, and proliferation besides its well-known role in immune response through activation of various intracellular signaling pathways (such as MAPK, Akt, NF-κB, etc.) via complex formation by ligand-activated TNFα receptors. TNFα tightly regulates the activity of key signaling proteins via their phosphorylation and/or ubiquitination which culminate in specific cellular responses. Deregulated TNFα signaling is implicated in inflammatory diseases, neurological disorders, and cancer. TNFα has been shown to exert opposite effects on cancer cells since it activates prosurvival as well as anti-survival pathways depending on various contexts such as cell type, concentration, cell density, etc. A detailed understanding of TNFα signaling phenomena is crucial for understanding its pleiotropic role in malignancies and its potential as a drug target or an anticancer therapeutic. This review enlightens complex cellular signaling pathways activated by TNFα and further discusses its role in various cancers.


Assuntos
Neoplasias , Fator de Necrose Tumoral alfa , Humanos , Transdução de Sinais , NF-kappa B , Neoplasias/tratamento farmacológico , Citocinas
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