Revealing the potential bioactive components and mechanism of Qianhua Gout Capsules in the treatment of gouty arthritis through network pharmacology, molecular docking and pharmacodynamic study strategies DOI Creative Commons
Gelin Xiang,

Luyin Yang,

Jing Qin

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(10), P. e30983 - e30983

Published: May 1, 2024

Recent clinical studies have confirmed the effectiveness of Qianhua Gout Capsules (QGC) in treatment gouty arthritis (GA). However, specific regulatory targets and mechanisms action QGC are still unclear. To address this gap, we utilized network pharmacology, molecular docking, pharmacodynamic approaches to investigate bioactive components associated GA. By employing UPLC-Q Exactive-MS, identified compounds present QGC, with active ingredients defined as those oral bioavailability ≥30 % drug similarity ≥0.18. Subsequently, these were determined using TCMSP database, while GA-related from DisGeNET, GeneCards, TTD, OMIM, DrugBank databases. Further analysis including PPI analysis, GO KEGG pathway enrichment was conducted on targets. Validation predicted results performed a GA rat model, evaluating pathological changes, inflammatory markers, protein expression. Our revealed total 130 components, 44 16 potential shared targets, GO-enriched terms, 47 signaling pathways related disease Key included quercetin, kaempferol, β-sitosterol, luteolin, wogonin. The highlighted five (PPARG, IL-6, MMP-9, IL-1β, CXCL-8) highest connectivity, predominantly enriched IL-17 pathway. Molecular docking experiments demonstrated strong binding CXCL8, MMP9, PPARG top compounds. Furthermore, animal efficacy treating rats, showing reductions TNF-α, MDA levels, increases SOD levels serum. In synovial tissues, upregulated CXCL8 expression, downregulating IL-6 conclusion, study applied pharmacology approach uncover composition predict its pharmacological interactions, demonstrate

Language: Английский

Neuroinflammation in Alzheimer’s Disease: Current Progress in Molecular Signaling and Therapeutics DOI
Sujata Thakur,

Rishika Dhapola,

Phulen Sarma

et al.

Inflammation, Journal Year: 2022, Volume and Issue: 46(1), P. 1 - 17

Published: Aug. 20, 2022

Language: Английский

Citations

265
Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis DOI Creative Commons
Lin Wang, Chengqi He

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 12, 2022

Macrophages are the most abundant immune cells within synovial joints, and also main innate effector triggering initial inflammatory responses in pathological process of osteoarthritis (OA). The transition macrophages between pro-inflammatory anti-inflammatory phenotypes can play a key role building intra-articular microenvironment. cascade induced by TNF-α, IL-1β, IL-6 is closely related to M1 macrophages, resulting production pro-chondrolytic mediators. However, IL-10, IL1RA, CCL-18, IGF, TGF M2 leading protection cartilage promoted regeneration. inhibition NF-κB signaling pathway central OA treatment via controlling while nuclear factor erythroid 2-related 2 (Nrf2) appears not attract widespread attention field. Nrf2 transcription encoding large number antioxidant enzymes. activation have effects, which complex crosstalk with pathway. inhibit polarization promote through potential transductions including TGF-β/SMAD, TLR/NF-κB, JAK/STAT pathways, regulation or cooperation Notch, NLRP3, PI3K/Akt, MAPK signaling. And expression heme oxygenase-1 (HO-1) negative for be mechanisms promotion. Furthermore, candidates activating phenotype reviewed this work, such as itaconate fumarate derivatives, curcumin, quercetin, melatonin, mesenchymal stem cells, low-intensity pulsed ultrasound.

Language: Английский

Citations

168
Ginseng root extract attenuates inflammation by inhibiting the MAPK/NF-κB signaling pathway and activating autophagy and p62-Nrf2-Keap1 signaling in vitro and in vivo DOI
Yang Song, Fangyu Li,

Shuyan Lu

et al.

Journal of Ethnopharmacology, Journal Year: 2021, Volume and Issue: 283, P. 114739 - 114739

Published: Oct. 12, 2021

Language: Английский

Citations

119
ABCC5 facilitates the acquired resistance of sorafenib through the inhibition of SLC7A11-induced ferroptosis in hepatocellular carcinoma DOI Creative Commons
Wenbin Huang,

Kunling Chen,

Yishi Lu

et al.

Neoplasia, Journal Year: 2021, Volume and Issue: 23(12), P. 1227 - 1239

Published: Nov. 9, 2021

Sorafenib is a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), and reducing sorafenib resistance an important issue to be resolved the clinical treatment of HCC. In current study, we identified that ABCC5 critical regulator promising therapeutic target acquired in human cells. The expression was dramatically induced sorafenib-resistant HCC cells remarkably associated with poor prognoses. down-regulation could significantly reduce Importantly, activation PI3K/AKT/NRF2 axis essential induce expression. increased intracellular glutathione (GSH) attenuated lipid peroxidation accumulation by stabilizing SLC7A11 protein, which inhibited ferroptosis. Additionally, inhibition enhanced anti-cancer activity vitro vivo. These findings demonstrate novel molecular mechanism also suggest new ferroptosis

Language: Английский

Citations

105
Gut Microbiota Participates in Polystyrene Microplastics-Induced Hepatic Injuries by Modulating the Gut–Liver Axis DOI

Kai-Kai Zhang,

Jian-Zheng Yang, Lijian Chen

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(15), P. 15125 - 15145

Published: July 24, 2023

Dietary pollution by polystyrene microplastics (MPs) can cause hepatic injuries and microbial dysbiosis. Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, exerts beneficial effects on liver modulating gut microbiota. However, role of microbiota MPs-induced protective effect EGCG have not been clarified. Here, 5 μm MPs were orally administered to mice induce injuries. Subsequently, antibiotic cocktail (ABX) fecal transplant (FMT) experiments performed investigate underlying mechanisms. Additionally, was explore its protection against Our results showed that activated systemic inflammation, promoted fibrosis, altered metabolome; meanwhile, damaged homeostasis disturbing microbiome, promoting colonic impairing intestinal barrier. Notably, reduced abundance probiotics Akkermansia, Mucispirillum, Faecalibaculum while increasing pathogenic Tuzzerella. Interestingly, elimination mitigated inflammation barrier impairment. Moreover, ABX ameliorated but fibrosis. Correspondingly, from MPs-administered induced colonic, systemic, their profibrosis observed. Finally, elevated effectively repressed inflammation. remodeling metabolome also attenuated EGCG. These findings illustrated contributed injuries, could serve as a potential prevention strategy for these adverse consequences.

Language: Английский

Citations

94
Ultrasmall iron‐gallic acid coordination polymer nanodots with antioxidative neuroprotection for PET/MR imaging‐guided ischemia stroke therapy DOI Creative Commons
Yujing Du,

Yan Huo,

Qi Yang

et al.

Exploration, Journal Year: 2023, Volume and Issue: 3(1)

Published: Jan. 17, 2023

Oxidative stress from reactive oxygen species (ROS) is a reperfusion injury factor that can lead to cell damage and death. Here, ultrasmall iron-gallic acid coordination polymer nanodots (Fe-GA CPNs) were developed as antioxidative neuroprotectors for ischemia stroke therapy guided by PET/MR imaging. As proven the electron spin resonance spectrum, Fe-GA CPNs with size, scavenged ROS efficiently. In vitro experiments revealed could protect viability after being treated hydrogen peroxide (H

Language: Английский

Citations

48
The Antioxidant Action of Astragali radix: Its Active Components and Molecular Basis DOI Creative Commons
Juan Yao, Ting Peng,

Changxin Shao

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(8), P. 1691 - 1691

Published: April 9, 2024

Astragali radix is a traditional medicinal herb with long history and wide application. It frequently used in prescriptions other materials to replenish Qi. According the classics of Chinese medicine, attributed properties such as Qi replenishing surface solidifying, sore healing muscle generating, inducing diuresis reduce edema. Modern pharmacological studies have demonstrated that some extracts active ingredients function antioxidants. The polysaccharides, saponins, flavonoids offer beneficial effects preventing controlling diseases caused by oxidative stress. However, there still lack comprehensive research on effective components molecular mechanisms through which exerts antioxidant activity. In this paper, we review radix; summarize content, bioavailability, mechanisms; reference for clinical application Astragalus future development novel

Language: Английский

Citations

18
Pharmacological modulation of PI3K/PTEN/Akt/mTOR/ERK signaling pathways in ischemic injury: a mechanistic perspective DOI
Heena Khan, Aditi Singh,

Yashpal Singh

et al.

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(3)

Published: Feb. 26, 2025

Language: Английский

Citations

3
Pharmacological activation of REV-ERBα represses LPS-induced microglial activation through the NF-κB pathway DOI Open Access
Dongkai Guo, Yao Zhu, Hongyang Sun

et al.

Acta Pharmacologica Sinica, Journal Year: 2018, Volume and Issue: 40(1), P. 26 - 34

Published: June 27, 2018

Language: Английский

Citations

96
Anti-inflammatory effects of mesenchymal stem cell-conditioned media inhibited macrophages activation in vitro DOI Creative Commons

Quan-He Jin,

Hyung-Keun Kim,

Ju-Yong Na

et al.

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: March 19, 2022

Abstract The immunomodulatory effects of mesenchymal stem cells (MSCs) on macrophages have been reported, however, the underlying mechanism remains unknown. Therefore, this study aimed to investigate anti-inflammatory MSCs lipopolysaccharide (LPS)-stimulated and subsequent downregulation their inflammatory mediators. Macrophages were treated with conditioned media from MSCs, without a change responding inflammation state. This also evaluated whether interleukin (IL) 4 stimulation can improve effects. Results demonstrated that MSC-conditioned medium (MSC-CM) stimulated IL4 significantly inhibited inducible nitric oxide synthase (iNOS) cyclooxygenase-2 (COX-2) protein expression LPS-activated macrophages. MSC-CM treatment mRNA transcription cytokines IL1β IL6, chemokines C–C motif ligand (CCL) 2, CCL3, CCL4, CCL5, chemokine receptors CCR2 CCR5, in LPS-stimulated As revealed through western blot immunofluorescence analyses, phosphorylation p38, JNK, ERK MAPKs, as well NF-κB macrophages, by MSC-CM. Further, more potent observed IL4-stimulated cells, compared those non-stimulated cells. effect while improved effect. These findings indicate could exert may be considered therapeutic agent treatment.

Language: Английский

Citations

67