Опубликована: Янв. 1, 2024
Язык: Английский
Inflammation, Год журнала: 2025, Номер unknown
Опубликована: Янв. 27, 2025
Inflammatory bone resorption represents a pathological condition marked by an increase in loss, commonly associated with chronic inflammatory conditions such as rheumatoid arthritis and periodontitis. Current therapies primarily focus on anti-inflammatory drugs bisphosphonates; however, these treatments are limited due to side effects, inadequate efficacy, unpredictable long-term complications. Kurarinone (KR), bioactive compound isolated from the traditional Chinese herb Sophora flavescens, exhibits range of biological activities, including anti-inflammatory, anticancer, cardiovascular protective effects. To address limitations existing enhance drug utilization, this study explores potential KR therapeutic agent for delineates its underlying mechanisms. In vitro experiments reveal that notably inhibits osteoclastogenesis reduces expression osteoclastic markers. Additionally, decreases levels pro-inflammatory cytokines IL-1β, IL-6, TNF-α, while downregulating NADPH oxidase 1 (NOX1) Kelch-like ECH-associated protein (Keap1) diminish ROS production. Furthermore, activates nuclear factor erythroid 2-related 2 (Nrf2), which enhances activity heme oxygenase-1 (HO-1) catalase (CAT), facilitating clearance excess ROS. The also hinders osteoclast formation functionality inhibiting PI3K/AKT/GSK-3β signaling pathway. Lentiviral knockdown CAT can partially reverse effects KR. Meanwhile, vivo indicate effectively mitigates loss LPS-induced model. summary, is promising new star breaking through previous treating resorption.
Язык: Английский
Процитировано
0
Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 1609 - 1626
Опубликована: Март 1, 2025
Purpose: Vaccarin is a natural flavonoid glycoside with anti-inflammatory, antioxidant and nephroprotective effects. However, the effects of vaccarin on renal fibrosis (RF) its molecular mechanisms remain unclear. This study aimed to investigate RF mechanisms. Methods: Network pharmacology was used analyze effect RF, docking dynamics simulations were performed assess binding nuclear factor erythroid 2-related 2 (Nrf2) vaccarin. A mouse model unilateral ureteral obstruction (UUO) established in vivo, human tubular epithelial (HK2) cells induced transforming growth factor-β (TGF-β) RSL3, respectively, as an vitro model. The anti-fibrotic observed by histopathological staining determination fibrous markers. Changes oxidative stress ferroptosis-related markers detected kits, Western blot (WB), qRT-PCR immunofluorescence (IF). Finally, Nrf2 inhibitors added observe ferroptosis. Results: cross genes are enriched for stress. binds stably Both vivo experiments showed that treatment reduced expression markers, decreased levels reactive oxygen species (ROS), malondialdehyde (MDA), lipid peroxidation (LPO) Fe 2+ , increased glutathione (GSH) secretion. In addition, down-regulated Long-chain acyl-CoA synthetase 4 (ACSL4), prostaglandin-endoperoxide synthase (PTGS2) NADPH oxidase 1 (NOX1), up-regulated downstream solute transport family 7 member 11 (SLC7A11) peroxidase (GPX4) expression. Mechanistic studies indicated activated Nrf2/SLC7A11/GPX4 pathway inhibit ferroptosis, this inhibition effectively reversed inhibitor. Conclusion: ameliorates inhibiting ferroptosis via pathway. Keywords: vaccarin, fibrosis, pathway, stress, network
Язык: Английский
Процитировано
0
Pharmaceutics, Год журнала: 2024, Номер 16(11), С. 1375 - 1375
Опубликована: Окт. 26, 2024
Chronic mountain sickness (CMS) poses a significant health risk to individuals who rapidly ascend high altitudes, potentially endangering their lives. Nanoparticles (NPs) offer an effective means of transporting and delivering drugs, protecting nucleic acids from nuclease degradation, mediating the expression target genes in specific cells. These NPs are almost non-toxic easy prepare store, possess large surface area, exhibit good biocompatibility degradability, maintain stability. They can be utilized treatment CMS enhance therapeutic efficacy drugs. This paper provides overview impact on CMS, discussing roles as nanocarriers potential treatment. It aims present novel strategies for clinical management summarizes relevant pathways through which contribute plateau disease treatment, providing theoretical foundation future research.
Язык: Английский
Процитировано
1
Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 178, С. 117205 - 117205
Опубликована: Июль 27, 2024
Язык: Английский
Процитировано
0
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0