BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Yumei Sun,Jihong Wang,Peiyao Hu,Yi Tang,Yanwen Wang,Jianzhou Ye,Xuesong Yang,Junlin Yin
Tripterygium hypoglaucum (Lévl.) Hutch rhizome (THH) is mainly used in the clinical setting for the treatment of autoimmune diseases such as rheumatoid arthritis. In total, four active compounds were isolated from THH methanol extract （THH-MeOH）and identified. The HPLC results showed that the proportions of the active ingredients in THH-MeOH (i.e., celastrol, triptolide, and 3- O -acetyloleanolic acid) were 0.79 ‰, 0.46 ‰, and 0.76 ‰, respectively. THH-MeOH attenuated the M5-induced hyperproliferation of HaCaT cells, decreased the mRNA expression levels of inflammatory cytokines, and inhibited the phosphorylation of I κ B α , NF- κ B p65, MAPK, and STAT3/JAK2. Furthermore, THH-MeOH significantly reduced PASI scores in mice; reduced the level of Ki67 expression in skin tissues; decreased the expression of inflammatory cytokines in the skin lesions and serum; and ameliorated the IMQ-induced imbalance in the ROR γ t / Foxp3 ratio. The extract can attenuate psoriasis-like lesions by inhibiting cellular hyperproliferation, ameliorating inflammatory reactions, and modulating immune responses. Our work provides a theoretical basis to support the use of THH for treating psoriasis.
研究领域:
药理学
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免疫学
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皮肤科
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
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2025
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IF 1.3
Jing Gao,Xiaohui Dong,Hang Li,Qing Yang,Wenting Ji,Xianying Lu,Xinyu Chen,Fei Wang,Chaoming Hou
Objective Fujin Shengji (FJSJ) Powder has a positive effect on healing Diabetic Ulcers (DU), but the specific compounds at work have not been identified. Methods Network pharmacology was employed to investigate the primary constituents, potential therapeutic targets, and pharmacological mechanisms of FJSJ Powder treating DU. In vitro experiments were further performed to validate these findings: an LPS-induced RAW264.7 cell model was established to assess the anti-inflammatory effects of FJSJ Powder active constituents treating DU, while a high glucose-induced HUVEC model was cultured to verify the pro angiogenic effect of FJSJ Powder active constituents treating DU. Additionally, the mechanisms by which the optimal active monomers suppress inflammation and enhance angiogenesis in DU were investigated, focusing on the JAK2/STAT3 and PI3K/AKT signaling pathways. Results Network pharmacology identified quercetin (Que), kaempferol (Kae), abietic acid (Aba) and acetyl-11-keto-β-boswellic acid (AKBA) as the primary active constituents of FJSJ Powder treating DU; IL6, TNF, AKT1, and VEGFA were the core targets; and anti-inflammatory effect was mainly enriched in the JAK2/STAT3 signaling pathway, while angiogenesis promotion was mainly enriched in the PI3K/AKT signaling pathway. The vitro experiments have confirmed Que, Kae, Aba, and AKBA could play important roles in anti-inflammatory and angiogenic effects, with AKBA and Aba playing important roles in anti-inflammatory and pro-angiogenic effects, respectively. AKBA can upregulate P-JAK2, P-STAT3, IL-4, and downregulate INOS protein levels to exert anti-inflammatory. Aba can upregulate the P-AKT, P-PI3K, HIF-1α, and VEGFA proteins levels to promote angiogenesis. Conclusion FJSJ Powder promotes DU healing through dual-pathway regulation in anti-inflammatory and pro-angiogenic effects, with AKBA mediating the best anti-inflammatory activity through the JAK2/STAT3 pathway and Aba driving the strongest pro-angiogenic effects via the PI3K/AKT/HIF-1α/VEGFA axis, providing a basis for formula optimization.
研究领域:
药理学
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网络药理学
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中医药
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分子生物学
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创面愈合
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糖尿病并发症
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Xiao-Lu Jie,Zi-Rui Luo,Jin Yu,Zhe-Ren Tong,Qiao-Qiao Li,Jia-Hui Wu,Yi Tao,Pei-Shi Feng,Ji-Ping Lan,Ping Wang
Ethnopharmacological relevance Pi-Pa-Run-Fei-Tang (PPRFT) is an empirical TCM prescription for treating asthma. However, the underlying mechanisms of PPRFT in asthma treatment have yet to be elucidated. Recent advances have revealed that some natural components could ameliorate asthma injury by affecting host metabolism. Untargeted metabolomics can be used to better understand the biological mechanisms underlying asthma development and identify early biomarkers that can help advance treatment. Aim of the study The aim of this study was to verification the efficacy of PPRFT in the treatment of asthma and to preliminarily explore its mechanism. Materials and methods A mouse asthma model was built by OVA induction. Inflammatory cell in BALF was counted. The level of IL-6, IL-1β, and TNF-α in BALF were measured. The levels of IgE in the serum and EPO , NO , SOD , GSH-Px, and MDA in the lung tissue were measured. Furthermore, pathological damage to the lung tissues was detected to evaluate the protective effects of PPRFT. The serum metabolomic profiles of PPRFT in asthmatic mice were determined by GC-MS. The regulatory effects on mechanism pathways of PPRFT in asthmatic mice were explored via immunohistochemical staining and western blotting analysis. Results PPRFT displayed lung-protective effects through decreasing oxidative stress, airway inflammation , and lung tissue damage in OVA-induced mice, which was demonstrated by decreasing inflammatory cell levels, IL-6, IL-1β, and TNF-α levels in BALF, and IgE levels in serum, decreasing EPO, NO, and MDA levels in lung tissue, elevating SOD and GSH-Px levels in lung tissue and lung histopathological changes. In addition, PPRFT could regulate the imbalance in Th17/Treg cell ratios, suppress RORγt, and increase the expression of IL-10 and Foxp3 in the lung. Moreover, PPRFT treatment led to decreased expression of IL-6, p-JAK2/Jak2, p-STAT3/STAT3, IL-17, NF-κB, p-AKT/AKT, and p-PI3K/PI3K. Serum metabolomics analysis revealed that 35 metabolites were significantly different among different groups. Pathway enrichment analysis indicated that 31 pathways were involved. Moreover, correlation analysis and metabolic pathway analysis identified three key metabolic pathways: galactose metabolism; tricarboxylic acid cycle; and glycine, serine , and threonine metabolism. Conclusion This research indicated that PPRFT treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating serum metabolism. The anti-asthmatic activity of PPRFT may be associated with the regulatory effects of IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB mechanistic pathways.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Hao Wu,Changcheng Chen,Jiangfeng Li,Dongmei Yu,Xun Wu,Hai Huang,Zhen Tang,Qi Wu,Shichao Yan,Ning Wang,Mo Wang,Feilong Wei,Yunlong Yu,Duan Wang,Mengting Shi,Xusong Yue,Pengfei Cao,Zenghui Zheng,Xiaokang Li,Baolin Guo,Lei Shi,Zheng Guo
Infectious bone defects pose significant clinical challenges due to persistent infection and impaired bone healing. Icam1+ macrophages were identified as crucial and previously unrecognized regulators in the repair of bone defects, where impaired oxidative phosphorylation within this macrophage subset represents a significant barrier to effective bone regeneration. To address this challenge, dual-responsive iron-doped barium titanate (BFTO) nanoparticles were synthesized with magnetic and ultrasonic properties. These nanoparticles were further loaded with the anti-inflammatory agent curcumin and coated with engineered mesenchymal stem cell membranes (EMM) modified with γ3 peptide, creating BFTO-Cur@EMM nanoparticles specifically designed to target Icam1+ macrophages. These nanoparticles were shown to disrupt bacterial biofilms under alternating magnetic fields (AMF) and to activate oxidative phosphorylation and osteogenic immune responses in Icam1+ macrophages via low-intensity pulsed ultrasound (LIPUS). Transcriptomic sequencing and validation experiments demonstrated that this approach activates oxidative phosphorylation (OXPHOS) by stimulating the JAK2-STAT3 pathway and inhibiting the MAPK-JNK pathway, thereby promoting the polarization of Icam1+ macrophages toward a pro-reparative phenotype and enhancing the secretion of pro-angiogenic and osteogenic cytokines. These nanoparticles were subsequently integrated into quaternized chitosan (QCS) and tricalcium phosphate (TCP) to create a bioink for three-dimensional (3D) printing anti-infection QT/BFTO-Cur@EMM bone repair scaffolds. In vivo studies indicated that these scaffolds significantly improved the healing of infectious bone defects without causing thermal damage to surrounding tissues. This work highlights the potential of this material and the targeting of Icam1+ macrophages as an effective strategy for simultaneously controlling infection and promoting bone regeneration.
研究领域:
生物材料
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纳米技术
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骨科
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免疫学
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
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