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NEUROPHARMACOLOGY · 2025 · IF 4.6

Ligustilide ameliorates cerebral ischemia-reperfusion injury by inhibiting NLRP3 inflammasome-dependent pyroptosis through enhancing Nrf2 signaling

Yang Wang,Zhihan Wan,Ning Wang,Qian Wu,Saiwang Seto

Pyroptosis is a type of proinflammatory programmed cell death, that closely related to the progress of cerebral ischemia / reperfusion injury (CIRI), and NLRP3 inflammasome is the most classic pathway mediating pyroptosis. Ligustilide (LIG) is a natural compound derived from the traditional Chinese herb chuanxiong hort and angelica sinensis which can penetrate the blood-brain barrier and has a good neuroprotective effect. However, it remains unclear whether LIG could alleviate CIRI by inhibiting pyroptosis. Here, the neuroprotective effect of LIG was verified by reducing NLRP3-mediated pyroptosis, and further exploring whether the inhibition of LIG on pyroptosis was related to Nuclear factor-erythropoietin 2-related factor 2(Nrf2)activation. The results showed that LIG can reduce the injury of brain tissue after ischemia, as well as NLRP3 inflammasome-mediated pyroptosis and neuroinflammation response after MCAO/R in rats. Mechanistically, the effect of LIG on Nrf2 was detected by molecular docking, protein levels and immunofluorescence analysis. We found that LIG promoted the Nrf2 expression and reduced the production of mitochondrial ROS (mtROS), and than inhibited NLRP3 inflammasome-mediated pyroptosis. Particularly revealing was that ML385, the inhibitor of Nrf2, partly blocked the above effects of LIG. All these findings suggest that LIG may ameliorate CIRI through inhibiting NLRP3 inflammasome-mediated pyroptosis dependent on Nrf2 signaling.

研究领域: 神经药理学 · 分子生物学 · 中医药学 · 药理学 · 神经科学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 17 ·8678 · IF 4.9

Neocnidilide and 6-Gingerol as Key Bioactives in Fresh and Dried Centipeda minima: Distinct Th1/Th2 Modulation via NF-κB/JAK-STAT Pathways for Allergic Rhinitis Therapy

Yamin Zhang,Jiajia Lin,Xiaomei Xu,Xuehua Lu,Lisha Li,Yuezhen Yang,Wenjin Lin

This study aimed to compare the therapeutic effects of fresh (CMF) and dried (CMD) Centipeda minima against allergic rhinitis (AR), elucidate their underlying molecular mechanisms, and identify the bioactive compounds responsible for their immunomodulatory actions. An ovalbumin-induced AR mouse model was treated with CMF or CMD extracts, followed by evaluation of nasal symptoms, serum biomarkers (IgE, histamine, cytokines), and nasal mucosa histopathology. Transcriptomics and widely targeted metabolomics were integrated with network pharmacology to identify differentially expressed genes and bioactive components, which were further validated in RAW264.7 and RBL-2H3 cells. CMF and CMD exhibited distinct anti-AR mechanisms: CMF predominantly suppressed Th2 responses (reducing IgE, IL-6, and histamine while elevating IL-10), whereas CMD enhanced Th1 activity (increasing IFN-γ). Metabolomic analysis revealed CMF was rich in amino acids while CMD contained higher flavonoids, with neocnidilide and 6-gingerol identified as key bioactive compounds that modulated TNF-α, IL-6, and IL-10 via NF-κB and JAK-STAT pathways. These findings demonstrate that CMF and CMD exert complementary anti-inflammatory effects through Th2 inhibition and Th1 activation, respectively, providing a molecular basis for the traditional use of Centipeda minima and highlighting its bioactive compounds as potential therapeutics for inflammatory diseases.

CAS / MDL: 9006-59-1
研究领域: 药理学 · 免疫学 · 民族药理学 · 分子生物学 · 植物学 · 生物医学
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Separation Science Plus · 2025 ·Vol. 8 ·期 8 ·e70105 · IF 1.6

Optimization of the Fatty Oil Extraction Process of Sanzi Yangqin Decoction Based on Network Pharmacology and Quantitative LC-MS/MS Methods

Wenya Xu,Hailing Wang,Yan Sun,Haojie Li,Jue Song

The fatty oil in Sanzi Yangqin Decoction is a crucial medicinal ingredient found in this renowned traditional Chinese medicine formula for the treatment of chronic obstructive pulmonary disease (COPD). However, a disadvantage of the extraction process using the conventional decoction approach is the poor extraction rate. In this study, we employed network pharmacology to screen for active components for the treatment of COPD, and we optimized the extraction procedure of the fatty oil of Sanzi Yangqin Decoction with the Box–Behnken response surface test. Based on the single-factor experiment and the Box–Behnken response surface test, the liquid chromatography-triple quadrupole mass spectrometry method (LC-MS/MS) to measure these four components has been constructed with the extraction time, extraction temperature, and liquid-to-feed ratio as examining factors and the composite scores of the extracted amounts of the four components as examining indexes. According to the results of the study, luteolin, arachidonic acid, sinoacutine, and sinapine thiocyanate have been selected as the analytes for determining the fat oil content of Sanzi Yangqin Decoction. The most effective extraction conditions were 4.1 h, 92°C, and a liquid-to-feed ratio of 10:1 mL/g, which achieved a composite score of 85.1. The methodological analysis of the LC-MS/MS methodology demonstrated that the precision, repeatability, and sample recovery all proved effective, and the linear relationship was good within the range of the four constituents. The optimized Sanzi Yangqin Decoction fatty oil extraction process is reasonable and feasible. And the LC-MS/MS content determination method is simple, rapid, sensitive, and specific. This work introduces an innovative approach to examining the fatty oils in Sanzi Yangqin Decoction.

CAS / MDL: 541-15-1
研究领域: 中医药 · 药理学 · 分析化学 · 呼吸系统疾病 · 工艺优化 · 质谱分析
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