Acute pancreatitis (AP) is a common acute abdominal condition in clinical practice, associated with high morbidity and mortality rates. Forsythia constitutes a component of traditional Chinese medicinal decoctions used for clinical AP treatment; however, the efficacy of its active monomer in treating AP has yet to be completely substantiated. Here, we engineered an AP cell and mouse model by administering a combination of caerulein and LPS. In vitro experiments utilizing AR42J cells demonstrated that forsythoside B (FST·B) was the most effective monomer in mitigating cellular inflammation. Subsequently, a comprehensive evaluation of FST·B concentrations and efficacy was performed in animal models. Next Mass spectrometry analysis of pancreatic from AP mice treated with 50 mg/kg FST·B was conducted to elucidate its primary regulatory molecular signaling and key targets. FST·B effectively mitigated pathological damage in mice with acute pancreatitis, leading to a reduction in the expression of inflammatory cytokines in both pancreatic tissue and serum. Proteomics and phosphoproteomic profiles revealed that FST·B significantly enhanced the level of oxidative phosphorylation and spliceosome pathway in the AP mice. This research provides initial evidence of the regulatory molecular signals and targets of FST·B in AP, laying a potential foundation for its clinical use in treating AP. SIGNIFICANCE: Acute pancreatitis (AP) is a common acute abdominal condition in clinical practice, associated with high morbidity and mortality rates, and the global incidence of AP has increased by approximately 25 % over the past 15 years. Despite the complexity of AP's causes and the high susceptibility of proteins to degradation during lesions, systems biology studies, such as proteomics, have been limited in investigating the molecular mechanisms involved in its pharmacological treatment. Forsythoside B, a phenylethanol glycoside isolated from the air-dried fruit of forsythia, is a traditional oriental anti-inflammatory drug commonly used in clinical practice. We demonstrated in the AP mouse model that forsythoside B can alleviate pancreatic inflammatory damage in vivo. To elucidate the molecular mechanisms underlying the anti-inflammatory effect of forsythoside B, a comprehensive proteomic and phosphoproteomic analysis was conducted on AP mice models prior to and subsequent to forsythoside B intervention. Finally, 1640 significantly differentially expressed proteins, 1448 significantly differentially expressed phosphoproteins corresponding to 2496 significantly differentially expressed phosphosites were identified. Functional analysis revealed that forsythoside B significantly enhanced the level of oxidative phosphorylation in the AP mice in proteomic profiles, and the spliceosome pathway at the phosphorylation level was significantly affected by forsythoside B. This research provides initial evidence of the regulatory molecular signals and targets of forsythoside B in AP, laying a potential foundation for its clinical use in treating AP.

01 Feb 2025·Food Chemistry

Metabolomics combined with biochemical analyses revealed phenolic profiles and antioxidant properties of rapeseeds

Article

Author: Yuan, Yongjun ; Chen, Hong ; Zhang, Yao ; Lv, Xin ; Wei, Fang ; Wang, Dan ; Zheng, Chang

Phenolic compounds, one of the most crucial lipid concomitants in rapeseed, have garnered heighten attention due to their numerous health benefits. Therefore, efficiently characterizing the phenolic profile of rapeseed is paramount for discerning their potential bioactivities. This study employed untargeted metabolomics in conjunction with molecular networking to trace the phenolic composition across three rapeseed genotypes. A total of 117 phenolic compounds were identified in rapeseed by mass spectrometry under positive and negative ionization modes, including 36 flavonoids, 23 coumarins, 12 phenolic acids, 10 lignans, 4 stilbenes, 4 diarylheptanes, 1 tannin, and several other phenolic constituents. Biochemical analyses revealed that Brassica napus rapeseed typically exhibited the highest total phenolic content and total flavonoid content as well as the strongest antioxidant capacity among three rapeseed genotypes. Through correlation analysis, 17 potential antioxidant phenolic compounds were tentatively screened from rapeseed, supporting the development and utilization of natural antioxidants from rapeseed.

01 Jan 2025·Brain Research Bulletin

Forsythoside B ameliorates neuroinflammation via inhibiting NLRP3 inflammasome of glial cells in experimental autoimmune encephalomyelitis mice

Article

Author: Xiao, Qinqin ; Wang, Rong ; Wang, Yue ; Chen, Yongmin ; Li, Ge ; Chen, Rong ; Zhang, Da-Qi ; Lu, Jing

Neuroinflammation mediated by glial cells plays a crucial role in demyelination in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Forsythoside B (FTS·B), a natural phenylethanoid glycoside isolated from the dried fruits and leaves of Forsythia suspensa (Thunb.) Vahl, has been found to have antioxidant, anti-apoptotic, and anti-inflammatory properties. However, there is currently no report or research on the effectiveness of FTS·B treatment for EAE. The aim of this study was to investigate the neuroprotective properties of (FTS·B) on EAE and reveal its potential mechanisms. Myelin oligodendrocyte glycoprotein-induced EAE mice were randomly categorized into the control, EAE model, and FTS·B treatment groups. Behavioral testing, pathology, immunohistochemistry, immunofluorescence staining, and western blot analysis of spinal cord tissue were used to determine the effects and mechanisms of FTS·B on EAE in mice. We found that FTS·B treatment could significantly alleviate and reduce the clinical symptoms and morbidity of EAE, respectively. In addition, FTS·B administration reduced inflammatory response and demyelination by inhibiting glial cell activation in the spinal cord of EAE mice. Further experiments confirmed that FTS·B inhibited the formation of NLRP3 inflammasome in microglia and astrocytes, thereby suppressing neuroinflammation and GSDMD-mediated pyroptosis. Altogether, these results suggest that FTS·B treatment attenuates central neuroinflammation and pyroptosis by inhibiting NLRP3 inflammasome of glial cells in EAE mice.

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Indication	Highest Phase	Country/Location	Organization	Date
Mucocutaneous Lymph Node Syndrome	Preclinical	China	Shaanxi University of Traditional Chinese Medicine	01 Apr 2024

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