JOURNAL OF ETHNOPHARMACOLOGY
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2025
·
IF 5.4
Zhen-yan Song,Wen-jing Yu,Yi-jie Jin,Meng-fen Zhou,Chun-xiang He,Ze Li,Jia-wei He,Qi Chen,Ping Li,Yaqiao Yi,Shao-wu Cheng
Ethnopharmacological relevance Derived from the plant Scutellaria baicalensis Georgi, baicalin is a naturally occurring flavonoid, has demonstrated anti-inflammatory, neuroprotective, hypoglycemic, and lipid-lowering properties. While its effects on Alzheimer's disease (AD) or type 2 diabetes mellitus (T2DM) have been studied individually, its therapeutic role in AD comorbid with T2DM remains unclear. Aim of the study This study aims to explore the potential therapeutic mechanisms associated with baicalin through a rat model featuring AD combined with T2DM. Materials and methods A dual-pathology rat model was developed using a streptozotocin (STZ) and a high-fat dietary regimen injections to induce T2DM, followed by intracerebroventricular STZ to induce AD pathology. Behavioral tests, biochemical assays, histological analyses, qPCR, and Western blotting were used to evaluate baicalin's effects. Untargeted metabolomics was applied to profile metabolic alterations, while network pharmacology and molecular docking were integrated to predict key targets and pathways. Finally, cellular thermal shift assay (CETSA) was conducted to validate the direct binding of baicalin to core proteins. Results Baicalin significantly improved cognitive performance, ameliorated glucose and lipid metabolism, and suppressed neuroinflammation in AD-T2DM rats. Metabolomics identified disruptions in energy metabolism, amino acid metabolism, and purine metabolism pathways. Network pharmacology analysis revealed ALDH2, NOS2, GOT1, GPT, and XDH as key targets associated with these metabolic disturbances. Molecular docking demonstrated strong binding affinities between baicalin and the identified targets. qPCR confirmed the regulation of ALDH2 and NOS2 gene expression by baicalin, and CETSA experiments further validated the thermal stabilization of these proteins, supporting direct interactions in vivo. Conclusions Baicalin exerts therapeutic effects by targeting ALDH2 and NOS2 to modulate arginine and proline metabolism and regulate key metabolites such as GABA and L-arginine. This mechanism improves neuronal function and insulin sensitivity, highlighting baicalin as a promising multi-target treatment for AD with T2DM.
研究领域:
药理学
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神经科学
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内分泌学
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代谢组学
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民族药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Integrative Neuroscience
·
2024
·Vol. 23
·期 1
·6
·
IF 2.5
Dongxia Duan,Xiaojin Wu,Usman Ali,Di Wang,Xue Li,Ruimei Liu,Le Ma,Yemeng Mao,Yan Ma
Background: Metformin has been shown to have potent analgesic effects; however, the underlying mechanism of synaptic plasticity mediating analgesia remained ambiguous. Methods: In this study, animal behavioral tests, whole-cell patch‑clamp recording, immunofluorescence staining, and network pharmacology techniques were applied to elucidate the mechanisms and potential targets of metformin-induced analgesia. Results: Single or consecutive injections of metformin significantly inhibited spinal nerve ligation (SNL)-induced neuropathic pain, and formalin-induced acute inflammatory pain. Network pharmacology analysis of metformin action targets in pain database-related targets revealed 25 targets, including five hub targets (nitric oxide synthase 1 (NOS1), NOS2, NOS3, epidermal growth factor receptor (EGFR), and plasminogen (PLG)). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that metformin-induced analgesia was markedly correlated with calcium signaling and synaptic transmission. Intrathecal injection of metformin significantly reversed nerve injury-induced c-Fos (neural activity biomarker) mRNA and protein expression in neuropathic rats by regulating NOS2 expression. In addition, whole-cell recordings of isolated spinal neurons demonstrated that metformin dose-dependently inhibited the enhanced frequency and amplitude of miniature excitatory synaptic currents (mEPSCs) but did not affect those of miniature inhibitory synaptic currents (mIPSCs) in neuropathic pain. Conclusions: This study further demonstrated that metformin might inhibit spinal glutamatergic transmission and abnormal nociceptive circuit transduction by monitoring synaptic transmission in pain. Results of this work provide an in-depth understanding of metformin analgesia via synaptic plasticity.
研究领域:
药理学
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神经科学
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疼痛研究
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突触生理学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Guangyu Xu,Xi Lv,Yanbo Feng,Han Li,Cong Chen,Hao Lin,He Li,Chunmei Wang,Jianguang Chen,Jinghui Sun
The aim of this study was to analyze the active components of Schisandra chinensis on liver injury and its mechanism in mice by network pharmacology . The active components of S. chinensis were found through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and their corresponding targets were predicted. The targets of liver injury were searched through Therapeutic Targets Database (TTD), DisGeNET and drugbank databases, and the Venn diagram was constructed to obtain the action targets. The “drug-active component-target” network and protein-protein interaction network (PPI) were constructed by using STRING database and Cytoscape software, and the key targets were further screened by the enrichment analysis of relevant KEGG pathways. Finally, a CCl 4 -induced mouse liver injury model was established to verify the efficacy and related targets of S. chinensis and clarify its mechanism. Eight active components and 56 related targets of S. chinensis were screened out based on their oral bioavailability (OB) and drug likeness (DL). Five targets of S. chinensis related to liver injury were found by using the Venn diagram. The key targets, namely Ptgs2 and Nos2 genes, were further screened out by constructing a PPI network, and Schisandrol B (SCB) was considered the key component most closely related to the liver injury in S. chinensis . The results indicate that SCB may play a role in the treatment of the CCl 4 -induced liver injury by down-regulating the expression of iNOS and COX-2, and regulating the expression of NF-κB and IL-17 signaling pathway to inhibit the expression of proinflammatory factors.
研究领域:
药理学
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分子生物学
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网络药理学
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肝脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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