Wang Yayun, Wu Dongming, Wang Yongxin, Sun Jingwen, Wang Xiaona, Huang Yanqin, Sun Mingliang
Department of Neurology, Qingdao Traditional Chinese Medicine Hospital (Qingdao Hiser Hospital) Qingdao Hiser Hospital Affiliated of Qingdao University, Qingdao, Shandong, China.
Department of Geriatric Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Front Mol Biosci. 2024 May 23;11:1339973. doi: 10.3389/fmolb.2024.1339973. eCollection 2024.
In recent years, the incidence of insulin resistance is increasing, and it can cause a variety of Metabolic syndrome. Ginsenosides have been clinically proven to improve fat metabolism and reduce insulin resistance, but their components and mechanism of action are still unclear.
Ginsenoside, a bioactive compound derived from ginseng, exhibits significant potential in treating obesity, diabetes, and metabolic disorders. Despite evidence supporting its efficacy in ameliorating insulin resistance (IR) in obesity, the specific bioactive components and underlying mechanisms remain obscure. In this study, we endeavored to elucidate the potential molecular targets and pathways influenced by ginsenoside Rh3 (GRh3) to ameliorate IR in liver tissue. We employed a comprehensive approach that integrates system pharmacology and bioinformatics analysis.
Our methodology involved the identification of candidate targets for GRh3 and the profiling of differentially expressed genes (DEGs) related to IR in individuals with insulin resistance. The coalescence of candidate targets and DEGs facilitated the construction of a "GRh3-targets-disease" network for each tissue type, ultimately yielding 38 shared target genes. Subsequently, we conducted pathway enrichment analysis, established protein-protein interaction (PPI) networks, and identified hub targets among the GRh3 targets and IR-related DEGs. Additionally, we conducted animal experiments to corroborate the role of these hub targets in the context of GRh3.
Our investigation identified a total of 38 overlapping targets as potential candidates. Notably, our analysis revealed crucial hub targets such as EGFR, SRC, ESR1, MAPK1, and CASP3, alongside implicated signaling pathways, including those related to insulin resistance, the FoxO signaling pathway, the PPAR signaling pathway, and the IL-17 signaling pathway. This study establishes a robust foundation for the mechanisms underlying GRh3's efficacy in mitigating IR. Furthermore, these results suggest that GRh3 may serve as a representative compound within the ginsenoside family.
This study elucidates the potential molecular targets and associated pathways through which GRh3 ameliorates IR, showcasing its multifaceted nature, spanning multiple targets, pathways, and mechanisms. These findings establish a robust foundation for subsequent experimental inquiries and clinical applications.
近年来，胰岛素抵抗的发生率不断上升，它可引发多种代谢综合征。人参皂苷已在临床上被证明能改善脂肪代谢并降低胰岛素抵抗，但其成分及作用机制仍不明确。
人参皂苷是从人参中提取的一种生物活性化合物，在治疗肥胖、糖尿病及代谢紊乱方面具有显著潜力。尽管有证据支持其在改善肥胖症患者胰岛素抵抗（IR）方面的疗效，但其具体生物活性成分及潜在机制仍不清楚。在本研究中，我们致力于阐明人参皂苷Rh3（GRh3）改善肝脏组织中IR所影响的潜在分子靶点和通路。我们采用了系统药理学和生物信息学分析相结合的综合方法。
我们的方法包括确定GRh3的候选靶点以及分析胰岛素抵抗个体中与IR相关的差异表达基因（DEG）。候选靶点与DEG的合并有助于构建每种组织类型的“GRh3-靶点-疾病”网络，最终产生38个共享靶基因。随后，我们进行了通路富集分析，建立了蛋白质-蛋白质相互作用（PPI）网络，并在GRh3靶点和IR相关DEG中确定了核心靶点。此外，我们进行了动物实验以证实这些核心靶点在GRh3背景下的作用。
我们的研究共确定了38个重叠靶点作为潜在候选靶点。值得注意的是，我们的分析揭示了关键的核心靶点，如表皮生长因子受体（EGFR）、原癌基因酪氨酸蛋白激酶（SRC）、雌激素受体1（ESR1）、丝裂原活化蛋白激酶1（MAPK1）和半胱天冬酶3（CASP3），以及与之相关的信号通路，包括与胰岛素抵抗、叉头框蛋白O（FoxO）信号通路、过氧化物酶体增殖物激活受体（PPAR）信号通路和白细胞介素-17（IL-17）信号通路相关的信号通路。本研究为GRh3减轻IR疗效的机制奠定了坚实基础。此外，这些结果表明GRh3可能为人参皂苷家族中的代表性化合物。
本研究阐明了GRh3改善IR的潜在分子靶点及相关通路，展示了其多方面的性质，涉及多个靶点、通路和机制。这些发现为后续实验研究和临床应用奠定了坚实基础。
