Ling-Gui-Zhu-Gan Decoction Ameliorates Heart Failure via Modulating Energy Metabolism and Lipid Homeostasis: Insights from Transcriptomics and Lipidomics
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PROVIDER: PRJNA1306500 | ENA |
REPOSITORIES: ENA
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Project description:Background: Heart failure (HF) remains a global health challenge with limited therapeutic options. Ling-Gui-Zhu-Gan Decoction (LGZGD), a traditional Chinese medicine formula, has shown clinical efficacy in HF treatment, yet its molecular mechanisms remain unclear. Methods: This study investigated LGZGD's cardioprotective effects and underlying mechanisms using a doxorubicin-induced HF mouse model. Mice were divided into blank (KB), model (M), trimetazidine (QM), and LGZGD (LG) groups. Cardiac function was assessed via echocardiography, while myocardial injury and fibrosis were evaluated through histopathology. Transcriptomics and lipidomics analyses were performed to identify molecular pathways. Results: LGZGD significantly improved ejection fraction (EF) and fractional shortening (FS), alleviated myocardial vacuolization, and reduced fibrosis, outperforming trimetazidine. Transcriptomics revealed LGZGD modulated oxidative phosphorylation and ATP synthase activity, restoring energy metabolism. Lipidomics highlighted its regulation of glycerophospholipid metabolism, particularly phosphatidylethanolamine (PE) and phosphatidylcholine (PC), linked to anti-inflammatory and lipid homeostasis effects. Conclusion: Integrated omics data suggested LGZGD ameliorates HF by enhancing mitochondrial function, mitigating oxidative stress, and balancing lipid metabolism. These findings provide mechanistic insights into LGZGD's therapeutic benefits, supporting its potential as a multi-targeted intervention for HF through energy and lipid metabolic regulation.
2025-08-20 | GSE305559 | GEO
Project description:Gan mice express Wnt1, Ptgs2, and Ptges, which develop inflammation-associated gastric tumors (Oshima et al, Gastroenterology 131: 1086, 2006). We examined the role of TNF-alpha in tumorigenesis by construction of TNF-/- Gan mice. We also examined genetic background difference in tumor phenotype by changing Gan mouse background from C57BL/6(B6) to BALB/c. Microarray analyses were performed to examine changes of expression profiles in tumors by TNF gene disruption or by changing genetic background. Total RNA was prepared from B6 Gan mice (n=3: Gan1-Gan3), B6-Gan TNF-/- mice (n=3: Gan(TNF KO)1-Gan(TNF KO)3), BALB-Gan mice (n=3: Gan(BALB/c)1-Gan(BALB/c)3), and wid-type normal glandular stomach (n=3: WT1-WT3). We used Affymetrix microarrays for hybridization, and examined expression profiles.
2012-12-27 | E-GEOD-43145 | biostudies-arrayexpress
Project description:To develop a syngeneic mouse model of metastatic gastric cancer, we established the tumor organoids from gastric tumor arising in GAstric Neoplasia (GAN) mice (GAN-WT) which express Wnt1 and the PGE2 synthesis enzymes COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) in the stomach epithelium. Furthemore, GAN-WT organoids were genetically manupilated into p53 knockout organoids (GAN-p53KO) and KrasG12V-expressing GAN-p53KO organoids (GAN-KP).
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Project description:Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and improved viral infection-induced mouse weight loss but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction both dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection. Screening and profiling of known plant microRNA in HS and HS decoction
2014-10-22 | E-GEOD-55268 | biostudies-arrayexpress
Project description:Gan mice express Wnt1, Ptgs2, and Ptges, which develop inflammation-associated gastric tumors (Oshima et al, Gastroenterology 131: 1086, 2006). We examined the role of TNF-alpha in tumorigenesis by construction of TNF-/- Gan mice. We also examined genetic background difference in tumor phenotype by changing Gan mouse background from C57BL/6(B6) to BALB/c. Microarray analyses were performed to examine changes of expression profiles in tumors by TNF gene disruption or by changing genetic background.
2012-12-27 | GSE43145 | GEO
Project description:We have now developed an organoid-based model of gastric cancer from GAstric Neoplasia (GAN) mice, which express Wnt1 and the enzymes COX2 and microsomal prostaglandin E synthase 1 in the stomach. Both p53 knockout (GAN-p53KO) organoids and KRASG12V-expressing GAN-p53KO (GAN-KP) organoids were generated by genetic manipulation of GAN mouse–derived tumor (GAN-WT) organoids. To uncover the molecular mechanism underlying the intratumoral heterogeneity of GAN-KP tumors, we performed spatial transcriptomics analysis with the 10× Genomics Visium platform, which allows characterization of the spatial topography of gene expression.
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Project description:Gene expression analysis of three tumor organoids (GAN-WT, GAN-p53 and GAN-KP) derived from gastric tumor in K19-Wnt1/C2mE (GAN) mouse.
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Project description:Chaihu-Shugan-San (CSS) is a classical prescription used to treat depression. According to the traditional Chinese medicine (TCM) principle, the 2 decomposed recipes in CSS exert synergistic effects, including Shu Gan (stagnated Gan-Qi dispersion) and Rou Gan (pain alleviation). However, the specific mechanism and compatibility rule remain to be explored. We aimed to analyze the advantage of TCM compatibility in CSS prescriptions and explore its anti-depression mechanisms.
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Project description:We aimed to investigate the syndrome of Sini decoction pattern. The Sini decoction was first mentioned in Shang Han Za Bing Lun, then was developed into Sini decoction pattern (SDP) by Sun Simiao’s Qian Jin Yi Fang. The syndromes of SDP were correlated with various extremely Yang deficiency related symptoms, but there does not exist common definition.
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Project description:Influenza A viruses (IAVs), particularly H1N1, H5N1 and H7N9, pose a substantial threat to public health worldwide. Here, we report that MIR2911, a honeysuckle (HS)-encoded atypical microRNA, directly targets IAVs with a broad spectrum. MIR2911 is highly stable in HS decoction, and continuous drinking or gavage feeding of HS decoction leads to a significant elevation of the MIR2911 level in mouse peripheral blood and lung. Bioinformatics prediction and a luciferase reporter assay showed that MIR2911 could target various IAVs, including H1N1, H5N1 and H7N9. Synthetic MIR2911 significantly inhibited H1N1-encoded PB2 and NS1 protein expression but did not affect mutants in which the MIR2911-binding nucleotide sequences were altered. Synthetic MIR2911, extracted RNA from HS decoction and HS decoction all significantly inhibited H1N1 viral replication and improved viral infection-induced mouse weight loss but did not affect infection with a mutant virus in which the MIR2911-binding nucleotide sequences of PB2 and NS1 were altered. Importantly, the inhibitory effect of HS decoction on viral replication was abolished by an anti-MIR2911 antagomir, indicating that the physiological concentration of MIR2911 in HS decoction could directly and sufficiently suppress H1N1 viral replication. MIR2911 also inhibited H5N1 and H7N9 viral replication in vitro and in vivo. Strikingly, administration of MIR2911 or HS decoction both dramatically reduced mouse mortality caused by H5N1 infection. Our results demonstrate that MIR2911 is the first active component identified in Traditional Chinese Medicine to directly target various IAVs and may represent a novel type of natural product that effectively suppresses viral infection.
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