Dataset Information

Transcriptomic Analysis of Fuzi Lizhong Decoction for the Treatment of Stomach Ulcers.

ABSTRACT: This study aims to understand the treatment of stomach ulcers with FLD and to identify its potential target genes as well as related pathways by transcriptomic analysis. Rat stomach mRNA from a blank group (BG), a model group (MG), an untreated-model group (u-MG), and a treated group (TG) was sequenced. A partial least-squares discriminant analysis (PLS-DA) was used to differentiate the MG from the BG, and the Deseq2 R Package was used to identify differentially expressed genes between these groups. Furthermore, t-tests based on transcripts per million (TPM) were used to select different genes between MG and BG and significantly retrieved genes in TG, except for self-retrieved genes in u-MG. Finally, pathways regulated by retrieved genes were analyzed with KEGG database. Results showed that 327 of the 32,623 total detected genes were different (p < 0.05) between the MG and BG. Among these genes, eighteen genes were significantly retrieved after rats were treated with FLD in TG, and they were considered as target genes on which FLD acted. In conclusion, FLD was deduced to cure stomach ulcers by affecting glycerolipid metabolism, fatty acid degradation, circadian entrainment, circadian rhythm, and dopaminergic synapse.

SUBMITTER: Xin Y

PROVIDER: S-EPMC7054793 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Transcriptomic Analysis of Fuzi Lizhong Decoction for the Treatment of Stomach Ulcers.

Xin Yang Y Wang Haijun H Xu Lei L

Evidence-based complementary and alternative medicine : eCAM 20200221

This study aims to understand the treatment of stomach ulcers with FLD and to identify its potential target genes as well as related pathways by transcriptomic analysis. Rat stomach mRNA from a blank group (BG), a model group (MG), an untreated-model group (u-MG), and a treated group (TG) was sequenced. A partial least-squares discriminant analysis (PLS-DA) was used to differentiate the MG from the BG, and the Deseq2 R Package was used to identify differentially expressed genes between these gro ...[more]

PMID: 32148538

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Project description:ObjectiveThis study aimed to decipher the bioactive compounds and potential mechanism of traditional Chinese medicine (TCM) formula Fuzi Lizhong Decoction (FLD) for nonalcoholic fatty liver disease (NAFLD) treatment via an integrative network pharmacology approach.MethodsThe candidate compounds of FLD and its relative targets were obtained from the TCMSP and PharmMapper web server, and the intersection genes for NAFLD were discerned using OMIM, GeneCards, and DisGeNET. Then, the PPI and component-target-pathway networks were constructed. Moreover, GO enrichment and KEGG pathway analysis were performed to investigate the potential signaling pathways associated with FLD's effect on NAFLD. Eventually, molecular docking simulation was carried out to validate the binding affinity between potential core components and key targets.ResultsA total of 143 candidate active compounds and 129 relative drug targets were obtained, in which 61 targets were overlapped with NAFLD. The PPI network analysis identified ALB, MAPK1, CASP3, MARK8, and AR as key targets, mainly focusing on cellular response to organic cyclic compound, steroid metabolic process, and response to steroid hormone in the biological processes. The KEGG pathway analysis demonstrated that 16 signaling pathways were closely correlated with FLD's effect on NALFD with cancer pathways, Th17 cell differentiation, and IL-17 signaling pathways as the most significant ones. In addition, the molecular docking analysis revealed that the core active compounds of FLD, such as 3'-methoxyglabridin, chrysanthemaxanthin, and Gancaonin H, had a high binding activity with such key targets as ALB, MAPK1, and CASP3.ConclusionsThis study suggested that FLD exerted its effect on NAFLD via modulating multitargets with multicompounds through multipathways. It also demonstrated that the network pharmacology-based approach might provide insights for understanding the interrelationship between complex diseases and interventions of the TCM formula.

Project description:BackgroundFuzi-Lizhong pill (FZLZP), which was first recorded in the Classic-"Taiping Huimin Heji Ju Fang" of the Song Dynasty, has been widely used to treat gastrointestinal disease in clinic for thousands of years in China. However, an in-depth understanding of the chemical constituents of FZLZP and its potential bioactive constituents is lacking.MethodsA simple, sensitive and selective method of high-performance liquid chromatography coupled with quadrupole-time-of-flight high-definition mass spectrometry (HPLC-Q-TOF/MS) and automated data analysis (Agilent MassHunter Qualitative Analysis B.06.00 Workstation Software) was developed to simultaneously identify the chemical constituents of FZLZP and the absorbed prototypes as well as the metabolites in rat serum after the oral administration of FZLZP.ResultsSixty-seven compounds, including alkaloids, flavonoids, triterpenes, gingerols, phenylpropanoids and volatile oil, in the FZLZP extract were tentatively characterized by comparing the retention time and mass spectrometry data and retrieving the reference literatures. Additionally, 23 prototype compounds and 3 metabolites in the rat serum samples were identified after oral administration of FZLZP, which might be the potential active components in vivo. In addition, the absorption of alkaloids decreased when Aconitum carmichaeli Debx. was in the form of combined application as a prescription compared to when it was in the form of herb powder.ConclusionsHerein, the chemical constituent in vitro and the absorbed compounds in the serum of a traditional Chinese formula, Fuzi-Lizhong pill, were fully characterized using a rapid and comprehensive analysis approach based on high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry coupled to MassHunter Qualitative Analysis software data processing approach. The results provide helpful chemical information on FZLZP for further pharmacology and active mechanism research. In view of the bioactive constitutes that basically were derived from these absorbed compounds in vivo, this work could provide a useful strategy to explore the bioactive substances of traditional Chinese medicine.

Project description:BackgroundFuzi decoction (FZD), a traditional Chinese medicine formula, was used to treat musculoskeletal diseases by warming channels, strengthening yang and dispelling pathogenic cold and dampness. In clinical practice, FZD has been used to treat rheumatoid arthritis and osteoarthritis. It alleviated osteoarticular disorders through ameliorating the degradation of cartilage and improving meniscal damage in osteoarthritis, while its roles and mechanisms in the treatment of bone loss diseases remain unclear. This study aims to investigate the underlying mechanisms of FZD in treating osteoporosis using an integrative method of network pharmacology and experimental study.MethodsIn this study, network pharmacology was used to predict the core targets and potential pathways of the bioactive ingredients of FZD to attenuate osteoporosis. Molecular docking was performed to evaluate the interactions between core compounds and key targets. In addition, both cell and animal experiments were carried out to validate the role and potential mechanism in treating osteoporosis.ResultsIn the present study, data revealed that kaempferol, beta-sitosterol, stigmasterol, fumarine, and (+)-catechin may be the primary bioactive ingredients of FZD in the treatment of osteoporosis, which were closely associated with the osteoporosis-related targets. And the KEGG results indicated that the NF-κB pathway was closely associated with the function of FZD in treating osteoporosis. In addition, in vivo demonstrated that FZD ameliorated osteoporosis. In vitro experiments showed that the pro-apoptotic factors indicators including CASP3 and BAX were decreased by FZD and the anti-apoptotic factor BCL2 was increased by FZD. In addition, FZD significantly suppressed the osteoclast differentiation in culture and the expression levels of osteoclast-related genes including TRAF6, CTSK, and MMP9. And the NF-κB pathway was confirmed, via in vitro experiment, to be involved in osteoclast differentiation.ConclusionsThis study demonstrated that FZD played a pivotal role in suppressing the osteoclast differentiation via regulating the NF-κB pathway, indicating that FZD could be a promising antiosteoporosis drug and deserve further investigation.

Project description:Shaogan Fuzi Decoction (SGFD), one of the classical prescriptions of Chinese Medicine, has a long history in the treatment of rheumatoid arthritis (RA), but definitive studies on its efficacy and mechanism of action are lacking. This study aims to elucidate the pharmacodynamic role of SGFD against RA and the potential mechanisms based on a combination of network pharmacology and experimental verification. The RA model in rats was induced by intradermal injection of bovine type Ⅱ collagen and incomplete Freund's adjuvant at the tail root. SGFD was administered once a day by oral gavage for 4 weeks. After SGFD administration, rat's arthritis index (AI) score and paw swelling decreased to some extent, and synovial inflammation, vascular hyperplasia, and cartilage destruction of the ankle joint were improved. Simultaneously, thymus and spleen index and serum levels of C-reactive protein (CRP) were lowered. Network pharmacology revealed that quercetin, kaempferol, naringenin, formononetin isorhamnetin and licochalcone A were the potentialiy active components, and IL6, TP53, TNF, PTGS2, MAPK3 and IL-1β were potential key targets for SGFD in the treatment of RA. Ingredients-targets molecular docking showed that the components had the high binding activity to these target proteins. The mechanism of SGFD for RA involves various biological functions and is closely correlated with TNF signaling pathway, Osteoclast differentiation, T cell receptor signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, NF-κB signaling pathway, toll-like receptor signaling pathway, and so on. Western blot and ELISA showed that the expression of toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB) p65, phosphorylated c-Jun N-terminal kinase (p-JNK), p-p38, phosphorylated extracellular regulated kinase (p-ERK) and TNF-α was significantly upregulated in the synovium of RA rats, and the levels of serum inflammatory factors were significantly increased. SGFD inhibits the activation of the TLR4/NF-κB/MAPK pathway and the expression/production of pro-inflammatory cytokines. In summary, SGFD could improve the symptoms and inflammatory response in collagen-induced arthritis (CIA) rat model. The mechanism might be related to the regulation of TLR4/MAPKs/NF-κB signaling pathway and the reduction of inflammatory factor release, which partially confirms the results predicted by network pharmacology.

Project description:Neuropathic pain (NeP) is a condition charactesized by nervous system injury or dysfunction that affects a significant portion of the population. Current treatments are ineffective, highlighting the need for novel therapeutic approaches. Mahuang Fuzi Xixin decoction (MFXD) has shown promise for treating pain conditions in clinical practice; however, its potential against NeP and the underlying mechanisms remain unclear. This study identified 35 compounds in MFXD using ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). The analgesic effects of MFXD on chronic constriction injury (CCI) rats were evaluated through the detection of mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The analgesic effects of MFXD in rats with chronic constriction injury (CCI) were evaluated by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Low-dose MFXD (L-MFXD) group (4.8 g/kg) and high-dose MFXD (H-MFXD) group (9.6 g/kg) exhibited significantly higher MWT and TWL values than the CCI group on days 11 and 15 post-CCI surgery, substantiating the remarkable analgesic efficacy of MFXD. Network pharmacology analysis identified 58 key targets enriched in pathways such as long-term potentiation (LTP) and glutamatergic synapse. The MCODE algorithm further identified core targets with significant enrichment in LTP. Molecular docking revealed that mesaconitine, rosmarinic acid, and delgrandine from MFXD exhibited high binding affinity with NMDAR2B (-11 kcal/mol), CaMKIIα (-14.3 kcal/mol), and ERK (-10.8 kcal/mol). Western blot and immunofluorescence confirmed that H-MFXD significantly suppressed the phosphorylation levels of NMDAR2B, CaMKIIα, ERK, and CREB in the spinal cord tissue of CCI rats. In conclusion, this study demonstrates that MFXD possesses potent analgesic effects on NeP by suppressing the NMDAR2B/CaMKIIα/ERK/CREB signalling pathway. This study unlocks a path toward potentially revolutionising NeP treatment with MFXD, encouraging further research and clinical development.

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Transcriptomic Analysis of Fuzi Lizhong Decoction for the Treatment of Stomach Ulcers.

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Transcriptomic Analysis of Fuzi Lizhong Decoction for the Treatment of Stomach Ulcers.

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