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Huang Lian Jiedu Decoction ameliorates lipid metabolic disorders in obese mice by modulating gastric inhibitory polypeptide release via intestinal microbiota regulation

ABSTRACT: Obesity is a chronic metabolic disorder that increases the risk of various metabolic diseases, such as type 2 diabetes and metabolic dysfunction-associated steatohepatitis (MASH). While previous studies have shown that Huang Lian Jiedu Decoction (HLJDD) can alters gut microbiota to improve glycolipid metabolism and obesity, the underlying mechanisms still need to be clarified. The present study aimed to explore the potential mechanisms of HLJDD in suppressing obesity more deeply through an integrated research strategy.

ORGANISM(S): Mus musculus

PROVIDER: GSE285884 | GEO | 2026/01/15

REPOSITORIES: GEO

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Project description:Introduction: Huang-Lian-Jie-Du Decoction (HLJDD), a botanical drug used in traditional medicine, has been used in the management of Alzheimer’s disease (AD). However, the mechanisms underlying its preventive effects remain inadequately understood, particularly due to the absence of metabolomic studies examining alterations in serum and cerebrospinal fluid (CSF) metabolites. Moreover, the potential toxicities and side effects of HLJDD necessitate further pharmacological investigation. This study aims to explore the differential effects of HLJDD on AD model rats and healthy controls through a metabolomics approach and uncover the underlying mechanisms based on changes in serum and CSF metabolites. The findings are expected to provide a scientific foundation for enhancing the clinical safety and rational use of HLJDD.Methods: The composition of HLJDD was characterized by UPLC-Q-Exactive Orbitrap HRMS. Aβ1-42-induced SD rats served as the AD animal model. Rats in the sham + HLJDD and Aβ1-42 + HLJDD groups (0.604 g/kg freeze-dried powder) were treated with HLJDD via gavage for 28 days. Nissl staining was performed to assess hippocampal neuronal changes, while H&E staining was used to evaluate histopathological alterations in the brain, liver, kidneys, stomach, large intestine, and small intestine. Aβ expression was determined using IHC and ELISA, and inflammatory levels in both peripheral and central systems were quantified by ELISA. MMP-2 and MMP-9 expression were analyzed through IHC. LC-MS was employed to investigate metabolic variations in serum and CSF.Results: HLJDD reduced Aβ deposition in Alzheimer's disease rats, enhanced neuronal survival, reduced inflammation, preserved blood-brain barrier (BBB) integrity, and alleviated damage to the brain, kidneys, and stomach. These therapeutic effects were associated with the arginine biosynthesis pathway and ferroptosis. In contrast, HLJDD induced peripheral and central inflammation, impaired neuronal function, compromised BBB integrity, and caused damage to the liver, kidneys, and large intestine in normal rats. These adverse effects were linked to disruptions in aminobenzoate degradation and nucleotide metabolism.Conclusion: HLJDD may alleviate Aβ-induced damage repair in Alzheimer’s disease rats, but it also induces varying degrees of toxicity in normal rats.

Project description:Trichophyton mentagrophytes (T. mentagrophytes) is a prevalent pathogen that causes human and animal dermatophytosis. The clinical treatment of these infections is challenging due to the prolonged treatment duration, limited efficacy, antifungal resistance and side effects of existing drugs. It has been reported that the classic Traditional Chinese medicine (TCM) prescription Huangqin decoction (HQD) along with its principal ingredients could exhibit antifungal properties. Given the valued advantages of TCM such as broad-spectrum antifungal activity, low incidence of drug resistance and low toxicity, this study investigated the antifungal activity of HQD against T. mentagrophytes and explored the potential inhibitory mechanism, aimed to provide new clues for the treatment of dermatophytosis. By detecting minimal inhibitory concentration (MIC) using the broth microdilution method, the result showed that HQD could significantly inhibit the growth of T. mentagrophytes, with a MIC of 3.13 mg/mL. The transcriptome sequencing and quantitative real-time PCR (qRT-PCR) technology were combined to shed light on the complicated adaptive responses of T. mentagrophytes upon HQD. The results demonstrated that a total of 730 differentially expressed genes (DEGs) were detected in T. mentagrophytes after HQD exposure, of which 547 were up-regulated and 183 were down-regulated. These DEGs were abundant in “single-organism metabolic process”, “catalytic activity” and “oxidoreductase activity”, and were significantly enriched in seven signaling pathways including glutathione metabolism, DNA replication, glyoxylate and dicarboxylate metabolism, taurine and hypotaurine metabolism, carotenoid biosynthesis, ubiquitin mediated proteolysis, and cyanoamino acid metabolism. The results of transcriptome profiling were verified using qRT-PCR for a subset of 10 DEGs. The overall evidence indicated that HQD had a significant anti-dermatophyte activity through the modulation of glutathione metabolism by regulating GST, γ-GT genes, the inhibition of DNA replication pathway by downgrading MCM3, MCM5, RNaseH1 genes, and the repressed expression of PSD gene related to phospholipid synthesis in T. mentagrophytes.

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Huang Lian Jiedu Decoction ameliorates lipid metabolic disorders in obese mice by modulating gastric inhibitory polypeptide release via intestinal microbiota regulation

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