ACS Applied Bio Materials
·
2025
·
IF 4.7
Dong Fan,Zhongyu Wang,Xingyi Yuan,Shixue Luo,Runsi Zhan,Weiyu Hu,Huitong Chen,Weiwen Wang,Jing Liu,Zongming Wang,Xin Wang
Aims Nonfunctioning pituitary adenomas (NFPAs) are a common intracranial tumor in clinical practice, and currently available treatments for NFPA include surgical resection and radiotherapy. However, this is due to the relatively high risk of recurrence and persistent side effects of these therapies. As a local treatment, photodynamic therapy (PDT) shows promise in solid tumors through spatiotemporally controlled cytotoxicity. The aim of this study was to investigate the mechanism of action of photosensitizer Ru2 in NFPA. Materials and methods [Ru(tpy)(tpy-Br)] (PF6)2 was synthesized from Ru(tpy)Cl3, and further synthesized into Ru2. Cell viability of Light+Ru2 or Dark+Ru2 was assayed using the CCK-8 assay and live–dead cell staining. RNA-seq of Light+Ru2-treated PDFS cells yielded differentially expressed genes. The expression of PI3K/ATK/P53 was detected using qPCR, Western blot. PI3K agonist 740Y–P and AKT agonist SC79 were added for further pathway validation. The effect of PDT on PDFS cell viability by 3D multicellular tumor spheroids (MCTSs) was evaluated. Key findings We untangle that Ru2-PDT specifically activates the p53 pathway and inhibits PI3K/AKT phosphorylation in PDFS cells. Under 595 nm illumination, Ru2 activates p53 and induces cell cycle arrest in the G0/G1 phase. Simultaneously, Ru2-PDT significantly suppressed the phosphorylation of the PI3K/AKT signaling pathway. Further investigation reveals that the PI3K/AKT agonist treatment partially inhibits p53 expression, alleviates Ru2-PDT-induced apoptosis, and reverses its inhibitory effects on PDFS cell migration and invasion. Significance This study, for the first time, elucidates the molecular mechanism of Ru2-PDT targeting the PI3K/AKT/p53 signaling axis, providing a theoretical basis for the clinical treatment of nonfunctioning pituitary adenomas.
研究领域:
肿瘤学
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神经外科
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分子生物学
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药理学
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生物化学
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医学科学
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DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Chen Pan,Wu Hao,Yao Hongliang,Zhang Jiashuo,Fan Weiyang,Chen Zhen,Su Weiwei,Wang Yonggang,Li Peibo
Sleep disorders were associated with oral health. Inflammation has especially been thought to be a key factor in linking oral diseases and sleep deficiency. However, how chronic sleep deprivation (CSD) affects oral homeostasis, particularly oral inflammation and oral microbiota, is still unknown. This study aimed to uncover the systematic relationship between oral homeostasis and CSD in rats. The metabolomics in serum, proteomics in the tongue tissues, and microbiome analysis in the oral cavity in CSD rats were performed. Multi-omics data integration analysis was performed to uncover the systematic relationship between oral homeostasis and CSD through the weighted correlation network analysis. We found that CSD could lead to oral inflammation in rats. CSD significantly increased systemic inflammation by enhancing the serum levels of IL-1β, IL-6 and inhibiting the serum level of IL-10. Serum levels of adrenocorticotropin hormone, corticosterone, and triiodothyronine were increased in CSD rats, and the steroid hormone biosynthesis pathway was also found to be involved in the perturbation resulting from CSD, together suggesting the activation of the hypothalamic-pituitary-adrenocortical and hypothalamic‐pituitary‐thyroid axis. CSD led to changes of oral microbiota composition, and g_Acinetobacter, Candidatus Chryseobacterium massiliae, and g_Moraxella were significantly correlated with multiple proteins in bacterial invasion of epithelial cells pathway, which may partially responsible for oral inflammation resulting from CSD. The changes of proteomic profiling expression caused by CSD in tongue tissues were mainly enriched in neurodegenerative diseases pathways and immune/inflammation-related pathways. Multi-omics analysis indicated that the inflammatory response-related modules were significantly correlated with the neurodegenerative disease-related module suggesting a possible link between neurodegenerative diseases and oral inflammation. Together, CSD induced oral inflammation and subtle changes on oral microbiota. Our study is helpful to further understand the role that oral homeostasis plays in the process by which CSD affects human health and disease.
研究领域:
睡眠医学
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口腔健康
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免疫学
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微生物学
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系统生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
International Journal of Environmental Research and Public Health
·
2017
·Vol. 14
·期 1
·44
·
IF 2.101
Xinwen Dong,Jin Dong,Yue Zhao,Jipeng Guo,Zhanju Wang,Mingqi Liu,Yunbo Zhang,Xiaolin Na
Di-(2-ethylhexyl)phthalate (DEHP) was a widely used chemical with human toxicity. Recent in vivo and in vitro studies suggested that DEHP-exposure may be associated with altered serum thyroid hormones (THs) levels, but the underlying molecular mechanisms were largely unknown. To explore the possible molecular mechanisms, 128 Wistar rats were dosed with DEHP by gavage at 0, 150, 300, and 600 mg/kg/day for 3 months (M) and 6 M, respectively. After exposure, expression of genes and proteins in the thyroid, pituitary, and hypothalamus tissues of rats were analyzed by Q-PCR and western blot, while the sera and urine samples were assayed by radioimmunoassay and ELISA. Results showed that serum THs levels were suppressed by DEHP on the whole. DEHP treatment influenced the levels of rats’ thyrotropin releasing hormone receptor (TRHr), Deiodinases 1 (D1), thyroid stimulating hormone beta (TSHβ), sodium iodide symporter (NIS), thyroid stimulating hormone receptor (TSHr), thyroperoxidase (TPO), thyroid transcription factor 1 (TTF-1), and thyroglobulin (TG) mRNA/protein expression in the hypothalamus-pituitary-thyroid (HPT) axis and decreased urine iodine. Taken together, observed findings indicate that DEHP could reduce thyroid hormones via disturbing the HPT axis, and the activated TSH/TSHR pathway is required to regulate thyroid function via altering TRHr, TSHβ, NIS, TSHr, TPO, TTF-1 and TG mRNA/protein expression of the HPT axis.Keywords:DEHP;hypothalamus-pituitary-thyroid axis;TSH/TSHR;signaling pathways;molecular mechanisms;thyroid function
研究领域:
毒理学
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
PLoS One
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2016
·Vol. 11
·期 5
·e0155762
·
IF 3.057
Pan-Pan Jia,Yan-Bo Ma,Chun-Jiao Lu,Zakaria Mirza,Wei Zhang,Yong-Fang Jia,Wei-Guo Li,De-Sheng Pei
Di-(2-ethylhexyl) phthalate (DEHP) has the potential to disrupt the thyroid endocrine system, but the underlying mechanism is unknown. In this study, zebrafish ( Danio rerio ) embryos were exposed to different concentrations of DEHP (0, 40, 100, 200, 400 μg/L) from 2 to 168 hours post fertilization (hpf). Thyroid hormones (THs) levels and transcriptional profiling of key genes related to hypothalamus-pituitary-thyroid (HPT) axis were examined. The result of whole-body thyroxine (T4) and triiodothyronine (T3) indicated that the thyroid hormone homeostasis was disrupted by DEHP in the zebrafish larvae. After exposure to DEHP, the mRNA expressions of thyroid stimulating hormone ( tshβ ) and corticotrophin releasing hormone ( crh ) genes were increased in a concentration dependent manner, respectively. The expression level of genes involved in thyroid development ( nkx2 . 1 and pax8 ) and thyroid synthesis (sodium/iodide symporter, nis , thyroglobulin, tg ) were also measured. The transcripts of nkx2 . 1 and tg were significantly increased after DEHP exposure, while those of nis and pax8 had no significant change. Down-regulation of uridinediphosphate-glucuronosyl-transferase ( ugt1ab) and up-regulation of thyronine deiodinase ( dio2) might change the THs levels. In addition, the transcript of transthyretin ( ttr ) was up-regulated, while the mRNA levels of thyroid hormone receptors ( trα and trβ ) remained unchanged. All the results demonstrated that exposure to DEHP altered the whole-body thyroid hormones in the zebrafish larvae and changed the expression profiling of key genes related to HPT axis, proving that DEHP induced the thyroid endocrine toxicity and potentially affected the synthesis, regulation and action of thyroid hormones.
研究领域:
环境科学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Xu Zhang,Xiaotong Wang,Rui Shi,Xiaoku Ran,Xiahong He,Deqiang Dou
Ethnopharmacological relevance Red ginseng (RG), a processed product of ginseng (GS), is a generally used qi -tonifying medicine in Traditional Chinese Medicine (TCM). According to the TCM principle, RG is also generally applied to spleen-deficiency syndrome (SDS) clinically for its warmer property. However, the effective substances and mechanism of RG on SDS have not been well investigated. Aim of the study The aim of this study was to explore the effective substances and their mechanism of RG on SDS. Materials and methods The SDS model was established with a compound factor method involving an irregular diet, excessive fatigue and sennae folium with a bitter-cold property. The medicine of RG was split by multi-mode separation methods and analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The appearance indexes such as body weight, body temperature, swimming endurance, urine output, and water content of fecal were determined. The biochemical indexes such as D-xylose, SP , VIP and AChE in the digestive system, CRH, ACTH, CORT, E, T3, T4, T, E2 and 5-HT in the endocrine system, CS, NCR , IDH1 , COX and Na + -K + -ATPase in the metabolism of substance and energy, cAMP and cGMP in the cyclic nucleotide system were analyzed by Enzyme-linked immunosorbent assay (ELISA) kits and biochemical kits. The serum metabolites were analyzed by UPLC-QTOF/MS. Furthermore, the gut microbiota and short-chain fatty acids (SCFAs) in feces were analyzed by 16S rRNA sequencing and headspace gas chromatography-mass method. Results The pharmacological experiments showed that total saponin fraction (RGTSF), less polar fraction (RGLPF), and polysaccharides faction (RGPSF) significantly modulated the “brain-gut” axis-related indexes (the levels of VIP, AChE, and 5-HT). Besides, RGTSF also significantly modulated the hypothalamic-pituitary-adrenal (HPA) axis-related indexes as well as the substance and energy metabolism-related indexes (the levels of ACTH, CORT, A, Na + -K + -ATPase, COX, NCR and CS). RGPSF also significantly modulated the hypothalamus-pituitary-thyroid (HPT) axis-related indexes (the levels of T3 and T4). Secondly, metabolomics indicated that RGTSF could significantly regulate the abnormal metabolic pathways associated with the development of SDS, which involved steroid hormone biosynthesis, taurine and hypotaurine metabolism, primary bile acid biosynthesis, and amino acid metabolism. Subsequently, the study of gut microbiota indicated that RGLPF could increase the diversities of the gut microbiota and the relative abundance of Firmicutes in rats with SDS, while RGWEF significantly increased the relative abundance of Bacteroidetes . At the genus level, RGLPF could increase the relative abundance of Lactobacillus in rats with SDS and decrease that of Akkermansia . Meanwhile, the water-eluted fraction (RGWEF) showed a stronger regulation in SCFAs. Conclusion It is for the first time that the effective substances of red ginseng on spleen-deficiency syndrome were studied systematically, and the different mechanisms of the RG fractions involved in substance and energy metabolism as well as the “brain-gut” axis were revealed. The present study demonstrated that RGTSF, RGPSF, and RGLPF were the effective substances of red ginseng for ameliorating spleen-deficiency syndrome, indicating that ginsenosides composed of primary and secondary saponins as well as polysaccharides were the main effective substances for red ginseng in ameliorating spleen-deficiency syndrome.
研究领域:
民族药理学
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中医药学
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药理学
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代谢组学
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微生物学
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产品关联
DOI
PubMed
高影响因子
CELL BIOLOGY AND TOXICOLOGY
·
2021
·Vol. 37
·期 4
·633-651
·
IF 6.691
Zhao Peng,Cheng Jianhua,Li Bin,Nie Ding,Li Chuzhong,Gui Songbai,Wang Hongyun,Zhang Yazhuo
This study explored the function of microRNAs (miRNAs) in invasive pituitary adenomas (IPA), and developed a microRNA-exosome strategy for the disease treatment. Differentially expressed miRNAs and tumor-associated markers in IPA, non-invasive pituitary adenoma (NIPA), and rat pituitary adenoma cells were identified by bioinformatics analysis and qRT-PCR. Then, the cells were treated by miR-149-5p and miR-99a-3p mimics or inhibitors, or incubated with modified exosome with overexpressed or silenced miRNAs. The cell behaviors were analyzed by molecular experiments. Xenograft assays were constructed by injection of pituitary adenoma cells and exosome into NU/NU nude mice. Tumor size, weight, and expressions of markers related to miRNAs and angiogenesis were determined. Target genes for miR-99a-3p and miR-149 were predicted and verified by bioinformatics analysis and molecular experiments. Twenty differentially expressed miRNAs were identified, among which miR-99a-3p and miR-149 were inhibited in both pituitary adenoma cells and tissues significantly. Expressions of E-cadherin and p53 were down-regulated, while those of MMP-2, MMP-9, N-cadherin, Vimentin, and VEGF were up-regulated in pituitary adenoma cells and tissues, especially in IPA. Further experiments revealed that overexpressed miR-149 and miR-99a-3p inhibited the growth and metastasis of pituitary adenoma cells and tube formation of endothelial cells. MiR-149 and miR-99a-3p overexpressed by exosome showed similar suppressive effects on cell viability, metastasis, tube formation ability, in vivo tumor growth, and expressions of angiogenesis-related markers . Further analysis showed that NOVA1, DTL, and RAB27B were targeted by miR-99a-3p. This study found that overexpressed miR-149-5p and miR-99a-3p induced by exosome could suppress the progression of IPA. Graphical abstract and graphical headlights
1. MiR-149-5p and miR-99a-3p affect the expression of EMT- and ECM-related markers and tumor-related genes in rat pituitary adenoma cells treated with exosomes. 2. Exosome inhibited the tumor growth. 3. Overexpressed miR-149-5p and miR-99a-3p induced by exosome
研究领域:
肿瘤学
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2023
·
IF 12.4
Lianxia Guo,Haobin Cen,Jiaxian Weng,Yiting He,Xiaocao Guo,Di He,Kaisheng Liu,Shuyi Duan,Jing Yang,Xiaojian Zhang,Zifei Qin,Yong Wan,Zhiyong Chen,Baojian Wu
Rationale: The role of circadian clock in pituitary tumorigenesis remains elusive. Here we investigate whether and how circadian clock modulates the development of pituitary adenomas. Methods and Results: We found altered expression of pituitary clock genes in patients with pituitary adenomas. In particular, PER2 is prominently upregulated. Further, jetlagged mice with PER2 upregulation have accelerated growth of GH3 xenograft tumor. Conversely, loss of Per2 protects mice against developing estrogen-induced pituitary adenoma. Similar antitumor effect is observed for SR8278, a chemical that can decrease pituitary PER2 expression. RNA-seq analysis suggests involvement of cell cycle disturbance in PER2 regulation of pituitary adenoma. Subsequent in vivo and cell-based experiments validate that PER2 induces pituitary expression of Ccnb2 , Cdc20 and Espl1 (three cell cycle genes) to facilitate cell cycle progression and inhibit apoptosis, thereby promoting pituitary tumorigenesis. Mechanistically, PER2 regulates the transcription of Ccnb2 , Cdc20 and Espl1 through enhancing the transcriptional activity of HIF-1α. HIF-1α trans-activates Ccnb2 , Cdc20 and Espl1 via direct binding to its specific response element in the gene promoters. Conclusion: PER2 integrates circadian disruption and pituitary tumorigenesis. These findings advance our understanding of crosstalk between circadian clock and pituitary adenomas and highlight the relevance of clock-based approaches in disease management.
研究领域:
肿瘤学
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内分泌学
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分子生物学
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昼夜节律
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Jia Luo,Zheng Yan,Yao Shen,Denong Liu,Mingli Su,Jie Yang,Jiarong Xie,Hui Gao,Julin Yang,Aiming Liu
Noise exposure induces metabolic disorders, in a latent, chronic and complex way. However, there is no direct evidence elucidating the relationship between low-intensity noise exposure and nonalcoholic fatty liver disease (NAFLD). Male mice ( n = 5) on high-fat diet (HFD) were exposed to an average of 75 dB SPL noise for 3 months to reveal the effect of noise exposure on NAFLD, where the potential mechanisms were explored. In vivo ( n = 5) and in vitro models challenged with dexamethasone (DEX) were used to verify the role of hypothalamus pituitary adrenal (HPA) axis activation in hepatic lipid metabolism. Typical chronic-restraint stress (CRS, n = 8) was used to explore the role of depression in modifying activity of HPA axis. Finally, animal experiment (n = 8) was repeated to validate the roles of depression and HPA axis activation in NAFLD development. Chronic low-intensity noise exposure exacerbated NAFLD in mice on HFD characterized by hepatocyte steatosis, modified lipid metabolism and inflammation level. Plasma ACTH in H + N group was 1.5-fold higher than that in HFD group. Transcription of glucocorticoid receptor target genes was increased by chronic low-intensity noise exposure in HFD-treated mice. Excessive glucocorticoids mimicking HPA axis activation induced NAFLD in vivo and in vitro . Plasma ACTH increase and lipid storage also occurred in depressive mice stressed by CRS. More interestingly, the same noise exposure simultaneously induced depression in mice, disrupted the HPA axis homeostasis and exacerbated NAFLD in a repeated experiment. Thus, three-month exposure to 75 dB SPL noise was sufficient to exacerbate NAFLD progress in mice, where activation of HPA axis played a critical role. Depression played an intermediate role and contributed to HPA axis activation up-stream of the exacerbation.
研究领域:
医学
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生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2024
·
IF 4.8
Mingyan Wang,Xin Wei,Yugai Jia,Chaonan Wang,Xinliu Wang,Xin Zhang,Depei Li,Yuanyuan Wang,Yonggang Gao
Background Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Chronic unpredictable mild stress (CUMS) can lead to a significant acceleration of depression development. Quercetin (Que) is a flavonoid compound with a wide range of pharmacological effects. Recent studies have shown that quercetin can improve CUMS‐induced depression‐like behavior, but the mechanism of its improvement is still unclear. α2δ‐1 is a regulatory subunit of voltage‐gated calcium channel, which can interact with N‐methyl‐D‐aspartate receptor (NMDAR) to form a complex. Objective In this study, we found that Que could inhibit the increase of α2δ‐1 and NMDAR expression in rat hypothalamus induced by CUMS. In pain, chronic hypertension and other studies have shown that α2δ‐1 interacts with the NMDAR to form a complex, which subsequently affects the expression level of NMDAR. Consequently, the present study aimed to investigate the antidepressant effect of Que in vivo and in vitro and to explore its mechanism of action in terms of the interaction between α2δ‐1 and NMDAR. Methods Rats were randomly exposed to two stressors every day for 4 weeks to establish a CUMS rat model, then sucrose preference test (SPT), forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were performed to detect the behavior of CUMS rats, so as to evaluate whether the CUMS rat model was successfully established and the improvement effect of Que on CUMS‐induced depression‐like behavior in rats. Experimental techniques such as serum enzyme‐linked immunosorbent assay (ELISA), immunofluorescence, Western blot, and co‐immunoprecipitation, as well as in vitro experiments, were used to investigate the mechanisms by which Que exerts its antidepressant effects. Results Behavioral and ELISA test results showed that Que could produce a reduction in the excitability of the hypothalamic–pituitary–adrenal (HPA) axis in CUMS rats and lead to significant improvements in their depressive behavior. Western blot, immunofluorescence, and co‐immunoprecipitation experiments showed that Que produced a decrease in NMDAR1 and α2δ‐1 expression levels and interfered with α2δ‐1 and NMDAR1 binding. In addition, the neural regulation mechanism of Que on antidepressant effect in PC12 cells knocked out α2δ‐1 gene was further verified. Cellular experiments demonstrated that Que led to a reversal of up‐regulation of NMDAR1 and α2δ‐1 expression levels in corticosterone‐injured PC12 cells, while Que had no effects on NMDAR1 expression in PC12 cells with the α2δ‐1 gene knockout. Conclusions Que has a good antidepressant effect and can significantly improve the depression‐like behavior caused by CUMS. It exerts antidepressant effects by inhibiting the expression level of α2δ‐1, interfering with the interaction between α2δ‐1 and NMDAR, and then reducing the excitability of the HPA axis.
研究领域:
神经科学
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药理学
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分子生物学
·
行为科学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2023
·
IF 4.5
Miao Zhang,Xiaowen Bi,Shuai Liu,Yu Liu,Qiyu Wang
Sodium p -perfluorous nonenoxybenzene sulfonate (OBS), an economical alternative to perfluorooctane sulfonate (PFOS) in multiple industrial fields, is widely detected in the environment. The toxicity of OBS has received increasing attention. Pituitary cells are components of the endocrine system and act as vital regulators of homeostatic endocrine balance. However, the effects of OBS on pituitary cells remain unknown. The present study explores the effects of OBS (0.5, 5, and 50 μM) on GH3 rat pituitary cells after treatment for 24, 48, and 72 h. We found that OBS significantly inhibited cell proliferation in GH3 cells with remarkable senescent phenotypes, including enhanced SA-β-gal activity and expression of senescence-associated secretory phenotype (SASP)-related genes, cell cycle arrest, and upregulation of the senescence-related proteins γ-H2A.X and Bcl-2. OBS caused significant cell cycle arrest of GH3 cells at the G1-phase and concomitantly downregulated the expression of some key proteins for the G1/S transition, including cyclin D1 and cyclin E1. Consistently, the phosphorylation of retinoblastoma (RB), which plays a central role in regulating the cell cycle, was prominently reduced after OBS exposure. Furthermore, OBS notably activated the p53-p21 signalling pathway in GH3 cells, as evidenced by increased p53 and p21 expressions, enhanced p53 phosphorylation, and augmented p53 nuclear import. To our knowledge, this study is the first to reveal that OBS triggers senescence in pituitary cells via the p53-p21-RB signalling pathway. Our study demonstrates a novel toxic effect of OBS in vitro, and provides new perspectives for understanding the potential toxicity of OBS.
研究领域:
毒理学
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细胞生物学
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内分泌学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Guizhu Wu,Lu Gao,Shaoming Zhang,Daolin Du,Yonglai Xue
Copper oxide nanoparticles (CuO NPs) were regarded as the versatile materials in daily life and the in-depth evaluation of their biological effects is of great concern. Herein the female and male zebrafishes were chosen as the model animals to analyze the reproductive toxicity caused by CuO NPs at low concentration (10, 50 and 100 μg/L) After 20-days exposure, the structure of zebrafish ovary and testis were impaired. Moreover, the contents of 17β-estradiol (E2) in both females and males were increased, while the contents of testosterone (T) were decreased, indicating the imbalanced sex hormones caused by CuO NPs. The expression of genes along the hypothalamic pituitary-gonad (HPG) axis, were examined with quantitative real-time PCR to further evaluate the toxic mechanisms. Meanwhile, the levels of erα/er2β and cyp19a in female zebrafishes and erα/er2β , lhr , hmgra/hmgrb , 3βhsd and 17βhsd in male zebrafishes were obviously up-regulated. While, the level of αr was obviously down-regulated in female and male zebrafishes. Thus, the obtained data uncovered that long-term exposure of CuO NPs with low dose could trigger the endocrine disorder, resulting in the disturbance of E2 and T level, inhibition of gonad development, and alteration of HPG axis genes. In brief, this study enriched the toxicological data of NPs on aquatic vertebrates and provided the theoretical support for assessing the environmental safety of NPs.
研究领域:
环境毒理学
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水生生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
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IF 4.8
Xiaoqing Shen,Jing Lian,Chao Zhang,Yixiang Miu,Yuan Zhang,Ji Shi,Nan Xu,Tianzhu Jia
Introduction: Kidney Yang Deficiency (KYD) is a metabolic disorder associated with kidney damage. Its slow progression means that causative factors and effective therapeutic agents remain unclear. Extensive evidence links KYD to gut microbiome metabolic diseases and the Hypothalamic-Pituitary-Thyroid (HPT) axis. Cistanche deserticola (CD) is a commonly used traditional Chinese medicine for treating KYD. However, the precise interactions between gut microbiota and KYD, as well as the mechanisms of raw and processed CD total glycosides (CDG) in modulating KYD, require further investigation. This study aims to evaluate the effects and mechanisms of CDG in a KYD rat model using 16S rRNA gene sequencing and fecal metabolomics.Methods: CDG was extracted from both raw and processed CD and analyzed via HPLC. Propylthiouracil-induced KYD rats were used to assess pharmacological effects, including serum levels of T3, T4, TSH, TRH, FFA, LPL, and NO; organ indices of the spleen, kidney, and thymus; blood cAMP/cGMP levels; and liver levels of glycogen, SDH, Ca2+-ATPase, and Na+-K+-ATPase. Immunohistochemistry was also performed.Results: Fecal non-targeted metabolomics identified 98 metabolites associated with KYD, while 16S rRNA sequencing revealed 13 key intestinal microbiotas linked to KYD. CDG therapy effectively alleviated KYD symptoms by modulating the gut microbiota, improving metabolic and microbial imbalances in KYD. RG/WG significantly improves KYD rats mainly through the relationship between the intestinal microbiota and arachidonic acid metabolism. The key bacterial genera lleibacterium and Streptococcus observed in the changes of intestinal flora and fecal metabolite content were significantly negatively correlated with phosphatidylcholine and phosphatidylethanolamine.Discussion: This integrative approach of gut microbiome and fecal metabolomics not only provides a scientific basis for CDG’s preventive effects on KYD via the HPT axis but also elucidates the potential mechanisms underlying CDG’s action against KYD.
研究领域:
中医药学
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药理学
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微生物学
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分子生物学
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代谢组学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）