Frontiers in Pharmacology
·
2025
·
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
·
药理学
·
微生物学
·
分子生物学
·
代谢组学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2024
·
IF 1.6
Qing-Gang Zhou,Bao-Xia Han,Huan Yi,Zhao Geng,Xiao-Jun Gou
Aim: The aim of this study was to elucidate the mechanism of action of Shenbao tablets using metabolomics approach. Background: Kidney-Yang deficiency is a common syndrome type in traditional Chinese Medicine (TCM) syndrome typology, closely related to disorders of multiple metabolic pathways and is the root cause and underlying syndrome type of many diseases. Shenbao tablets can significantly improve the main symptoms of kidney yang deficiency syndrome, but the mechanism of action of Shenbao tablets on kidney yang deficiency syndrome is still unknown. Methods: The rats were intraperitoneally injected with hydrocortisone once a day for 40 days to simulate the syndrome. Traditional pharmacodynamic indicators (body mass, biochemical indicators and pathology) were used to evaluate the efficacy of the medicine. Serum, urine and feces were collected from rats. UPLC/MS metabolomics method was used to study the overall metabolic profile of serum, while GC/MS metabolomics method was used to study the metabolic spectrum of urine and feces. Results: Results showed that the syndrome was significantly improved in the treatment group, and obvious metabolic disorders were observed in rats with the syndrome, with 47 potential biomarkers identified. Pathway analysis showed that nicotinate and nicotinamide metabolism, glycine, serine and trione metabolism, aminoacyl tRNA biosynthesis, glycoxylate and dicarboxylate metabolism were the major ways for Shenbao tablet to improve kidney-yang deficiency syndrome. Conclusion: The mechanism of action of Shenbao tablet in improving the syndrome involves the regulation of energy metabolism, amino acid metabolism, bile acid metabolism, fatty acid metabolism and intestinal microorganisms. This work shows that metabolomics is a promising tool for studying the essence of syndrome theory in TCM and the mechanisms of TCM.
研究领域:
中医药学
·
代谢组学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Sun E.,Huang Ran,Ding Ke,Wang Ling,Hou Jian,Tan Xiaobin,Wei Yingjie,Feng Liang,Jia Xiaobin
Introduction: Epimedium, a traditional Chinese medicine (TCM) commonly used in ancient and modern China, is one of the traditional Chinese medicines clinically used to treat kidney yang deficiency syndrome (KYDS). There are differences in the efficacy of Epimedium before and after processing, and the effect of warming the kidney and enhancing yang is significantly enhanced after heating with suet oil. However, the active compounds, corresponding targets, metabolic pathways, and synergistic mechanism of frying Epimedium in suet oil to promote yang, remain unclear.Methods: Herein, a strategy based on comprehensive GC-TOF/MS metabolomics and network pharmacology analysis was used to construct an “active compounds-targets-metabolic pathways” network to identify the active compounds, targets and metabolic pathways involved. Subsequently, the targets in kidney tissue were further validated by real-time quantitative polymerase chain reaction (RT-qPCR). Histopathological analysis with physical and biochemical parameters were performed.Results: Fifteen biomarkers from urine and plasma, involving five known metabolic pathways related to kidney yang deficiency were screened. The network pharmacology results showed 37 active compounds (13 from Epimedium and 24 from suet oil), 159 targets, and 267 pathways with significant correlation. Importantly, integrated metabolomics and network pharmacologic analysis revealed 13 active compounds (nine from Epimedium and four from suet oil), 7 corresponding targets (ALDH2, ARG2, GSTA3, GSTM1, GSTM2, HPGDS, and NOS2), two metabolic pathways (glutathione metabolism, arginine and proline metabolism), and two biomarkers (Ornithine and 5-Oxoproline) associated with improved kidney yang deficiency by Epimedium fried with suet oil.Discussion: These finds may elucidate the underlying mechanism of yang enhancement via kidney warming effects. Our study indicated that the mechanism of action mainly involved oxidative stress and amino acid metabolism. Here, we demonstrated the novel strategies of integrating metabolomics and network pharmacology in exploring of the mechanisms of traditional Chinese medicines.
研究领域:
药理学
·
中医药学
·
代谢组学
·
系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2025
·
IF 2.5
Xizhi Chen,Yao Chen,Weibo Wen
This study aimed to explore effectiveness and related mechanisms of Polygala crotalarioides in treating erectile dysfunction (ED). Hydrocortisone was used to establish a kidney- Yang deficiency ED rat model. Levels of triiodothyronine(T3), thyroxine(T4), testosterone(T), estradiol(E2) and expressions of RhoA, ROCK1, ROCK2 were determined. Immunofluorescence staining was used to detect CD34 in penile tissues. Compared with normal rats, T3, T4, T, E2 levels in serum of ED rat model were significantly reduced (P < 0.05), while RhoA, ROCK1, ROCK2 expressions were significantly higher (P < 0.05). High- and medium-dose of Polygala crotalarioides significantly attenuated erectile dysfunction, but low-doses of Polygala crotalarioides were ineffective. High and medium dose of Polygala crotalarioides and sildenafil significantly increased weight of ED rats compared to Model group (P < 0.05). T3, T4, E2, and T levels in low-dose, medium-dose, and high-dose of Polygala crotalarioides group were increased compared to Model group (P < 0.05). Compared with Model group, RhoA, ROCK1, and ROCK2 expressions in penile tissue of rats in low-, medium-, high-dose of Polygala crotalarioides group were reduced (P < 0.05). High-, medium-, and low-dose Polygala crotalarioides significantly increased CD34 compared with ED rat (P < 0.05). In conclusion, Polygala crotalarioides attenuated erectile dysfunction and improved thyroid and gonadal function by regulating Rho/ROCK pathway in kidney Yang- deficiency ED rat.
研究领域:
药理学
·
内分泌学
·
中医药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Danping Liu,Yi Wang,Hongyi Zhao,Xiuwen Xia,Jie Zhou,Li Xie,Pei Guo,Weihong Li
Ethnopharmacological relevance Wenyang-Tianjing-Jieyu Decoction (WTJD) is a traditional Chinese herbal formula with a history of ethnopharmacological use for depression, specifically targeting the Kidney-Yang deficiency (KYD) subtype. Its therapeutic rationale is well-documented in classical Chinese materia medica. However, the molecular mechanisms underpinning its clinical efficacy remain largely unelucidated. Aim of the study This study aimed to investigate the therapeutic effects and elucidate the underlying molecular mechanisms of WTJD, a traditional herbal formula, in ameliorating KYD-type depression in a rat model. Materials and methods The chemical profile of WTJD was characterized using UPLC-Q-Exactive/MS. Using a rat model of KYD-type depression established by combining Phellodendri chinensis Cortex decoction gavage, cold exposure, and chronic unpredictable mild stress (CUMS), we evaluated the therapeutic effects of WTJD. This randomized controlled study included five groups (n = 7/group): Control, Model, Fluoxetine, WTJD-Medium, and WTJD-High, with a 3-week intervention period. Furthermore, we integrated network pharmacology with hippocampal transcriptomics to identify key therapeutic targets, which converged on the FOXO signaling pathway. Finally, the predicted mechanism was validated by assessing key protein phosphorylation, nuclear translocation, hippocampal neurogenesis, and synaptic plasticity. Moreover, the regulatory mechanism was further corroborated in vitro using LPS-induced PC12 cells treated with WTJD-containing serum and the AKT inhibitor MK-2206. Results WTJD administration significantly ameliorated both the KYD phenotype and depressive-like behaviors in the rat model. Strikingly, both network pharmacology and hippocampal transcriptomic analyses converged on the FOXO signaling pathway as the central therapeutic target. Mechanistically, it was confirmed that WTJD activated the FOXO pathway by inhibiting AKT phosphorylation, which in turn promoted the nuclear translocation of FOXO4. Consistently, in vitro assays demonstrated that WTJD-containing serum protected PC12 cells and rescued downstream gene expression by modulating the FOXO signaling pathway, effects that were mimicked by AKT inhibition. This cascade of molecular events ultimately restored impaired adult hippocampal neurogenesis and synaptic plasticity. Conclusion WTJD ameliorates KYD-type depression by modulating the hippocampal FOXO signaling pathway to restore neurogenesis and synaptic plasticity. These results validate the FOXO pathway as a high-value target for subtype-specific antidepressant drug design.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Ling Xin,Mengxin Ren,Yanwei Lou,Huawen Yin,Feng Qin,Zhili Xiong
Gushudan (GSD) was a traditional Chinese prescription with the remarkable effect of kidney-tonifying and bone-strengthening. However, the potential prevention mechanisms of the GSD on kidney-yang-deficiency-syndrome (KYDS) and its regulation on gut microbe metabolism still need to be further systematically investigated. This study established untargeted urinary metabolomics based on RP/HILIC-UHPLC-Q-Orbitrap HRMS and combined with multivariate statistical analysis to discover differential metabolites and key metabolic pathways. And the gut microbe metabolism pathway-targeted metabolomic based on HILIC-UHPLC-MS/MS was developed and validated to simultaneously determine 15 gut microbe-mediated metabolites in urine samples from the control group (CON), KYDS model group (MOD), GSD-treatment group (GSD) and positive group (POS). The results showed that a total of 36 differential metabolites were discovered in untargeted metabolomics. These differential metabolites included proline, cytosine, butyric acid and nicotinic acid, which were primarily involved in the gut microbe metabolism, amino acid metabolism, energy metabolism and nucleotide metabolism. And GSD played a role in preventing KYDS by regulating these metabolic pathways. The targeted metabolomics found that the levels of 10 gut microbe-mediated metabolites had significant differences in different groups. Among them, compared with the CON group, the levels of lysine, tryptophan, phenylacetylglycine and hippuric acid were increased in the MOD group, while the levels of threonine, leucine, dimethylamine, trimethylamine, succinic acid and butyric acid were decreased, which verified the disorders of gut microbe metabolism in the KYDS rats and GSD had a significant regulatory effect on this disorder. As well as by comparing analysis, it was found that the experimental results were consistent with previous metabolomics and microbiomics of fecal samples. Therefore, this integrated strategy of untargeted and targeted metabolomics not only elucidated the potential prevention mechanism of GSD on KYDS, but also provided a scientific basis for GSD preventing KYDS via the “gut-kidney” axis.
研究领域:
药理学
·
代谢组学
·
中医药
·
系统生物学
·
肠道微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Tianshi Li,Mengqi Shi,Yan Zhao,Zhongmei He,Ying Zong,Weijia Chen,Rui Du
As a traditional Chinese herbal medicine, Cornu Cervi Degelatinatum (CCD) has the effect of warming the kidney to support yang, astringing, and stopping bleeding, and is used for spleen kidney yang deficient (SKYD). This experiment was to investigate the therapeutic effects of different processes of CCD on SKYD type ulcerative colitis (UC) rats and to explore its impact on the intestinal flora of rats. Methods: ELISA was used to study the anti-inflammatory activity of Cornu Cervi Degelatinatum processed with water (WCCD) and Cornu Cervi Degelatinatum processed with vinegar (VCCD). 16SrRNA and transcriptome sequencing were used to detect the composition of rat intestinal flora and gene expression; RT-PCR and Western blot were used to verify the role of WCCD and VCCD in treating UC. Results: WCCD and VCCD have therapeutic effects on UC, could reduce tissue damage. VCCD performed better in improving Bacteroidetes/Firmicutes ratios and species evenness and abundance; performed better in increasing the quantity of lactobacillus. VCCD simultaneously inhibit the intestinal inflammatory response through NCK2, PAK4, and JNK signaling pathways. Conclusions: WCCD and VCCD play a therapeutic role in UC by regulating the proportion of different flora in the intestinal flora. VCCD regulates the intestinal flora and inflammatory response by interfering with the NCK2, PAK4 and JNK signaling pathways.
研究领域:
中医中药
·
药理学
·
分子生物学
·
胃肠病学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2025
·
IF 4.1
Jiaxin Di,Meifang Guo,Maijiao Peng,Leyao Fang,Junxi Shen,Nenqun Xiao,Zhoujin Tan
Purpose To investigate the therapeutic mechanisms of sodium butyrate combined with SSP in treating diarrhea with kidney-yang deficiency syndrome, providing experimental evidence for the modern application of classical Chinese medicine formulas.Methods A mouse model of diarrhea with kidney-yang deficiency syndrome was established via adenine combined with Folium sennae gavage. After successful model establishment, the drug intervention groups were administered by gavage with 100% SSP decoction, 300 mg/mL sodium butyrate, and 100 mg/kg sodium butyrate + 50% SSP decoction, respectively. General physical conditions and organ indices were assessed. Serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, as well as colonic immunoglobulin A (sIgA) and mucin 2 (MUC2) levels, were determined via ELISA. Kidney and intestinal histology were evaluated via hematoxylin‒eosin (HE) staining. The characteristics of the small intestinal mucosal microbiota under different interventions were analysed via 16S rRNA sequencing.Results Compared with natural recovery, the combination of 100 mg/kg sodium butyrate + 50% SSP significantly restored colonic sIgA levels (p< 0.05) and MUC2 levels, indicating an improvement in intestinal mucosal barrier function. Histological analysis revealed that the combination of 100 mg/kg sodium butyrate + 50% SSP improved renal inflammation and restored intestinal villus length and crypt depth. The combination therapy controlled the relative abundance of Corynebacterium while restoring Dwaynesavagella and Megasphaera_A. Correlation analysis indicated that Mammaliicoccus and Corynebacterium were significantly negatively correlated with sIgA and MUC2 levels and that their relative abundances were inhibited by the combination therapy.Conclusion Sodium butyrate enhanced the therapeutic efficacy of SSP. The combination therapy effectively repaired damaged kidneys and intestines and alleviated diarrhea with kidney-Yang deficiency syndrome by modulating the relative abundance of intestinal microbiota and enhancing intestinal immunity as well as mucosal barrier function. The interaction between the intestinal microbiota and intestinal mucosal protective factors may be a key mechanism in the combined treatment of diarrhea with kidney-yang deficiency syndrome.
研究领域:
药理学
·
中医学
·
微生物学
·
免疫学
·
胃肠病学
·
分子生物学
✓ 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）