Ganoderma lucidum sporoderm-broken spore powder alleviates kidney aging by modulating gut microbiota.

IF 5.4 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2025-09-25 Epub Date: 2025-08-05 DOI:10.1016/j.jep.2025.120344

Xiaojing Liu, Jiamin Zhao, Jia Liu, Wei Deng, Luwen Yan, Yan Huang, Liao Zhang, Zhihong Liu, Ming Cui, Huiwen Xiao, Xingzhong Liu

{"title":"Ganoderma lucidum sporoderm-broken spore powder alleviates kidney aging by modulating gut microbiota.","authors":"Xiaojing Liu, Jiamin Zhao, Jia Liu, Wei Deng, Luwen Yan, Yan Huang, Liao Zhang, Zhihong Liu, Ming Cui, Huiwen Xiao, Xingzhong Liu","doi":"10.1016/j.jep.2025.120344","DOIUrl":null,"url":null,"abstract":"Ethnopharmacological relevance: Ganoderma lucidum (G. lucidum), a revered medicinal mushroom in traditional Chinese medicine (TCM), has been historically documented for its anti-aging properties and nephroprotective effects. Nevertheless, its mechanism of action through gut microbiota modulation to attenuate renal and systemic aging remains incompletely understood.Aim of the study: To elucidate the gut microbiota-dependent anti-aging mechanisms of G. lucidum on renal and systemic senescence using integrative multi-omics approaches.Materials and methods: We systematically evaluated the anti-aging efficacy of G. lucidum sporoderm-broken spore powder (Gl-SBSP) via the gut-kidney axis in naturally aged and radiation-induced premature senescence mouse models. Renal aging phenotypes were assessed using histopathological analyses (hematoxylin-eosin and Masson staining), immunofluorescence (IF), complete blood counts, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time PCR (RT-qPCR). Gut microbiota involvement was confirmed via antibiotic-treated mice and fecal microbiota transplantation (FMT). Multi-omics integration of 16S rRNA sequencing and metabolomic profiling identified microbiota-derived metabolites, functionally validated in HK-2 cells and aged mice. Mechanistic pathways were elucidated via transcriptomic analysis.Results: Gl-SBSP attenuated kidney aging phenotypes in both natural aging and irradiation models. It selectively enriched Lachnospiraceae, whose metabolite nicotinamide riboside (NR) elevated renal NAD+ levels (in vitro and in vivo), rejuvenated senescent kidneys, and improved renal function through steroid metabolism regulation.Conclusion: Gl-SBSP counters renal aging through Lachnospiraceae-driven gut microbiota remodeling, where NR serves as the core rejuvenating metabolite. By activating NAD+ biosynthesis and modulating steroid metabolism via the gut-kidney axis, this mechanism offers a novel therapeutic strategy against age-related renal decline and validates Ganoderma lucidum's ethnopharmacological relevance.","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120344"},"PeriodicalIF":5.4000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2025.120344","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/5 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Ethnopharmacological relevance: Ganoderma lucidum (G. lucidum), a revered medicinal mushroom in traditional Chinese medicine (TCM), has been historically documented for its anti-aging properties and nephroprotective effects. Nevertheless, its mechanism of action through gut microbiota modulation to attenuate renal and systemic aging remains incompletely understood.

Aim of the study: To elucidate the gut microbiota-dependent anti-aging mechanisms of G. lucidum on renal and systemic senescence using integrative multi-omics approaches.

Materials and methods: We systematically evaluated the anti-aging efficacy of G. lucidum sporoderm-broken spore powder (Gl-SBSP) via the gut-kidney axis in naturally aged and radiation-induced premature senescence mouse models. Renal aging phenotypes were assessed using histopathological analyses (hematoxylin-eosin and Masson staining), immunofluorescence (IF), complete blood counts, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time PCR (RT-qPCR). Gut microbiota involvement was confirmed via antibiotic-treated mice and fecal microbiota transplantation (FMT). Multi-omics integration of 16S rRNA sequencing and metabolomic profiling identified microbiota-derived metabolites, functionally validated in HK-2 cells and aged mice. Mechanistic pathways were elucidated via transcriptomic analysis.

Results: Gl-SBSP attenuated kidney aging phenotypes in both natural aging and irradiation models. It selectively enriched Lachnospiraceae, whose metabolite nicotinamide riboside (NR) elevated renal NAD⁺ levels (in vitro and in vivo), rejuvenated senescent kidneys, and improved renal function through steroid metabolism regulation.

Conclusion: Gl-SBSP counters renal aging through Lachnospiraceae-driven gut microbiota remodeling, where NR serves as the core rejuvenating metabolite. By activating NAD⁺ biosynthesis and modulating steroid metabolism via the gut-kidney axis, this mechanism offers a novel therapeutic strategy against age-related renal decline and validates Ganoderma lucidum's ethnopharmacological relevance.

查看原文本刊更多论文

灵芝破孢子粉通过调节肠道菌群缓解肾脏衰老。

民族药理学相关性：灵芝（Ganoderma lucidum）是一种受人尊敬的中药药用蘑菇，具有抗衰老和保护肾脏的作用。然而，其通过肠道菌群调节来减轻肾脏和全身衰老的作用机制仍不完全清楚。研究目的：利用综合多组学方法，阐明灵芝对肾脏和全身衰老的肠道微生物依赖的抗衰老机制。材料与方法：通过肠肾轴对自然衰老和辐射致早衰小鼠模型进行系统评价透明果破孢子粉（Gl-SBSP）的抗衰老作用。采用组织病理学分析（苏木精-伊红和马松染色）、免疫荧光（IF）、全血细胞计数、酶联免疫吸附测定（ELISA）和实时荧光定量PCR （RT-qPCR）评估肾脏衰老表型。通过抗生素治疗的小鼠和粪便微生物群移植（FMT）证实了肠道微生物群的参与。16S rRNA测序和代谢组学分析的多组学整合鉴定了微生物来源的代谢物，在HK-2细胞和老年小鼠中进行了功能验证。通过转录组学分析阐明了机制途径。结果：Gl-SBSP在自然衰老和辐照模型中均能减轻肾脏衰老表型。其代谢物烟酰胺核苷（NR）可提高肾脏（体外和体内）NAD+水平，使衰老的肾脏恢复活力，并通过类固醇代谢调节改善肾功能。结论：Gl-SBSP通过lachnospiraceae驱动的肠道微生物群重塑来对抗肾脏衰老，其中NR是核心的返老还老代谢物。通过激活NAD+生物合成并通过肠肾轴调节类固醇代谢，这一机制为对抗年龄相关性肾衰退提供了一种新的治疗策略，并验证了灵芝的民族药理学相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.