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Multi‑omics analysis reveals gut microbiota‑ovary axis contributed to the follicular development difference between Meishan and Landrace×Yorkshire sows

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畜牧与生物技术杂志:英文版 2023年第5期14卷 1954-1968页

作者： Baoyang Xu wenxia qin Yuwen Chen Yimei Tang Shuyi Zhou Juncheng Huang Libao Ma Xianghua Yan State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhan 430070HubeiChina The Cooperative Innovation Center for Sustainable Pig Production Wuhan 430070HubeiChina Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Wuhan 430070HubeiChina

Background The mechanism by which Meishan(MS)sows are superior to white crossbred sows in ovarian follicle development remains unclear.Given gut microbiota could regulate female ovarian function and reproductive capacity,this study aimed to determine the role of gut microbiota-ovary axis on follicular development in sows.Methods We compared the ovarian follicular development,gut microbiota,plasma metabolome,and follicular fluid metabolome between MS and Landrace×Yorkshire(L×Y)sows.A H_(2)O_(2)-induced cell apoptosis model was used to evaluate the effects of multi-omics identified metabolites on the apoptosis of porcine ovarian granulosa cells in vitro.Results Compared with L×Y sows,MS sows have greater ovary weight and improved follicular development,including the greater counts of large follicles of diameter≥5 mm,secondary follicles,and antral follicles,but lesser atretic follicles.The ovarian granulosa cells in MS sows had alleviated apoptosis,which was indicated by the increased BCL-2,decreased caspases-3,and decreased cleaved caspases-3 than in L×Y sows.The ovarian follicular fluid of MS sows had higher concentrations of estradiol,progesterone,follicle-stimulating hormone,luteinizing hormone,and insulin like growth factor 1 than L×Y sows.Gut microbiota of MS sows formed a distinct cluster and had improved alpha diversity,including increased Shannon and decreased Simpson than those of L×Y sows.Corresponding to the enhanced function of carbohydrate metabolism and elevated short-chain fatty acids(SCFAs)in feces,the differential metabolites in plasma between MS and L×Y sows are also mainly enriched in pathways of fatty acid metabolism.There were significant correlations among SCFAs with follicular development,ovarian granulosa cells apoptosis,and follicular fluid hormones,respectively.Noteworthily,compared with L×Y sows,MS sows had higher follicular fluid SCFAs concentrations which could ameliorate H_(2)O_(2)-induced porcine granulosa cells apoptosis in vitro.Conclusion MS sows have more secondary and antral foll

关键词： Follicular development Granulosa cells apoptosis Gut microbiota Short-chain fatty acids Sows

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Rice bran oil supplementation protects swine weanlings against diarrhea and lipopolysaccharide challenge

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第5期24卷 430-441页

作者： Juncheng HUANG wenxia qin Baoyang XU Haihui SUN Fanghua JING Yunzheng XU Jianan ZHAO Yuwen CHEN Libao MA Xianghua YAN State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhan 430070China The Cooperative Innovation Center for Sustainable Pig Production Wuhan 430070China Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Wuhan 430070China Yichun Dahaigui Life Science Co. Ltd.Yichun 336000China

Early weaned piglets suffer from oxidative stress and enteral infection,which usually results in gut microbial dysbiosis,serve diarrhea,and even death.Rice bran oil(RBO),a polyphenol-enriched by-product of rice processing,has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro.Here,we ascertained the proper RBO supplementation level,and subsequently determined its effects on lipopolysaccharide(LPS)-induced intestinal dysfunction in weaned piglets.A total of 168 piglets were randomly allocated into four groups of seven replicates(42 piglets each group,(21±1)d of age,body weight(7.60±0.04)kg,and half males and half females)and were given basal diet(Ctrl)or basal diet supplemented with 0.01%(mass fraction)RBO(RBO1),0.02%RBO(RBO2),or 0.03%RBO(RBO3)for 21 d.Then,seven piglets from the Ctrl and the RBO were treated with LPS(100μg/kg body weight(BW))as LPS group and RBO+LPS group,respectively.Meanwhile,seven piglets from the Ctrl were treated with the saline vehicle(Ctrl group).Four hours later,all treated piglets were sacrificed for taking samples of plasma,jejunum tissues,and feces.The results showed that 0.02%was the optimal dose of dietary RBO supplementation based on diarrhea,average daily gain,and average daily feed intake indices in early weaning piglets.Furthermore,RBO protected piglets against LPS-induced jejunal epithelium damage,which was indicated by the increases in villus height,villus height/crypt depth ratio,and Claudin-1 levels,as well as a decreased level of jejunal epithelium apoptosis.RBO also improved the antioxidant ability of LPS-challenged piglets,which was indicated by the elevated concentrations of catalase and superoxide dismutase,and increased total antioxidant capacity,as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma.Meanwhile,RBO improved the immune function of LPS-challenged weaned piglets,which was indicated by elevated immunoglobulin A(IgA),IgM,β-defensin-1,and lysozyme levels in the plasma.In addition,RBO supp

关键词： Rice bran oil Gut microbiota Weaned piglets Oxidative stress Lipopolysaccharide

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Dietary ellagic acid supplementation attenuates intestinal damage and oxidative stress by regulating gut microbiota in weanling piglets

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Animal Nutrition 2022年第4期11卷 322-333页

作者： wenxia qin Baoyang Xu Yuwen Chen Wenbo Yang Yunzheng Xu Juncheng Huang Ting Duo Yihua Mao Guozong Zhou Xianghua Yan Libao Ma State Key Laboratory of Agricultural Microbiology College of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhanChina The Cooperative Innovation Center for Sustainable Pig Production WuhanChina Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology WuhanChina Wuhan Huayang Animal Pharmaceutical Co. Ltd WuhanChina Hubei Tianxin Biotech Co. LtdShiyanChina

Intestinal oxidative stress triggers gut microbiota dysbiosis,which is involved in the etiology of postweaning diarrhea and enteric infections.Ellagic acid(EA)can potentially serve as an antioxidant supplement to facilitate weaning transition by improving intestinal oxidative stress and gut microbiota dysbiosis.Therefore,we aimed to investigate the effects of dietary EA supplementation on the attenuation of intestinal damage,oxidative stress,and dysbiosis of gut microbiota in weanling piglets.A total of126 piglets were randomly assigned into 3 groups and treated with a basal diet and 2 m L saline orally(Ctrl group),or the basal diet supplemented with 0.1%EA and 2 m L saline orally(EA group),or the basal diet and 2 m L fecal microbiota suspension from the EA group orally(FEA group),respectively,for 14 d.Compared with the Ctrl group,EA group improved growth performance by increasing average daily feed intake and average daily weight gain(P<0.05)and decreasing fecal scores(P<0.05).EA group also alleviated intestinal damage by increasing the tight junction protein occludin(P<0.05),villus height,and villus height-to-crypt depth ratio(P<0.05),while decreasing intestinal epithelial apoptosis(P<0.05).Additionally,EA group enhanced the jejunum antioxidant capacity by increasing the total antioxidant capacity(P<0.01),catalase(P<0.05),and glutathione/oxidized glutathione(P<0.05),but decreased the oxidative metabolite malondialdehyde(P<0.05)compared to the Ctrl group.Compared with the Ctrl group,EA and FEA groups increased alpha diversity(P<0.05),enriched beneficial bacteria(Ruminococcaceae and Clostridium ramosum),and increased metabolites short-chain fatty acids(P<0.05).Correspondingly,FEA group gained effects comparable to those of EA group on growth performance,intestinal damage,and intestinal antioxidant capacity.In addition,the relative abundance of bacteria shifted in EA and FEA groups was significantly related to the examined indices(P<0.05).Overall,dietary EA supplementation could improve growth performance and atte

关键词： Ellagic acid Gut microbiota Weanling piglets Intestinal damage Oxidative stress

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Gut microbiota contributes to the development of endometrial glands in gilts during the ovary-dependent period

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Journal of Animal Science and Biotechnology 2021年第4期12卷 1610-1622页

作者： Baoyang Xu wenxia qin Yiqin Yan Yimei Tang Shuyi Zhou Juncheng Huang Chunlin Xie Libao Ma Xianghua Yan State Key Laboratory of Agricultural Microbiology College of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhan 430070HubeiChina The Cooperative Innovation Center for Sustainable Pig Production Wuhan 430070HubeiChina Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Technology Wuhan 430070HubeiChina

Background:The hyper-prolificacy Meishan gilts achieved a superior endometrial gland development(EGD)than white crossbred gilts during the ovary-independent period(before 60 d of age).Then,the EGD continues under the management of ovary-derived steroid hormones that regulated by gut microbiota(after 60 d of age).However,whether Meishan gilts’superiority in EGD lasting to the ovary-dependent period(after 60 d of age)and the role of gut microbiota in this period both remain unclear.Methods:Meishan gilts and Landrace x Yorkshire(LxY)gilts were raised under the same housing and feeding conditions until sexual maturity and then we compared their EGD and gut microbiota.Meanwhile,we transplanted fecal microbiota from Meishan gilts to L×Y gilts to explore the role of gut microbiota in EGD.We sampled plasma every 3 weeks and collected the uterus,ovary,liver,and rectal feces after the sacrifice.We then determined the hormone concentrations and expressions of the EGD-related genes.We also profiled the gut microbiota using 16S rDNA sequencing and metabolites of plasma and liver tissue using untargeted metabolomics.Finally,the correlation analysis and significant test was conducted between FMT-shifted gut microbes and EGD-related indices.Results:Meishan gilts have larger endometrial gland area(P<0.001),longer uterine horn length(P<0.01)but lighter uterine horn weight(P<0.05),a distinctive gut microbiota compared with L×Y gilts.Fecal microbiota transplantation(FMT)increased endometrial gland area(P<0.01).FMT markedly shifted the metabolite profiles of both liver and plasma,and these differential metabolites enriched in steroid hormone biosynthesis pathway.FMT increased estradiol and insulin-like growth factor 1 but decreased progesterone dynamically.FMT also increased the expression of the EGD-related genes estrogen receptor 1 gene,epithelial cadherin,and forkhead box protein A2.There is a significant correlation between FMT-shifted gut microbes and EGD-related indices.Conclusion:Sexually matured Meishan gilts achieved a super

关键词： Endometrial gland Fecal microbiota transplantation Gut microbiota Meishan gilts Steroid hormones Untargeted metabolomics Uterus

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Expert consensus on difficulty assessment of endodontic therapy

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International Journal of Oral Science 2024年第1期16卷 15-25页

作者： Dingming Huang Xiaoyan Wang Jingping Liang Junqi Ling Zhuan Bian qing Yu Benxiang Hou Xinmei Chen Jiyao Li Ling Ye Lei Cheng Xin Xu Tao Hu Hongkun Wu Bin Guo qin Su Zhi Chen Lihong Qiu wenxia Chen Xi Wei Zhengwei Huang Jinhua Yu Zhengmei Lin Qi Zhang Deqin Yang Jin Zhao Shuang Pan Jian Yang Jiayuan Wu Yihuai Pan Xiaoli Xie Shuli Deng Xiaojing Huang Lan Zhang Lin Yue Xuedong Zhou State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Department of Operative Dentistry and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Clinical Research Center for Oral DiseasesNational Center for StomatologyShanghai Key Laboratory of StomatologyShanghaiChina Department of Operative Dentistry and Endodontics Hospital of StomatologyGuanghuaSchool of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of StomatologyWuhan UniversityWuhanChina Department of Operative Dentistry&Endodontics School of StomatologyThe Fourth Military Medical UniversityXi’anChina Department of Endodontics Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Department of Preventive Dentistry West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Department of Geriatric dentistry West China Hospital of Stomatology

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

关键词： anatomy difficulty treatment

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六味地黄苷糖对创伤应激致恐惧敏化的保护作用

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军事医学 2024年第2期48卷 129-135页

作者：李奉安秦钰石天尧周文霞南京中医药大学南京210023 军事科学院军事医学研究院毒物药物研究所抗毒药物与毒理学国家重点实验室北京100850

目的探究六味地黄苷糖对创伤应激致恐惧敏化的保护作用及潜在机制。方法选取6周龄雄性SPF级C57BL/6J小鼠,分为空白对照组、对照组、创伤应激组和创伤后药物保护组[LW-AFC,1.6 g/(kg·d),创伤后连续灌胃2周],考察各组小鼠在新环境、社会... 详细信息

目的探究六味地黄苷糖对创伤应激致恐惧敏化的保护作用及潜在机制。方法选取6周龄雄性SPF级C57BL/6J小鼠,分为空白对照组、对照组、创伤应激组和创伤后药物保护组[LW-AFC,1.6 g/(kg·d),创伤后连续灌胃2周],考察各组小鼠在新环境、社会交互以及观察性恐惧测试等非联想记忆依赖的恐惧敏化反应,并用Z-Score标准化的方法整合并评估运动距离、僵直时间、角落区停留时间等多个行为变量,以获得一个综合恐惧敏化得分,考察各组小鼠的恐惧敏化行为。ELISA法检测各组小鼠血清中促肾上腺皮质激素释放激素、促肾上腺皮质激素、皮质酮、肾素、血管紧张素Ⅱ、醛固酮的浓度。结果与对照组相比,创伤应激组小鼠在新环境测试时运动距离显著减少(P<0.0001)、僵直时间显著增加(P<0.0001)、角落区停留时间有增加趋势但差异无统计学意义、综合恐惧敏化得分显著升高(P<0.0001);在社会交互测试中,其运动距离显著减少(P<0.0001)、僵直时间显著增加(P<0.0001)、角落区停留时间显著增加(P<0.05)、综合恐惧敏化得分显著升高(P<0.0001);在观察性恐惧测试时,其运动距离显著减少(P<0.05)、僵直时间显著增加(P<0.0001)、角落停留时间显著增加(P<0.05)、综合恐惧敏化得分显著增加(P<0.0001)。与创伤应激组相比,创伤后药物保护组小鼠在3个测试中的各行为指标和综合恐惧敏化得分均有改善趋势,且在社会交互测试中的僵直时间(P<0.05)及综合恐惧敏化得分(P<0.05)存在统计学差异,在观察性恐惧测试中的僵直时间(P<0.05)及综合恐惧敏化得分(P<0.01)存在统计学差异。与空白对照组相比,对照组和创伤应激组小鼠在恐惧敏化测试后肾素和醛固酮水平均有升高趋势,且创伤应激组小鼠肾素和醛固酮水平均显著升高(P<0.01、P<0.05);与创伤应激组相比,创伤后药物保护组小鼠肾素和醛固酮水平有所降低且醛固酮水平差异存在统计学意义(P<0.05)。结论创伤应激小鼠在新环境、社会交互和观察性恐惧中均具有明显的恐惧敏化行为,其可能与肾素-血管紧张素-醛固酮系统的过度激活有关;LW-AFC对创伤应激小鼠在社会交互和观察性恐惧中的恐惧敏化行为具有明显的改善作用,其可能与调节创伤应激小鼠肾素-血管紧张素-醛固酮系统有关。

关键词：创伤应激恐惧敏化下丘脑-垂体-肾上腺轴肾素-血管紧张素-醛固酮系统六味地黄苷糖

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Hepatic metabolomics combined with network pharmacology to reveal the correlation between the anti-depression effect and nourishing blood effect of Angelicae Sinensis Radix

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Chinese Journal of Natural Medicines 2023年第3期21卷 197-213页

作者： GONG wenxia XU Shaohua SONG Yapeng ZHOU Yuzhi qin Xuemei Modern Research Center for Traditional Chinese Medicine Shanxi UniversityTaiyuan 030006China Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education Taiyuan 030006China Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province Taiyuan 030006China

Angelicae Sinensis Radix(AS)is reproted to exert anti-depression effect(ADE)and nourishing blood effect(NBE)in a rat model of depression.The correlation between the two therapeutic effects and its underlying mechanisms deserves further study.The current study is designed to explore the underlying mechanisms of correlation between the ADE and NBE of AS based on hepatic metabonomics,network pharmacology and molecular docking.According to metabolomics analysis,30 metabolites involved in 11 metabolic pathways were identified as the potential metabolites for depression.Furthermore,principal component analysis and correlation analysis showed that glutathione,sphinganine,and ornithine were related to pharmacodynamics indicators including behavioral indicators and hematological indicators,indicating that metabolic pathways such as sphingolipid metabolism were involved in the ADE and NBE of AS.Then,a target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis,where a total of 107 pathways were collected.Moreover,37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer(UPLC-Triple-TOF/MS)in AS extract that passed the filtering criteria were used for network pharmacology,where 46 targets were associated with the ADE and NBE of AS.Pathway enrichment analysis further indicated the involvement of sphingolipid metabolism in the ADE and NBE of AS.Molecular docking analysis indciated that E-ligustilide in AS extract exhibited strong binding activity with target proteins(PIK3CA and PIK3CD)in sphingolipid metabolism.Further analysis by Western blot verified that AS regulated the expression of PIK3CA and PIK3CD on sphingolipid metabolism.Our results demonstrated that sphingolipid metabolic pathway was the core mechanism of the correlation between the ADE and NBE of AS.

关键词： Angelicae Sinensis Radix Blood deficiency syndrome Depression Metabonomics Network pharmacology Sphingolipid metabolism

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大柴旦热泉成因及其富硼锂机制研究进展

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盐湖研究 2024年第1期32卷 120-127页

作者：莫生鹏李庆宽李雯霞袁秦秦占杰都永生中国科学院青海盐湖研究所中国科学院盐湖资源综合高效利用重点实验室青海西宁810008 青海省盐湖地质与环境重点实验室青海西宁810008 中国科学院大学北京100049

大柴旦热泉成因及其硼锂富集机制研究是系统揭示该区域富硼锂盐湖卤水矿床成矿规律的关键环节,同时对青藏高原同类型富硼锂热泉深部水文过程的精细研究具有重要的参考价值。本文从地热学的视角梳理并评述了大柴旦热泉成因的研究现状,重... 详细信息

大柴旦热泉成因及其硼锂富集机制研究是系统揭示该区域富硼锂盐湖卤水矿床成矿规律的关键环节,同时对青藏高原同类型富硼锂热泉深部水文过程的精细研究具有重要的参考价值。本文从地热学的视角梳理并评述了大柴旦热泉成因的研究现状,重点探讨了大柴旦热泉的水源补给端元、热源及其储热机制、热泉的硼锂物源及其富集过程。研究结果初步显示,大柴旦热泉水源以大气降水为主,在高山区为冰雪融水,补给高程约为5980 m,热储温度约为194.5℃,循环深度约为7630 m,上升过程中混入了约66%的冷水;岩浆流体的补给或岩浆脱气过程可能为热泉提供了热量;热泉中硼锂的物源可能来自花岗岩源岩的高温水岩淋滤、岩浆流体补给或岩浆脱气输入以及风成沉积物中易溶盐类矿物溶解的共同贡献。大柴旦热泉地热系统及其战略资源元素富集过程的整体研究仍比较薄弱,尤其是不同补给端元贡献的定量研究,硼锂岩石地球化学行为的厘定,深部水岩作用的模拟等仍需要进一步开展详细的研究工作。

关键词：热泉成因岩浆流体硼锂物源地热系统大柴旦

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轻型汽油车NH_(3)排放研究

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汽车工程 2024年第3期46卷 483-488页

作者：方娜陈涛管永超方勇万建刘成田颖秦建宾王小涛康文霞东风汽车集团有限公司技术中心武汉430058

研究了某1.5T SUV车不同排放测试循环(WLTC与CLTC)和催化剂不同状态(新鲜和老化)对NH_(3)排放的影响。通过试验研究表明:发动机原始NH_(3)排放量很低,而经过第一块三元催化剂后,NH_(3)排放量大幅增加。催化剂老化后OSC降低,内部空燃比... 详细信息

研究了某1.5T SUV车不同排放测试循环(WLTC与CLTC)和催化剂不同状态(新鲜和老化)对NH_(3)排放的影响。通过试验研究表明:发动机原始NH_(3)排放量很低,而经过第一块三元催化剂后,NH_(3)排放量大幅增加。催化剂老化后OSC降低,内部空燃比波动幅度大,经过老化催化剂的NH_(3)排放相对新鲜催化剂的NH_(3)排放有所增加。催化剂状态、排放测试循环和发动机空燃比等对NH_(3)排放有明显影响,这些对于催化剂设计和标定优化均有指导意义。

关键词： NH_(3)排放三元催化剂排放循环空燃比

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Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase

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Journal of Pharmaceutical Analysis 2023年第6期13卷 640-659页

作者： Congcong Chen wenxia Gong Junshen Tian Xiaoxia Gao Xuemei qin Guanhua Du Yuzhi Zhou Modern Research Center for Traditional Chinese Medicine The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of EducationShanxi UniversityTaiyuan030006China Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province Shanxi UniversityTaiyuan030006China Institute of Materia Medica Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

关键词： Radix Bupleuri Radix Paeoniae Alba Hepatotoxicity Gut microbiota Saikosaponins Combination mechanisms

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