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Berberine ameliorates chronic kidney disease through inhibiting the production of gut-derived uremic toxins in the gut microbiota

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1537-1553页

作者： Libin Pan Hang Yu Jie Fu Jiachun Hu Hui Xu Zhengwei Zhang Mengmeng Bu Xinyu Yang Haojian Zhang Jinyue Lu Jiandong Jiang Yan Wang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences/Peking Union Medical CollegeBeijing 100050China Received 5 September 2022Revised 8 November

At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long ***,studies on the gut—kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney *** study showed that berberine,a natural drug with low oral availability,significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins,including ***,berberine reduced the content of pcresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine—p-cresol pathway of the intestinal ***,berberine increased the butyric acid producing bacteria and the butyric acid content in feces,while decreased the renal toxic trimethylamine *** findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut—kidney axis.

关键词： Chronic kidney disease Gut microbiota Berberine Gut—kidney axis Clostridium p-Cresol uremic toxins p-Cresol sulfate

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Understanding and Therapeutic Strategies of Chinese Medicine on Gut-Derived uremic toxins in Chronic Kidney Disease

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Chinese Journal of Integrative Medicine 2018年第6期24卷 403-405页

作者： GUO Chuan RAO XIANG-rong Department of Nephrology Guang'anmen HospitalChina Academy of Chinese Medical Sciences

Chronic kidney disease （CKD） is a major disease that threatens human health. With the progression of CKD, the risk of cardiovascular death increases, which is associated with the elevated levels of uremic toxins （UTs）. Representative toxins such as indoxyl sulfate and p-cresyl sulfate are involed in CKD progression and cardiovascular events inseparable from the key role of endothelial dysfunction. The therapeutic strategies of UTs are aimed at signaling pathways that target the levels and damage of toxins in modem medicine. There is a certain relevance between toxins and ＂turbid toxin＂ in the theory of Chinese medicine （CM）. CM treatments have been demonstrated to reduce the damage of gut-derived toxins to the heart, kidney and blood vessels. Modern medicine still lacks evidence-based therapies, so it is necessary to explore the treatments of CM.

关键词： chronic kidney disease uremic toxins therapeutic strategies Chinese medicine

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Cardiorenal syndrome： pathophysiological mechanism, preclinical models, novel contributors and potential therapies

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Chinese Medical Journal 2014年第16期127卷 3011-3018页

作者： Fu Qiang Cao Longxing Li Huang Wang Binghui Li Zhiliang Cardiovascular Division Zhujiang Hospital Southern Medical University Guangzhou Guangdong 510280 China Centre of Cardiovascular Research and Education in Therapeutics Department of Epidemiology and Preventive Medicine School ofPublic Health and Preventive Medicine Faculty of Medicine Nursingand Health Sciences Monash University Melbourne Australia

Objective To review the current knowledge about the pathophysiological mechanisms,preclinical models,novel contributors and potential therapies of cardiorenal *** sources The literature concerning cardioranal syndrome in this review was collected from PubMed published in English up to January *** selection Original articles and critical reviews related to cardiorenal syndrome were selected and carefully *** Cardiorenal syndrome is a condition characterized by kidney and heart failure where failure of one organ worsens the function of the other thus further accelerating the progressive failure of both *** pathophysiology of cardiorenal syndrome is not fully understood,but may be caused by a complex combination of neurohormonal system activation,endothelial dysfunction,proteinuria,oxidative stress,uremic toxins and other *** cardiorenal syndrome is still a major therapeutic challenge in clinical practice because many of the drugs used to control heart failure can worsen renal function,and vice ***-dialyzable uremic toxins,such as indoxyl sulfate,causing detrimental effects on the heart and kidney as well as stimulation of inflammatory responses,may be an effective therapeutic target for cardiorenal *** Suitable disease models of cardiorenal syndrome are urgently needed to investigate the pathophysiology and effective therapeutic approaches to the ***-dialyzable protein-bound uremic toxins that may have cardiac and renal effects may provide therapeutic benefit to cardiorenal syndrome patients.

关键词： cardiorenal syndrome pathophysiology preclinical models uremic toxins

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Role of β2-microglobulin in uremic patients may be greater than originally suspected

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World Journal of Nephrology 2015年第1期4卷 98-104页

作者： Aysegul Zumrutdal Nephrology Department Baskent University Adana Teaching and Research Center Baskent University Hospital YuregirAdana 01230Turkey

The role of beta2-microglobulin(β2M) in dialysisrelated amyloidosis as a specific amyloid precursor was defined in the 1980 s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was probably the first time in the available literature, we provided data about the association betweenβ2M and early-onset atherosclerosis in hemodialysis patients without co-morbidities. In recent years, the role of uremic toxins in uremic atherosclerosis and the interest in β2M as a marker of cardiovascular(CV) and/or mortality risk have grown. In the current literature,clinical studies suggest that β2M is an independent, significant predictor of mortality, not only in dialysis patients, but also in predialysis patients and in the highrisk portion of the general population, and it seems to be a factor strongly linked to the presence and severity of CV disease. It is still unknown whether β2M is only a uremic toxin marker or if it also has an active role in vascular damage, but data support that it may reflect an increased burden of systemic atherosclerosis in a setting of underlying chronic kidney disease. Thus, although there have been some inconsistencies among the various analyses relating to β2M, it promises to be a novel risk marker of kidney function in the awareness and detection of high-risk patients. However, more research is required to establish the pathophysiological relationships between retained uremic toxins and further biochemical modifications in the uremic milieu to get answers to the questions of why and how. In this review, the recent literature about the changing role of β2M in uremic patients will be examined.

关键词： Beta2-microglobulin Carotid atherosclerosis Cardiovascular disease Cardiovascular risk Coronary artery disease Hemodialysis Mortality Uremia uremic toxins

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