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Huang-Kui-Si-Wu Formula decreases uremic toxin production by modulating intestinal microbial metabolic pathways
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Jing-bo LU1, 2, 3, Ying-yi WANG1, 2, 3, Sen ZHANG1, 2, 3, Jian-ping LI1, 2, 3, Cheng-xi LI1, 2, 3, Xue-jun XU1, 2, 3, Yin PENG1, 2, 3, Chen-kai CHEN1, 2, 3, Jian-ming GUO1, 2, 3, *, Jin-ao DUAN1, 2, 3, *
Acta Pharmaceutica Sinica | 2020, 55(6) : 1229 - 1236
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Acta Pharmaceutica Sinica | 2020, 55(6): 1229-1236
Original Articles
Huang-Kui-Si-Wu Formula decreases uremic toxin production by modulating intestinal microbial metabolic pathways
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Jing-bo LU1, 2, 3, Ying-yi WANG1, 2, 3, Sen ZHANG1, 2, 3, Jian-ping LI1, 2, 3, Cheng-xi LI1, 2, 3, Xue-jun XU1, 2, 3, Yin PENG1, 2, 3, Chen-kai CHEN1, 2, 3, Jian-ming GUO1, 2, 3, *, Jin-ao DUAN1, 2, 3, *
Affiliations
  • 1. Jiangsu Key Laboratory of High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China
  • 2. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources, Nanjing University of Chinese Medicine, Nanjing 210023, China
  • 3. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
Published: 2020-06-12 doi: 10.16438/j.0513-4870.2019-0852
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Huang-Kui-Si-Wu Formula (HKSWF) can reduce the accumulation of uremic toxin p-cresyl sulfate (PCS) and its precursor p-cresol (PC) in a rat model of chronic kidney disease (CKD) and delay the progression of CKD. However, the mechanism by which HKSWF decreases PC accumulation is not clear. This study investigated the effect of HKSWF on PC production in intestinal microbes as well as its mechanism of action. After CKD model rats were given HKSWF by intragastric administration, feces were collected to analyze the gut bacterial composition by 16S rDNA sequencing technology. All procedures were approved by the Institutional Animal Care and Use Committee of the Nanjing University of Chinese Medicine. The results showed that HKSWF inhibited PC production without decreasing the abundance of harmful bacteria. HPLC-UV-FLD was used to detect p-cresol. An in vitro anaerobic culture system was used to study the effect and mechanism of action of HKSWF on PC production in gut bacteria. The results show that food-derived tyrosine (Tyr) could significantly promote PC production in intestinal bacteria, and HKSWF (4000, 400, 40 μg·mL-1) could dose-dependently inhibit PC production in gut bacteria in vitro. HKSWF inhibited bacterial PC synthesis by two pathways: it decreased the oxidation pathway from 82.83% to 38.87%, and increased the reductive pathway from 17.17% to 61.13%. This result suggests that HKSWF could inhibit PC production by switching tyrosine metabolism from an oxidative pathway to a reductive pathway. Secondly, HKSWF could directly inhibit the oxidative pathway of tyrosine and decrease the decomposition of PHA, thereby inhibiting PC production. These results suggest that HKSWF could inhibit the formation of harmful uremic toxins by modulating the metabolic pathway of PC in gut microbiota and thereby delaying CKD progression.

chronic kidney disease  /  uremic toxin  /  p-cresyl sulfate  /  p-cresol  /  gut bacteria  /  Huang-Kui-Si-Wu Formula
Jing-bo LU, Ying-yi WANG, Sen ZHANG, Jian-ping LI, Cheng-xi LI, Xue-jun XU, Yin PENG, Chen-kai CHEN, Jian-ming GUO, Jin-ao DUAN. Huang-Kui-Si-Wu Formula decreases uremic toxin production by modulating intestinal microbial metabolic pathways[J]. Acta Pharmaceutica Sinica, 2020 , 55 (6) : 1229 -1236 . DOI: 10.16438/j.0513-4870.2019-0852
Year 2020 volume 55 Issue 6
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Article Info
doi: 10.16438/j.0513-4870.2019-0852
  • Receive Date:2019-10-29
  • Online Date:2026-01-21
  • Published:2020-06-12
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History
  • Received:2019-10-29
  • Revised:2020-01-07
Funding
Affiliations
    1. Jiangsu Key Laboratory of High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China
    2. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources, Nanjing University of Chinese Medicine, Nanjing 210023, China
    3. National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
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Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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