Anti-Inflammatory Activation of Phellodendri Chinensis Cortex is Mediated by Berberine Erythrocytes Self-Assembly Targeted Delivery System

BACKGROUND: Berberine (BBR) is the primary active component of Phellodendri Chinensis Cortex (PCC), which has been traditionally used to treat inflammatory diseases. However, the discrepancy between its low bioavailability and significant therapeutic effect remains obscure. The purpose of this study...

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Autores principales: Li, Minhua, Qin, Zehui, Yu, Qiuxia, Huang, Ziwei, Cheng, Juanjuan, Zhong, Linjiang, Liu, Yuhong, Xie, Jianhui, Li, Yucui, Chen, Jiannan, Zhan, Ruoting, Su, Ziren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793729/
https://www.ncbi.nlm.nih.gov/pubmed/36583113
http://dx.doi.org/10.2147/DDDT.S385301
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author Li, Minhua
Qin, Zehui
Yu, Qiuxia
Huang, Ziwei
Cheng, Juanjuan
Zhong, Linjiang
Liu, Yuhong
Xie, Jianhui
Li, Yucui
Chen, Jiannan
Zhan, Ruoting
Su, Ziren
author_facet Li, Minhua
Qin, Zehui
Yu, Qiuxia
Huang, Ziwei
Cheng, Juanjuan
Zhong, Linjiang
Liu, Yuhong
Xie, Jianhui
Li, Yucui
Chen, Jiannan
Zhan, Ruoting
Su, Ziren
author_sort Li, Minhua
collection PubMed
description BACKGROUND: Berberine (BBR) is the primary active component of Phellodendri Chinensis Cortex (PCC), which has been traditionally used to treat inflammatory diseases. However, the discrepancy between its low bioavailability and significant therapeutic effect remains obscure. The purpose of this study was to explore the previously unsolved enigma of the low bioavailability of BBR and its appreciable anti-inflammatory effect to reveal the action mechanism of BBR and PCC. METHODS: The quantitative analysis of BBR and its metabolite oxyberberine (OBB) in blood and tissues was performed using high-performance liquid chromatography to investigate the conversion and distribution of BBR/OBB mediated by erythrocytes. Routine blood tests and immunohistochemical staining were used to explore the potential relationship between the amounts of monocyte/macrophage and the drug concentration in erythrocytes and tissues (liver, heart, spleen, lung, kidney, intestine, muscle, brain and pancreas). To comparatively explore the anti-inflammatory effects of BBR and OBB, the acetic acid-induced vascular permeability mice model and lipopolysaccharide-induced RAW 264.7 macrophages were employed. RESULTS: Nearly 92% of BBR existed in the erythrocytes in rats. The partition coefficient of BBR between plasma and erythrocytes (Kp/b) decreased with time. OBB was found to be the oxidative metabolite of BBR in erythrocytes. Proportion of BBR/OBB in erythrocytes changed from 9.38% to 16.30% and from 13.50% to 46.24%, respectively. There was a significant relationship between the BBR/OBB concentration in blood and monocyte depletion after a single administration of BBR. BBR/OBB was transported via erythrocytes to various tissues (liver, kidney, spleen, lung, and heart, etc), with the liver achieving the highest concentration. OBB exhibited similar anti-inflammatory effect in vitro and in vivo as BBR with much smaller dosage. CONCLUSION: BBR was prodominantly found in erythrocytes, which was critically participated in the biodistribution, pharmacokinetics, metabolism and target delivery of BBR and its metabolite. The anti-inflammatory activity of BBR and PCC was intimately associated with the metabolism into the active congener OBB and the targeted delivery to monocytes/macrophages mediated by the erythrocytes.
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spelling pubmed-97937292022-12-28 Anti-Inflammatory Activation of Phellodendri Chinensis Cortex is Mediated by Berberine Erythrocytes Self-Assembly Targeted Delivery System Li, Minhua Qin, Zehui Yu, Qiuxia Huang, Ziwei Cheng, Juanjuan Zhong, Linjiang Liu, Yuhong Xie, Jianhui Li, Yucui Chen, Jiannan Zhan, Ruoting Su, Ziren Drug Des Devel Ther Original Research BACKGROUND: Berberine (BBR) is the primary active component of Phellodendri Chinensis Cortex (PCC), which has been traditionally used to treat inflammatory diseases. However, the discrepancy between its low bioavailability and significant therapeutic effect remains obscure. The purpose of this study was to explore the previously unsolved enigma of the low bioavailability of BBR and its appreciable anti-inflammatory effect to reveal the action mechanism of BBR and PCC. METHODS: The quantitative analysis of BBR and its metabolite oxyberberine (OBB) in blood and tissues was performed using high-performance liquid chromatography to investigate the conversion and distribution of BBR/OBB mediated by erythrocytes. Routine blood tests and immunohistochemical staining were used to explore the potential relationship between the amounts of monocyte/macrophage and the drug concentration in erythrocytes and tissues (liver, heart, spleen, lung, kidney, intestine, muscle, brain and pancreas). To comparatively explore the anti-inflammatory effects of BBR and OBB, the acetic acid-induced vascular permeability mice model and lipopolysaccharide-induced RAW 264.7 macrophages were employed. RESULTS: Nearly 92% of BBR existed in the erythrocytes in rats. The partition coefficient of BBR between plasma and erythrocytes (Kp/b) decreased with time. OBB was found to be the oxidative metabolite of BBR in erythrocytes. Proportion of BBR/OBB in erythrocytes changed from 9.38% to 16.30% and from 13.50% to 46.24%, respectively. There was a significant relationship between the BBR/OBB concentration in blood and monocyte depletion after a single administration of BBR. BBR/OBB was transported via erythrocytes to various tissues (liver, kidney, spleen, lung, and heart, etc), with the liver achieving the highest concentration. OBB exhibited similar anti-inflammatory effect in vitro and in vivo as BBR with much smaller dosage. CONCLUSION: BBR was prodominantly found in erythrocytes, which was critically participated in the biodistribution, pharmacokinetics, metabolism and target delivery of BBR and its metabolite. The anti-inflammatory activity of BBR and PCC was intimately associated with the metabolism into the active congener OBB and the targeted delivery to monocytes/macrophages mediated by the erythrocytes. Dove 2022-12-23 /pmc/articles/PMC9793729/ /pubmed/36583113 http://dx.doi.org/10.2147/DDDT.S385301 Text en © 2022 Li et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Li, Minhua
Qin, Zehui
Yu, Qiuxia
Huang, Ziwei
Cheng, Juanjuan
Zhong, Linjiang
Liu, Yuhong
Xie, Jianhui
Li, Yucui
Chen, Jiannan
Zhan, Ruoting
Su, Ziren
Anti-Inflammatory Activation of Phellodendri Chinensis Cortex is Mediated by Berberine Erythrocytes Self-Assembly Targeted Delivery System
title Anti-Inflammatory Activation of Phellodendri Chinensis Cortex is Mediated by Berberine Erythrocytes Self-Assembly Targeted Delivery System
title_full Anti-Inflammatory Activation of Phellodendri Chinensis Cortex is Mediated by Berberine Erythrocytes Self-Assembly Targeted Delivery System
title_fullStr Anti-Inflammatory Activation of Phellodendri Chinensis Cortex is Mediated by Berberine Erythrocytes Self-Assembly Targeted Delivery System
title_full_unstemmed Anti-Inflammatory Activation of Phellodendri Chinensis Cortex is Mediated by Berberine Erythrocytes Self-Assembly Targeted Delivery System
title_short Anti-Inflammatory Activation of Phellodendri Chinensis Cortex is Mediated by Berberine Erythrocytes Self-Assembly Targeted Delivery System
title_sort anti-inflammatory activation of phellodendri chinensis cortex is mediated by berberine erythrocytes self-assembly targeted delivery system
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793729/
https://www.ncbi.nlm.nih.gov/pubmed/36583113
http://dx.doi.org/10.2147/DDDT.S385301
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