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Qiu Q, Fu F, Wu Y, Han C, Pu W, Wen L, Xia Q, Du D. Rhei Radix et Rhizoma and its anthraquinone derivatives: Potential candidates for pancreatitis treatment. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 129:155708. [PMID: 38733906 DOI: 10.1016/j.phymed.2024.155708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 04/22/2024] [Accepted: 05/02/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND Pancreatitis is a common exocrine inflammatory disease of the pancreas and lacks specific medication currently. Rhei Radix et Rhizoma (RR) and its anthraquinone derivatives (AQs) have been successively reported for their pharmacological effects and molecular mechanisms in experimental and clinical pancreatitis. However, an overview of the anti-pancreatitis potential of RR and its AQs is limited. PURPOSE To summarize and analyze the pharmacological effects of RR and its AQs on pancreatitis and the underlying mechanisms, and discuss their drug-like properties and future perspectives. METHODS The articles related to RR and its AQs were collected from the Chinese National Knowledge Infrastructure, Wanfang data, PubMed, and the Web of Science using relevant keywords from the study's inception until April first, 2024. Studies involving RR or its AQs in cell or animal pancreatitis models as well as structure-activity relationship, pharmacokinetics, toxicology, and clinical trials were included. RESULTS Most experimental studies are based on severe acute pancreatitis rat models and a few on chronic pancreatitis. Several bioactive anthraquinone derivatives of Rhei Radix et Rhizoma (RRAQs) exert local protective effects on the pancreas by maintaining pancreatic acinar cell homeostasis, inhibiting inflammatory signaling, and anti-fibrosis, and they improve systemic organ function by alleviating intestinal and lung injury. Pharmacokinetic and toxicity studies have revealed the low bioavailability and wide distribution of RRAQs, as well as hepatotoxicity and nephrotoxicity. However, there is insufficient research on the clinical application of RRAQs in pancreatitis. Furthermore, we propose effective strategies for subsequent improvement in terms of balancing effectiveness and safety. CONCLUSION RRAQs can be developed as either candidate drugs or novel lead structures for pancreatitis treatment. The comprehensive review of RR and its AQs provides references for optimizing drugs, developing therapies, and conducting future studies on pancreatitis.
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Affiliation(s)
- Qi Qiu
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Fei Fu
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China
| | - Yaling Wu
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China
| | - Chenxia Han
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Weiling Pu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Li Wen
- State Key Laboratory of Complex, Severe, and Rare Diseases, Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100073, China
| | - Qing Xia
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Dan Du
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China.
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Pan G, Wu Y, Liu Y, Zhou F, Li S, Yang S. Dachengqi decoction ameliorates sepsis-induced liver injury by inhibiting the TGF-β1/Smad3 pathways. J Tradit Complement Med 2024; 14:256-265. [PMID: 38707919 PMCID: PMC11068991 DOI: 10.1016/j.jtcme.2023.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 08/02/2023] [Accepted: 09/11/2023] [Indexed: 05/07/2024] Open
Abstract
Background Sepsis-induced acute liver injury (ALI) is a major contributor to mortality in septic patients. Exploring the pathogenesis and developing effective treatment strategies for sepsis-induced ALI is critical for improving patient outcomes. Dachengqi decoction (DCQD), which is a classic Chinese herbal medicine, has been shown to possess potent anti-inflammatory properties. However, the protective effects and underlying mechanisms of DCQD against sepsis-induced ALI remain unclear. This study aimed to investigate the protective effect of DCQD on sepsis-induced ALI and elucidate the involvement of the TGF-1β/Smad3 pathways. Methods A septic mouse model was established using caecal ligation and puncture (CLP) to evaluate the protective effect of DCQD on sepsis-induced ALI in vivo. An in vitro cellular inflammation model was established using LPS-stimulated LO2 cells to further investigate the underlying mechanism. Results DCQD (2.5, 5.0, and 10.0 g/kg body weight) was administered twice daily for 2 days and exerted a dose-dependent protective effect against sepsis-induced ALI. DCQD treatment significantly inhibited inappropriate inflammatory responses and oxidative stress in liver tissue. Moreover, DCQD maintained liver homeostasis by inhibiting hepatocyte apoptosis and improving sepsis-induced liver damage. In vivo and in vitro studies indicated that the TGF-β1/Smad3 signalling pathway played an important role in sepsis-induced ALI, and DCQD treatment significantly inhibited the activation of this pathway. Conclusions DCQD can effectively suppress excessive inflammatory responses and oxidative stress, leading to a substantial reduction in hepatocyte apoptosis in sepsis-induced ALI.
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Affiliation(s)
- Guangtao Pan
- Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, 224000, Yancheng, Jiangsu Province, PR China
| | - Yanran Wu
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei Province, PR China
| | - Yuhan Liu
- Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei Province, PR China
| | - Fangyuan Zhou
- Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei Province, PR China
| | - Sen Li
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei Province, PR China
| | - Shenglan Yang
- Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei Province, PR China
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Nie B, Yu R, Xu G, Chen Y, Deng C, Du J. Analysing pharmacodynamic interactions of traditional Chinese medicine in treating acute pancreatitis based on OPLS method. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2024; 16:1252-1260. [PMID: 38323334 DOI: 10.1039/d3ay02305b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
Acute pancreatitis (AP) is a surgical abdominal disease for which the Dachengqi Decoction (DCQD) of traditional Chinese medicine (TCM) is widely used in China. This study aims to analyse the pharmacodynamic interactions and quantitative relationship of DCQD in the treatment of AP based on orthogonal partial least squares (OPLS) analysis. The experimental data show organic chemical components as candidate pharmacodynamic substances (PS) in the blood and include pharmacodynamic indicators (PIs). Taking each PI as the target and using OPLS method to construct three types of mathematical equations, including the mathematical relationship between the pharmacodynamic substances and each target pharmacodynamic indicator (PS-TPI); the mathematical relationship between the pharmacodynamic substances, the pharmacodynamics indicators and each target pharmacodynamic indicator (PS, PI-TPI); and the mathematical relationship between the pharmacodynamic indicators and each target pharmacodynamic indicator (PI-TPI). Through analysis, we find that the R2Y(cum) values and VIP values indicate that PS and PI are the follow-up factors of TPI; the coefficient value indicates that there is a quantitative relationship between the PS and the TPI; and there also is a quantitative relationship between PI and TPI. The results demonstrated that PS and other PIs are the important influencing factors of TPI, and that there are interactions and quantitative relationships among the PIs.
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Affiliation(s)
- Bin Nie
- School of Computer Science, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
| | - Riyue Yu
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
| | - Guoliang Xu
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
| | - Yinfang Chen
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
| | - Chunhui Deng
- Department of Chemistry, Fudan University, Shanghai 200433, China.
| | - Jianqiang Du
- School of Computer Science, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
- School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004, China.
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Jiang J, Hou X, Xu K, Ji K, Ji Z, Xi J, Wang X. Bacteria-targeted magnolol-loaded multifunctional nanocomplexes for antibacterial and anti-inflammatory treatment. Biomed Mater 2024; 19:025029. [PMID: 38290149 DOI: 10.1088/1748-605x/ad2406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 01/30/2024] [Indexed: 02/01/2024]
Abstract
Natural plant-derived small molecules have shown great potential for their antimicrobial and anti-inflammatory properties. In this study, we successfully developed a nanocomplex consisting of magnolol (Mag), a surfactant with an 18 carbon hydrocarbon chain and multi-amine head groups (C18N3), and a peptide (cyclic 9-amino acid peptide (CARG)) with targeting capabilities forStaphylococcus aureus(S. aureus). The obtained Mag/C18N3/CARG nanocomplexes exhibited strong antibacterial activity againstS. aureus. Furthermore, they demonstrated anti-inflammatory effects by reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1βfrom macrophage inflammatory cells. This was achieved through downregulating the activation of NF-κB, KEAP1, and NRF2 signaling pathways. In a murine skin infection model, the Mag/C18N3/CARG nanocomplexes effectively suppressed the growth ofS. aureusin the infected area and promoted wound healing. Additionally, in a mouse model of acute kidney injury (AKI), the nanocomplexes significantly reduced the levels of blood urea nitrogen and creatinine, leading to a decrease in mortality rate. These findings demonstrate the potential of combining natural plant-derived small molecules with C18N3/CARG assemblies as a novel approach for the development of effective and safe antibacterial agents.
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Affiliation(s)
- Jian Jiang
- Central Laboratory, Binhai County People's Hospital, Clinical Medical College of Yangzhou University, Yancheng 224000, People's Republic of China
- Institute of Translational Medicine, Yangzhou University, Yangzhou 225009, People's Republic of China
| | - Xuefeng Hou
- Central Laboratory, Binhai County People's Hospital, Clinical Medical College of Yangzhou University, Yancheng 224000, People's Republic of China
| | - Kangjie Xu
- Central Laboratory, Binhai County People's Hospital, Clinical Medical College of Yangzhou University, Yancheng 224000, People's Republic of China
| | - Kangkang Ji
- Central Laboratory, Binhai County People's Hospital, Clinical Medical College of Yangzhou University, Yancheng 224000, People's Republic of China
| | - Zhongkai Ji
- Department of Orthopaedics, Binhai County People's Hospital, Yancheng 224000, People's Republic of China
| | - Juqun Xi
- Central Laboratory, Binhai County People's Hospital, Clinical Medical College of Yangzhou University, Yancheng 224000, People's Republic of China
- Institute of Translational Medicine, Yangzhou University, Yangzhou 225009, People's Republic of China
| | - Xin Wang
- Department of Critical Care Medicine, Binhai County People's Hospital, Yancheng 224000, People's Republic of China
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Shen X, Xie A, Li Z, Jiang C, Wu J, Li M, Yue X. Research Progress for Probiotics Regulating Intestinal Flora to Improve Functional Dyspepsia: A Review. Foods 2024; 13:151. [PMID: 38201179 PMCID: PMC10778471 DOI: 10.3390/foods13010151] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/05/2023] [Accepted: 12/08/2023] [Indexed: 01/12/2024] Open
Abstract
Functional dyspepsia (FD) is a common functional gastrointestinal disorder. The pathophysiology remains poorly understood; however, alterations in the small intestinal microbiome have been observed. Current treatments for FD with drugs are limited, and there are certain safety problems. A class of active probiotic bacteria can control gastrointestinal homeostasis, nutritional digestion and absorption, and the energy balance when taken in certain dosages. Probiotics play many roles in maintaining intestinal microecological balance, improving the intestinal barrier function, and regulating the immune response. The presence and composition of intestinal microorganisms play a vital role in the onset and progression of FD and serve as a critical factor for both regulation and potential intervention regarding the management of this condition. Thus, there are potential advantages to alleviating FD by regulating the intestinal flora using probiotics, targeting intestinal microorganisms. This review summarizes the research progress of probiotics regarding improving FD by regulating intestinal flora and provides a reference basis for probiotics to improve FD.
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Affiliation(s)
- Xinyu Shen
- College of Food Science, Shenyang Agricultural University, Shenyang 110866, China; (X.S.); (Z.L.); (C.J.); (J.W.)
| | - Aijun Xie
- Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 119077, Singapore;
| | - Zijing Li
- College of Food Science, Shenyang Agricultural University, Shenyang 110866, China; (X.S.); (Z.L.); (C.J.); (J.W.)
| | - Chengxi Jiang
- College of Food Science, Shenyang Agricultural University, Shenyang 110866, China; (X.S.); (Z.L.); (C.J.); (J.W.)
| | - Jiaqi Wu
- College of Food Science, Shenyang Agricultural University, Shenyang 110866, China; (X.S.); (Z.L.); (C.J.); (J.W.)
| | - Mohan Li
- College of Food Science, Shenyang Agricultural University, Shenyang 110866, China; (X.S.); (Z.L.); (C.J.); (J.W.)
| | - Xiqing Yue
- Shenyang Key Laboratory of Animal Product Processing, Shenyang Agricultural University, Shenyang 110866, China
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Sun J, Meng X, Huang D, Gong Z, Liu C, Liu T, Pan J, Lu Y, Zheng L. Pharmacokinetics and tissue distribution of four major bioactive components of Cynanchum auriculatum extract: a UPLC-MS/MS study in normal and functional dyspepsia rats. Front Pharmacol 2023; 14:1279971. [PMID: 37915410 PMCID: PMC10616469 DOI: 10.3389/fphar.2023.1279971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 10/04/2023] [Indexed: 11/03/2023] Open
Abstract
Introduction: Cynanchum auriculatum (CA) is usually used to treat digestive disorders, such as anorexia, enteritis, dysentery, and indigestion. Functional dyspepsia (FD) is characterized by a group of symptoms associated with the gastroduodenal region. Recent pharmacological studies have demonstrated the efficacy of CA for treating FD. However, the pharmacokinetics (PK) and tissue distribution of CA in physiological and FD states is still unclear. The present study aimed to clarify the differences in PK parameters and tissue distribution of the four major active components of CA (baishouwu benzophenone, deacylmet-aplexigenin, qingyangshengenin, and syringic acid) under both physiological and FD states. Methods: For this, normal and FD rats were orally administered 10 mg/kg CA extract. Then, plasma and tissue (heart, liver, spleen, lung, kidney, brain, stomach, and small intestine) samples were obtained. The four active components of CA in rat plasma and tissues were quantified by developing and validating a fast and reliable ultra-high-performance liquid chromatography-mass spectrometry method. Results: The area under the plasma concentration-time curve from time zero to time t (AUC0-t) of baishouwu benzophenone was significantly lower in the FD group than in the normal group (p < 0.01). The FD group had significantly lower (p < 0.001) apparent volume of distribution and plasma clearance of qing-yangshengenin and significantly higher (p < 0.05) AUC0-t of deacylmetaplexigenin and qingyangshengenin. The four active components were rapidly distributed into various tissues, and the main target organs of CA activity were the stomach and small intestine. In addition, baishouwu benzophenone, deacylmetaplexigenin, and qingyangshengenin could cross the blood-brain barrier, indicating that the brain may be another target organ in the treatment of FD. Discussion: These results indicate that the pathological state of FD alters the PK behavior and tissue distribution characteristics of baishouwu benzophenone, deacylmetaplexigenin, qingyangshengenin, and syringic acid in the CA extract, providing an experimental basis for the role of CA in FD treatment.
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Affiliation(s)
- Jia Sun
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China
- National Engineering Research Center of Miao’s Medicines, Guiyang, China
| | - Xin Meng
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China
- School of Pharmacy, Guizhou Medical University, Guiyang, China
| | - Di Huang
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China
- School of Pharmacy, Guizhou Medical University, Guiyang, China
| | - Zipeng Gong
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China
| | - Chunhua Liu
- Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guiyang, China
| | - Ting Liu
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China
| | - Jie Pan
- Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guiyang, China
| | - Yuan Lu
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China
| | - Lin Zheng
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China
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He X, Zhong Z, Wang Q, Jia Z, Lu J, Chen J, Liu P. Pharmacokinetics and tissue distribution of bleomycin-induced idiopathic pulmonary fibrosis rats treated with cryptotanshinone. Front Pharmacol 2023; 14:1127219. [PMID: 36969870 PMCID: PMC10034131 DOI: 10.3389/fphar.2023.1127219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/27/2023] [Indexed: 03/12/2023] Open
Abstract
Introduction: Cryptotanshinone(CTS), a compound derived from the root of Salvia miltiorrhiza, has been linked to various of diseases, particularly pulmonary fibrosis. In the current study, we investigated the benefit of CTS on Sprague-Dawley (SD) rats induced by bleomycin (BLM) and established high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods to compare pharmacokinetics and tissue distribution in subsequent normal and modulated SD rats.Methods: The therapeutic effect of CTS on BLM-induced SD rats was evaluated using histopathology, lung function and hydroxyproline content measurement, revealing that CTS significantly improved SD rats induced by BLM. Additionally, a simple, rapid, sensitive and specific HPLC-MS/MS method was developed to determine the pharmacokinetics of various components in rat plasma.Results: Pharmacokinetic studies indicated that CTS was slowly absorbed by oral administration and had low bioavailability and a slow clearance rate. The elimination of pulmonary fibrosis in 28-day rats was slowed down, and the area under the curve was increased compared to the control group. Long-term oral administration of CTS did not accumulate in vivo, but the clearance was slowed down, and the steady-state blood concentration was increased. The tissue distribution study revealed that CTS exposure in the lungs and liver.Discussion: The lung CTS exposure was significantly higher in the model group than in the control group, suggesting that the pathological changes of pulmonary fibrosis were conducive to the lung exposure of CTS and served as the target organ of CTS.
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Affiliation(s)
- Xiangjun He
- National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China
| | - Zhi Zhong
- National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China
| | - Quan Wang
- National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China
| | - Zhenmao Jia
- National and Local United Engineering Lab of Druggability and New Drugs Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China
| | - Jing Lu
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China
- *Correspondence: Jing Lu, ; Jianwen Chen, ; Peiqing Liu,
| | - Jianwen Chen
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China
- *Correspondence: Jing Lu, ; Jianwen Chen, ; Peiqing Liu,
| | - Peiqing Liu
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China
- *Correspondence: Jing Lu, ; Jianwen Chen, ; Peiqing Liu,
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Guo S, Yang L, Zhang Q, Zhang L, Li A. Metabolomics combined with serum pharmacochemistry discovering the potential effective compounds of Fangji Huangqi Tang against nephrotic syndrome. J Chromatogr B Analyt Technol Biomed Life Sci 2023; 1214:123532. [PMID: 36462401 DOI: 10.1016/j.jchromb.2022.123532] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 10/28/2022] [Accepted: 11/03/2022] [Indexed: 11/19/2022]
Abstract
Fangji Huangqi Tang (FHT) was first recorded in "Jin Gui Yao Lue," invented by the archaic Chinese medical doctor Zhongjing Zhang, and is a classic medicine that tonifies qi and expels wind, invigorates spleen for diuresis. A large number of literatures indicated that FHT showed a significant effect on Nephrotic Syndrome (NS). A comprehensive strategy was proposed to discover the potential effective compounds and therapeutic targets of FHT against NS as a case study. Serum metabolomics combined with multivariate statistical analysis was employed to analysis and screen the differential endogenous metabolites in serum samples of the control and model rats induced by Adriamycin. The correlation analysis between the efficacy biomarkers and different compounds absorbed in serum of FHT was conducted to explore the potential effective compounds of FHT against NS. With the help of network pharmacology, the therapeutic targets and the possible molecular mechanisms of FHT against NS were further investigated. Fifteen metabolites, including l-phenylalanine, 3-Hydroxybutyric acid and linolenic acid, were associated with renal damage based on the serum metabolomic results. Metabolic pathway analysis indicated that phenylalanine, tyrosine and tryptophan biosynthesis and linoleic acid metabolism were the key pathways associated with NS. Among them, 6 metabolites were defined as efficacy biomarkers such as uric acid, 2-methylbutyrylcarnitine and 10-HDA. The results of correlation analysis suggested that 14 constituents such as fanGhinoline, cycloastragenol, atractylenolide III, and glycyrrhetinic acid were recognized as potential effective compounds, whose potential protein targets participated in the MAPK signaling pathway, GnRH signaling pathway and aldoaterone-regulated sodium reabsorption. This study has clarified the potential effective compounds and therapeutic targets of FHT against NS. The results provided new evidence for the pharmacological mechanism of FHT on NS.
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Affiliation(s)
- Songjia Guo
- Nephrology Department, Shanxi Provincial People's Hospital, Taiyuan, China
| | - Liu Yang
- Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, China; Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, China; Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, China
| | - Qingyu Zhang
- Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, China; Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, China; Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, China
| | - Lichao Zhang
- Institutes of Biomedical Sciences of Shanxi University, Taiyuan 030006, China.
| | - Aiping Li
- Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, China; Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi Province, China; Modern Research Center for Traditional Chinese Medicine, The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, China.
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Yang X, Geng H, You L, Yuan L, Meng J, Ma Y, Gu X, Lei M. Rhein Protects Against Severe Acute Pancreatitis In vitro and In vivo by Regulating the JAK2/STAT3 Pathway. Front Pharmacol 2022; 13:778221. [PMID: 35370748 PMCID: PMC8969574 DOI: 10.3389/fphar.2022.778221] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 02/28/2022] [Indexed: 01/30/2023] Open
Abstract
Rhein is widely used in inflammation treatment in China, but its effects on severe acute pancreatitis (SAP) have not been studied closely. This study investigated rhein’s protective effects against SAP using in vitro and in vivo models to determine whether its protective mechanism regulated the Janus kinase two and signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway. Thirty-six male Sprague–Dawley rats were randomised into sham operation, SAP and rhein groups. The SAP model was induced by retrograde pancreatic bile duct injection of sodium taurocholate. Serum TNF-α and interleukin (IL)-6 levels were determined by ELISA, whereas serum amylase and lipase concentrations were measured using test kits. Western blot and/or immunohistochemistry quantified JAK2 and STAT3 expression. Furthermore, histopathological pancreatic changes were detected by haematoxylin and eosin staining. AR42J cells were randomly divided into the control, cerulein and rhein groups. Amylase activity was assessed using an amylase test kit; the tumour necrosis factor-α (TNF-α) expression was determined by enzyme-linked immunosorbent assay (ELISA). JAK2 and STAT3 protein expression were evaluated by western blot. SAP was concomitant with increased JAK2 and STAT3 expressions in vivo. Pre-treatment with rhein attenuated serum TNF–α and IL-6 levels effectively, and notably reduced p-JAK2, p-STAT3, JAK2 and STAT3 protein expression. Rhein significantly alleviated pancreatic histopathology. Compared to untreated groups, rhein significantly reduced amylase activity in supernatants of AR42J cells induced by cerulein in vitro. Furthermore, rhein altered JAK2 and STAT3 protein levels in AR42J cells after cerulein induction. Overall, rhein exerted protective effect on SAP in vitro and in vivo, possibly through the JAK2/STAT3 signalling pathway.
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Affiliation(s)
- Xiaofang Yang
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Huan Geng
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lijiao You
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lin Yuan
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jialei Meng
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yuhui Ma
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xuelian Gu
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ming Lei
- Department of Critical Care Medicine, Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Wang D, Wang XH, Yu X, Cao F, Cai X, Chen P, Li M, Feng Y, Li H, Wang X. Pharmacokinetics of Anthraquinones from Medicinal Plants. Front Pharmacol 2021; 12:638993. [PMID: 33935728 PMCID: PMC8082241 DOI: 10.3389/fphar.2021.638993] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 02/03/2021] [Indexed: 12/23/2022] Open
Abstract
Anthraquinones are bioactive natural products, some of which are active components in medicinal medicines, especially Chinese medicines. These compounds exert actions including purgation, anti-inflammation, immunoregulation, antihyperlipidemia, and anticancer effects. This study aimed to review the pharmacokinetics (PKs) of anthraquinones, which are importantly associated with their pharmacological and toxicological effects. Anthraquinones are absorbed mainly in intestines. The absorption rates of free anthraquinones are faster than those of their conjugated glycosides because of the higher liposolubility. A fluctuation in blood concentration and two absorption peaks of anthraquinones may result from the hepato-intestinal circulation, reabsorption, and transformation. Anthraquinones are widely distributed throughout the body, mainly in blood-flow rich organs and tissues, such as blood, intestines, stomach, liver, lung, kidney, and fat. The metabolic pathways of anthraquinones are hydrolysis, glycuronidation, sulfation, methylation/demethylation, hydroxylation/dehydroxylation, oxidation/reduction (hydrogenation), acetylation and esterification by intestinal flora and liver metabolic enzymes, among which hydrolysis, glycuronidation and sulfation are dominant. Of note, anthraquinones can be transformed into each other. The main excretion routes for anthraquinones are the kidney, recta, and gallbladder. Conclusion: Some anthraquinones and their glycosides, such as aloe-emodin, chrysophanol, emodin, physcion, rhein and sennosides, have attracted the most PK research interest due to their more biological activities and/or detectability. Anthraquinones are mainly absorbed in the intestines and are mostly distributed in blood flow-rich tissues and organs. Transformation into another anthraquinone may increase the blood concentration of the latter, leading to an increased pharmacological and/or toxicological effect. Drug-drug interactions influencing PK may provide insights into drug compatibility theory to enhance or reduce pharmacological/toxicological effects in Chinese medicine formulae and deserve deep investigation.
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Affiliation(s)
- Dongpeng Wang
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.,Biomedical Research Institute, Hubei Key Laboratory of Wudang Local Chinese Medicine Research and School of Pharmacy, Hubei University of Medicine, Shiyan, China
| | - Xian-He Wang
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiongjie Yu
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Fengjun Cao
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Xiaojun Cai
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Ping Chen
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Minglun Li
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Yibin Feng
- School of Chinese Medicine, The University of Hong Kong, Hong Kong, China
| | - Hongliang Li
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.,Biomedical Research Institute, Hubei Key Laboratory of Wudang Local Chinese Medicine Research and School of Pharmacy, Hubei University of Medicine, Shiyan, China
| | - Xuanbin Wang
- Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.,Biomedical Research Institute, Hubei Key Laboratory of Wudang Local Chinese Medicine Research and School of Pharmacy, Hubei University of Medicine, Shiyan, China.,Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
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11
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Yao JQ, Zhu L, Miao YF, Zhu L, Chen H, Yuan L, Hu J, Yi XL, Wu QT, Yang XJ, Wan MH, Tang WF. Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis. World J Gastroenterol 2020; 26:3056-3075. [PMID: 32587448 PMCID: PMC7304110 DOI: 10.3748/wjg.v26.i22.3056] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 03/26/2020] [Accepted: 05/12/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute pancreatitis (AP) is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction. Dachengqi decoction (DCQD) has a potential role in protecting the extrapancreatic organs, but the optimal oral administration time remains unclear.
AIM To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats.
METHODS This study consisted of two parts. In the first part, 24 rats were divided into a sham-operated group and three model groups. The four groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 4 h, 12 h, and 24 h postoperatively, respectively. Tail vein blood was taken at nine time points after administration, and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected. Finally, the concentrations of the major DCQD components in all samples were detected. In the second part, 84 rats were divided into a sham-operated group, as well as 4 h, 12 h, and 24 h treatment groups and corresponding control groups (4 h, 12 h, and 24 h control groups). Rats in the treatment groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 12 h, and 24 h postoperatively, respectively, and rats in the control groups were administered with normal saline at the same time points. Then, six rats from each group were euthanized at 4 h and 24 h after administration. Serum amylase and inflammatory mediators, and pathological scores of extrapancreatic organ tissues were evaluated.
RESULTS For part one, the pharmacokinetic parameters (C max, T max, T 1/2, and AUC 0 → t) of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later (12 h and 24 h) time points. For part two, delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels, and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration, while the results were similar between the treatment and corresponding control groups at 24 h after administration.
CONCLUSION Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats, demonstrating that the late time is the optimal dosing time.
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Affiliation(s)
- Jia-Qi Yao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lin Zhu
- Digestive System Department, Sichuan Integrative Medicine Hospital, Chengdu 610041, Sichuan Province, China
| | - Yi-Fan Miao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lv Zhu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Huan Chen
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ling Yuan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jing Hu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Lin Yi
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Qiu-Ting Wu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xi-Jing Yang
- Animal Experiment Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Mei-Hua Wan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Fu Tang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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12
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Wang Z, Gao Z, Wang A, Jia L, Zhang X, Fang M, Yi K, Li Q, Hu H. Comparative oral and intravenous pharmacokinetics of phlorizin in rats having type 2 diabetes and in normal rats based on phase II metabolism. Food Funct 2019; 10:1582-1594. [PMID: 30806398 DOI: 10.1039/c8fo02242a] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Phlorizin (PHZ), a type of dihydrochalcone widely found in Rosaceae such as apples, is the first compound discovered as a sodium-glucose cotransporter (SGLT) inhibitor. It has been confirmed to improve the symptoms of diabetes and diabetic complications effectively. Like other flavonoids, the bioavailability challenge of PHZ is the wide phase I and II metabolism in the digestive tract. In this study, we investigated the pharmacokinetics and contribution of phase II metabolism after the oral and intravenous administrations of PHZ in rats having type 2 diabetes (T2D) and in normal rats. The phase II metabolism characteristics of PHZ were investigated by treating plasma samples with β-glucuronidase/sulfatase. The contribution ratio of phase II metabolism of PHZ ranged from 41.9% to 69.0% after intravenous injection with three doses of PHZ in normal rats. Compared with the observations for normal rats, AUC0-t and Cmax of PHZ significantly increased and T1/2 of PHZ significantly decreased in T2D rats. PHZ was converted into phloretin (PHT) through an enzyme-catalyzed hydrolysis reaction, and PHT was further transformed into conjugates with glycose after both oral and intravenous administrations. Moreover, it was found that the bioavailability of PHZ was about 5% in T2D rats, which was significantly higher than that in normal rats (0%). In conclusion, compared with the observations for normal rats, the pharmacokinetic characteristics of PHZ significantly changed in T2D rats through oral and intravenous administrations. The bioavailability of PHZ significantly increased in T2D rats. Besides, the phase II metabolites of PHT were the major existing forms in blood after oral and intravenous administrations. Our results indicated that the phase II metabolism characteristics of PHZ should be considered when PHZ is applied for the treatment of diabetes as a drug or functional food.
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Affiliation(s)
- Zhanguo Wang
- Chengdu Holistic Integrative Medicine Collaborative Innovation Research Center, Aba Tibetan and Qiang Medicine Quality Evaluation Innovation Research Laboratory, School of Medicine and Nursing, Chengdu University, Longquan, Chengdu 610106, China
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Hu X, Liu S, Zhu J, Ni H. Dachengqi decoction alleviates acute lung injury and inhibits inflammatory cytokines production through TLR4/NF‐κB signaling pathway in vivo and in vitro. J Cell Biochem 2019; 120:8956-8964. [PMID: 30838705 DOI: 10.1002/jcb.27615] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 08/12/2018] [Accepted: 08/14/2018] [Indexed: 12/16/2022]
Affiliation(s)
- XingXing Hu
- Department of Emergency, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing China
| | - Shang Liu
- Physical & Environmental Sciences University of Toronto Toronto Canada
| | - Jin Zhu
- Department of Emergency Medicine Nanjing University of Chinese Medicine Nanjing China
| | - HaiBin Ni
- Department of Emergency, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing China
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14
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Nong F, Zhao Z, Luo X, Liu C, Li H, Liu Q, Wen B, Zhou L. Evaluation of the influence of mirabilite on the absorption and pharmacokinetics of the ingredients in Dahuang‐mudan decoction by a validated UPLC/QTOF–MS/MS method. Biomed Chromatogr 2018; 33:e4423. [DOI: 10.1002/bmc.4423] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 09/21/2018] [Accepted: 10/25/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Feifei Nong
- School of Pharmaceutical ScienceGuangzhou University of Chinese Medicine Guangzhou China
- Pi‐Wei InstituteGuangzhou University of Chinese Medicine Guangzhou China
| | - Zhongxiang Zhao
- School of Pharmaceutical ScienceGuangzhou University of Chinese Medicine Guangzhou China
| | - Xia Luo
- School of Pharmaceutical ScienceGuangzhou University of Chinese Medicine Guangzhou China
| | - Chang Liu
- School of Pharmaceutical ScienceGuangzhou University of Chinese Medicine Guangzhou China
| | - Hui Li
- School of Pharmaceutical ScienceGuangzhou University of Chinese Medicine Guangzhou China
| | - Qi Liu
- School of Pharmaceutical ScienceGuangzhou University of Chinese Medicine Guangzhou China
| | - Bin Wen
- Pi‐Wei InstituteGuangzhou University of Chinese Medicine Guangzhou China
| | - Lian Zhou
- School of Pharmaceutical ScienceGuangzhou University of Chinese Medicine Guangzhou China
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15
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Protective Effects of Rhubarb in Rats with Acute Pancreatitis and the Role of Its Active Compound Rhein on Mitochondria of Exocrine Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:7321352. [PMID: 30140298 PMCID: PMC6081545 DOI: 10.1155/2018/7321352] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 06/25/2018] [Indexed: 02/05/2023]
Abstract
Da-Cheng-Qi-Decoction (DCQD) has been used in the treatment of acute pancreatitis (AP) in China for many years. The aim of the current study was to examine the principal ingredient rhubarb of DCQD and its potential link to the pancreatic repair effects in rats with AP. The pancreatitis was induced in SD rats by intraperitoneal injections of cerulein. The results showed that rhubarb significantly increased blood perfusion of pancreatic tissue, reversed mitochondrial damage, and promoted pancreatic acinar and stellate cell proliferation. In addition, the rhein (from rhubarb) had high distribution in pancreas tissue and protected mitochondria in AR42J cells via the activation of PI3K/AKT/mTOR signaling pathway and activity inhibition of AMPK (P < 0.05). The results provide some preclinical evidence on the protective effects of DCQD for the treatment of acute pancreatitis. Rhein is regarded to be the active compound of rhubarb and can be expected to be a new compound for the treatment of AP.
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16
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Yuan L, Zhu L, Zhang Y, Chen H, Kang H, Li J, Zhao X, Wan M, Miao Y, Tang W. Effect of Da-Cheng-Qi decoction for treatment of acute kidney injury in rats with severe acute pancreatitis. Chin Med 2018; 13:38. [PMID: 30013616 PMCID: PMC6045888 DOI: 10.1186/s13020-018-0195-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 07/09/2018] [Indexed: 02/05/2023] Open
Abstract
Background The traditional Chinese formula Da-Cheng-Qi-decoction (DCQD) has been used to treat acute pancreatitis for decades. DCQD could ameliorate the disease severity and the complications of organ injuries, including those of the liver and lungs. However, the pharmacological effects in the kidney, a target organ, are still unclear. This study aimed to investigate the herbal tissue pharmacology of DCQD for acute kidney injury (AKI) in rats with severe acute pancreatitis (SAP). Methods Rats were randomly divided into the sham-operation group (SG), the model group (MG) and the low-, medium- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Sodium taurocholate (3.5%) was retrogradely perfused into the biliopancreatic duct to establish the model of SAP in rats. Different doses of DCQD were administered to the treatment groups 2 h after the induction of SAP. The major components of DCQD in kidney tissues were detected by HPLC–MS/MS. Inflammatory mediators in the kidney tissues, as well as serum creatinine (Scr), blood urea nitrogen (BUN) and pathologic scores, were also evaluated. Results Ten components of DCQD were detected in the kidneys of the treatment groups, and their concentrations increased dose-dependently. Compared with the SG, the levels of inflammatory mediators, Scr, BUN and pathological scores in the MG were obviously increased (p < 0.05). The high dose of DCQD showed a maximal effect in downregulating the pro-inflammatory mediators interleukin-6 (IL)-6 and tumour necrosis factor-α (TNF-α), upregulating anti-inflammatory mediators IL-4 and IL-10 in the kidney and alleviating the pathological damages. DCQD decreased the pancreas and kidney pathological scores of rats with SAP, especially in the HDG (p < 0.05). Compared with the MG, the level of Scr in the HDG was significantly decreased (p < 0.05). Conclusions DCQD ameliorated AKI in rats with SAP via regulating the inflammatory response, which might be closely related to the distribution of its components in the kidney. Electronic supplementary material The online version of this article (10.1186/s13020-018-0195-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ling Yuan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Lv Zhu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Yumei Zhang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Huan Chen
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Hongxin Kang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Juan Li
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Xianlin Zhao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Meihua Wan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Yifan Miao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Wenfu Tang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
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Zhu L, Li JY, Zhang YM, Kang HX, Chen H, Su H, Li J, Tang WF. Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury. World J Gastroenterol 2017; 23:8169-8181. [PMID: 29290653 PMCID: PMC5739923 DOI: 10.3748/wjg.v23.i46.8169] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 10/24/2017] [Accepted: 11/14/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction (SJD) in rats with acute pancreatitis (AP) for protecting against multiple organ injury.
METHODS An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group (CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD (CG + SJD) and a model group treated with SJD (MG + SJD), both of which were orally administered with SJD (5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male Sprague-Dawley rats were randomly divided into a CG, an AP model group (MG), and an SJD treated AP group (SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination.
RESULTS The MG + SJD displayed significantly shorter mean residence time (MRT) and higher clearance (CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve (AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α levels in the MG were higher than those in the CG (P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG (P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG (P < 0.05).
CONCLUSION AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro- and anti- inflammatory responses, which might guide the clinical application of SJD for AP treatment.
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Affiliation(s)
- Lv Zhu
- Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jun-Yi Li
- Department of Traditional Chinese Medicine, Wuhan Union Hospital, Wuhan 430000, Hubei Province, China
| | - Yu-Mei Zhang
- Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hong-Xin Kang
- Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Huan Chen
- Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hang Su
- Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Juan Li
- Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Fu Tang
- Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Anchi P, Khurana A, Bale S, Godugu C. The Role of Plant-derived Products in Pancreatitis: Experimental and Clinical Evidence. Phytother Res 2017; 31:591-623. [DOI: 10.1002/ptr.5792] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Revised: 02/03/2017] [Accepted: 02/06/2017] [Indexed: 12/13/2022]
Affiliation(s)
- Pratibha Anchi
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
| | - Amit Khurana
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
| | - Swarna Bale
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
| | - Chandraiah Godugu
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
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Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal micron Liuhe Pill ointment in rats. Chin J Integr Med 2015; 21:922-7. [PMID: 26138330 DOI: 10.1007/s11655-015-2080-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2011] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To explore the effect of acute pancreatitis (AP) on the pharmacokinetics of herbal ointment micron Liuhe Pill, MLHP) components in anesthetized rats. METHODS Rats were randomly divided into a AP model group (n=6) and a normal group as a control (n=6). The rat model of AP was induced by intraperitoneal injection of L-arginine in rats (15 mg/kg, twice, interval 1 h). Chinese herbal ointment MLHP was used externally on the belly after the 2nd injection for 48 h in both groups. Emodin, rhein, aloe emodin, physcion, chrysophanol from MLHP were detected and quantified in rat serum and pancreas (at 48 h) by high performance liquid chromatography-tandem mass spectrometry. RESULTS Among the five components, only emodin, aloe emodin and physcion from MLHP were detected in all rat serum and most of the rats' pancreas. Rhein and chrysophanol were not detected in both serum and pancreas. T1/2α of emodin and physcion in MLHP were obviously shorter in the AP model group than those in the normal group (P<0.05), while there was no difference for T1/2α of aloe emodin. The peak concentration and area under curve of all three components were much higher in the AP group than those in the normal group with MLHP in external application for 48 h (P<0.05). Furthermore, the mean residence time (MRT) and maximum plasma concentration (Tmax) of emodin and aloe emodin were obviously longer in the AP model group than those in the normal control group (P<0.05). There was no significant difference for Ka of all components between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in the AP model group than in the normal group (0.61±0.54 ng/mL, 0.42±0.37 ng/mL, respectively,P<0.05). Aloe emodin could be detected in all rats' pancreas at 48 h in both groups and their mean pancreatic concentration were similar (0.31±0.24 ng/mL, 0.33±0.17 ng/mL, respectively,P>0.05). Physcion could be detected in pancreas of most rats in the AP model while only two rats in the normal group. CONCLUSION AP could significantly affect the pharmacokinetics of absorbed components of Chinese herbal MLHP ointment in rats.
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Tissue Pharmacology of Da-Cheng-Qi Decoction in Experimental Acute Pancreatitis in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015. [PMID: 26199633 PMCID: PMC4493295 DOI: 10.1155/2015/283175] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Objectives. The Chinese herbal medicine Da-Cheng-Qi Decoction (DCQD) can ameliorate the severity of acute pancreatitis (AP). However, the potential pharmacological mechanism remains unclear. This study explored the potential effective components and the pharmacokinetic characteristics of DCQD in target tissue in experimental acute pancreatitis in rats. Methods. Acute pancreatitis-like symptoms were first induced in rats and then they were given different doses of DCQD (6 g/kg, 12 g/kg, and 24 g/kg body weight) orally. Tissue drug concentration, tissue pathological score, and inflammatory mediators in pancreas, intestine, and lung tissues of rats were examined after 24 hours, respectively. Results. Major components of DCQD could be found in target tissues and their concentrations increased in conjunction with the intake dose of DCQD. The high-dose compounds showed maximal effect on altering levels of anti-inflammatory (interleukin-4 and interleukin-10) and proinflammatory markers (tumor necrosis factor α and interleukin-6) and ameliorating the pathological damage in target tissues (P < 0.05). Conclusions. DCQD could alleviate pancreatic, intestinal, and lung injury by altering levels of inflammatory cytokines in AP rats with tissue distribution of its components.
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Li J, Zhao XL, Liu YX, Peng XH, Zhu SF, Guo H, Liu YL, Wan MH, Tang WF. 1HNMR-based metabolomic profile of rats with experimental acute pancreatitis. BMC Gastroenterol 2014; 14:115. [PMID: 24975214 PMCID: PMC4100530 DOI: 10.1186/1471-230x-14-115] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Accepted: 06/19/2014] [Indexed: 02/08/2023] Open
Abstract
Background Acute pancreatitis (AP) is a common inflammatory disease of the pancreas accompanied by serious metabolic disturbances. Nevertheless, the specific metabolic process of this disease is still unclear. Characterization of the metabolome may help identify biomarkers for AP. To identify potential biomarkers, this study therefore investigated the 1H-nuclear magnetic resonance (NMR)-based metabolomic profile of AP. Methods Fourteen male adult Sprague–Dawley rats were randomized into two groups: the AP group, in which AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate; and the sham operation group (SO), in which rats were infused with 0.9% saline. Blood samples were obtained 12 hours later and a 600 MHz superconducting NMR spectrometer was used to detect plasma metabolites. Principal components analysis (PCA) and partial least squares-discriminant analysis after orthogonal signal correction (OSC-PLS-DA) were used to analyze both longitudinal Eddy-delay (LED) and Carr–Purcell–Meiboom–Gill (CPMG) spectra. Results Differences in plasma metabolites between the two groups were detected by PCA and PLS-DA of 1HNMR spectra. Compared with the SO group, plasma levels of lactate (δ 1.3, 1.34, 4.1), valine (δ 0.98, 1.02), succinic acid (δ 2.38), 3-hydroxybutyric acid (3-HB, δ 1.18), high density lipoprotein (HDL, δ 0.8), and unsaturated fatty acid (UFA, δ 2.78, 5.3) were elevated in the AP group, while levels of glycerol (δ 3.58, 3.66), choline (δ 3.22), trimethylamine oxide (TMAO, δ 3.26), glucose (δ 3–4), glycine (δ 3.54), very low density lipoprotein (VLDL, δ 1.34) and phosphatidylcholine (Ptd, δ 2.78) were decreased. Conclusions AP has a characteristic metabolic profile. Lactate, valine, succinic acid, 3-HB, HDL, UFA, glycerol, choline, TMAO, glucose, glycine, VLDL, and Ptd may be potential biomarkers of early stage AP.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Wen-fu Tang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
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Zhao X, Li J, Zhu S, Liu Y, Zhao J, Wan M, Tang W. Rhein induces a necrosis-apoptosis switch in pancreatic acinar cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2014; 2014:404853. [PMID: 24959186 PMCID: PMC4053146 DOI: 10.1155/2014/404853] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Revised: 04/05/2014] [Accepted: 04/23/2014] [Indexed: 02/05/2023]
Abstract
Objectives. The Chinese herbal medicine Da-Cheng-Qi decoction can regulate a necrosis-apoptosis switch in injured pancreatic acinar cells. This study investigated the effects of rhein, a component of this medicine, on a necrosis-apoptosis switch in pancreatic rat AR42J cells. Methods. Cerulein-treated AR42J cells were used. After pretreatment with 479, 119.8, or 29.9 μ g/L rhein, cells were cocultured with rhein and cerulein (10(-8) M) for 4, 8, or 16 h. Apoptosis and necrosis were examined using annexin V and propidium iodide costaining. Mitochondria-dependent apoptosis-associated proteins were examined using enzyme-linked immunosorbent assays and western blotting. Results. Few cells died in untreated samples. The number was significantly higher in 16-h-cerulein-treated samples and treatment with 479 μ g/L rhein most effectively increased the apoptotic-to-necrotic cell ratio (P < 0.05). In cerulein-treated cells, rhein increased the concentrations of p53, cytochrome C, and caspase-3, and increased the Bax/Bcl-2 ratio in a time- and dose-dependent manner, with the maximum effect in cells treated with 479 μ g/L rhein for 16 h (P < 0.05). Conclusions. Rhein induces the necrosis-apoptosis switch in injured pancreatic acinar cells in a time- and dose-dependent manner. Mitochondria-dependent apoptosis signaling pathways might play an important role in this effect.
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Affiliation(s)
- Xianlin Zhao
- Pancreatic Diseases Research Group, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Juan Li
- Pancreatic Diseases Research Group, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Shifeng Zhu
- Pancreatic Diseases Research Group, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yiling Liu
- Pancreatic Diseases Research Group, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jianlei Zhao
- Pancreatic Diseases Research Group, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Meihua Wan
- Pancreatic Diseases Research Group, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wenfu Tang
- Pancreatic Diseases Research Group, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
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Pharmacokinetic and pharmacodynamic comparison of chinese herbal ointment liu-he-dan and micron liu-he-dan ointment in rats with acute pancreatitis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 2014:389576. [PMID: 24693322 PMCID: PMC3947679 DOI: 10.1155/2014/389576] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 12/05/2013] [Accepted: 12/26/2013] [Indexed: 02/05/2023]
Abstract
Aim. To compare the pharmacokinetics and pharmacodynamics of herbal ointment Liu-He-Dan (LHD) and micron LHD (MLHD) in rats with acute pancreatitis (AP). Methods. Twenty rats were allocated into normal, AP, LHD, and MLHD groups. LHD or MLHD was applied on rats' abdomens. Plasma levels of emodin, rhein, aloe emodin, physcion, and chrysophanol were determined by high performance liquid chromatography-mass spectrometry-mass spectrometry (HPLC-MS-MS) at different time points, and the pharmacokinetic parameters were calculated. Serum amylase, TNF- α , IL-6, and IL-10 levels, and the pancreatic pathological scores were determined at 48 h after LHD or MLHD treatment. Results. T 1/2 α and area under the curve (AUC) of emodin in the MLHD group were lower than those in the LHD group, while T 1/2 α and AUC of aloe emodin in the MLHD group were higher than those in the LHD group (P < 0.05). T 1/2 α and T max of physcion in the MLHD group were significantly shorter than those in the LHD group (P < 0.05). Compared with the AP group, the amylase, malondialdehyde (MDA), TNF- α , and IL-6 levels decreased significantly after three days of treatment in LHD and MLHD groups, while the levels of superoxide dismutase (SOD), TNF- α , and the pancreatic pathological score, were similar. The pharmacodynamic parameters between the LHD and MLHD groups were similar. Conclusion. MLHD had better pharmacokinetics than, and similar pharmacodynamics to, LHD in the management of rats with AP, which indicated that MLHD might be substituted for LHD in the treatment of AP and thus reduce the amount of medicinal herbs used.
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Zhao J, Tang W, Wang J, Xiang J, Gong H, Chen G. Pharmacokinetic and pharmacodynamic studies of four major phytochemical components of Da-Cheng-Qi decoction to treat acute pancreatitis. J Pharmacol Sci 2013; 122:118-27. [PMID: 23739595 DOI: 10.1254/jphs.13037fp] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
The medicinal herb formulation Da-Cheng-Qi decoction (DCQD) has been shown to ameliorate the severity of acute pancreatitis by regulating an apoptosis-necrosis switch in cells. The active components responsible for this effect and their detailed mechanism of action remain unclear. Here we determine the pharmacokinetic characteristics of the four most abundant compounds in DCQD using a rat model of severe acute pancreatitis. Acute pancreatitis-like symptoms were first induced in rats and then they were given DCQD orally. Rhein was found in rat serum at much higher levels than magnolol, hesperidin, or naringin, even though it was the least abundant of the four compounds in the DCQD. We also examined pharmacodynamics in AR42J cells stimulated with 10(-8) M cerulein as a cellular model of acute pancreatitis. After pretreating AR42J cells with individual compounds and then exposing them to cerulein, we determined cell viability, levels of apoptosis and necrosis, and numbers of cells positive for reactive oxygen species (ROS). Pretreatment with any of the four DCQD compounds increased cell viability and the apoptosis index, while also reducing necrosis and ROS generation. The compounds showed maximal effect in AR42J cells around the same time that they showed maximum serum concentration in rats. Although all four components appear to play a role in an apoptosis-necrosis cellular switch in vitro, rhein may be the most bioactive DCQD ingredient.
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Affiliation(s)
- Jianlei Zhao
- Department of Pharmacology, School of Preclinical and Forensic Medicine, West China Medical Center, Sichuan University, Chengdu, China.
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Zhao XL, Xiang J, Wan MH, Yu Q, Chen WW, Chen GY, Tang WF. Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal ointment Liu-He-Dan in anaesthetized rats. JOURNAL OF ETHNOPHARMACOLOGY 2013; 145:94-99. [PMID: 23127650 DOI: 10.1016/j.jep.2012.10.036] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2011] [Revised: 08/24/2012] [Accepted: 10/05/2012] [Indexed: 06/01/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Chinese herbal preparation of Liu-He-Dan ointment has been adapted for acute pancreatitis in external application for many years in West China. AIM OF THE STUDY To investigate the effect of acute pancreatitis on the pharmacokinetics of Liu-He-Dan ointment in rats while it was used externally on belly. MATERIALS AND METHODS Twelve male Sprague-Dawley rats were randomly divided into acute pancreatitis model group (n=6) and normal group as a control (n=6). Chinese herbal Liu-He-Dan ointment was used externally on belly. Emodin, rhein, aloe emodin, physcion and chrysophanol in plasma and pancreas (at 48 h) were detected and quantified by liquid chromatography-tandem mass spectrometry. Amylase in plasma were determined with iodide process. RESULTS Among the five components, only emodin, aloe emodin and physcion from Liu-He-Dan were detected in plasma and pancreas. The absorption of each component was tended to decrease in acute pancreatitis group after topically management with Liu-He-Dan ointment on rats' abdomen. The T(max), C(max) and area under curve (AUC) of each component were distinctly lower in AP group than those in normal group (p<0.05). However, the T(1/2α) and mean retention time (MRT) of emodin lasted longer in acute pancreatitis group than those in normal group (p<0.05). There was no statistical difference in the MRT of aloe emodin and physcion between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in acute pancreatitis model group than in normal group (0.91 ± 0.68, 0.41 ± 0.36, respectively). Physcion could be detected in pancreas of most acute pancreatitis models, but not in normal rats. Aloe emodin was found in all pancreas from acute pancreatitis models while only one in normal group. The level of amylase in Liu-He-Dan group was obviously lower than that in the AP model group (p=0.0055). CONCLUSION We concluded that acute pancreatitis may significantly affect the pharmacokinetics of Liu-He-Dan while external applied on belly, which indicated the dosage modification in AP. However, acute pancreatitis seems to promote the distribution of the detected components into pancreas. The ointment could help relieve the disease of pancreatitis.
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Affiliation(s)
- Xian-Lin Zhao
- Department of Integrative Medicine, Sichuan University, Sichuan Province, Chengdu 610041, China
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Wang J, Chen G, Gong H, Huang W, Long D, Tang W. Amelioration of experimental acute pancreatitis with Dachengqi Decoction via regulation of necrosis-apoptosis switch in the pancreatic acinar cell. PLoS One 2012; 7:e40160. [PMID: 22768339 PMCID: PMC3388070 DOI: 10.1371/journal.pone.0040160] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2012] [Accepted: 06/01/2012] [Indexed: 02/05/2023] Open
Abstract
Severity of acute pancreatitis contributes to the modality of cell death. Pervious studies have demonstrated that the herb medicine formula “Dachengqi Decoction” (DCQD) could ameliorate the severity of acute pancreatitis. However, the biological mechanisms governing its action of most remain unclear. The role of apoptosis/necrosis switch within acute pancreatitis has attracted much interest, because the induction of apoptosis within injured cells might suppress inflammation and ameliorate the disease. In this study, we used cerulein (10−8 M)-stimulated AR42J cells as an in vitro model of acute pancreatitis and retrograde perfusion into the biliopancreatic duct of 3.5% sodium taurocholate as an in vivo rat model. After the treatment of DCQD, cell viability, levels of apoptosis and necrosis, reactive oxygen species positive cells, serum amylase, concentration of nitric oxide and inducible nitric oxide syntheses, pancreatic tissue pathological score and inflammatory cell infiltration were tested. Pretreatment with DCQD increased cell viability, induced apoptosis, decreased necrosis and reduced the severity of pancreatitis tissue. Moreover, treatment with DCQD reduced the generation of reactive oxygen species in AR42J cells but increased the concentration of nitric oxide of pancreatitis tissues. Therefore, the regulation of apoptosis/necrosis switch by DCQD might contribute to ameliorating the pancreatic inflammation and pathological damage. Further, the different effect on reactive oxygen species and nitric oxide may play an important role in DCQD-regulated apoptosis/necrosis switch in acute pancreatitis.
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Affiliation(s)
- Jia Wang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, PR China
| | - Guangyuan Chen
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, PR China
| | - Hanlin Gong
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, PR China
| | - Wei Huang
- Physiological Laboratory, University of Liverpool, Liverpool, United Kingdom
| | - Dan Long
- Department of Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, PR China
| | - Wenfu Tang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, PR China
- * E-mail:
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Liu Z, Shen Y, Cui N, Yang J. Clinical observation of immunity for severe acute pancreatitis. Inflammation 2012; 34:426-31. [PMID: 20842417 DOI: 10.1007/s10753-010-9249-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The aim of our study was to observe the dynamic changes of immunity for patients with severe acute pancreatitis (SAP) and intervention by traditional Chinese medicine. Twenty-three patients who met the inclusion criteria were randomized to combined treatment of traditional Chinese medicine and Western medicine (TCM) or conventional western medicine treatment (WM) groups. The clinical data for all patients were collected. Peripheral venous blood samples were obtained from patients on days 1, 7, 14, and 28 after admission. Biochemical data including the percentage of CD4+/CD8+/natural killer (NK) cells/B lymphocytes/HLA-DR and CD4+/CD8+ ratio in serum were determined by flow cytometer. Patients' characteristics and immunity at admission were similar between the two groups. The secondary infection was different. The levels of T-lymphocyte subsets in the TCM group were quite different from the WM group, with much more the percentage of CD4+ and the CD4+/CD8+ ratio on days 7, 14, and 28 and much less the percentage of CD8+ on days 4 and 28. On days 14 and 28, the levels of NK cells and B lymphocytes were significantly higher in the TCM group compared with the controls. Compared with the TCM group, the levels of HLA-DR were significantly decreased in the WM group on days 7, 14, and 28. The immune dysregulation exists in the development and progression of SAP. The combined treatment of traditional Chinese medicine and western medicine can upregulate the patient's immune and maintain the immune balance.
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Affiliation(s)
- ZhiMin Liu
- Nankai Hospital, Nankai Clinical School, Tianjin Medical University, Tianjin, 300010, People's Republic of China
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Tang Y, Liao Y, Kawaguchi-Sakita N, Raut V, Fakhrejahani E, Qian N, Toi M. Sinisan, a traditional Chinese medicine, attenuates experimental chronic pancreatitis induced by trinitrobenzene sulfonic acid in rats. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2011; 18:551-8. [PMID: 21234610 DOI: 10.1007/s00534-010-0368-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND/PURPOSE Sinisan, a traditional Chinese medicine, is effective for the treatment of gastrointestinal disorders. In this study, we investigated the potential protective role of Sinisan against chronic pancreatitis (CP) in rats. METHODS CP was induced in rats by intrapancreatic injection of trinitrobenzene sulfonic acid (TNBS). Rats were randomly divided into a sham group, a TNBS-induced CP group and a Sinisan-treated group. Serum amylase and histological score were used to evaluate the severity of disease. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), interleukin-10 (IL-10) and α-smooth muscle actin (α-SMA) were also measured in the three groups. Mechanical allodynia was measured with von Frey filaments. In addition, the protein levels of nerve growth factor (NGF) were measured in pancreatic tissues. RESULTS Administration of Sinisan significantly decreased the severity of CP. In the Sinisan-treated group, serum amylase, TNF-α, IL-1β, COX-2 and α-SMA levels were lower and the level of IL-10 was upregulated compared with the TNBS-induced CP group. Furthermore, treatment with Sinisan significantly, though not completely, attenuated the allodynia. Simultaneously NGF expression was also significantly downregulated in the Sinisan-treated group compared with the TNBS-induced CP group. CONCLUSIONS Sinisan could be an effective treatment modality for CP via its anti-inflammatory, anti-fibrotic and analgesic properties. It may be a promising drug candidate for the treatment of patients with CP.
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Affiliation(s)
- Yu Tang
- Department of Medical Image Center, Chinese PLA 302 Hospital, Beijing, China
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