1
|
Tang Y, Zhou L, Zhang T, Jiang F, Pu Y, Wang Z, Liu J, Feng L, Zhou T, Wang X. Population transcriptome reveals genetic divergence and expression diversity of medicinally effective ingredients-related genes for Rheum palmatum complex derived from the top-geoherb area. PLANTA 2025; 261:90. [PMID: 40089954 DOI: 10.1007/s00425-025-04643-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Accepted: 02/11/2025] [Indexed: 03/18/2025]
Abstract
MAIN CONCLUSION The study revealed genetic diversity and moderate differentiation among the R. palmatum complex within the top-geoherb area. RNA-seq-derived SNP datasets hold the potential to trace geographic origins of the core germplasm. The Rheum palmatum complex, the source plant of rhubarb, has been widely used for centuries due to its diverse functions in clinical treatments. However, the wild resources of rhubarb are currently declining and even facing depletion. Therefore, revealing the genetic background of the R. palmatum complex within the top-geoherb area is important for the efficient utilization and conservation of its wild resources. In this study, population transcriptomic analyses were conducted to assess the genetic diversity and gene expression diversity of different populations in the R. palmatum complex within the top-geoherb area. Candidate single nucleotide polymorphisms (SNPs) were identified as specific molecular markers for tracing the origin of the R. palmatum complex from various top-geoherb areas. Based on the reference genome, a total of 30,480 transcripts and 100,966 SNPs were generated across 82 individuals from 17 populations of the R. palmatum complex. Moderate genetic differentiation was detected for the two genetic lineages of the R. palmatum complex derived from the top-geoherb area. Fourteen genes encoding key enzymes were differentially expressed between two genetic lineages. Besides, 26 specific SNPs located on the genes involved in the biosynthesis of the active components were screened out, and these SNPs were highly differentiated between 2 genetic lineages. A large-scale reference-based assembly transcriptome of the R. palmatum complex from the top-geoherb area provided insights into the genetic divergence and expression differentiation of genetic lineages. The results not only help to understand the genetic background of the R. palmatum complex in the top-geoherb area but also contribute to future genetic conservation and directive breeding of rhubarb.
Collapse
Affiliation(s)
- Yadi Tang
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China
| | - Lipan Zhou
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China
| | - Tianyi Zhang
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China
| | - Fan Jiang
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China
| | - Yang Pu
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China
| | - Zhengyuan Wang
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China
| | - Jie Liu
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China
| | - Li Feng
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China
| | - Tao Zhou
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
| | - Xumei Wang
- School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
| |
Collapse
|
2
|
Cao JP, Piao XH, Zhu LX, Feng PF. Xuebijing and somatostatin against acute pancreatitis: A systematic review and network pharmacology. Medicine (Baltimore) 2024; 103:e40964. [PMID: 39686429 PMCID: PMC11651499 DOI: 10.1097/md.0000000000040964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Acute pancreatitis (AP) is a common pancreatic disease. Xuebijing injection (XBJ) combined with somatostatin in the treatment of AP is frequently used in clinical practice. There is, however, a lack of high-quality evidence-based evidence and network pharmacology to regard the therapeutic efficacy and pharmacological mechanisms. PURPOSE The purpose of this study is to investigate the potential therapeutic targets and pharmacological mechanism of XBJ in AP using integrating evidence-based medicine and network pharmacology. METHODS PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Weipu, and Wanfang databases were searched. Randomized controlled trials of XBJ combined with somatostatin (experimental group) versus somatostatin alone (control group) in the treatment of AP were collected. After extracting data from the literature that meets the inclusion criteria, and using the Cochrane Scale to evaluate the quality of the literature, we used Rev Man 5.3.0 statistical software to perform meta-analysis of the effective rate, the disappearance time of abdominal pain and bloating, the recovery of gastrointestinal motility, serum-related indicators, inflammatory factors, ventilator evacuation time, and hospitalization time. A network pharmacology is used to analyze the potential active ingredients and related crucial targets of the XBJ in the treatment of AP, and we explored key regulatory pathways and potential biomarkers related to XBJ for AP with integrated bioinformatics analysis. RESULTS It was significant that the total effective rate in the study group was higher than that in the control group (P < .05). The time of recovery of gastrointestinal motility, serum-related indicators, inflammatory factors, ventilator withdrawal time, and hospitalization time were significantly lower than that of the control group. The differences were statistically significant (P < .05). Signal transducer and activator of transcription 3, tumor protein P53, interleukin 6, tumor necrosis factor, Jun Proto-Oncogene, SRC Proto-Oncogene, Heat Shock Protein 90 Alpha Family Class A Member 1, Vascular Endothelial Growth Factor A, Epidermal Growth Factor Receptor, and Mitogen-Activated Protein Kinase 1 were identified as the key hub of the protein-protein interaction network according to an analysis of network centrality. According to the Kyoto Encyclopedia of Genes and Genomes pathway analysis, the main pathways are involved in PI3K-Akt signaling pathway, HIF-1 signaling pathway, and tumor necrosis factor signaling pathway. CONCLUSIONS The effectiveness of combination therapy of XBJ and somatostatin on AP is likely to be better than somatostatin. In addition, XBJ and somatostatin synergistically treated AP through a multi-pathway network.
Collapse
Affiliation(s)
- Ji-Ping Cao
- Department of Pharmacy, Affiliated Hospital 2 of Nantong University, And First People’s Hospital of Nantong City, Nantong, Jiangsu Province, P.R. China
| | - Xiang-Hua Piao
- Department of Pharmacy, Jiangwan Hospital of Shanghai Hongkou District, Shanghai, P.R. China
| | - Long-Xun Zhu
- Department of Pharmacy, Affiliated Hospital 2 of Nantong University, And First People’s Hospital of Nantong City, Nantong, Jiangsu Province, P.R. China
| | - Pan-Feng Feng
- Department of Pharmacy, Affiliated Hospital 2 of Nantong University, And First People’s Hospital of Nantong City, Nantong, Jiangsu Province, P.R. China
| |
Collapse
|
3
|
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.
Collapse
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.
| |
Collapse
|
4
|
Zhang HF, Su ZX, Feng YH, Li SJ, Xie BY. Chaiqin Chengqi Decoction as an adjuvant treatment for mild/moderately severe hypertriglyceridemic acute pancreatitis: A retrospective study. World J Clin Cases 2024; 12:1918-1928. [PMID: 38660541 PMCID: PMC11036510 DOI: 10.12998/wjcc.v12.i11.1918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 02/06/2024] [Accepted: 03/20/2024] [Indexed: 04/11/2024] Open
Abstract
BACKGROUND Hypertriglyceridemia is the third leading cause of acute pancreatitis (AP), and its incidence is increasing. Due to its relatively insidious etiology, it is easy to be ignored in the early stages. In China, Chaiqin Chengqi Decoction (CQCQD) has long been employed for treating AP. AIM To evaluate the effectiveness of CQCQD in patients diagnosed with mild/ moderately severe hypertriglyceridemic AP (HTG-AP). METHODS In this study, the clinical data of 39 patients with HTG-AP admitted from January 2019 to November 2022 were collected. The changes of blood lipids, gastrointestinal symptoms, and abdominal pain before and after treatment were analyzed and compared between the two groups. RESULTS Twenty patients were treated with the conventional HTG-AP regimen, and 19 patients were additionally treated with CQCQD. After receiving treatment, the triglycerides (TG) level of the CQCQD group was lower than that of the CQCQD group (3.14 ± 0.25 mmol/L vs 4.96 ± 0.47 mmol/L, P < 0.01). After 3 d of treatment, the patients in the CQCQD group had more bowel movements than the control group (2.51 ± 0.25 times vs 1.00 ± 0.17 times, P = 0.01). The gastrointestinal function of most patients returned to normal, and the acute gastrointestinal injury score was significantly lower than that of the control group (0.11 ± 0.07 vs 0.42 ± 0.11, P < 0.01). CONCLUSION In patients with HTG-AP, CQCQD can significantly reduce the TG level, shorten the recovery time of defecation, significantly improve the gastrointestinal function.
Collapse
Affiliation(s)
- Hai-Fu Zhang
- Department of Internal Medicine, The First People's Hospital of Fuyang, Hangzhou 311400, Zhejiang Province, China
| | - Ze-Xuan Su
- Department of Internal Medicine, The First People's Hospital of Fuyang, Hangzhou 311400, Zhejiang Province, China
| | - Yong-Hang Feng
- Department of Internal Medicine, The First People's Hospital of Fuyang, Hangzhou 311400, Zhejiang Province, China
| | - Shuo-Jun Li
- Department of Internal Medicine, The First People's Hospital of Fuyang, Hangzhou 311400, Zhejiang Province, China
| | - Bi-Yun Xie
- Department of Internal Medicine, The First People's Hospital of Fuyang, Hangzhou 311400, Zhejiang Province, China
| |
Collapse
|
5
|
Lin J, Han C, Dai N, Bi S, Du D, Xia Q. Effectiveness of Chengqi-series decoctions in treating severe acute pancreatitis: A Systematic review and meta-analysis. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 113:154727. [PMID: 36913877 DOI: 10.1016/j.phymed.2023.154727] [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: 12/11/2022] [Revised: 01/31/2023] [Accepted: 02/20/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Evidence suggests that Dachengqi and its modified decoctions are effective for treating abdominal pain, multiple organ dysfunction syndrome (MODS) and inflammation in various disease conditions. We performed a meta-analysis to ascertain the effectiveness of a series of chengqi decoctions in patients with severe acute pancreatitis (SAP). METHODS We searched Pubmed, Embase, Cochrane library, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature, Wanfang database and China Science and Technology Journal Database before August 2022 to identify eligible randomized controlled trials (RCTs). Mortality and MODS were chosen as primary outcomes. Secondary outcomes included time until relief of abdominal pain, APACHE II score, complications, effectiveness, IL-6 and TNF-α levels. The risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (CI) were selected as effect measures. The quality of evidence was independently assessed by two reviewers using Grading of Recommendations Assessment Development and Evaluation (GRADE) system. RESULTS Twenty-three RCTs (n = 1865) were finally included. The results showed that, compared with routine therapies, chengqi-series decoctions (CQSDs) treatment groups were associated with lower mortality rate (RR: 0.41, 95%CI: 0.32 to 0.53, p = 0.992) and incidence of MODS (RR: 0.48, 95%CI: 0.36 to 0.63, p = 0.885). They also reduced remission time of abdominal pain (SMD: -1.66, 95%CI: -1.98 to -1.35, p = 0.000), complications (RR: 0.52, 95%CI: 0.39 to 0.68, p = 0.716), APACHE II score (SMD: -1.04, 95%CI:-1.55 to -0.54, p = 0.003), IL-6 (SMD: -1.5, 95%CI: -2.16 to -0.85, p = 0.000), TNF-α (SMD: -1.18, 95%CI: -1.71 to -0.65, p = 0.000), and improved curative effectiveness (RR:1.22, 95%CI: 1.14 to 1.31, p = 0.757). The certainty of the evidence for these outcomes was low to moderate. CONCLUSION CQSDs seem to be effective therapy for SAP patients with notable reductions in mortality, MODS and abdominal pain, with low quality evidence. Large-scale, multi-center RCTs that are more meticulous are advised in order to produce superior evidence.
Collapse
Affiliation(s)
- Juan Lin
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chenxia Han
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Ning Dai
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100010, China
| | - Siwei Bi
- Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu 610000, Sichuan, China
| | - Dan Du
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Qing Xia
- West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China.
| |
Collapse
|
6
|
Guo Y, Cao Q, Guo M, Wang J, Kou R, Ye L. Comparative study of the Rheum tanguticum's chemical contents based on spatial distribution characteristics. PLoS One 2022; 17:e0278113. [PMID: 36445877 PMCID: PMC9707769 DOI: 10.1371/journal.pone.0278113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 11/10/2022] [Indexed: 12/03/2022] Open
Abstract
Rheum tanguticum (R. tanguticum) has been widely used for the treatment of inflammatory diseases in clinical. However, limited research exist on the quality evaluation of various R. tanguticum locations, which has certain drawbacks. In this study, Fourier-transform infrared spectroscopy (FTIR) and high-performance liquid chromatography (HPLC) were used to comparative study on the chemical contents of R. tanguticum, to clarify the relationship between the chemical contents and the spatial distribution of R. tanguticum. First of all, the FTIR spectra of 18 batches of R. tanguticum were examined. Following the cluster analysis, the FTIR spectra of various production locations differed. To some extent, establishing the double index analysis sequence of common and variation peaks may differentiate distinct production locations of medicinal materials. The HPLC fingerprint of R. tanguticum was constructed to further explore the link between components and their origin. PCA of common peaks of 18 batches of R. tanguticum indicated that R. tanguticum grown in Gannan and Qinghai had a tendency to separate t[2], however this trend was not noticeable. Then, OPLS-DA model was established, and the key differential components of R. tanguticum produced in Gannan and Qinghai were discovered to be R16, R37, R46, and R47 (Aloe emodin) (VIP ≥ 1 and P < 0.05). At last, Pearson's test was used to examine the relationship between longitude, latitude, altitude, and composition. Longitude was significantly positively correlated with R28 and R30 (P < 0.05), and a very significantly positively correlated with R35, R36, R37, R46, and R47 (P < 0.01). Latitude was significantly negatively correlated with R34, R35, and R40 (P < 0.05), and extremely significantly negatively correlated with R28, R30, R36, R37, R46, and R47 (P < 0.01). Altitude was significantly positive correlation with R36 and R37 (P < 0.01). The results of our study can provide insights into R. tanguticum quality control and aid in establishing a natural medication traceability system.
Collapse
Affiliation(s)
- Yafei Guo
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China
| | - Qiang Cao
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China
| | - Mei Guo
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China
- Key Laboratory for Chemistry and Quality of Traditional Chinese Medicine & Tibetan Medicine of Gansu Provincial Colleges, Lanzhou, China
- * E-mail:
| | - Junmei Wang
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China
| | - Renbo Kou
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China
| | - Leilei Ye
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China
| |
Collapse
|
7
|
Chen Z, Yang X, Guo J, Jin T, Lin Z, Zhu P, Li J, Li L, Sun X, Du D, Jiang K, He Y, Cai F, Li L, Hu C, Tan Q, Huang W, Deng L, Xia Q. AGI grade-guided chaiqin chengqi decoction treatment for predicted moderately severe and severe acute pancreatitis (CAP trial): study protocol of a randomised, double-blind, placebo-controlled, parallel-group, pragmatic clinical trial. Trials 2022; 23:933. [PMID: 36348365 PMCID: PMC9644559 DOI: 10.1186/s13063-022-06792-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 09/24/2022] [Indexed: 11/09/2022] Open
Abstract
Background Acute pancreatitis (AP) is a common digestive disease with increased incidence globally but without internationally licenced pharmacological therapy. Moderately severe and severe acute pancreatitis (MSAP/SAP) contributes predominately for its morbidities and mortality and has been managed in West China Hospital for decades using the traditional Chinese medicinal formula chaiqin chengqi decoction (CQCQD). The current study tests whether the early administration of CQCQD will result in improved clinical outcomes in predicted MSAP/SAP patients. Methods This is a single-centre, randomised, controlled, double-blind pragmatic clinical trial. AP patients aged 18–75 admitted within 72 h of onset will be assessed at admission for enrolment. We excluded the predicted mild acute pancreatitis (Harmless Acute Pancreatitis Score > 2 at admission) and severe organ failure (Sequential Organ Failure Assessment [SOFA] score of respiratory, cardiovascular, or renal systems > 3) at admission. Eligible patients will be randomly allocated on a 1:1 basis to CQCQD or placebo control administration based on conventional therapy. The administration of CQCQD and placebo is guided by the Acute Gastrointestinal Injury grade-based algorithm. The primary outcome measure will be the duration of respiratory failure (SOFA score of respiratory system ≥ 2) within 28 days after onset. Secondary outcome measures include occurrence of new-onset any organ failure (SOFA score of respiratory, cardiovascular, or renal system ≥ 2) and new-onset persistent organ failure (organ failure lasts > 48 h), dynamic surrogate biochemical markers and clinical severity scores, gut-centred treatment modalities, local complications status, intensive care need and duration, surgical interventions, mortality, and length of hospital stay. Follow-up will be scheduled on 6, 12, and 26 weeks after enrolment to assess AP recurrence, local complications, the requirement for surgical interventions, all-cause mortality, and patient-reported outcomes. Discussion The results of this study will provide high-quality evidence to appraise the efficacy of CQCQD for the early management of AP patients. Trial registration Chictr.org.cn Registry (ChiCTR2000034325). Registered on 2 July, 2020. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-022-06792-x.
Collapse
|
8
|
Li Y, Ye Z, He H, Hu Y, Wu M, Li L, Chen L, Qian H, Shi Q, Zhang C, Yu H, Zhao Q, Liu X, Qin K, Ye Q. The application of Tong-fu therapeutic method on ulcerative colitis: A systematic review and meta-analysis for efficacy and safety of rhubarb-based therapy. Front Pharmacol 2022; 13:1036593. [DOI: 10.3389/fphar.2022.1036593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 10/11/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Tong-fu therapeutic method (TFTM) is a traditional Chinese medicine treatment method for ulcerative colitis, which is a novel treatment strategies and have purgative effect. As the most representative medicinal of TFTM, Rhubarb has been reported to have a therapeutic impact on ulcerative colitis by regulating intestinal flora, anti-inflammation, and improving intestinal microcirculation. Although rhubarb has been widely used in Chinese medicine for the treatment of ulcerative colitis, the appropriate protocol is still demanded to its rational use in clinic, which promoted to evaluate the efficacy and safety for rhubarb-based therapy on ulcerative colitis.Method: Clinical trials were searched through PubMed, Cochrane Library, Web of Science, Excerpta Medica Database, Chinese National Knowledge Infrastructure, WAN FANG Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. The subgroup analyses were performed with three groups: medication, course of treatment, and route of administration. The statistical analyses were performed on Review Manager software (version 5.4.1).Results: A total of 2, 475 patients in 30 original studies were analyzed in this article. It was found that rhubarb-based therapy could increase clinical efficacy and reduce the recurrence rate. Subgroup analyses showed that rhubarb-based therapy was more effective than 5-aminosalicylic acid or sulfasalazine alone. In addition, the hypercoagulable state of ulcerative colitis could be ameliorated by decreasing platelet (PLT) and fibrinogen (FIB), and increasing prothrombin time (PT) significantly. Moreover, C-reaction protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-1β expression were significantly reduced, while IL-10 production was increased, which mediated the alleviation of intestinal inflammation stress.Conclusion: Rhubarb-based therapy could effectively improve ulcerative colitis. Of note, the rhubarb-based medicinal formulas combined with 5-ASA or SASP are more effective than the 5-ASA or SASP alone. In addition, although rhubarb has side effect, the results of our analysis showed that rhubarb-based therapy did not exhibit significant side effects. This means it has a high safety profile in clinical use. Moreover, the use of rhubarb-based therapy is recommend to use within 1–13 weeks or 3 months via administered orally or by enema, which is contributes to ensure the curative effect and avoid its toxic and side effects. As an important case of TFTM, rhubarb-based therapy provides evidence for the practical application of TFTM.
Collapse
|
9
|
Effects of Anthraquinones on Immune Responses and Inflammatory Diseases. Molecules 2022; 27:molecules27123831. [PMID: 35744949 PMCID: PMC9230691 DOI: 10.3390/molecules27123831] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 06/03/2022] [Accepted: 06/09/2022] [Indexed: 12/12/2022] Open
Abstract
The anthraquinones (AQs) and derivatives are widely distributed in nature, including plants, fungi, and insects, with effects of anti-inflammation and anti-oxidation, antibacterial and antiviral, anti-osteoporosis, anti-tumor, etc. Inflammation, including acute and chronic, is a comprehensive response to foreign pathogens under a variety of physiological and pathological processes. AQs could attenuate symptoms and tissue damages through anti-inflammatory or immuno-modulatory effects. The review aims to provide a scientific summary of AQs on immune responses under different pathological conditions, such as digestive diseases, respiratory diseases, central nervous system diseases, etc. It is hoped that the present paper will provide ideas for future studies of the immuno-regulatory effect of AQs and the therapeutic potential for drug development and clinical use of AQs and derivatives.
Collapse
|
10
|
Al Mamun A, Suchi SA, Aziz MA, Zaeem M, Munir F, Wu Y, Xiao J. Pyroptosis in acute pancreatitis and its therapeutic regulation. Apoptosis 2022; 27:465-481. [PMID: 35687256 DOI: 10.1007/s10495-022-01729-w] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/18/2022] [Indexed: 12/20/2022]
Abstract
Pyroptosis defines a new type of GSDMs-mediated programmed cell death, distinguishes from the classical concepts of apoptosis and necrosis-mediated cell death and is prescribed by cell swelling and membrane denaturation, leading to the extensive secretion of cellular components and low-grade inflammatory response. However, NLRP3 inflammasome activation can trigger its downstream inflammatory cytokines, leading to the activation of pyroptosis-regulated cell death. Current studies reveal that activation of caspase-4/5/11-driven non-canonical inflammasome signaling pathways facilitates the pathogenesis and progression of acute pancreatitis (AP). In addition, a large number of studies have reported that NLRP3 inflammasome-dependent pyroptosis is a crucial player in driving the course of the pathogenesis of AP. Excessive uncontrolled GSDMD-mediated pyroptosis has been implicated in AP. Therefore, the pyroptosis-related molecule GSDMD may be an independent prognostic biomarker for AP. The present review paper summarizes the molecular mechanisms of pyroptotic signaling pathways and their pathophysiological impacts on the progress of AP. Moreover, we briefly present some experimental compounds targeting pyroptosis-regulated cell death for exploring novel therapeutic directions for the treatment and management of AP. Our review investigations strongly suggest that targeting pyroptosis could be an ideal therapeutic approach in AP.
Collapse
Affiliation(s)
- Abdullah Al Mamun
- Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang Province, Wenzhou, 325035, China
| | - Suzia Aktar Suchi
- Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 501759, South Korea
| | - Md Abdul Aziz
- Department of Pharmacy, Faculty of Pharmacy and Health Sciences, State University of Bangladesh, Dhaka, 1205, Bangladesh.,Laboratory of Pharmacogenomics and Molecular Biology, Department of Pharmacy, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh
| | - Muhammad Zaeem
- Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang Province, Wenzhou, 325035, China
| | - Fahad Munir
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, Wenzhou, 325000, China
| | - Yanqing Wu
- Institute of Life Sciences, Wenzhou University, Zhejiang Province, Wenzhou, 325035, China
| | - Jian Xiao
- Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang Province, Wenzhou, 325035, China. .,Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, Wenzhou, 325035, China.
| |
Collapse
|
11
|
Zhao X, Zhu S, Li J, Long D, Wan M, Tang W. Epigenetic changes in inflammatory genes and the protective effect of cooked rhubarb on pancreatic tissue of rats with chronic alcohol exposure. Biomed Pharmacother 2022; 146:112587. [PMID: 35062061 DOI: 10.1016/j.biopha.2021.112587] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/20/2021] [Accepted: 12/23/2021] [Indexed: 02/08/2023] Open
Abstract
Chronic alcohol consumption, which is observed worldwide, can damage pancreatic tissue and promote pancreatitis. Rhubarb is a widely used traditional Chinese herbal medicine for treating pancreatitis in China. However, few pharmacological studies have investigated its epigenetic regulation. In this study, we investigated whether chronic exposure to alcohol can alter inflammatory gene expression and the epigenetic regulation effect of cooked rhubarb in the pancreatic tissue of rats. First, changes in inflammatory cytokine DNA methylation (IL-10, IL-1α, TNF-α, NF-κB and TGF-β) were detected in pancreatic tissue of Sprague-Dawley rats with varying alcohol exposure times (4, 6, 8, or 12 weeks), and then with varying doses of cooked rhubarb treatment (3, 6, or 12 g/day). DNA methylation levels, related RNA concentrations and protein expression of specific inflammatory cytokines, and histopathological score were analysed in pancreatic tissue of Sprague-Dawley rats. The results showed that chronic alcohol exposure (8 weeks) reduced the level of IL-1α DNA methylation and increased its protein expression in acinar cells (P < 0.05). In the acinar cells, the level of IL-10 DNA methylation increased, resulting in a reduction of protein expression (P < 0.05). Simultaneously, chronic alcohol exposure increased the pathological damage to the pancreas (P < 0.05). Finally, cooked rhubarb treatment (3 g/kg/day) effectively alleviated these changes in pancreatic tissue from chronic alcohol exposure (P < 0.05). These results indicate that chronic exposure to alcohol leads to changes in DNA methylation and protein expression of inflammatory genes, and cooked rhubarb may have a protective effect on the pancreatic tissue of rats.
Collapse
Affiliation(s)
- Xianlin Zhao
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Shifeng Zhu
- Zhejiang Provincial Tongde Hospital, Hangzhou, Zhejiang, China.
| | - Juan Li
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Dan Long
- Key Laboratory of Transplant Engineering and Immunology, Sichuan University, Chengdu, Sichuan, China.
| | - Meihua Wan
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Wenfu Tang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| |
Collapse
|
12
|
Zhang X, Wang M, Wang W, Li L, Sun X. Utilization of traditional Chinese medicine in the intensive care unit. Chin Med 2021; 16:84. [PMID: 34425877 PMCID: PMC8382104 DOI: 10.1186/s13020-021-00496-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 08/13/2021] [Indexed: 02/08/2023] Open
Abstract
Previous studies showed that traditional Chinese medicine (TCM) may be effective for patients with critical conditions. However, the extent to which TCM is used in intensive care units (ICUs) remains less investigated. This study aimed to investigate the utilization of TCM among ICU patients. Using a cross-sectional study design, we examined the use of TCMs among ICU patients. The data were from a well-established ICU registry from a large teaching hospital in west China. Our study found that TCM was widely used among ICU, in particular TCM injections and oral liquids. The use of TCM often differed by ICUs, and TCM injections and oral liquids were mostly used in neurological ICU, while Chinese herbal medicines (CHMs) were often used in general ICU. The use of TCM was also highly associated with patient characteristics. Patients with pancreatitis were administered with most TCM, patients with cerebrovascular disease with most TCM injections and those with chronic renal failure with most oral liquids. Future efforts should include generation of high-quality evidence guidelines about clinical effects of TCM interventions among ICU patients.
Collapse
Affiliation(s)
- Xia Zhang
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China.,NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, China.,Sichuan Center of Technology Innovation for Real World Data, Chengdu, China
| | - Mingqi Wang
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China.,NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, China.,Sichuan Center of Technology Innovation for Real World Data, Chengdu, China
| | - Wen Wang
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China.,NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, China.,Sichuan Center of Technology Innovation for Real World Data, Chengdu, China
| | - Ling Li
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China.,NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, China.,Sichuan Center of Technology Innovation for Real World Data, Chengdu, China
| | - Xin Sun
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China. .,NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, China. .,Sichuan Center of Technology Innovation for Real World Data, Chengdu, China.
| |
Collapse
|
13
|
Hu Y, Huang W, Luo Y, Xiang L, Wu J, Zhang Y, Zeng Y, Xu C, Meng X, Wang P. Assessment of the anti-inflammatory effects of three rhubarb anthraquinones in LPS-Stimulated RAW264.7 macrophages using a pharmacodynamic model and evaluation of the structure-activity relationships. JOURNAL OF ETHNOPHARMACOLOGY 2021; 273:114027. [PMID: 33741438 DOI: 10.1016/j.jep.2021.114027] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 02/10/2021] [Accepted: 03/11/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rhubarb (Rhei Radix et Rhizoma) is a traditional Chinese medicine, has been used as a strong astringent in China to treat inflammation-related diseases, such as acute pancreatitis, acute cholecystitis, appendicitis and so on. Rhein, emodin and aloe-emodin are the important active anthraquinone in rhubarb, and are considered to be the main ingredients contributing to anti-inflammatory. AIM OF THE STUDY Rhein, emodin and aloe-emodin, anthraquinones with the same parent structure that are found in rhubarb, have beneficial anti-inflammatory effects in vitro and in vivo. Anthraquinone derivatives also have important clinical roles. However, their pharmacodynamic differences and the structure-activity relationships associated with their anti-inflammatory properties have not been systematically explored. The present study was designed to quantify the effects of three rhubarb anthraquinones on inflammation and to explore the structure-activity relationships of these compounds. MATERIALS AND METHODS In this study, we detected NF-κB phosphorylation, iNOS protein expression, and IL-6 and NO production in LPS-stimulated RAW264.7 cells and then calculated median effect equations and built a dynamic pharmacodynamic model to quantitatively evaluate the efficacy of these three anthraquinones. Additionally, to determine the structure-activity relationships, we investigated the physicochemical properties and molecular electrostatic potentials of the drug molecules. RESULTS We found that rhein, emodin, and aloe-emodin exerted at least dual-target (NF-κB, iNOS) inhibition of LPS-induced inflammatory responses. Compared with rhein and emodin, aloe-emodin had a stronger anti-inflammatory effect, and its inhibition of iNOS protein expression was approximately twice that of NF-κB phosphorylation. In addition, aloe-emodin had the strongest hydrophobic effect among the three anthraquinones. CONCLUSIONS Overall, we concluded that the receptor binding the rhubarb anthraquinones had a hydrophobic pocket. Anthraquinone molecules with stronger hydrophobic effects had higher affinity for the receptor, resulting in greater anti-inflammatory activity. These results suggest that the addition of a hydrophobic group is a potential method for structural modification to design anti-inflammatory anthraquinone derivatives with enhanced potency.
Collapse
Affiliation(s)
- Yingfan Hu
- School of Preclinical Medicine, Chengdu University, Chengdu, 610106, Sichuan, China; Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China
| | - Wen'ge Huang
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China
| | - Yu Luo
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China
| | - Li Xiang
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China
| | - Jiasi Wu
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China
| | - Yan Zhang
- School of Preclinical Medicine, Chengdu University, Chengdu, 610106, Sichuan, China
| | - Yong Zeng
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China
| | - Chensi Xu
- Chengdu Pharmoko Tech Corp., Ltd., Chengdu, 610041, China
| | - Xianli Meng
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.
| | - Ping Wang
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan, China.
| |
Collapse
|
14
|
Liang G, Yang J, Liu T, Wang S, Wen Y, Han C, Huang Y, Wang R, Wang Y, Hu L, Wang G, Li F, Tyndall JDA, Deng L, Du D, Xia Q. A multi-strategy platform for quality control and Q-markers screen of Chaiqin chengqi decoction. PHYTOMEDICINE 2021; 85:153525. [PMID: 33740732 DOI: 10.1016/j.phymed.2021.153525] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 02/03/2021] [Accepted: 02/18/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that is associated with substantial morbidity and mortality. Chaiqin chengqi decoction (CQCQD) has been proven clinically to be an effective treatment for AP for decades in West China Hospital. Quality control for CQCQD containing many hundreds of characteristic phytochemicals poses a challenge for developing robust quality assessment metrics. PURPOSE To evaluate quality consistency of CQCQD with a multi-strategy based analytical method, identify potential quality-markers (Q-markers) based on drug properties and effect characteristics, and endeavor to establish CQCQD as a globally-accepted medicine. METHODS A typical analysis of constitutive medicinal plant materials was performed following the Chinese Pharmacopoeia. The extraction process was optimized through an orthogonal array (L9(34)) to evaluate three levels of liquid to solid ratio, soaking time, duration of extraction, and the number of extractions. An ultra-high-performance liquid chromatography (UHPLC) fingerprinting combined with absolute quantitation of multi chemical marker compounds, coupled with similarity, hierarchical clustering analysis (HCA), and principal component analyses (PCA) were performed to evaluate 10 batches of CQCQD. On the basis of systematic analysis of fundamental features of CQCQD in treating AP, the potential Q-marker screen was proposed through detection of quality transfer and efficacy for chemical markers. UHPLC coupled with quadrupole orbitrap mass spectrometry were used to determine compounds in medicinal materials, decoctions and plasma. Network pharmacology and taurolithocholic acid 3-sulfate induced pancreatic acinar cell death were used to evaluate the correlation between chemical markers and anti-pancreatitis activity. A cerulein induced AP murine model was used to validate quality assessed CQCQD batches at clinically-equivalent dose. The effective content of chemical markers was predicted using linear regression analysis on quantitative information between validated batches and the other batches. RESULTS The chemical markers and other physical and chemical indices in the original materials met Chinese Pharmacopoeia standards. A total of 22 co-existing fingerprint peaks were selected and the similarity varied between 0.946 and 0.990. Batch D10 possessed the highest similarity index. HCA classified the 10 batches into 2 main groups: 7 batches represented by D10 and 3 batches represented by D1. During the initial Q-marker screen stage, 22 compounds were detected in both plant materials and decoctions, while 13 compounds were identified in plasma. Network pharmacology predicted the potential targets and pathway of AP related to the 22 compounds. All 10 batches showed reduced necrosis below 60% with the best effect achieved by D10 (~40%). The spectrum-efficacy relationship analyzed by Pearson correlation analysis indicated that emodin, rhein, aloe emodin, geniposide, hesperridin, chrysin, syringin, synephrine, geniposidic acid, magnolol, physcion, sinensetin, and baicalein showed positive correlation with pancreatic acinar cell death protection. Similar to the in vitro evaluation, batch D10 significantly reduced total histopathological scores and biochemical severity indices at a clinically-equivalent dose but batch D1 did not. The content of naringin, narirutin and baicalin in batches D1, D5 and D9 consistently exceeds the upper limit of the predicted value. Eight markers whose lower limit is predicted to be close to 0 contributed less to the material basis for AP protection. CONCLUSION Despite qualified materials used for CQCQD preparation, the clinical effect depends on appropriate content range of Q-markers. Emodin, rhein, aloe emodin, magnolol, hesperidin, synephrine, baicalein, and geniposide are considered as vital Q-markers in the primary screen. This study proposed a feasible platform for producing highly consistent batches of CQCQD in future study.
Collapse
Affiliation(s)
- Ge Liang
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; West China-Washington Mitochondria and Metabolism Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jingyu Yang
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Tingting Liu
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Shisheng Wang
- West China-Washington Mitochondria and Metabolism Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yongjian Wen
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chenxia Han
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yan Huang
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Rui Wang
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yiqin Wang
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Liqiang Hu
- West China-Washington Mitochondria and Metabolism Centre, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Guangzhi Wang
- Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Fei Li
- Laboratory of metabolomics and drug-induced liver injury, Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Joel D A Tyndall
- School of Pharmacy, University of Otago, Dunedin 9054, New Zealand
| | - Lihui Deng
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Dan Du
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China; West China-Washington Mitochondria and Metabolism Centre, 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 610041, China.
| | - Qing Xia
- Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China.
| |
Collapse
|
15
|
Saikosaponin A-Induced Gut Microbiota Changes Attenuate Severe Acute Pancreatitis through the Activation of Keap1/Nrf2-ARE Antioxidant Signaling. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:9217219. [PMID: 33204401 PMCID: PMC7652616 DOI: 10.1155/2020/9217219] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 07/11/2020] [Accepted: 07/21/2020] [Indexed: 12/16/2022]
Abstract
Objective Severe acute pancreatitis (SAP) is a serious and life-threatening disease associated with multiple organ failure and a high mortality rate and is accompanied by distinct oxidative stress and inflammatory responses. Saikosaponin A has strong antioxidant properties and can affect the composition of gut microbiota. We sought to determine the effects of Saikosaponin A interventions on SAP by investigating the changes of gut microbiota and related antioxidant signaling. Methods A SAP model was established in Sprague-Dawley (SD) rats through the injection of sodium taurocholate into the biliopancreatic duct and confirmed by elevated levels of serum lipase and amylase. The model was fed a standard diet either with saline solution or with Saikosaponin A. Fecal microbiota transplantation (FMT) from Saikosaponin A-induced rats into the rat model was performed to test the effects of gut microbiota. The composition of gut microbiota was analyzed by using 16S rRNA gene sequencing. We measured apoptotic status, inflammatory biomarkers, and Keap1-Nrf2-ARE ((Kelch-like ECH-associated protein 1) nuclear factor erythroid 2-related factor 2-antioxidant response element) antioxidant signaling. Results Saikosaponin A intervention attenuated SAP lesions and reduced the levels of serum amylase and lipase, oxidative stress, and inflammatory responses by reducing pathological scores and affecting the serum level of oxidative and inflammatory factors. Meanwhile, the expression of Keap1-Nrf2-ARE was increased. Saikosaponin A intervention improved microbiota composition by increasing the relative abundance of Lactobacillus and Prevotella species. FMT resulted in similar results as those caused by the Saikosaponin A intervention, suggesting Saikosaponin A may exert its function via the improvement of gut microbiota composition. Conclusions Saikosaponin A-induced gut microbiota changes attenuate SAP progression in the rat model and may be a potential natural drug for adjuvant treatment of SAP. Further work is needed to clear up the points.
Collapse
|
16
|
Jiang X, Zheng YW, Bao S, Zhang H, Chen R, Yao Q, Kou L. Drug discovery and formulation development for acute pancreatitis. Drug Deliv 2020; 27:1562-1580. [PMID: 33118404 PMCID: PMC7598990 DOI: 10.1080/10717544.2020.1840665] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Acute pancreatitis is a sudden inflammation and only last for a short time, but might lead to a life-threatening emergency. Traditional drug therapy is an essential supportive method for acute pancreatitis treatment, yet, failed to achieve satisfactory therapeutic outcomes. To date, it is still challenging to develop therapeutic medicine to redress the intricate microenvironment promptly in the inflamed pancreas, and more importantly, avoid multi-organ failure. The understanding of the acute pancreatitis, including the causes, mechanism, and severity judgment, could help the scientists bring up more effective intervention and treatment strategies. New formulation approaches have been investigated to precisely deliver therapeutics to inflammatory lesions in the pancreas, and some even could directly attenuate the pancreatic damages. In this review, we will briefly introduce the involved pathogenesis and underlying mechanisms of acute pancreatitis, as well as the traditional Chinese medicine and the new drug option. Most of all, we will summarize the drug delivery strategies to reduce inflammation and potentially prevent the further development of pancreatitis, with an emphasis on the bifunctional nanoparticles that act as both drug delivery carriers and therapeutics.
Collapse
Affiliation(s)
- Xue Jiang
- Municipal Key Laboratory of Paediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.,Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ya-Wen Zheng
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Shihui Bao
- Municipal Key Laboratory of Paediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hailin Zhang
- Municipal Key Laboratory of Paediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Department of Children's Respiration Disease, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ruijie Chen
- Municipal Key Laboratory of Paediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Qing Yao
- Municipal Key Laboratory of Paediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Longfa Kou
- Municipal Key Laboratory of Paediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| |
Collapse
|
17
|
Chaiqin chengqi decoction alleviates severity of acute pancreatitis via inhibition of TLR4 and NLRP3 inflammasome: Identification of bioactive ingredients via pharmacological sub-network analysis and experimental validation. PHYTOMEDICINE 2020; 79:153328. [PMID: 33007730 DOI: 10.1016/j.phymed.2020.153328] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 06/08/2020] [Accepted: 06/22/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Chaiqin chengqi decoction (CQCQD) is a Chinese herbal formula derived from dachengqi decoction. CQCQD has been used for the management of acute pancreatitis (AP) in the West China Hospital for more than 30 years. Although CQCQD has a well-established clinical efficacy, little is known about its bioactive ingredients, how they interact with different therapeutic targets and the pathways to produce anti-inflammatory effects. PURPOSE Toll-like receptor 4 (TLR4) and the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated pro-inflammatory signaling pathways, play a central role in AP in determining the extent of pancreatic injury and systemic inflammation. In this study, we screened the bioactive ingredients using a pharmacological sub-network analysis based on the TLR4/NLRP3 signaling pathways followed by experimental validation. METHODS The main CQCQD bioactive compounds were identified by UPLC-QTOF/MS. The TLR4/NLRP3 targets in AP for CQCQD active ingredients were confirmed through a pharmacological sub-network analysis. Mice received 7 intraperitoneal injections of cerulein (50 μg/kg; hourly) to induce AP (CER-AP), while oral gavage of CQCQD (5, 10, 15 and 20 g/kg; 3 doses, 2 hourly) was commenced at the 3rd injection of cerulein. Histopathology and biochemical indices were used for assessing AP severity, while polymerase chain reaction, Western blot and immunohistochemistry analyses were used to study the mechanisms. Identified active CQCQD compounds were further validated in freshly isolated mouse pancreatic acinar cells and cultured RAW264.7 macrophages. RESULTS The main compounds from CQCQD belonged to flavonoids, iridoids, phenols, lignans, anthraquinones and corresponding glycosides. The sub-network analysis revealed that emodin, rhein, baicalin and chrysin were the compounds most relevant for directly regulating the TLR4/NLRP3-related proteins TLR4, RelA, NF-κB and TNF-α. In vivo, CQCQD attenuated the pancreatic injury and systemic inflammation of CER-AP and was associated with reduced expression of TLR4/NLRP3-related mRNAs and proteins. Emodin, rhein, baicalin and chrysin significantly diminished pancreatic acinar cell necrosis with varied effects on suppressing the expression of TLR4/NLRP3-related mRNAs. Emodin, rhein and chrysin also decreased nitric oxide production in macrophages and their combination had synergistic effects on alleviating cell death as well as expression of TLR4/NLRP3-related proteins. CONCLUSIONS CQCQD attenuated the severity of AP at least in part by inhibiting the TLR4/NLRP3 pro-inflammatory pathways. Its active ingredients, emodin, baicalin, rhein and chrysin contributed to these beneficial effects.
Collapse
|
18
|
Xiang H, Zuo J, Guo F, Dong D. What we already know about rhubarb: a comprehensive review. Chin Med 2020; 15:88. [PMID: 32863857 PMCID: PMC7448319 DOI: 10.1186/s13020-020-00370-6] [Citation(s) in RCA: 86] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 08/19/2020] [Indexed: 02/06/2023] Open
Abstract
Rhubarb (also named Rhei or Dahuang), one of the most ancient and important herbs in traditional Chinese medicine (TCM), belongs to the Rheum L. genus from the Polygonaceae family, and its application can be traced back to 270 BC in "Shen Nong Ben Cao Jing". Rhubarb has long been used as an antibacterial, anti-inflammatory, anti-fibrotic and anticancer medicine in China. However, for a variety of reasons, such as origin, variety and processing methods, there are differences in the effective components of rhubarb, which eventually lead to decreased quality and poor efficacy. Additionally, although some papers have reviewed the relationship between the active ingredients of rhubarb and pharmacologic actions, most studies have concentrated on one or several aspects, although there has been great progress in rhubarb research in recent years. Therefore, this review aims to summarize recent studies on the geographic distribution, taxonomic identification, pharmacology, clinical applications and safety issues related to rhubarb and provide insights into the further development and application of rhubarb in the future.
Collapse
Affiliation(s)
- Hong Xiang
- Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jiaxin Zuo
- Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Pharmacy, Dalian Medical University, Dalian, China
| | - Fangyue Guo
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Deshi Dong
- Department of Clinical Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian, China
| |
Collapse
|
19
|
Chen X, Yang K, Jing G, Yang J, Li K. Meta‐Analysis of Efficacy of Rhubarb Combined With Early Enteral Nutrition for the Treatment of Severe Acute Pancreatitis. JPEN J Parenter Enteral Nutr 2020; 44:1066-1078. [PMID: 32187391 DOI: 10.1002/jpen.1789] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 10/24/2019] [Accepted: 01/06/2020] [Indexed: 02/06/2023]
Affiliation(s)
- Xinrong Chen
- West China Hospital/West China School of NursingSichuan University Chengdu Sichuan Province China
| | - Kun Yang
- Department of Gastrointestinal SurgeryWest China HospitalSichuan University Chengdu Sichuan Province China
| | - Guanda Jing
- West China Hospital/West China School of NursingSichuan University Chengdu Sichuan Province China
| | - Jie Yang
- Department of Gastrointestinal SurgeryWest China HospitalSichuan University Chengdu Sichuan Province China
| | - Ka Li
- West China Hospital/West China School of NursingSichuan University Chengdu Sichuan Province China
| |
Collapse
|
20
|
Chen C, Fu Z, Zhou W, Chen Q, Wang C, Xu L, Wang Z, Zhang H. Ionic liquid-immobilized NaY zeolite-based matrix solid phase dispersion for the extraction of active constituents in Rheum palmatum L. Microchem J 2020. [DOI: 10.1016/j.microc.2019.104245] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
|
21
|
Zheng Y, Gou X, Zhang L, Gao H, Wei Y, Yu X, Pang B, Tian J, Tong X, Li M. Interactions Between Gut Microbiota, Host, and Herbal Medicines: A Review of New Insights Into the Pathogenesis and Treatment of Type 2 Diabetes. Front Cell Infect Microbiol 2020; 10:360. [PMID: 32766169 PMCID: PMC7379170 DOI: 10.3389/fcimb.2020.00360] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 06/10/2020] [Indexed: 12/12/2022] Open
Abstract
Herbal medicines (HMs) are a major subset of complementary and alternative medicine. They have been employed for the efficient clinical management of type 2 diabetes mellitus (T2DM) for centuries. However, the related underlying mechanisms still remain to be elucidated. It has been found out that microbiota is implicated in the pathogenesis and treatment of T2DM. An interplay between gut microbiota and host occurs mainly at the gastrointestinal mucosal barrier. The host movements influence the composition and abundance of gut microbiota, whereas gut microbiota in turn modulate the metabolic and immunological activities of the host. Intestinal dysbiosis, endotoxin-induced metabolic inflammation, immune response disorder, bacterial components and metabolites, and decreased production of short-chain fatty acids are considered significant pathogenic mechanisms underlying T2DM. The interaction between gut microbiota and HMs during T2DM treatment has been investigated in human, animal, and in vitro studies. HMs regulate the composition of beneficial and harmful bacteria and decrease the inflammation caused by gut microbiota. Furthermore, the metabolism of gut microbiota modulates HM biotransformation. In this review, we have summarized such research findings, with the aim to improve our understanding of the pathogenesis and potential therapeutic mechanisms of HMs in T2DM and to provide new insights into specific targeted HM-based therapies and drug discovery.
Collapse
Affiliation(s)
- Yujiao Zheng
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaowen Gou
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Lili Zhang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hanjia Gao
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Yu Wei
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaotong Yu
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Bing Pang
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiaxing Tian
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Jiaxing Tian
| | - Xiaolin Tong
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Xiaolin Tong
| | - Min Li
- Molecular Biology Laboratory, Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing, China
- Min Li
| |
Collapse
|
22
|
Luo Y, Wang CZ, Hesse-Fong J, Lin JG, Yuan CS. Application of Chinese Medicine in Acute and Critical Medical Conditions. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2019; 47:1223-1235. [PMID: 31505937 DOI: 10.1142/s0192415x19500629] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Western medicine is routinely used in developed nations as well as in Eastern countries, where traditional medicine is frequently used by a selection of patients or family member as a complement to mainstream Western medicine. Chinese medicine plays an important role in the treatment of chronic diseases, especially when Western medicine is not very effective. Many published reports have shown that Chinese medicine could also be successfully used in the management of acute and critical illnesses. Chinese medicine has a holistic view of the human body, and emphasizes individualization based on body balance and mind-body interaction and employs herbal medicines and acupuncture. This review paper gives a brief overview of Chinese medicine theory and therapeutic modality and then addresses the application of Chinese medicine in the treatment of acute and critical medical conditions, including epidemics. Using this ancient therapy as a complementary medicine, the management of serious medical conditions, such as SARS, acute heart diseases, and ischemic cerebral stroke, are presented. In order to promote more widespread application of Chinese medicine, well-designed controlled clinical trials are urgently needed to prove its safety and effectiveness.
Collapse
Affiliation(s)
- Yun Luo
- Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P. R. China.,Tang Center for Herbal Medicine Research, University of Chicago, Chicago, Illinois 60637, USA.,Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637, USA
| | - Chong-Zhi Wang
- Tang Center for Herbal Medicine Research, University of Chicago, Chicago, Illinois 60637, USA.,Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637, USA
| | - Julia Hesse-Fong
- Tang Center for Herbal Medicine Research, University of Chicago, Chicago, Illinois 60637, USA.,Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637, USA
| | - Jaung-Geng Lin
- School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
| | - Chun-Su Yuan
- Tang Center for Herbal Medicine Research, University of Chicago, Chicago, Illinois 60637, USA.,Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637, USA.,Committee on Clinical Pharmacology and Pharmacogenomics, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637, USA
| |
Collapse
|
23
|
Xiong Y, Chen L, Fan L, Wang L, Zhou Y, Qin D, Sun Q, Wu J, Cao S. Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis. Front Pharmacol 2018; 9:75. [PMID: 29487524 PMCID: PMC5816759 DOI: 10.3389/fphar.2018.00075] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Accepted: 01/23/2018] [Indexed: 12/18/2022] Open
Abstract
Intestinal mucosal immune barrier dysfunction plays a key role in the pathogenesis of severe acute pancreatitis (SAP). Rhubarb is a commonly used traditional Chinese medicine as a laxative in China. It markedly protects pancreatic acinar cells from trypsin-induced injury in rats. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of antibacteria, anti-inflammation, antivirus, and anticancer. The principal aim of the present study was to investigate the effects of FTRAs on the protection of intestinal injury and modification of the intestinal barrier function through regulation of intestinal immune function in rats with SAP. We established a rat model of SAP by injecting 3.5% sodium taurocholate (STC, 350 mg/kg) into the biliopancreatic duct via retrograde injection and treated the rats with FTRAs (36 or 72 mg/kg) or normal saline (control) immediately and 12 h after STC injection. Then, we evaluated the protective effect of FTRAs on intestinal injury by pathological analysis and determined the levels of endotoxin (ET), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), nitric oxide (NO), myeloperoxidase (MPO), capillary permeability, nucleotide-binding oligomerization domain-like receptors 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC), casepase-1, secretary immunoglobulin A (SIgA), regulatory T cells (Tregs), and the ratio of Th1/Th2 in the blood and/or small intestinal tissues or mesenteric lymph node (MLN) cells. Moreover, the chemical profile of FTRAs was analyzed by HPLC-UV chromatogram. The results showed that FTRAs significantly protected intestinal damage and decreased the levels of ET, IL-1β, TNF-α, and NO in the blood and TNF-α, IL-1β, and protein extravasation in the intestinal tissues in SAP rats. Furthermore, FTRAs significantly decreased the expressions of NLRP3, ASC, and caspase-1, the number of Tregs and the ratio of Th1/Th2, while significantly increased the expression of SIgA in the intestinal tissues and/or MLN cells in SAP rats. Our results indicate that FTRAs could protect intestinal injury and improve intestinal mucosal barrier function through regulating immune function of SAP rats. Therefore, FTRAs may have the potential to be developed as the novel agent for the treatment of SAP clinically.
Collapse
Affiliation(s)
- Yuxia Xiong
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Li Chen
- Department of Pharmacy, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou, China
| | - Ling Fan
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Lulu Wang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Yejiang Zhou
- Department of Gastrointestinal Surgery, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China
| | - Dalian Qin
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Qin Sun
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Jianming Wu
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Shousong Cao
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| |
Collapse
|
24
|
Cao YJ, Pu ZJ, Tang YP, Shen J, Chen YY, Kang A, Zhou GS, Duan JA. Advances in bio-active constituents, pharmacology and clinical applications of rhubarb. Chin Med 2017; 12:36. [PMID: 29299052 PMCID: PMC5745730 DOI: 10.1186/s13020-017-0158-5] [Citation(s) in RCA: 113] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 12/14/2017] [Indexed: 01/06/2023] Open
Abstract
Rhubarb is one of the most ancient, commonly used and important herbs in Chinese medicine. The modern researches of rhubarb clarified the efficacies, ingredients and mechanisms in a more scientific and rigorous way. The main chemical compositions of rhubarb include anthraquinones, anthrones, stilbenes, tannins, polysaccharides etc. These compositions show extensive pharmacological activities including regulating gastrointestinal, anticancer, antimicrobial, hepatoprotective, anti-inflammatory, protecting cardiovascular, cerebrovascular and so on. This paper reviews the recent studies on the active ingredients, pharmacological effects, clinical application and functional mechanism.
Collapse
Affiliation(s)
- Yu-Jie Cao
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023 Jiangsu China
| | - Zong-Jin Pu
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023 Jiangsu China
| | - Yu-Ping Tang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023 Jiangsu China
- College of Pharmacy and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang, 712046 China
| | - Juan Shen
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023 Jiangsu China
| | - Yan-Yan Chen
- College of Pharmacy and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xianyang, 712046 China
| | - An Kang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023 Jiangsu China
| | - Gui-Sheng Zhou
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023 Jiangsu China
| | - Jin-Ao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023 Jiangsu China
| |
Collapse
|
25
|
Li J, Zhang S, Zhou R, Zhang J, Li ZF. Perspectives of traditional Chinese medicine in pancreas protection for acute pancreatitis. World J Gastroenterol 2017; 23:3615-3623. [PMID: 28611514 PMCID: PMC5449418 DOI: 10.3748/wjg.v23.i20.3615] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 03/13/2017] [Accepted: 05/04/2017] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis (AP) is one of the most common diseases. AP is associated with significant morbidity and mortality, but it lacks specific and effective therapies. Traditional Chinese medicine (TCM) is one of the most popular complementary and alternative medicine modalities worldwide for the treatment of AP. The current evidence from basic research and clinical studies has shown that TCM has good therapeutic effects on AP. This review summarizes the widely used formulas, single herbs and monomers that are used to treat AP and the potential underlying mechanisms of TCM. Because of the abundance, low cost, and safety of TCM as well as its ability to target various aspects of the pathogenesis, TCM provides potential clinical benefits and a new avenue with tremendous potential for the future treatment of AP.
Collapse
|
26
|
Chai-Qin-Cheng-Qi Decoction and Carbachol Improve Intestinal Motility by Regulating Protein Kinase C-Mediated Ca 2+ Release in Colonic Smooth Muscle Cells in Rats with Acute Necrotising Pancreatitis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:5864945. [PMID: 28529530 PMCID: PMC5424168 DOI: 10.1155/2017/5864945] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 02/06/2017] [Accepted: 03/01/2017] [Indexed: 02/05/2023]
Abstract
Chai-Qin-Cheng-Qi decoction (CQCQD) improves intestinal motility in acute pancreatitis (AP), but the mechanism(s) require elucidation. We investigated the effects of CQCQD and carbachol, a prokinetic agent, on colonic smooth muscle cells (SMCs) in L-arginine-induced necrotising AP model in rats. In treatment groups, intragastric CQCQD (20 g/kg, 2 hourly × 3 doses) or intraperitoneal carbachol (60 μg/kg) was given 24 hours after induction of AP. Both CQCQD and carbachol decreased the severity of pancreatic and colonic histopathology (all P < 0.05). Both CQCQD and carbachol reduced serum intestinal fatty acid binding protein, vasoactive intestinal peptide, and substance P and increased motility levels. CQCQD upregulated SMC phospholipase C-beta 1 (PLC-β1) mRNA and PLC protein (both P < 0.05), while both treatments upregulated protein kinase C-alpha (PKC-α) mRNA and PKC protein and downregulated adenylate cyclase (AC) mRNA and protein compared with no treatment (all P < 0.05). Neither treatment significantly altered L-arginine-induced PKC-β1 and PKC-ε mRNA reduction. Both treatments significantly increased fluorescence intensity of SMC intracellular calcium concentration [Ca2+]i (3563.5 and 3046.9 versus 1086.9, both P < 0.01). These data suggest CQCQD and carbachol improve intestinal motility in AP by increasing [Ca2+]i in colonic SMCs via upregulating PLC, PKC and downregulating AC.
Collapse
|
27
|
Liu W, Yuan Q, Guo S, Fu Z. Emodin in Severe Acute Pancreatitis Treatment. Chin Med 2017. [DOI: 10.4236/cm.2017.84008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
|