Paeoniflorin modulates gut microbial production of indole-3-lactate and epithelial autophagy to alleviate colitis in mice.

Published on Sep 19, 2020in Phytomedicine4.268
路 DOI :10.1016/J.PHYMED.2020.153345
Qilin Fan2
Estimated H-index: 2
(CPU: China Pharmaceutical University),
Xiaojing Guan3
Estimated H-index: 3
(CPU: China Pharmaceutical University)
+ 7 AuthorsHaiping Hao53
Estimated H-index: 53
(CPU: China Pharmaceutical University)
Source
Abstract
Abstract Background : Total glucosides of peony (TGP), extracted from the root and rhizome of Paeonia lactiflora Pall, has well-confirmed immunomodulatory efficacy in the clinic. However, the mechanism and active ingredients remain largely unclear. Hypothesis/Purpose : Our previous study revealed a low systemic exposure but predominant gut distribution of TGP components. The aim of this study was to investigate involvement of the gut microbiota in the immunoregulatory effects and identify the active component. Methods : Mice received 3% DSS to establish a model of colitis. The treatment group received TGP or single paeoniflorin (PF) or albiflorin (AF). Body weight, colon length, inflammatory and histological changes were assessed. Gut microbiota structure was profiled by 16s rRNA sequencing. Antibiotic treatment and fecal transplantation were used to explore the involvement of gut microbiota. Metabolomic assay of host and microbial metabolites in colon was performed. Results : TGP improved colonic injury and gut microbial dysbiosis in colitis mice, and PF was responsible for the protective effects. Fecal microbiota transfer from TGP-treated mice conferred resilience to colitis, while antibiotic treatment abrogated the protective effects. Both TGP and PF decreased colonic indole-3-lactate (ILA), a microbial tryptophan metabolite. ILA was further identified as an inhibitor of epithelial autophagy and ILA supplementation compromised the benefits of TGP. Conclusion : Our findings suggest that TGP acts in part through a gut microbiota-ILA-epithelial autophagy axis to alleviate colitis.
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References41
Newest
#1Yali Liu (CPU: China Pharmaceutical University)H-Index: 3
#2Yuanlong Hou (CPU: China Pharmaceutical University)H-Index: 4
Last. Haiping Hao (CPU: China Pharmaceutical University)H-Index: 53
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Gut microbial metabolism is intimately coupled with host health and disease. Aromatic amino acid (AAA) catabolism by the gut microbiome yields numerous metabolites that may regulate immune, metabolic, and neuronal responses at local and distant sites. Such a chemical dialog between host cells and the gut microbiome is shaped by environmental cues, and may become dysregulated in gastrointestinal and systems diseases. Increasing knowledge of the bacterial pathway and signaling basis may shed addit...
Source
#1Ge Liu (CPU: China Pharmaceutical University)H-Index: 3
#2Ziyu Wang (CPU: China Pharmaceutical University)H-Index: 4
Last. Weirong Fang (CPU: China Pharmaceutical University)H-Index: 20
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Abstract Ethnopharmacological relevance Sjogren's syndrome (SS) is an autoimmune disease and can cause gastrointestinal disorders such as constipation and intestinal inflammation. As a kind of medicinal material, Paeonia lactiflora Pall has a variety of pharmacological effects, and it is also an indispensable component in many pharmaceutical preparations, which has been widely concerned by the medical and pharmaceutical circles. Total glucosides of paeony (TGP) is a mixture of biologically activ...
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#1Hua-Juan Jiang (CDUTCM: Chengdu University of Traditional Chinese Medicine)H-Index: 2
#2Jie Li (CDUTCM: Chengdu University of Traditional Chinese Medicine)H-Index: 3
Last. Yao He (CDUTCM: Chengdu University of Traditional Chinese Medicine)H-Index: 4
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Abstract Ethnopharmacological relevance Paeoniae Radix Alba (PRA, called baishao in China), the root of Paeonia lactiflora Pall., has shown a rich medicinal value for more than 2000 years. PRA is used in local medicine and traditional medicine for autoimmune diseases associated with inflammation. At present, total glucosides of paeony (TGP), the main active ingredient of PRA, has been developed into a preparation for the treatment of autoimmune diseases, as TGP exhibits the effect of regulating ...
Source
#1Wenhan Zhu (UTSW: University of Texas Southwestern Medical Center)H-Index: 15
#2Maria G. Winter (UTSW: University of Texas Southwestern Medical Center)
Last. Sebastian E. Winter (UTSW: University of Texas Southwestern Medical Center)H-Index: 45
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Summary During short-lived perturbations, such as inflammation, the gut microbiota exhibits resilience and reverts to its original configuration. Although microbial access to the micronutrient iron is decreased during colitis, pathogens can scavenge iron by using siderophores. How commensal bacteria acquire iron during gut inflammation is incompletely understood. Curiously, the human commensal Bacteroides thetaiotaomicron does not produce siderophores but grows under iron-limiting conditions usi...
Source
#1Lingling Zhang (Anhui Medical University)H-Index: 1
#2Wei Wei (Anhui Medical University)H-Index: 1
Abstract As a Traditional Chinese Medicine, Paeonia lactiflora Pallas has been used to treat pain, inflammation and immune disorders for more than 1000鈥痽ears in China. Total glycoside of paeony (TGP) is extracted from the dried root of Paeonia lactiflora Pallas. Paeoniflorin (Pae) is the major active component of TGP. Our research group has done a lot of work in the pharmacological mechanisms of Pae and found that Pae possessed extensive anti-inflammatory and immune regulatory effects. Pae could...
Source
#1Aonghus Lavelle (French Institute of Health and Medical Research)H-Index: 4
#2Harry SokolH-Index: 68
A key role of the gut microbiota in the establishment and maintenance of health, as well as in the pathogenesis of disease, has been identified over the past two decades. One of the primary modes by which the gut microbiota interacts with the host is by means of metabolites, which are small molecules that are produced as intermediate or end products of microbial metabolism. These metabolites can derive from bacterial metabolism of dietary substrates, modification of host molecules, such as bile ...
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#2Xin-Yue Cao (Fudan University)H-Index: 2
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Abstract Background The development of rheumatoid arthritis (RA) is related to germinal center (GC) response and autoreactive T cells, which mediate adaptive immunity and play an important role in stimulating the production of autoantibodies and pro-inflammatory cytokines by B cells and macrophages. Total Glucosides of Paeony (TGP) has anti-inflammatory, immunomodulatory and analgesic effects and is widely used to treat RA. However, few studies investigated whether the therapeutic effect of TGP ...
Source
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Abstract: Ethnopharmacological relevance Paeonia lactiflora Pall. (peony) is a medicinal plant used in the Xiaoqinglong decoction, a commonly prescribed traditional Chinese medicine for asthma. The main active ingredients of peony roots鈥攄escribed as the total glucosides of peony (TGP)鈥攈ave anti-inflammatory, immunomodulatory, and protective effects on endothelial cells, and they are known to improve rheumatoid arthritis. This study explored the underlying mechanism of TGP activity in the treatme...
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#1Xiao Zheng (CPU: China Pharmaceutical University)H-Index: 17
#2Miaomiao Hu (CPU: China Pharmaceutical University)H-Index: 2
Last. Haiping Hao (CPU: China Pharmaceutical University)H-Index: 53
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Abstract Psychological stress is well known to increase colitis susceptibility and promote relapse. Metabolic changes are commonly observed under psychological stress, but little is known how this relates to the progression of colitis. Here we show that kynurenic acid (KA) is an endogenous driver of social stress-exacerbated colitis via regulating the magnitude of NLRP3 inflammasome. Chronic social defeat stress (CSDS) in mice induced colonic accumulation of KA, and mice receiving KA during CSDS...
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Metronomic chemotherapy, a relatively new dosing paradigm for anticancer therapy, is an alternative to traditional chemotherapy that uses maximal tolerated dose (MTD). Although these two dosing regimens both lead to tumor cell death, how cell metabolism is differentially affected during apoptosis remains elusive. Herein, we employed metabolomics to monitor the metabolic profiles of MCF-7 cells in response to the two dosing regimens that mimic MTD and MN treatments using a model chemotherapeutic ...
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