Wogonoside alleviates colitis by improving intestinal epithelial barrier function via the MLCK/pMLC2 pathway

Huang, Shaowei; Fu, Yajun; Xu, Bo; Liu, Chang; Wang, Qing; Luo, Shuang; Nong, Feifei; Wang, Xiaojing; Huang, Songyu; Chen, Jinyan; Zhou, Lian; Luo, Xia

doi:10.1016/j.phymed.2020.153179

Cited by 85 publications

(53 citation statements)

References 28 publications

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“…The node of m/z 561.161 was annotated as 5-hydroxy-7-methoxy avone 6-C-arabinoside-8-C-glucoside or 7hydroxy-5-methoxy avone 6-C-arabinoside-8-C-glucoside [16] (Figure 4d). Basing on the cluster, six avone C-glycosides were identi ed from Scutellariae radix by comparison with literatures [16,17].…”

Section: Flavone C-glycosidesmentioning

confidence: 99%

“…The types of aglycone are mainly avone and avanone. It was well known that baicalin and wogonoside were mainly active components in Scutellariae radix[16,17]. Peak 72 was identi ed as wogonoside by comparison with its standard compound, and its MS/MS spectra showed three characteristic fragments of m/z 283.061, m/z 268.038, and m/z 240.042, which in turn lost C 6 H 8 O 6 , CH 3 and CO, the fragment of m/z 283.061 corresponding to the aglycone moiety of wogonoside by the loss of Da 176 (C 6 H 8 O 6 ) from the [M-H] -[18] (Figure S2).…”

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confidence: 99%

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The Combination of UHPLC-HRMS and Molecular Networking Improving Discovery Efficiency of Chemical Components in Chinese Classical Formula

Xue

Jiao

Jin

et al. 2021

Preprint

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Background It is essential to identify the chemical components for the quality control methods establishment of Chinese Classical Formula (CCF). However, CCF are complex mixture of several herbal medicines with huge number of different compounds and they are not equal to the combination of chemical components from each herb due to particular formula ratio and preparation techniques. Therefore, it is time-consuming to identify compounds in a CCF by analyzing the LC-MS/MS data one by one, especially for unknown components. Methods An ultra-high pressure liquid chromatography-linear ion trap-orbitrap high resolution mass spectrometry (UHPLC-LTQ-Orbitrap-MS/MS) approach was developed to comprehensively profile and characterize multi-components in CCF with Erdong decoction composed of eight herbal medicines as an example. Then the MS data of Erdong decoction was analyzed by MS/MS-based molecular networking and these compounds with similar structures were connected to each other into a cluster in the network map. Then the unknown compounds connected to known compounds in a cluster of the network map were identified due to their similar structures. Results Based on the clusters in the molecular networking, 113 compounds were rapidly identified from Erdong decoction for the first time, which including steroidal saponins, triterpenoid saponins, flavone O-glycosides and flavone C-glycosides. Conclusion MS/MS-based molecular networking technique is very useful for the rapid identification of components in CCF. In Erdong decoction, this method was very suitable for the identification of major steroidal saponins, triterpenoid saponins, and flavone C-glycosides.

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Section: Flavone C-glycosidesmentioning

confidence: 99%

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confidence: 99%

The Combination of UHPLC-HRMS and Molecular Networking Improving Discovery Efficiency of Chemical Components in Chinese Classical Formula

Xue

Jiao

Jin

et al. 2021

Preprint

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“…It has been reported that HQD was con rmed to contain the indicator components paeoni orin, glycyrrhizic acid, baicalin, wogonoside, and liquiritin, among which baicalin had the highest concentration, followed by wogonoside and glycyrrhizic acid [18] . And our results showed that the sample similarity of the 10 batches of HQD was more than 0.980, based on the HQD ngerprints (Fig.…”

Section: Hplc Analysis Of Hqdmentioning

confidence: 99%

Effect of Huangqin Decoction on Regulating Intestinal Flora in Colitis Mice Characterized as The Inhibition of NOD2-Dependent Pathway

Huang

Chen

et al. 2020

Preprint

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Background: Dysfunction of the intestinal flora is an important factor in the occurrence and development of ulcerative colitis (UC). Chinese herb Huangqin decoction (HQD) can regulate intestinal flora in UC mice, yet its specific mechanism remains unclear. Our study aimed to clarify the mechanism of HQD in regulating intestinal flora of UC mice.Methods: 3%DSS - induced colitis mice were used to explore the pharmacodynamics of HQD. Colonic bacterial infiltration and the changes of intestinal flora were detected by FISH and 16SrDNA. Expression of RegⅢγ and PRRs (NOD2, TLR5, TLR4) were detected by FCM and WB, respectively. In addition, WB, SqPCR, or IHC were used for the expression of Nod2, MyD88, Rip2, and NF-κB p65 in colon. Cytokines were determined by ELISA.Results: HQD significantly restored the weight, the colonic length, and peripheral blood cell counts of colitis mice; reduced the DAI score and the histological score. 16SrDNA identification showed HQD regulated the balance of intestinal flora. Moreover, the expression of RegⅢγ was suppressed and colonic bacterial infiltration was prevented by HQD. Furthermore, the results of WB showed expression of NOD2 and TLR4 was inhibited by HQD, especially NOD2. And the data of WB, SqPCR and IHC explained that the NOD2-dependent pathway was inhibited by HQD.Conclusions: Our results reveal the mechanism of HQD(1g/kg) in regulating the intestinal flora of colitis mice, which may be closely characterized as the inhibition of the activation of Pattern Recognition Receptors (PRRs), especially NOD2.

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“…Short or smooth muscle MLCK is not expressed in the intestinal epithelium, whereas long MLCK is highly expressed in intestinal epithelial cells and regulates TJ permeability by inducing phosphorylation of myosin light-chain 2 (MLC-2) [ 14 – 16 ], which, in turn, leads to remodeling of the TJ structure. Tumor necrosis factor α (TNF- α ) has been shown to promote TJ dysregulation and induce epithelial barrier loss by elevating the expression and activity of long MLCK [ 17 , 18 ]. This elevation is in part mediated by NF- κ B [ 19 , 20 ], and a few κ B sites have been identified in the upstream promoter region that specifically drives long MLCK activation [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

HO‐1/CO Maintains Intestinal Barrier Integrity through NF‐κB/MLCK Pathway in Intestinal HO‐1^-/- Mice

Zhang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background. Intestinal barrier injury is an important contributor to many diseases. We previously found that heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal barrier. This study is aimed at elucidating the molecular mechanisms of HO-1/CO in barrier loss. Materials and Methods. We induced gut leakiness by injecting carbon tetrachloride (CCl4) to wildtype or intestinal HO-1-deficient mice. In addition, we administrated tumor necrosis factor-α (TNF-α) to cells with gain- or loss-of-HO-1 function. The effects of HO-1/CO maintaining intestinal barrier integrity were investigated in vivo and in vitro. Results. Cobalt protoporphyrin and CO-releasing molecule-2 alleviated colonic mucosal injury and TNF-α levels; upregulated tight junction (TJ) expression; and inhibited epithelial IκB-α degradation and phosphorylation, NF-κB p65 phosphorylation, long MLCK expression, and MLC-2 phosphorylation after administration of CCl4. Zinc protoporphyrin completely reversed these effects. These findings were further confirmed in vitro, using Caco-2 cells with gain- or loss-of-HO-1-function after TNF-α. Pretreated with JSH-23 (NF-κB inhibitor) or ML-7 (long MLCK inhibitor), HO-1 overexpression prevented TNF-α-induced TJ disruption, while HO-1 shRNA promoted TJ damage even in the presence of JSH-23 or ML-7, thus suggesting that HO-1 dependently protected intestinal barrier via the NF-κB p65/MLCK/p-MLC-2 pathway. Intestinal HO-1-deficient mice further demonstrated the effects of HO-1 in maintaining intestinal barrier integrity and its relative mechanisms. Alleviated hepatic fibrogenesis and serum ALT levels finally confirmed the clinical significance of HO-1/CO repairing barrier loss in liver injury. Conclusion. HO-1/CO maintains intestinal barrier integrity through the NF-κB/MLCK pathway. Therefore, the intestinal HO-1/CO-NF-κB/MLCK system is a potential therapeutic target for diseases with a leaky gut.

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Wogonoside alleviates colitis by improving intestinal epithelial barrier function via the MLCK/pMLC2 pathway

Cited by 85 publications

References 28 publications

The Combination of UHPLC-HRMS and Molecular Networking Improving Discovery Efficiency of Chemical Components in Chinese Classical Formula

The Combination of UHPLC-HRMS and Molecular Networking Improving Discovery Efficiency of Chemical Components in Chinese Classical Formula

Effect of Huangqin Decoction on Regulating Intestinal Flora in Colitis Mice Characterized as The Inhibition of NOD2-Dependent Pathway

HO‐1/CO Maintains Intestinal Barrier Integrity through NF‐κB/MLCK Pathway in Intestinal HO‐1^-/- Mice

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Wogonoside alleviates colitis by improving intestinal epithelial barrier function via the MLCK/pMLC2 pathway

Cited by 85 publications

References 28 publications

The Combination of UHPLC-HRMS and Molecular Networking Improving Discovery Efficiency of Chemical Components in Chinese Classical Formula

The Combination of UHPLC-HRMS and Molecular Networking Improving Discovery Efficiency of Chemical Components in Chinese Classical Formula

Effect of Huangqin Decoction on Regulating Intestinal Flora in Colitis Mice Characterized as The Inhibition of NOD2-Dependent Pathway

HO‐1/CO Maintains Intestinal Barrier Integrity through NF‐κB/MLCK Pathway in Intestinal HO‐1-/- Mice

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HO‐1/CO Maintains Intestinal Barrier Integrity through NF‐κB/MLCK Pathway in Intestinal HO‐1^-/- Mice