Emodin targeting the colonic metabolism via PPARγ alleviates UC by inhibiting facultative anaerobe

Luo, Shuang; He, Ju-Liang; Huang, Shaowei; Wang, Xiaojing; Su, Yu‐Lin; Li, Yanyang; Chen, Yanping; Yang, Guanghua; Huang, Bin; Guo, Shaoju; Zhou, Lian; Luo, Xia

doi:10.1016/j.phymed.2022.154106

Cited by 24 publications

(8 citation statements)

References 39 publications

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“…In in vitro and in vivo studies, PPARγ may have a potential benefit on IBD through the crosstalk with metabolism and inflammation [ 1 , 8 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. However, there is a lack of evidence to support such a benefit in humans.…”

Section: Discussionmentioning

confidence: 99%

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Rosiglitazone Does Not Affect the Risk of Inflammatory Bowel Disease: A Retrospective Cohort Study in Taiwanese Type 2 Diabetes Patients

Tseng

2023

Pharmaceuticals

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Human studies on the effect of rosiglitazone on inflammatory bowel disease (IBD) are still lacking. We investigated whether rosiglitazone might affect IBD risk by using the reimbursement database of Taiwan’s National Health Insurance to enroll a propensity-score-matched cohort of ever users and never users of rosiglitazone. The patients should have been newly diagnosed with diabetes mellitus between 1999 and 2006 and should have been alive on 1 January 2007. We then started to follow the patients from 1 January 2007 until 31 December 2011 for a new diagnosis of IBD. Propensity-score-weighted hazard ratios were estimated with regards to rosiglitazone exposure in terms of ever users versus never users and in terms of cumulative duration and cumulative dose of rosiglitazone therapy for dose–response analyses. The joint effects and interactions between rosiglitazone and risk factors of psoriasis/arthropathies, dorsopathies, and chronic obstructive pulmonary disease/tobacco abuse and the use of metformin were estimated by Cox regression after adjustment for all covariates. A total of 6226 ever users and 6226 never users were identified and the respective numbers of incident IBD were 95 and 111. When we compared the risk of IBD in ever users to that of the never users, the estimated hazard ratio (0.870, 95% confidence interval: 0.661–1.144) was not statistically significant. When cumulative duration and cumulative dose of rosiglitazone therapy were categorized by tertiles and hazard ratios were estimated by comparing the tertiles of rosiglitazone exposure to the never users, none of the hazard ratios reached statistical significance. In secondary analyses, rosiglitazone has a null association with Crohn’s disease, but a potential benefit on ulcerative colitis (UC) could not be excluded. However, because of the low incidence of UC, we were not able to perform detailed dose–response analyses for UC. In the joint effect analyses, only the subgroup of psoriasis/arthropathies (-)/rosiglitazone (-) showed a significantly lower risk in comparison to the subgroup of psoriasis/arthropathies (+)/rosiglitazone (-). No interactions between rosiglitazone and the major risk factors or metformin use were observed. We concluded that rosiglitazone has a null effect on the risk of IBD, but the potential benefit on UC awaits further investigation.

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Section: Discussionmentioning

confidence: 99%

“…Emodin is a Chinese herb drug that has been used to treat IBD. Its potential mode of action is through the activation of PPARγ-related signaling [ 53 ].…”

Section: Introductionmentioning

confidence: 99%

Rosiglitazone Does Not Affect the Risk of Inflammatory Bowel Disease: A Retrospective Cohort Study in Taiwanese Type 2 Diabetes Patients

Tseng

2023

Pharmaceuticals

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“…β‐actin served as an internal reference. The relative expression of each protein was determined using ImageJ software (Luo et al., 2022).…”

Section: Methodsmentioning

confidence: 99%

β‐Sitosterol attenuates anlotinib resistance in non‐small cell lung cancer cells by inhibiting miR‐181a‐3p/SHQ1 signaling

Wang,

Sun,

Liu

et al. 2024

Chem Biol Drug Des

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Anlotinib is used for the treatment of advanced non‐small cell lung cancer; however, the emergence of drug resistance limits its clinical application. β‐sitosterol may also be used to treat lung cancer, but there have been no studies evaluating β‐sitosterol against anlotinib‐resistant lung cancer. The purpose of this study was to determine the mechanism by which β‐sitosterol enhances the sensitivity of lung cancer cells to anlotinib. A549 cells were treated with different concentrations of anlotinib to generate anlotinib‐resistant cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. A549 and A549/anlotinib cells were treated with β‐sitosterol at various concentrations. The Cell Counting Kit‐8 (CCK‐8) assay was used to measure cell proliferation. Apoptosis was assessed by flow cytometry. Real‐time quantitative PCR was used to measure the expression of miR‐181a‐3p. The interaction of miR‐181a‐3p with the H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted using the miRDB and TargetScan Human databases and verified with a luciferase reporter assay. The expression of SHQ1, activating transcription factor 6 (ATF6), and glucose‐regulated protein 78 (GRP78) were measured by western blot analysis. β‐Sitosterol effectively suppressed A549/anlotinib cell proliferation and promoted apoptosis. SHQ1 is a downstream target of miR‐181a‐3p. The expression of miR‐181a‐3p was inhibited; however, SHQ1 expression was increased by β‐sitosterol treatment of A549/anlotinib cells. The inhibition of SHQ1, ATF6, and GRP78 protein expression by β‐sitosterol in A549/anlotinib cells was rescued by increased miR‐181a‐3p. β‐Sitosterol markedly promotes anlotinib‐resistant A549 cell apoptosis and inhibits cell proliferation by activating SHQ1/UPR signaling through miR‐181a‐3p inhibition.

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“…The results showed that SMS reconstructs mitochondria to achieve therapeutic effects by altering AST/ALT ratio, regulating glycolysis and TCA cycle. Luo et al (2022) found that emodin ameliorates ulcerative colitis by modulating the PPARγ signaling pathway. Wang et al (2022b) evaluated the metabolites of honeysuckle by UPLC-QTOF-MS isolation and found that chlorogenic acid and swertiamarin could regulate the main mediators of inflammation, which in turn affected the phosphatidylinositol-3-kinase-AKT and MAPK pathways.…”

Section: Mechanism Of Action and Target Explorationmentioning

confidence: 99%

Mass spectrometry-based metabolomics for discovering active ingredients and exploring action mechanism of herbal medicine

et al. 2023

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Natural products derived from herbal medicine are a fruitful source of lead compounds because of their structural diversity and potent bioactivities. However, despite the success of active compounds derived from herbal medicine in drug discovery, some approaches cannot effectively elucidate the overall effect and action mechanism due to their multi-component complexity. Fortunately, mass spectrometry-based metabolomics has been recognized as an effective strategy for revealing the effect and discovering active components, detailed molecular mechanisms, and multiple targets of natural products. Rapid identification of lead compounds and isolation of active components from natural products would facilitate new drug development. In this context, mass spectrometry-based metabolomics has established an integrated pharmacology framework for the discovery of bioactivity-correlated constituents, target identification, and the action mechanism of herbal medicine and natural products. High-throughput functional metabolomics techniques could be used to identify natural product structure, biological activity, efficacy mechanisms, and their mode of action on biological processes, assisting bioactive lead discovery, quality control, and accelerating discovery of novel drugs. These techniques are increasingly being developed in the era of big data and use scientific language to clarify the detailed action mechanism of herbal medicine. In this paper, the analytical characteristics and application fields of several commonly used mass spectrometers are introduced, and the application of mass spectrometry in the metabolomics of traditional Chinese medicines in recent years and its active components as well as mechanism of action are also discussed.

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Emodin targeting the colonic metabolism via PPARγ alleviates UC by inhibiting facultative anaerobe

Cited by 24 publications

References 39 publications

Rosiglitazone Does Not Affect the Risk of Inflammatory Bowel Disease: A Retrospective Cohort Study in Taiwanese Type 2 Diabetes Patients

Rosiglitazone Does Not Affect the Risk of Inflammatory Bowel Disease: A Retrospective Cohort Study in Taiwanese Type 2 Diabetes Patients

β‐Sitosterol attenuates anlotinib resistance in non‐small cell lung cancer cells by inhibiting miR‐181a‐3p/SHQ1 signaling

Mass spectrometry-based metabolomics for discovering active ingredients and exploring action mechanism of herbal medicine

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