Inula japonica ameliorated bleomycin-induced pulmonary fibrosis via inhibiting soluble epoxide hydrolase

Zhao, Wen‐Yu; Luan, Zhilin; Liu, Tiantian; Ming, Wenhua; Huo, Xiaokui; Huang, Huilian; Sun, Cheng‐Peng; Zhang, Baojing; Ma, Xiaochi

doi:10.1016/j.bioorg.2020.104065

Cited by 23 publications

(6 citation statements)

References 46 publications

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“…Glycogen synthase kinase 3 beta (GSK3β) is an important serine/threonine kinase involved in neuroinflammation; meanwhile, EETs are able to regulate its activity ( 36 , 37 ). Therefore, the effect of the inhibition of sEH by kurarinone toward GSK3β was also determined.…”

Section: Resultsmentioning

confidence: 99%

Kurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model

Sun

Zhou

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN), causing bradykinesia and rest tremors. Although the molecular mechanism of PD is still not fully understood, neuroinflammation has a key role in the damage of dopaminergic neurons. Herein, we found that kurarinone, a unique natural product from Sophora flavescens, alleviated the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced behavioral deficits and dopaminergic neurotoxicity, including the losses of neurotransmitters and tyrosine hydroxylase (TH)–positive cells (SN and striatum [STR]). Furthermore, kurarinone attenuated the MPTP-mediated neuroinflammation via suppressing the activation of microglia involved in the nuclear factor kappa B signaling pathway. The proteomics result of the solvent-induced protein precipitation and thermal proteome profiling suggest that the soluble epoxide hydrolase (sEH) enzyme, which is associated with the neuroinflammation of PD, is a promising target of kurarinone. This is supported by the increase of plasma epoxyeicosatrienoic acids (sEH substrates) and the decrease of dihydroxyeicosatrienoic acids (sEH products), and the results of in vitro inhibition kinetics, surface plasmon resonance, and cocrystallization of kurarinone with sEH revealed that this natural compound is an uncompetitive inhibitor. In addition, sEH knockout (KO) attenuated the progression of PD, and sEH KO plus kurarinone did not further reduce the protection of PD in MPTP-induced PD mice. These findings suggest that kurarinone could be a potential natural candidate for the treatment of PD, possibly through sEH inhibition.

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Section: Resultsmentioning

confidence: 99%

Kurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model

Sun

Zhou

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…In Chinese medicine practice, Xuan-Fu-Hua decoction is mainly used to treat inflammation-associated liver and lung diseases, which is simple in components and have mild temperament. Zhao et al reported in a previous study that treatment with Xuan-Fu-Hua extract could attenuate bleomycin-induced murine pulmonary fibrosis and systemic inflammation (10). In a study on the effects of Xuan-Fu-Hua decoction on serum inflammatory indexes and T lymphocyte subset of patients with chronic atrophic gastritis (CAG), the levels of TNF-α, IL-6 and IL-8 in patients treated with Xuan-Fu-Hua decoction were significantly lower than before and in control group, while CD3+, CD4+ and CD4+/CD8+ were significantly increased.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic and network pharmacology approaches revealed possible mechanisms underlying the 5-fluorouracil (5-FU)-sensitizing effect of Xuan-Fu-Hua decoction treatment on liver cancer cells

Luo¹,

Dang²,

Wu³

et al. 2022

Transl Cancer Res TCR

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Background: Xuan-Fu-Hua decoction is a traditional Chinese medicine formula widely used for the treatment of inflammation-related disease in the lung and liver. This study aimed to investigate the effect of Xuan-Fu-Hua decoction treatment on liver cancer cells and its mechanism of action. Methods:The impact of Xuan-Fu-Hua decoction treatment on the proliferation and apoptosis of SMMC-7721 liver cancer cells with or without 5-fluorouracil (5-FU) cotreatment was determined in both in vitro and in vivo settings. Alterations in gene expression patterns in SMMC-7721 cells induced by Xuan-Fu-Hua decoction treatment were explored by transcriptomic sequencing. Effective components of Xuan-Fu-Hua decoction and their target proteins were investigated using network pharmacology approaches.Results: Xuan-Fu-Hua decoction alone did not significantly influence SMMC-7721 liver cancer cell growth, but it significantly increased the 5-Fu-induced growth inhibition and apoptosis of SMMC-7721 liver cancer cells in vitro and in vivo. Most differentially expressed genes in SMMC-7721 liver cancer cells with or without Xuan-Fu-Hua decoction treatment were enriched in cell apoptosis-related pathways. Xuan-Fu-Hua decoction treatment significantly increased the transcription levels of DDIT3, PMAIP1, and ZMAT3 genes while decreasing that of WNT4, AXIN2, NFE2L2, TGFBR1, MITF, and IGFBP3 genes. An interaction network between the effective components and their possible target proteins was constructed by predicting compound-target protein and protein-protein interactions. Gene set enrichment analysis revealed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway as well as Bcl-2 and Mcl-1 proteins as potential regulatory targets of Xuan-Fu-Hua decoction in sensitizing SMMC-7721 cells to the cytotoxicity of 5-FU treatment.Conclusions: Xuan-Fu-Hua decoction increased the sensitivity of liver cancer cells to the cytotoxicity of 5-FU treatment, possibly by potentiating cell apoptosis and inhibiting the prosurvival machinery.

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“…Notably, britanin isolated from Inulae flos, a flower of I. japonica , inhibits the expression of proinflammatory cytokines by suppressing NF-κB and MAPK kinase activity [ 27 , 28 ]. Zhao et al reported that I. japonica extract inhibited the expression level of cytokines, such as TGF-β1 and IL-6, in bleomycin-induced mice [ 15 ]. Our findings showed that ISE081 significantly lowered the mRNA expression of cytokines related to inflammation, such as IL-6, IL-8, and TGF-β1 ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…The I. japonica extract has recently been shown to have beneficial pharmacological effects, such as antidiabetic, antihyperlipidemic, antiallergic, and antiasthmatic properties [ 11 , 12 , 13 , 14 ]. Furthermore, it demonstrates inhibitory effects on pulmonary fibrosis in both in vivo and in vitro studies [ 15 , 16 ]. Furthermore, P. ginseng has been traditionally utilized for its efficacy in alleviating fatigue and weakness [ 17 ], along with treating a variety of conditions including cancer, Alzheimer’s disease, cognitive impairments, and respiratory illnesses [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Fibrosis Effect of Panax ginseng and Inula japonica Formula in Human Pulmonary Fibroblasts

Jung,

Yim,

Lee

et al. 2024

Nutrients

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Panax ginseng Meyer and Inula japonica Thunb. are well established in traditional medicine and are known for their therapeutic properties in managing a range of ailments such as diabetes, asthma, and cancer. Although P. ginseng and I. japonica can alleviate pulmonary fibrosis (PF), the anti-fibrosis effect on PF by the combination of two herbal medicines remains unexplored. Therefore, this study explores this combined effect. In conditions that were not cytotoxic, MRC-5 cells underwent treatment using the formula combining P. ginseng and I. japonica (ISE081), followed by stimulation with transforming growth factor (TGF)-β1, to explore the fibroblast-to-myofibroblast transition (FMT). After harvesting the cells, mRNA levels and protein expressions associated with inflammation and FMT-related markers were determined to evaluate the antiinflammation activities and antifibrosis effect of ISE081. Additionally, the anti-migratory effects of ISE081 were validated through a wound-healing assay. ISE081 remarkably reduced the mRNA levels of interleukin (IL)-6, IL-8, α-smooth muscle actin (SMA), and TGF-β1 in MRC-5 cells and suppressed the α-SMA and fibronectin expressions, respectively. Furthermore, ISE081 inhibited Smad2/3 phosphorylation and wound migration of MRC-5 cells. Under the same conditions, comparing those of ISE081, P. ginseng did not affect the expression of α-SMA, fibronectin, and Smad2/3 phosphorylation, whereas I. japonica significantly inhibited them but with cytotoxicity. The results indicate that the synergistic application of P. ginseng and I. japonica enhances the anti-fibrotic properties in pulmonary fibroblasts and concurrently diminishes toxicity. Therefore, ISE081 has the potential as a prevention and treatment herbal medicine for PF.

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Inula japonica ameliorated bleomycin-induced pulmonary fibrosis via inhibiting soluble epoxide hydrolase

Cited by 23 publications

References 46 publications

Kurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model

Kurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model

Transcriptomic and network pharmacology approaches revealed possible mechanisms underlying the 5-fluorouracil (5-FU)-sensitizing effect of Xuan-Fu-Hua decoction treatment on liver cancer cells

Anti-Fibrosis Effect of Panax ginseng and Inula japonica Formula in Human Pulmonary Fibroblasts

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