Genipin ameliorates hypertension-induced renal damage via the angiotensin II-TLR/MyD88/MAPK pathway

Yu, Debing; Shi, Mengsong; Bao, Jinwei; Yu, Xin-Yan; Li, Yuhui; Liu, Wenbo

doi:10.1016/j.fitote.2016.06.010

Cited by 23 publications

(13 citation statements)

References 48 publications

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“…GP has been demonstrated to prevent or treat cardiovascular diseases, diabetes, nervous system diseases, pathogenic infections and inflammation (26-30). Lin et al (28) reported that GP protected renal tissue from oxidative stress-associated injury by suppressing oxidative stress and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Genipin protects against H2O2-induced oxidative damage in�retinal pigment epithelial cells by promoting Nrf2 signaling

Zhao

Wang

et al. 2018

Int J Mol Med

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Oxidative stress serves a vital function in the pathogenesis of age-related macular degeneration (AMD); genipin (GP) possesses antioxidative properties. The present study aimed to investigate the effects of GP on retinal pigment epithelial (RPE) cells induced by H2O2 and the underlying mechanism. ARPE-19 cells were subjected to H2O2 treatment to induce oxidative damage. Cell viability was determined via an MTT assay. Reactive oxygen species (ROS) levels and cell apoptosis were detected by flow cytometry. Nuclear factor-erythroid 2-related factor-2 (Nrf2) signaling-associated and the expression of apoptosis-associated factors were measured using reverse transcription-quantitative polymerase chain reaction assay and western blotting. The results revealed that 200 µM H2O2 and 30 µM GP were determined to be the optimal concentrations for subsequent experimentation. GP reversed the inhibitory effects of H2O2 by promoting cell viability, attenuating ROS accumulation and cell apoptosis, and increased the expression of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: Quinine oxidoreductase 1 (NQO1); Nrf2 silencing inhibited HO-1 and NQO1 expression. In addition, Nrf2 silencing enhanced the effects of H2O2 by promoting ROS production and cell apoptosis. Compared with H2O2, Nrf2 silencing further decreased the expression levels of B-cell lymphoma-2 (Bcl-2), but increased that of Bcl-2-associated X protein and cleaved-caspase-3. The results of the present study revealed that Nrf2 silencing attenuated the protective effects of GP on H2O2-induced injury in ARPE-19 cells by promoting apoptosis and oxidation. Collectively, GP attenuated oxidative damage induced by H2O2 in ARPE-19 cells. Furthermore, the molecular mechanism may be associated with the Nrf2 signaling pathway. The findings of the present study nay provide insight into a potential therapeutic agent for the treatment of AMD.

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Section: Discussionmentioning

confidence: 99%

Genipin protects against H2O2-induced oxidative damage in�retinal pigment epithelial cells by promoting Nrf2 signaling

Zhao

Wang

et al. 2018

Int J Mol Med

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“…The TLR7/8, signaling pathway, which includes recruitment of MyD88, could be an important target for treating psoriasis. The role of MyD88 protein in the TLR7/8 signaling pathway has been established (26,27). Blocking of the MyD88-dependent signaling pathway aids in the treatment of psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Paeonol ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice by inhibiting the maturation and activation of dendritic cells

Meng

Wang

Xie

et al. 2017

International Journal of Molecular Medicine

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Paeonol, an active component derived from the traditional Chinese medicine Cortex Moutan, possesses anti-inflammatory, analgesic, antioxidant and anti-allergic properties. Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of Toll-like receptors (TLRs) in dendritic cells (DCs), which are primarily responsible for initiating an immune response. We investigated the effect of paeonol on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by R848. Mice were intragastrically administered 100 mg/kg (high), 50 mg/kg (medium) and 25 mg/kg (low) paeonol, respectively. We evaluated inflammation of psoriasis-like lesions based on histological changes, protein levels of myeloid differentiation factor 88 (MyD88) and TLR8 in skin lesions by western blotting, and levels of CD11c+ DCs in skin by immunoassay and in spleens by flow cytometry. Inflammatory cytokines [interleukin (IL)-23, IL-12 and IL-1β] in skin lesions and BMDCs were also assessed by RT-PCR and ELISA. Application of paeonol decreased IMQ-induced keratinocyte proliferation, and infiltration of CD3+ cells, while the treatment ameliorated CD11c+ cells in the spleen and skin, and reduced MyD88 and TLR8 proteins in skin lesions. Paeonol inhibited IMQ-induced mRNA expression of IL-23, but not IL-12 and IL-1β in BMDCs, along with significantly lower levels of DCs expressing MHCII, CD80 and CD86 in vitro. These results indicate that paeonol suppresses the maturation and activation of DCs by decreasing MyD88 and TLR8 proteins in the TLR7/8 signaling pathway which finally alleviates psoriasis-like skin lesions. The TLR7/8 signaling pathway in DCs provides an important insight into the mechanism of psoriasis, and paeonol may be a potent therapeutic drug for psoriasis.

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“…DUSP1, FOS and JUN were significantly enriched in the mitogen‐activated protein kinase (MAPK) signalling pathway. The MAPK signalling pathway is involved in ang II‐induced renal damage and renal fibrosis . DUSP1 can inhibit ERK, JNK and p38 MAPK cascade through a dephosphorylation process, which was a key regulating link in this pathway .…”

Section: Resultsmentioning

confidence: 99%

Bioinformatic analysis reveals novel hub genes and pathways associated with hypertensive nephropathy

et al. 2019

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Aim Hypertensive nephropathy (HTN) is one of the leading causes of end‐stage renal disease and is closely associated with inflammation and tubule‐interstitial fibrosis. The molecular mechanism underlying HTN remains unclear. This study used bioinformatic analysis to identify the novel gene targets for HTN. Methods We downloaded the microarray data of GSE99325 and GSE32591 from Gene Expression Omnibus. The dataset comprised 20 HTN and 15 normal samples. The differentially expressed genes (DEG) were identified, and then gene ontology (GO) enrichment was performed, and a GO tree was constructed by using clusterProfiler and ClueGO. In addition, a protein–protein interaction network was established using the Search Tool for the Retrieval of Interacting Genes database and visualized by Cytoscape. The novel hub genes were validated in in vitro experiments. Results A total of 267 genes (117 up‐regulated and 150 down‐regulated genes) were identified as DEG. GO analysis and the GO tree indicated that the DEG were mainly associated with steroid hormone response and the extracellular matrix. Based on the protein–protein interaction network, we screened out several novel hub genes. Considering the findings and the literature review, we focused on and validated the dual specificity phosphatase 1, tissue inhibitor of matrix metalloproteinases 1, fos proto‐oncogene and jun proto‐oncogenes, which may play significant roles in the pathogenesis of HTN. These findings were consistent with the bioinformatic results for the in vitro validation. Conclusion This study identified for the first time novel hub genes with microarray data in HTN by using bioinformatic analysis and provided novel evidence and clues for future works.

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Genipin ameliorates hypertension-induced renal damage via the angiotensin II-TLR/MyD88/MAPK pathway

Cited by 23 publications

References 48 publications

Genipin protects against H2O2-induced oxidative damage in�retinal pigment epithelial cells by promoting Nrf2 signaling

Genipin protects against H2O2-induced oxidative damage in�retinal pigment epithelial cells by promoting Nrf2 signaling

Paeonol ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice by inhibiting the maturation and activation of dendritic cells

Bioinformatic analysis reveals novel hub genes and pathways associated with hypertensive nephropathy

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