Shikonin inhibits CEBPD downregulation in IL‑17‑treated HaCaT cells and in an imiquimod‑induced psoriasis model

Lan, Xiaoou; Wang, Hexiao; Qi, Ruiqun; Xu, Yuanyuan; Yan, Yu; Yang, Yang; Guo, Hao; Gao, Xing‐Hua; Geng, Long

doi:10.3892/mmr.2020.11315

Cited by 17 publications

(20 citation statements)

References 49 publications

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“…Preclinical research mainly includes animal and cell experiments. For animal experiments, one study ( Zhao, 2016a ) was a doctoral thesis and the other five ( Yu et al, 2019 ; Wang et al, 2016 ; Wang et al, 2015 ; Lan et al, 2020 ; Zhang et al, 2019 ) were published in English. All six studies used BALB/c mice.…”

Section: Resultsmentioning

confidence: 99%

“…The body weight of the mice varied between 17 and 25 g, and two of the studies ( Zhao, 2016a ; Yu et al, 2019 ) did not mention the weight of the mice. One study ( Zhao, 2016a ) used 45 female mice, whereas five others ( Yu et al, 2019 ; Wang et al, 2016 ; Wang et al, 2015 ; Lan et al, 2020 ; Zhang et al, 2019 ) used 140 male mice. All mice were imiquimod-induced psoriasis models.…”

Section: Resultsmentioning

confidence: 99%

“…To induce anesthesia, two studies ( Wang et al, 2016 ; Wang et al, 2015 ) used sodium pentobarbital, while the remaining four did not mention anesthesia. The methods of intervention mainly included the following: three studies ( Zhao, 2016a ; Yu et al, 2019 ; Zhang et al, 2019 ) used the SHI intervention, two ( Wang et al, 2016 ; Wang et al, 2015 ) used the DMA intervention, and one ( Lan et al, 2020 ) used the SHI oil (SO) intervention. Among the outcome measures, five studies ( Zhao, 2016a ; Yu et al, 2019 ; Wang et al, 2015 ; Lan et al, 2020 ; Zhang et al, 2019 ) evaluated the PASI score, two ( Zhao, 2016a ; Zhang et al, 2019 ) evaluated hematoxylin and eosin (HE) staining and IL-17A, and three ( Zhao, 2016a ; Yu et al, 2019 ; Wang et al, 2015 ) evaluated epidermal thickness.…”

Section: Resultsmentioning

confidence: 99%

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Evidence and Potential Mechanism of Action of Lithospermum erythrorhizon and Its Active Components for Psoriasis

Wang

Liu

Sun³

et al. 2022

Front. Pharmacol.

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Background: Traditional Chinese medicine is effective in the treatment of psoriasis and can significantly reduce skin inflammation and psoriatic lesions with minimal side effects. Shikonin (SHI) and β,β-dimethylacryloyl alkannin (DMA), the main active components of Lithospermum erythrorhizon, have strong anti-inflammatory effects. This systematic review aimed to evaluate the efficacy and safety of Lithospermum erythrorhizon and its main active components and to elucidate the potential mechanisms of their action in psoriasis treatment.Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Scientific Journals, Wan Fang, and Chinese Biomedicine databases were systematically searched for articles published between 1 January 1970, and 31 February 2021. We included clinical and preclinical studies that examined the effects of Lithospermum erythrorhizon and its active components on psoriasis. All data were analyzed using RevMan 5.3 software. The Cochrane and SYRCLE’s risk-of-bias tools were used to assess the quality of all studies.Results: Eleven clinical trials including 1024 participants and 23 preclinical studies were assessed. Meta-analysis showed that when treating patients with psoriasis, the Chinese herbal medicine (CHM) formulas with Lithospermum erythrorhizon as the sovereign herb can significantly improve psoriatic dermatitis, which can significantly reduce the psoriasis area and severity index (PASI) score (mean difference [MD] = -2.00, 95% confidence interval [CI] [-3.19, -0.80], p = 0.001; I2 = 85%). The incidence rates of diarrhea (risk ratio = 0.21, 95% CI [0.06, 0.81], p = 0.02) were higher in the CHM formulas group than in the control group, whereas other adverse events were not significantly different between the two groups (p > 0.05). We evaluated the PASI score of mice on day 7 and found that SHI and DMA also alleviated psoriatic lesions (MD = -3.36, 95% CI [-4.67, -2.05], p < 0.00001, I2 = 94%). Furthermore, the epidermal thickness decreased more after SHI or DMA treatment than in the control group (MD = -34.42, 95%CI [-41.25, -27.59], p < 0.00001, I2 = 93%). Based on preclinical studies, we also summarized and mapped the mechanisms of SHI and DMA in the treatment of psoriasis.Conclusion: Available findings demonstrated that Lithospermum erythrorhizon combined with other conventional treatments is useful in treating psoriasis. Preclinical evidence has shown that the active components of Lithospermum erythrorhizon exhibit a potential anti-inflammatory effect, promote keratinocyte apoptosis, inhibit keratinocyte proliferation and angiogenesis, and block the cell cycle. In summary, our findings suggest that Lithospermum erythrorhizon and its active components can be used to treat psoriasis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Evidence and Potential Mechanism of Action of Lithospermum erythrorhizon and Its Active Components for Psoriasis

Wang

Liu

Sun³

et al. 2022

Front. Pharmacol.

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“…There are several published reports suggesting a biomedical relevance of the link between the C/EBPδ and S100A8/A9 alarmin under other inflammatory conditions as well. For example, C/EBPδ has been shown to play a role in the pathogenesis of psoriasis (Lan et al , 2020) and in acute inflammatory signaling by regulating COX-2 (Wadleigh et al , 2000), IL-6 (Litvak et al , 2009) and TLR4 (Balamurugan et al , 2013). Analysis of the genome-wide transcription pattern of monocytes revealed IL-6 as the top gene induced by S100 alarmin stimulation via interaction with TLR4 (Fassl et al , 2015), and targeted deletion of S100A9 ameliorated inflammation in a murine psoriasis model(Zenz et al , 2007).…”

Section: Discussionmentioning

confidence: 99%

C/EBPδ-induced epigenetic changes control the dynamic gene transcription of S100A8 and S100A9

Jauch-Speer

Wolf

Herrera-Rivero

et al. 2021

Preprint

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The proinflammatory alarmins S100A8 and S100A9 are among the most abundant proteins in neutrophils and monocytes but completely silenced after differentiation to macrophages. The molecular mechanisms of the extraordinarily dynamic transcriptional regulation of s100a8 and s100a9 genes, however, are only barely understood. Using an unbiased genome-wide CRISPR/Cas9 knockout based screening approach in immortalized murine monocytes we identified the transcription factor C/EBPδ as a central regulator of S100A8 and S100A9 expression. S100a8 and S100a9 expression was further controlled by the C/EBPδ-antagonists ATF3 and FBXW7. We confirmed the clinical relevance of this regulatory network in subpopulations of human monocytes in a clinical cohort of cardiovascular patients. Moreover, we identified specific C/EBPδ-binding sites within s100a8 and s100a9 promoter regions, and demonstrated that C/EBPδ-dependent JMJD3-mediated demethylation of H3K27me3 is indispensable for their expression. Overall, our work uncovered C/EBPδ as a novel regulator of S100A8 and S100A9 expression. Therefore, C/EBPδ represents a promising target for modulation of inflammatory conditions that are characterised by S100A8 and S100A9 overexpression.

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“…[27] Real Time-Polymerase Chain Reaction Extraction and Detection of Total CELL RNA Total RNA was extracted and detected by agarose gel electrophoresis, referring to the literature. [28,29]…”

Section: Determination Of Inflammatory and Apoptotic Cytokinesmentioning

confidence: 99%

Anti‐Inflammatory Effects of Opuntia Milpa Alta Polysaccharides Fermented by Lactic Acid Bacteria in Human Keratinocyte HaCaT Cells

Zhang

You

et al. 2022

Chemistry & Biodiversity

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Opuntia milpa alta polysaccharides (ODP) are bioactive compounds extracted from Opuntia milpa alta and widely used in the treatment of diseases, but the therapeutic mechanism of ODP on inflammatory injury remains unclear. Therefore, this study explores the effects and mechanisms of ODP in lipopolysaccharide (LPS)-induced inflammation of human keratinocytes (HaCaT). In this experiment, ODP was extracted via the water extraction and fermentation methods, respectively. LPS was then used to induce inflammatory damage in HaCaT cells, and the stimulated cells were treated with different concentrations of ODP. Cell viability was detected by MTT assay, and the concentrations of COX-2, iNOS, IL-6, IL-8, IL-10 and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Changes in inflammatory cytokines and related mRNA expression were observed to assess LPS-induced cell damage. In the experiment, it was found that the LPS stimulation of HaCaT cells can induce cellular inflammatory response, reduce cell viability, increase cell apoptosis and increase the expression of COX-2, iNOS, IL-6, IL-8, IL-10 and TNF-α. However, the experimental data shows that ODP can reverse the above results by increasing cell viability, inhibiting cell apoptosis, reducing the expression of the above genes and inactivating antioxidant pathways, which revealed the specific mechanism of ODP repairing LPS-induced inflammatory damage to Hacat cell. In addition, The experimental results showed that fermentation could improve the anti-inflammatory effect of ODP. In conclusion, our experimental results indicate that ODP fermented by lactic acid bacteria can be used as an anti-inflammatory agent.

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Shikonin inhibits CEBPD downregulation in IL‑17‑treated HaCaT cells and in an imiquimod‑induced psoriasis model

Cited by 17 publications

References 49 publications

Evidence and Potential Mechanism of Action of Lithospermum erythrorhizon and Its Active Components for Psoriasis

Evidence and Potential Mechanism of Action of Lithospermum erythrorhizon and Its Active Components for Psoriasis

C/EBPδ-induced epigenetic changes control the dynamic gene transcription of S100A8 and S100A9

Anti‐Inflammatory Effects of Opuntia Milpa Alta Polysaccharides Fermented by Lactic Acid Bacteria in Human Keratinocyte HaCaT Cells

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