Ingenane-type diterpene compounds from<i>Euphorbia kansui</i>modulate IFN-γ production through NF-κB activation

Oh, Sehyun; Oh, Hyun Woo; Lee, Ha‐Reum; Yoon, Sun Young; Oh, Sei‐Ryang; Ko, Young Bok; Yoo, Nina; Jeong, Jinseon; Kim, Jae Wha

doi:10.1002/jsfa.7380

Cited by 10 publications

(6 citation statements)

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“…However, NF-κB site was also identified within the promoter region of IFN-γ gene demonstrating that NF-κB may be involved in the molecular mechanisms controlling gene transcription of IFN-γ in human T lymphocytes [ 78 ] which could directly explain the relationships between SIRT1 and IFN-γ observed in our studies. This signaling pathway was then confirmed in other studies performed on human NK-92 cells [ 81 , 82 ].…”

Section: Discussionsupporting

confidence: 78%

CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2

et al. 2018

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BackgroundNK cells are cytotoxic lymphocytes of innate immunity composed of: cytotoxic CD56dim and immunoregulatory CD56bright cells. The study aimed to analyze the expression of cellular protective proteins: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in CD56dim and CD56bright NK cells of the young, seniors aged under 85 (‘the old’) and seniors aged over 85 (‘the oldest’). We studied both non-stimulated NK cells and cells stimulated by IL-2, LPS or PMA with ionomycin. The expression level of proinflammatory cytokines TNF and IFN-γ was also assessed in NK cell subsets and some relationships between the studied parameters were analyzed.ResultsCD56bright cells showed sensitivity to most of the applied stimulatory agents until very advanced age in regards to the expression of SIRT1 and intracellular HSP70. On the contrary, CD56dim cells, sensitive to stimulation by most of the stimulatory agents in the young and the old, in the oldest lost this sensitivity and presented rather high, constant expression of SIRT1 and HSP70, resistant to further stimulation. With reference to SOD2 expression, CD56dim cells were insensitive to stimulation in the young, but their sensitivity increased with ageing. CD56bright cells were sensitive to most of the applied agents in the young and the old but in the oldest they responded to all of the stimulatory agents used in the study. Similarly, both NK cell subsets were sensitive to stimulation until very advanced age in regards to the expression of TNF and IFN-γ.ConclusionsCD56bright cells maintained sensitivity to stimulation until very advanced age presenting also an increased expression of SIRT1 and HSP70. CD56dim cells showed a constantly increased expression of these cellular protective proteins in the oldest, insensitive for further stimulation. The oldest, however, did not reveal an increased level of SOD2 expression, but it was significantly elevated in both NK cell subsets after stimulation.The pattern of expression of the studied cellular protective proteins in ageing process revealed the adaptation of NK cells to stress response in the oldest seniors which might accompany the immunosenescence and contribute to the long lifespan of this group of the elderly.

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Section: Discussionsupporting

confidence: 78%

CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2

et al. 2018

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“…8 of these met with the criteria that had OB ≥ 30% and DL ≥ 0.18 [34]. In addition, 13 compounds below this specification (GE05-GE08, GE12, GE14, GE15, GE17, GE18 and GE24-GE27) were also taken as the active compounds that had promising treatment to the malignant ascites [4,5,16,35]. Thus, a total of 21 compounds were selected for further analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Ho, is a commonly used Chinese herbal medicine (CHM) and is recorded in Sheng Nungs Herbal for multiple medical applications [4]. As we know, kansui has promising biological effects on cancer [5], pancreatitis [6], immune regulation [7], intestinal obstruction [8] and diabetes [9]. Among these, kansui is particularly applied to edema, ascites and asthma [10].…”

Section: Introductionmentioning

confidence: 99%

“…And euphol, a triterpene in kansui, induced the ERK 1/2 activation to promote the apoptosis of human gastric cancer cells [17]. Recent study also demonstrated that ingenane-type diterpene compounds from kansui induced IFN-γ secretion and activated the translocation of p65 to the nucleus in natural killer cells [5]. CHMs are composed of multiple components with diverse structures that are against multiple targets [18].…”

Section: Introductionmentioning

confidence: 99%

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Interpretation of Euphorbia Kansui Stir-Fried with Vinegar Treating Malignant Ascites by a UPLC-Q-TOF/MS Based Rat Serum and Urine Metabolomics Strategy Coupled with Network Pharmacology

Zhang

Wang

et al. 2018

Molecules

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Euphorbia kansui stir-fried with vinegar (V-kansui) has promising biological activities toward treating malignant ascites with reduced toxicity compared to crude kansui. But the mechanism concerning promoting the excretion of ascites has not been systematically studied. The purpose of this paper was to investigate the possible mechanism of V-kansui in treating malignant ascites, including metabolic pathways and molecular mechanism using an integrated serum and urine metabolomics coupled with network pharmacology. Serum and urine samples of rats were collected and analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A comparison with crude kansui was also made to demonstrate the feasibility of processing. Principle component analysis (PCA) and orthogonal partial least square discriminate analysis (OPLS-DA) were conducted to discriminate the groups, search important variables and reveal the possible pathways. A compound-target-metabolite network was finally constructed to identify the crucial targets to further understand the molecular mechanism. Sixteen significant metabolites contributing to the discrimination of model and control groups were tentatively screened out. They were mainly involved in the arachidonic acid metabolism, steroid hormone biosynthesis and primary bile acid to possibly reduce inflammatory and modulate the renin-angiotensin-aldosterone system to achieve treating malignant ascites. A bio-network starting from the compounds and ending in the metabolites was constructed to elucidate the molecular mechanism. HSP90AA1, ANXA2, PRDX6, PCNA, SOD2 and ALB were identified as the potential key targets that were responsible for the treatment of malignant ascites by the parameter combining the average shortest path length and betweenness centrality. The correlated 17 compounds were considered as the potential active ingredients in V-kansui. In addition, the metabolomics showed that the effect of V-kansui was almost in accordance with crude kansui. These results systematically revealed the mechanism of V-kansui against malignant ascites for the first time using metabolomics coupled with network pharmacology. V-kansui could be a promising safe and therapeutic medicine for the excretion of ascites.

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“…Terpenoid compounds derived from the roots of E. kansui showed a significant inhibition of proliferative activity of embryonic cells and intestinal epithelioid cells [35, 36]. It was reported that ingenane-type diterpenes from Kansu modulated IFN- γ production by regulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κ B) [37]. …”

Section: Introductionmentioning

confidence: 99%

Therapeutic Effects of Methanol Extract from Euphorbia kansui Radix on Imiquimod-Induced Psoriasis

Kim

Jang

Hyung

et al. 2017

Journal of Immunology Research

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The roots of Euphorbia kansui, which belong to the family Euphorbiaceae, have been used as a traditional medicine for the treatment of various diseases such as diabetes, ascites, and leukemia. Recently, it was reported that the methylene chloride fraction of E. kansui radix (EKC) regulated the differentiation of Th17 cells and alleviated the symptoms of Th17-related inflammatory bowel disease. Imiquimod (IMQ), a TLR7/8 agonist, has been used to induce psoriasis in a mouse model. In this study, we evaluated the effect of EKC in an IMQ-induced psoriasis model. EKC effectively inhibited the production of interleukin-17A and interferon-γ in vitro. On this basis, EKC was administered to an animal model of psoriasis. Acanthosis and the infiltration of inflammatory cells into the dermis were significantly reduced by EKC. EKC also inhibited the expression of IL-17A, IL-22, IL-23, IL-12, and RAR-related orphan receptor gamma t (RORγt) in the spleen, skin-draining lymph nodes, and the skin. Additionally, EKC inhibited the activity of dendritic cells but not that of keratinocytes. In conclusion, EKC ameliorated the symptoms of psoriasis through inhibition of Th17 differentiation and activation of dendritic cells. These effects are expected to be beneficial in the treatment and prevention of psoriasis.

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Ingenane-type diterpene compounds fromEuphorbia kansuimodulate IFN-γ production through NF-κB activation

Abstract: These findings suggest that E. kansui enhances IFN-γ secretion through the NF-κB pathway in NK cells. © 2015 Society of Chemical Industry.

Cited by 10 publications

References 56 publications

CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2

CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2

Interpretation of Euphorbia Kansui Stir-Fried with Vinegar Treating Malignant Ascites by a UPLC-Q-TOF/MS Based Rat Serum and Urine Metabolomics Strategy Coupled with Network Pharmacology

Therapeutic Effects of Methanol Extract from Euphorbia kansui Radix on Imiquimod-Induced Psoriasis

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