Background
Sulforaphane (SFN) known as [1-isothiocyanato-4-(methylsulfinyl)butane]. It is an isothiocyanate that is present naturally in widely consumed vegetables and has a particularly high concentration in broccoli[1,10]. Sulforaphane is a phytocompound with antioxidant, anti-inflammatory, and antiapoptotic effects[2].
Sulforaphane amplifies ALDH2 activity in HepaRG cells and suppresses acetaldehyde-induced proliferation and activation in LX-2 cells[3]. Sulforaphane reversed mesenchymal-like changes induced by TGF-β1 and restored cells to their epithelial-like morphology. The expression of the epithelial marker, E-cadherin, increased after Sulforaphane treatment, while expression of the mesenchymal markers, N-cadherin, vimentin, and α-SMA decreased in A549 cells after SFN treatment[4]. Sulforaphane inhibited cell growth and reduced collagen at the mRNA and protein levels in keloid fibroblasts. Moreover, sulforaphane markedly suppressed the expression of IL-6 and α-SMA and inhibited Stat3 and Smad3 signaling pathways in keloid fibroblast KF112 cells[8]. Sulforaphane inhibited XWLC-05 cell growth with inhibitory concentration (IC)50 of 4.04, 3.38, and 3.02 μg/mL at 24, 48, and 72 hours, respectively. Sulforaphane affected the XWLC-05 cell cycle as cells accumulated in the G2/M phase[9].
Sulforaphane exerts antioxidative effects with ALDH2 induction in liver fibrosis induced by ethanol exposure in CCl4-treated mice[3]. Nrf2 plays the indispensable role for Sulforaphane cardiac protection from T2DM with significant induction of MT and other antioxidants. MT expression induced by Sulforaphane is Nrf2 dependent, but is not indispensable for SFN-induced cardiac protection from T2DM[5]. Sulforaphane significantly reduced the incidence and size of 4NQO-induced tongue tumors in mice[6]. Sulforaphane suppresses skin cancer via blocking sulfatase-2 with subsequent elevation in HSPGs and reduction in glypican-3. Moreover, sulforaphane attenuated skin cancer-induced activation of inflammatory and apoptotic pathways[7].
参考文献:
[1]. Panjwani AA, Liu H, et,al. Crucifers and related vegetables and supplements for neurologic disorders: what is the evidence? Curr Opin Clin Nutr Metab Care. 2018 Nov;21(6):451-457. doi: 10.1097/MCO.0000000000000511. PMID: 30199394.
[2]. Schepici G, Bramanti P, et,al. Efficacy of Sulforaphane in Neurodegenerative Diseases. Int J Mol Sci. 2020 Nov 16;21(22):8637. doi: 10.3390/ijms21228637. PMID: 33207780; PMCID: PMC7698208.
[3]. Ishida K, Kaji K, et,al. Sulforaphane ameliorates ethanol plus carbon tetrachloride-induced liver fibrosis in mice through the Nrf2-mediated antioxidant response and acetaldehyde metabolization with inhibition of the LPS/TLR4 signaling pathway. J Nutr Biochem. 2021 Mar;89:108573. doi: 10.1016/j.jnutbio.2020.108573. Epub 2020 Dec 31. PMID: 33388347.
[4]. Kyung SY, Kim DY, et,al. Sulforaphane attenuates pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition. BMC Pharmacol Toxicol. 2018 Apr 2;19(1):13. doi: 10.1186/s40360-018-0204-7. PMID: 29609658; PMCID: PMC5879815.
[5]. Gu J, Cheng Y, et,al. Metallothionein Is Downstream of Nrf2 and Partially Mediates Sulforaphane Prevention of Diabetic Cardiomyopathy. Diabetes. 2017 Feb;66(2):529-542. doi: 10.2337/db15-1274. Epub 2016 Nov 30. PMID: 27903744; PMCID: PMC5248986.
[6]. Bauman JE, Zang Y, et,al. Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane. Cancer Prev Res (Phila). 2016 Jul;9(7):547-57. doi: 10.1158/1940-6207.CAPR-15-0290. Epub 2016 Jun 23. PMID: 27339168; PMCID: PMC4930727.
[7]. Alyoussef A, Taha M. Antitumor activity of sulforaphane in mice model of skin cancer via blocking sulfatase-2. Exp Dermatol. 2019 Jan;28(1):28-34. doi: 10.1111/exd.13802. Epub 2018 Dec 11. PMID: 30315662.
[8]. Kawarazaki A, Horinaka M, et,al. Sulforaphane suppresses cell growth and collagen expression of keloid fibroblasts. Wound Repair Regen. 2017 Apr;25(2):224-233. doi: 10.1111/wrr.12512. Epub 2017 Feb 20. PMID: 28120534.
[9]. Zhou L, Yao Q, et,al. Sulforaphane-induced apoptosis in Xuanwei lung adenocarcinoma cell line XWLC-05. Thorac Cancer. 2017 Jan;8(1):16-25. doi: 10.1111/1759-7714.12396. Epub 2016 Nov 23. PMID: 27878984; PMCID: PMC5217876.
[10].Gamet-Payrastre L, Li P, et,al. Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res. 2000 Mar 1;60(5):1426-33. PMID: 10728709.
萝卜硫素 (SFN) 称为 [1-isothiocyanato-4-(methylsulfinyl)butane]。它是一种异硫氰酸酯，天然存在于广泛食用的蔬菜中，在西兰花中含量特别高[1,10]。萝卜硫素是一种具有抗氧化、抗炎和抗细胞凋亡作用的植物化合物[2]。
萝卜硫素可增强 HepaRG 细胞中的 ALDH2 活性并抑制乙醛诱导的 LX-2 细胞增殖和活化[3]。萝卜硫素可逆转 TGF-β1 诱导的间充质样变化，并将细胞恢复到上皮样形态。 SFN 处理后 A549 细胞上皮标志物 E-cadherin 的表达增加，而间充质标志物 N-cadherin、vimentin 和 α-SMA 的表达减少[4] .萝卜硫素抑制细胞生长并减少瘢痕疙瘩成纤维细胞 mRNA 和蛋白质水平的胶原蛋白。此外，萝卜硫素显着抑制瘢痕疙瘩成纤维细胞KF112细胞IL-6和α-SMA的表达，抑制Stat3和Smad3信号通路[8]。萝卜硫素抑制 XWLC-05 细胞生长，抑制浓度 (IC)50 在 24、48 和 72 小时时分别为 4.04、3.38 和 3.02 μg/mL。萝卜硫素影响XWLC-05细胞周期，细胞在G2/M期聚集[9]。
在 CCl4 处理的小鼠中，萝卜硫素通过 ALDH2 诱导在乙醇暴露诱导的肝纤维化中发挥抗氧化作用[3]。 Nrf2 通过显着诱导 MT 和其他抗氧化剂，在萝卜硫素心脏保护免受 T2DM 方面发挥着不可或缺的作用。萝卜硫素诱导的 MT 表达依赖于 Nrf2，但对于 SFN 诱导的 T2DM 心脏保护作用并非必不可少[5]。萝卜硫素显着降低了 4NQO 诱导的小鼠舌肿瘤的发生率和大小[6]。萝卜硫素通过阻断 sulfatase-2 并随后升高 HSPG 和减少 glypican-3 来抑制皮肤癌。此外，萝卜硫素减弱了皮肤癌诱导的炎症和细胞凋亡通路的激活[7]。
Protocol
| Cell experiment [1]: |
Cell lines | HepaRG cells |
Preparation Method | HepaRG cells at a concentration of 1.5 104 cells/mL were seeded on uncoated plastic tissue culture dishes and treated with sulforaphane at different concentrations (0 -40 uM) over a time course (12-48 h). The cells as well as the homogenates from liver tissues were solubilized, and the activity solution including a reporter dye were added to the supernatants. |
Reaction Conditions | 0 -40 uM sulforaphane for 12-48 h |
Applications | Sulforaphane amplifies ALDH2 activity in HepaRG cells and suppresses acetaldehyde-induced proliferation and activation in LX-2 cells. |
| Animal experiment [2]: |
Animal models | Ten-week-old female C57BL/6J mice |
Preparation Method | Mice in the CD/ CCl4 group were fed the normal liquid diet and received 1 mL/kg body weight CCl4 dissolved in corn oil by intraperitoneal injection twice weekly. Mice in the ED/ CCl4 group were fed a 2.5% (v/v) ethanol-containing Lieber-DeCarli liquid diet (Research Diets) (ED) and received intraperitoneal CCl4 injection twice weekly (1 mL/kg body weight). Mice in the ED/ CCl4/SFN group were fed the ED with sulforaphane and received intraperitoneal CCl4 injection (1 mL/kg body weight) twice weekly; in this group, sulforaphane was administered peroral as a mixture of ED (5 μmoL/d/body weight). |
Dosage form | Sulforaphane was administered peroral as a mixture of ED (5 μmoL/d/body weight) twice weekly |
Applications | Sulforaphane exerts antioxidative effects with ALDH2 induction in liver fibrosis induced by ethanol exposure in CCl4-treated mice. |
参考文献: [1]. Ishida K, Kaji K, et,al. Sulforaphane ameliorates ethanol plus carbon tetrachloride-induced liver fibrosis in mice through the Nrf2-mediated antioxidant response and acetaldehyde metabolization with inhibition of the LPS/TLR4 signaling pathway. J Nutr Biochem. 2021 Mar;89:108573. doi: 10.1016/j.jnutbio.2020.108573. Epub 2020 Dec 31. PMID: 33388347. |
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