Journal of Traditional Chinese Medicine ›› 2024, Vol. 44 ›› Issue (3): 427-436.DOI: 10.19852/j.cnki.jtcm.20240308.001
• Original articles • Previous Articles Next Articles
CHEN Youlan1, DING Mingming3, HUANG Chaoyuan4, ZHENG Yiyuan2(), LIU Fengbin2,5()
Received:
2023-08-02
Accepted:
2023-11-15
Online:
2024-06-15
Published:
2024-03-08
Contact:
ZHENG Yiyuan, Department of Gastroenterology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Supported by:
CHEN Youlan, DING Mingming, HUANG Chaoyuan, ZHENG Yiyuan, LIU Fengbin. Chang'an decoction (肠安方) alleviates endoplasmic reticulum stress by regulating mitofusin 2 to improve colitis[J]. Journal of Traditional Chinese Medicine, 2024, 44(3): 427-436.
Figure 1 CAD alleviated DSS-induced colitis in mice A: animal experimental flow; B: body weight change; C: DAI scores; D: length of colons; E: statistical graph of colon length; F: HE staining in colon tissues, Scale bars: 100 μm; F1: CON; F2: DSS; F3: CAD-L; F4: CAD-M; F5: CAD-H. CON: control group; DSS: ulcerative coloits group; CAD-L: low-dose Chang'an decoction (0.5 g/mL); CAD-M: medium-dose Chang'an decoction (1 g/mL); CAD-H: high-dose Chang'an decoction (2 g/mL). The drug was administered by gavage once daily for 6 d. CAD: Chang'an decoction; DAI: disease activity index; DSS: dextran sulfate sodium; HE: hematoxylin and eosin. Results are presented as mean ± standard deviation. aP < 0.001 vs CON; bP < 0.001 vs DSS, n = 3-6.
Figure 2 Effects of CAD on ER stress and NLRP3 inflammasome activation in mice colon tissue A: Western blot analyses of GRP78, p-PERK, PERK, p-eIF2α and eIF2α in colon tissues; B: statistical graphs of GRP78/β-actin; C: statistical graphs of pPERK/PERK; D: statistical graphs of p-eIF2α/eIF2α; E: IHC staining of GRP78 in colon tissues; F: statistical graphs of GRP78 expression in IHC; Scale bars: 50 μm; E1: CON; E2: DSS; E3: CAD-L; E4: CAD-H. G: Western blot analyses of NLRP3 and ASC in colon tissues. H: The statistical graphs of NLRP3/β-actin. I: statistical graphs of ASC/β-actin; J: IHC staining of ASC in colon tissues; J1: CON; J2: DSS; J3: CAD-L; J4: CAD-H. K: statistical graph of ASC expression in IHC; Scale bars: 50 μm; CON: control group; DSS: ulcerative coloits group; CAD-L: low-dose Chang'an decoction (0.5 g/mL); CAD-H: high-dose Chang'an decoction (2 g/mL). The drug was administered by gavage once daily for 6 d. CAD: Chang'an decoction; ER: endoplasmic reticulum; NLRP3: nucleotide oligomerization domain-like receptor thermal protein domain associated protein 3; GRP78: glucose-regulated protein 78; PERK: protein kinase-related like endoplasmic reticulum kinase; eIF2α: eukaryotic translation initiation factor 2α; IHC: immunohistochemistry; ASC: apoptosis-associated speck-like protein containing a caspase-1 recruitment domain. Results are presented as mean ± standard deviation. aP < 0.01, dP < 0.001, fP < 0.05 vs CON; bP < 0.05, cP < 0.01, eP < 0.001 vs DSS, n = 3.
Figure 3 CAD enhanced MFN2 expression to restore ER stress and mitochondrial function A: IF staining of ROS in colon tissues; Scale bars: 20 μm; A1: CON; A2: DSS; A3: CAD-L; A4: CAD-H. B: representative electron microscopy images of colon tissues; mitochondria (Mito: pink areas) and endoplasmic reticulum (ER: yellow areas) are shown, red asterisk shows mitochondria in contact with ER; Scale bars: 1 μm; B1: CON; B2: DSS; B3: CAD-L; B4: CAD-H; C: Western blot analyses of MFN2 in colon tissues; D: statistical graphs of MFN2 relative expression level; E: IHC statistical graphs; F: IHC staining of MFN2 in colon tissues; Scale bars: 50 μm; F1: CON; F2: DSS; F3: CAD-L; F4: CAD-H. CON: control group; DSS: ulcerative coloits group; CAD-L: low-dose Chang'an decoction (0.5 g/mL); CAD-H: high-dose Chang'an decoction (2 g/mL). The drug was administered by gavage once daily for 6 d. CAD: Chang'an decoction; MFN2: mitofusin 2; ER: endoplasmic reticulum; IF: immunofluorescence; ROS: reactive oxygen species; DSS: dextran sulfate sodium; IHC: immunohistochemistry. Results are presented as mean ± standard deviation. aP < 0.001 vs CON; bP < 0.05, cP < 0.01 vs DSS, n = 3.
Figure 4 MFN2 mediated ER stress and mitochondrial damage A: representative electron microscopy images of Caco-2 cells; mitochondria (Mito: pink areas) and endoplasmic reticulum (ER: yellow areas) are shown, red asterisk shows mitochondria in contact with ER; Scale bars: 1 μm; A1: shCtrl; A2: shMFN2; A3: MFN2; shCtrl: plasmid vector group; shMFN2: MFN2 knockdown group; MFN2: MFN2 overexpression group. Cells were respective incubated with plasmid vectors for 48 h. B: Western blot analyses of GRP78, NLRP3 in Caco-2 cells; C: statistical graphs of GRP78, NLRP3 relative protein levels; D: relative mRNA expressions of CHOP, GRP78 and NLRP3 in Caco-2 cells; E: Western blot analyses of GRP78, NLRP3 in Caco-2 cells; F: statistical graphs of GRP78, NLRP3 relative protein levels; G: relative mRNA expressions of CHOP, GRP78 and NLRP3 in Caco-2 cells. Results are presented as mean ± standard deviation. aP < 0.05, bP < 0.01 vs shCtrl/Vector, n = 3. MFN2: mitofusin 2; ER: endoplasmic reticulum; GRP78: glucose-regulated protein 78; NLRP3: nucleotide oligomerization domain -like receptor thermal protein domain associated protein 3; CHOP: CCAAT enhance-binding protein homologous protein.
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