MOLECULAR NUTRITION & FOOD RESEARCH
·
2022
·Vol. 67
·期 6
·2200774
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IF 6.575
Jiawen Lu,Ying Yang,Elisabeth Varga,Doris Marko,Qiang Yu,Jianhua Xie,Chang Li,Yi Chen
Scope The previous in vivo studies show Ganoderma atrum polysaccharide (PSG-F 2 ) has a protective effect against the acrylamide (AA)-induced intestinal oxidative damage in rats. Now, this study aims to explore the protective mechanism with IEC-6 cell model. Methods and results Based on RNA Sequencing (RNA-Seq), the study screens MAPK signaling pathway as one of the most crucial pathways for pretreatment with PSG-F 2 against AA-induced damage in IEC-6 cells. In total, six key MAPK signaling pathway-related proteins (p-P38/P38, p-ERK/ERK, and p-JNK/JNK), and three tight junction key proteins ( Zonula Occludens protein-1, Claudin -1, and Occludin ) are detected by Western blot and immunofluorescence, which verify the RNA-Seq data. Moreover, PD98059 interference inhibits critical proteins in the MAPK signaling pathway, thus uncovering the precise molecular mechanisms of MAPK/ERK signaling pathway involve in the protective effects of PSG-F 2 against AA-induced intestinal barrier damage. Conclusion These findings confirm that PSG-F 2 can be used as a daily dietary supplement to protect the intestinal cells from damage caused by thermal processing hazards AA.
研究领域:
分子生物学
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细胞生物学
·
药理学
·
毒理学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Peizhi Jia,Daxin Chen,Ying Zhu,Meiling Wang,Jianwei Zeng,Ling Zhang,Qiaoyan Cai,Dawei Lian,Chunyu Zhao,Yaoyao Xu,Jianfeng Chu,Shan Lin,Jun Peng,Wei Lin
Ethnopharmacological relevance Liensinine(Lien, C 37 H 42 N 2 O 6 ) is an alkaloid compound from plumula nelumbinis that demonstrates an antihypertensive effect. The protective effects of Lien on target organs during hypertension are still unclear. Aim of the study : This study aimed to understand the mechanism of Lien during the treatment of hypertension, with emphasis on vascular protection. Materials and methods Lien was extracted and isolated from plumula nelumbinis for further study. In vivo model of Ang II-induced hypertension, non-invasive sphygmomanometer was used to detect the blood pressure in and out of the context of Lien intervention. Ultrasound was used to detect the abdominal aorta pulse wave and media thickness of hypertensive mice, and RNA sequencing was used to detect the differential genes and pathways of blood vessels. The intersection of Lien and MAPK protein molecules was detected by molecular interconnecting technique. The pathological conditions of abdominal aorta vessels of mice were observed by HE staining. The expression of PCNA, α-SMA, Collagen Type Ⅰ and Collagen Type Ⅲ proteins were detected by IHC. The collagen expression in the abdominal aorta was detected by Sirius red staining. The MAPK/TGF-β1/Smad2/3 signaling and the protein expression of PCNA and α-SMA was detected by Western blot. In vitro , MAPK/TGF-β1/Smad2/3 signaling and the protein expression of PCNA and α-SMA were detected by Western blot, and the expression of α-SMA was detected by immunofluorescence; ELISA was used to detect the effect of ERK/MAPK inhibitor PD98059 on Ang Ⅱ-induced TGF-β1secrete; and the detection TGF-β1and α-SMA protein expression by Western blot; Western blot was used to detect the effect of ERK/MAPK stimulant12-O-tetradecanoyl phorbol-13-acetate (TPA) on the protein expression of TGF-β1 and α-SMA. Results Lien displayed an antihypertensive effect on Ang Ⅱ-induced hypertension, reducing the pulse wave conduction velocity of the abdominal aorta and the thickness of the abdominal aorta vessel wall, ultimately improving the pathological state of blood vessels. RNA sequencing further indicated that the differential pathways expressed in the abdominal aorta of hypertensive mice were enriched in proliferation-related markers compared with the Control group. The profile of differentially expressed pathways was ultimately reversed by Lien. Particularly, MAPK protein demonstrated good binding with the Lien molecule. In vivo, Lien inhibited Ang Ⅱ-induced abdominal aorta wall thickening, reduced collagen deposition in the ventral aortic vessel, and prevented the occurrence of vascular remodeling by inhibiting MAPK/TGF-β1/Smad2/3 signaling activation. In addition, Lien inhibited the activation of Ang II-induced MAPK and TGF-β1/Smad2/3 signaling, attenuating the expression of PCNA and inhibiting the reduction of α-SMA, collectively playing a role in the inhibition of Ang Ⅱ-induced hypertensive vascular remodeling. PD98059 alone could inhibit Ang Ⅱ-induced elevation of TGF-β1 and the decrease of α-SMA expression. Further, PD98059 combined with Lien had no discrepancy with the inhibitors alone. Simultaneously TPA alone could significantly increase the expression of TGF-β1 and decrease the expression of α-SMA. Further, Lien could inhibit the effect of TPA. Conclusion This study helped clarify the protective mechanism of Lien during hypertension, elucidating its role as an inhibitor of vascular remodeling and providing an experimental basis for the research and development of novel antihypertensive therapies.
研究领域:
药理学
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心血管疾病
·
分子生物学
·
民族药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）