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Anti-liver fibrosis effect of total flavonoids from Scabiosa comosa Fisch. ex Roem. et Schult. on liver fibrosis in rat models and its proteomics analysis.
Ann Palliat Med. 2020 Mar; 9(2):272-285.AP

Abstract

BACKGROUND

To explore the potential therapeutic effect of total flavonoids (TFs) extracted from Scabiosa comosa Fisch. ex Roem. et Schult on liver fibrosis in rat models and to identify the possible targets and pathways of TF in treating liver fibrosis by using a quantitative proteomics method.

METHODS

Sixty Wistar rats were equally randomized into five groups: a blank control group, a model group, and high-, intermediate-, and low-dose TF treatment groups. Except for the blank control group, rats in the other four groups were intragastrically administered with CCL4 2 mL/kg to establish the liver fibrosis models. Furthermore, the high-, intermediate-, and low-dose TF groups were intragastrically given TF at a dose of 200, 100 and 50 mg/kg, respectively. After 10 weeks, the rats were sacrificed, and blood and liver samples were collected. Serum alanine transaminase (ALT), Aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels were measured, and hematoxylin and eosin (HE) staining and Masson's trichrome staining were used to observe the pathological changes in each group. The hydroxyproline content was also determined. Real-time polymerase chain reaction (PCR) and Western blotting (WB) were performed to detect the mRNA and protein expressions of α-smooth muscle actin (αSMA) and Collagen I. Mass spectrometry was performed for proteomic analysis.

RESULTS

Compared with the blank control group, the model group had significantly higher ALT, AST, ALP, and hydroxyproline levels; also, HE and Masson staining showed fibrotic lesions and inflammatory cell infiltration in the model group. Compared with the model group, the high-, intermediate-, and lowdose TF groups had significantly decreased ALT, AST, and ALP levels (P<0.05), and a significantly lower hydroxyproline level (P<0.05), along with remarkably improved fibrotic lesions and inflammatory cell infiltration. Real-time PCR and WB showed that the model group had significantly higher expressions of αSMA and collagen I than those in the blank control group, whereas the TF groups had significantly lower expressions of αSMA and collagen I than those in the model group. A total of 5,014 proteins were detected by quantitative proteomics, among which 205 proteins were differentially expressed, 77 of which were upregulated and 128 of which were down-regulated. KEGG pathway analysis indicated that the peroxisome proliferator activated receptor (PPAR) and ECM-receptor interaction pathways were down-regulated in the TF groups compared with the model group. Among them, fatty-acid-binding protein (FABP) and von Willebrand factor (vWF) were the key proteins in the PPAR and extracellular matrix (ECM)-receptor interaction pathways. The proteomic results were validated by using WB, yielding consistent results.

CONCLUSIONS

Our result demonstrated that the TF extract of Scabiosa comosa Fisch. ex Roem. et Schult has a good anti-liver fibrosis effect and may prevent liver fibrosis by reducing the content of α-SMA, CollagenⅠ in liver tissue. The anti-fibrosis mechanism of TF extract of Scabiosa comosa Fisch. ex Roem. et Schult may be the inhibition of key proteins FABP and vWF in PPAR, ECM RECEPTOR INTERACTION pathway.

Authors+Show Affiliations

Department of Pharmacology, School of Basic Medicine, Inner Mongolia Medical University, Hohhot City 010107, China.Department of Pathology, School of Basic Medicine, Inner Mongolia Medical University, Hohhot City 010107, China.Department of Nephrology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot City 010107, China.Department of Pharmaceutical Engineering, School of Pharmacy, Inner Mongolia Medical University, Hohhot City 010107, China.Department of Biochemistry, School of Basic Medicine, Inner Mongolia Medical University, Hohhot City 010107, China.Department of Pharmacology, School of Basic Medicine, Inner Mongolia Medical University, Hohhot City 010107, China.Department of Pharmacology, School of Basic Medicine, Inner Mongolia Medical University, Hohhot City 010107, China.Department of Pharmacology, School of Basic Medicine, Inner Mongolia Medical University, Hohhot City 010107, China.Department of Pharmacology, School of Basic Medicine, Inner Mongolia Medical University, Hohhot City 010107, China.Department of Pharmacology, School of Basic Medicine, Inner Mongolia Medical University, Hohhot City 010107, China.Department of Biochemistry, School of Basic Medicine, Inner Mongolia Medical University, Hohhot City 010107, China.Functional Science laboratory, Institute of Basic Medicine, Inner Mongolia Medical University, Hohhot City 010107, China.Department of Pharmacology, Inner Mongolia Medical University, Hohhot City 010107, China. myh19982002@sina.com.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

32233617

Citation

Menggensilimu, et al. "Anti-liver Fibrosis Effect of Total Flavonoids From Scabiosa Comosa Fisch. Ex Roem. Et Schult. On Liver Fibrosis in Rat Models and Its Proteomics Analysis." Annals of Palliative Medicine, vol. 9, no. 2, 2020, pp. 272-285.
Menggensilimu, Yuan H, Zhao C, et al. Anti-liver fibrosis effect of total flavonoids from Scabiosa comosa Fisch. ex Roem. et Schult. on liver fibrosis in rat models and its proteomics analysis. Ann Palliat Med. 2020;9(2):272-285.
Yuan, H., Zhao, C., Bao, X., Wang, H., Liang, J., Yan, Y., Zhang, C., Jin, R., Ma, L., Zhang, J., Su, X., & Ma, Y. (2020). Anti-liver fibrosis effect of total flavonoids from Scabiosa comosa Fisch. ex Roem. et Schult. on liver fibrosis in rat models and its proteomics analysis. Annals of Palliative Medicine, 9(2), 272-285. https://doi.org/10.21037/apm.2020.02.29
Menggensilimu, et al. Anti-liver Fibrosis Effect of Total Flavonoids From Scabiosa Comosa Fisch. Ex Roem. Et Schult. On Liver Fibrosis in Rat Models and Its Proteomics Analysis. Ann Palliat Med. 2020;9(2):272-285. PubMed PMID: 32233617.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-liver fibrosis effect of total flavonoids from Scabiosa comosa Fisch. ex Roem. et Schult. on liver fibrosis in rat models and its proteomics analysis. AU - ,, AU - Yuan,Hongwei, AU - Zhao,Chunmei, AU - Bao,Xiaomei, AU - Wang,Haisheng, AU - Liang,Jie, AU - Yan,Yuxin, AU - Zhang,Chunyan, AU - Jin,Rong, AU - Ma,Lijie, AU - Zhang,Jianyu, AU - Su,Xiaoli, AU - Ma,Yuehong, Y1 - 2020/03/18/ PY - 2019/11/11/received PY - 2020/02/04/accepted PY - 2020/4/3/pubmed PY - 2021/1/12/medline PY - 2020/4/3/entrez KW - ECM-receptor interaction (extracellular matrix-receptor interaction) KW - Liver fibrosis KW - Scabiosa comosa Fisch. ex Roem. et Schult. KW - peroxisome proliferator activated receptor (PPAR) KW - proteomics KW - total flavonoids (TFs) SP - 272 EP - 285 JF - Annals of palliative medicine JO - Ann Palliat Med VL - 9 IS - 2 N2 - BACKGROUND: To explore the potential therapeutic effect of total flavonoids (TFs) extracted from Scabiosa comosa Fisch. ex Roem. et Schult on liver fibrosis in rat models and to identify the possible targets and pathways of TF in treating liver fibrosis by using a quantitative proteomics method. METHODS: Sixty Wistar rats were equally randomized into five groups: a blank control group, a model group, and high-, intermediate-, and low-dose TF treatment groups. Except for the blank control group, rats in the other four groups were intragastrically administered with CCL4 2 mL/kg to establish the liver fibrosis models. Furthermore, the high-, intermediate-, and low-dose TF groups were intragastrically given TF at a dose of 200, 100 and 50 mg/kg, respectively. After 10 weeks, the rats were sacrificed, and blood and liver samples were collected. Serum alanine transaminase (ALT), Aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels were measured, and hematoxylin and eosin (HE) staining and Masson's trichrome staining were used to observe the pathological changes in each group. The hydroxyproline content was also determined. Real-time polymerase chain reaction (PCR) and Western blotting (WB) were performed to detect the mRNA and protein expressions of α-smooth muscle actin (αSMA) and Collagen I. Mass spectrometry was performed for proteomic analysis. RESULTS: Compared with the blank control group, the model group had significantly higher ALT, AST, ALP, and hydroxyproline levels; also, HE and Masson staining showed fibrotic lesions and inflammatory cell infiltration in the model group. Compared with the model group, the high-, intermediate-, and lowdose TF groups had significantly decreased ALT, AST, and ALP levels (P<0.05), and a significantly lower hydroxyproline level (P<0.05), along with remarkably improved fibrotic lesions and inflammatory cell infiltration. Real-time PCR and WB showed that the model group had significantly higher expressions of αSMA and collagen I than those in the blank control group, whereas the TF groups had significantly lower expressions of αSMA and collagen I than those in the model group. A total of 5,014 proteins were detected by quantitative proteomics, among which 205 proteins were differentially expressed, 77 of which were upregulated and 128 of which were down-regulated. KEGG pathway analysis indicated that the peroxisome proliferator activated receptor (PPAR) and ECM-receptor interaction pathways were down-regulated in the TF groups compared with the model group. Among them, fatty-acid-binding protein (FABP) and von Willebrand factor (vWF) were the key proteins in the PPAR and extracellular matrix (ECM)-receptor interaction pathways. The proteomic results were validated by using WB, yielding consistent results. CONCLUSIONS: Our result demonstrated that the TF extract of Scabiosa comosa Fisch. ex Roem. et Schult has a good anti-liver fibrosis effect and may prevent liver fibrosis by reducing the content of α-SMA, CollagenⅠ in liver tissue. The anti-fibrosis mechanism of TF extract of Scabiosa comosa Fisch. ex Roem. et Schult may be the inhibition of key proteins FABP and vWF in PPAR, ECM RECEPTOR INTERACTION pathway. SN - 2224-5839 UR - https://www.unboundmedicine.com/medline/citation/32233617/Anti_liver_fibrosis_effect_of_total_flavonoids_from_Scabiosa_comosa_Fisch__ex_Roem__et_Schult__on_liver_fibrosis_in_rat_models_and_its_proteomics_analysis_ L2 - https://doi.org/10.21037/apm.2020.02.29 DB - PRIME DP - Unbound Medicine ER -