PMID- 33815106
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210406
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Centella asiatica Extract Attenuates Kidney Fibrosis Through Reducing Mesenchymal 
      Transition and Inflammation in Ureteral Ligation Model in Mice.
PG  - 621894
LID - 10.3389/fphar.2021.621894 [doi]
LID - 621894
AB  - Background: Kidney fibrosis is the common final pathway of chronic kidney disease 
      (CKD), and is characterized by inflammation, mesenchymal transition with 
      myofibroblast formation and epithelial to mesenchymal transition (EMT). Centella 
      asiatia (CeA) is an herb that has a reno-protective effect. However, its 
      mechanism of action in kidney fibrosis has not been elucidated. Aim: To elucidate 
      the effect of CeA in amelioration of kidney fibrosis in a unilateral ureteral 
      obstruction (UUO) model and focus on mesenchymal transition and inflammation. 
      Methods: Unilateral ureteral obstruction was performed in male Swiss-background 
      mice (age: 2-3 months, weight: 30-40 g, UUO group n = 6) to induce kidney 
      fibrosis. Two doses of CeA extract with oral administration, 210 and 840 mg/kg 
      body weight were added in UUO (U+C210 and U+C840 groups, each n = 6). The sham 
      operation procedure was performed for the control group (SO, n = 6). The mice 
      were euthanized at day-14 after operation. Tubular injury and interstitial 
      fibrosis area fractions in kidney tissues of the mice were quantified based on 
      periodic acid-Schiff (PAS) and Sirius Red (SR) staining. Immunostaining was 
      performed for examination of fibroblast (PDGFR-beta), myofibroblast (alpha-SMA), 
      Monocyte Chemoattractant Protein-1 (MCP-1) and macrophage (CD68), meanwhile 
      double immunofluorescence was performed with PDGFR-beta and alpha-SMA. Reverse 
      transcriptase-polymerase chain reaction (RT-PCR) was performed to examine mRNA 
      expression of TGF-beta, Collagen-1, Snail, E-cadherin, vimentin, fibroblast-specific 
      protein 1 (FSP-1), CD68, toll-like receptor 4 (TLR4), and MCP-1. Results: We 
      observed a significantly higher interstitial fibrosis area fraction and tubular 
      injury (p < 0.001) with fibroblast expansion and myofibroblast formation in the 
      UUO group than in the SO group. These findings were associated with higher mRNA 
      expression of TGF-beta, Collagen-1, Snail, vimentin, FSP-1, CD68, TLR4, and MCP-1 
      and lower mRNA expression of E-cadherin. The U+C840 group had a significantly 
      lower tubular injury score and interstitial fibrosis area fraction, which 
      associated with downregulation of mRNA expression of TGF-beta, Collagen-1, Snail, 
      vimentin, FSP-1, CD68, TLR4, and MCP-1, with upregulation of mRNA expression of 
      E-cadherin. Immunostaining observation revealed the U+C840 group demonstrated 
      reduction of macrophage infiltration and myofibroblast expansion. Conclusion: CeA 
      treatment with dose-dependently ameliorates mesenchymal transition and 
      inflammation in kidney fibrosis in mice.
CI  - Copyright (c) 2021 Sari, Budiharjo, Afifah, Jasmin, Kokasih, Putri, Arifiani, 
      Setyaningsih and Arfian.
FAU - Sari, Dwi Cahyani Ratna
AU  - Sari DCR
AD  - Department of Anatomy, Faculty of Medicine, Public Health and Nursing, 
      Universitas Gadjah Mada, Yogyakarta, Indonesia.
FAU - Budiharjo, Santosa
AU  - Budiharjo S
AD  - Department of Anatomy, Faculty of Medicine, Public Health and Nursing, 
      Universitas Gadjah Mada, Yogyakarta, Indonesia.
FAU - Afifah, Husnari
AU  - Afifah H
AD  - Undergraduate Student, Faculty of Medicine, Public Health and Nursing, 
      Universitas Gadjah Mada, Yogyakarta, Indonesia.
FAU - Jasmin, Destantry
AU  - Jasmin D
AD  - Undergraduate Student, Faculty of Medicine, Public Health and Nursing, 
      Universitas Gadjah Mada, Yogyakarta, Indonesia.
FAU - Kokasih, Orisativa
AU  - Kokasih O
AD  - Undergraduate Student, Faculty of Medicine, Public Health and Nursing, 
      Universitas Gadjah Mada, Yogyakarta, Indonesia.
FAU - Putri, Tiara Gitami
AU  - Putri TG
AD  - Undergraduate Student, Faculty of Medicine, Public Health and Nursing, 
      Universitas Gadjah Mada, Yogyakarta, Indonesia.
FAU - Arifiani, Karina
AU  - Arifiani K
AD  - Siloam Hospitals Group, Ancillary and Medical Affairs Regional Head, Depok, 
      Indonesia.
FAU - Setyaningsih, Wiwit Ananda Wahyu
AU  - Setyaningsih WAW
AD  - Department of Anatomy, Faculty of Medicine, Public Health and Nursing, 
      Universitas Gadjah Mada, Yogyakarta, Indonesia.
FAU - Arfian, Nur
AU  - Arfian N
AD  - Department of Anatomy, Faculty of Medicine, Public Health and Nursing, 
      Universitas Gadjah Mada, Yogyakarta, Indonesia.
LA  - eng
PT  - Journal Article
DEP - 20210317
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8010664
OTO - NOTNLM
OT  - Centella asiatica
OT  - inflammation
OT  - kidney fibrosis
OT  - mesenchymal transition
OT  - unilateral ureteral obstruction
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/04/06 06:00
MHDA- 2021/04/06 06:01
PMCR- 2021/03/17
CRDT- 2021/04/05 05:56
PHST- 2020/10/27 00:00 [received]
PHST- 2021/01/06 00:00 [accepted]
PHST- 2021/04/05 05:56 [entrez]
PHST- 2021/04/06 06:00 [pubmed]
PHST- 2021/04/06 06:01 [medline]
PHST- 2021/03/17 00:00 [pmc-release]
AID - 621894 [pii]
AID - 10.3389/fphar.2021.621894 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Mar 17;12:621894. doi: 10.3389/fphar.2021.621894. 
      eCollection 2021.