PMID- 34095305
OWN - NLM
STAT- MEDLINE
DCOM- 20210929
LR  - 20210929
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2021
DP  - 2021
TI  - A Combination of Geniposide and Chlorogenic Acid Combination Ameliorates 
      Nonalcoholic Steatohepatitis in Mice by Inhibiting Kupffer Cell Activation.
PG  - 6615881
LID - 10.1155/2021/6615881 [doi]
LID - 6615881
AB  - The incidence of nonalcoholic steatohepatitis (NASH) is increasing worldwide. 
      Activation of Kupffer cells (KCs) is central to the development of diet-induced 
      NASH. We investigated whether a combination of two active chemical components, 
      geniposide and chlorogenic acid (GC), at a specific ratio (67 : 1), ameliorates 
      diet-induced NASH and the underlying mechanisms involved. C57BL/6J mice exposed 
      to a high-fat and high-cholesterol (HFHC) diet containing cholesterol, choline, 
      and high-sugar drinking water, as well as RAW264.7 cells stimulated with 
      lipopolysaccharide (LPS) were studied. The combination exerted a therapeutic 
      effect on HFHC-induced NASH in mice. Simultaneously, GC was found to reduce the 
      expression of cytokines secreted by hepatic macrophages, including tumor necrosis 
      factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, monocyte chemotactic 
      protein 1 (MCP-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). 
      Moreover, GC reduced the number of KCs expressing F4/80. Furthermore, TNF-alpha, 
      inducible nitric oxide synthase (INOS), IL-1beta, and IL-6 mRNA and TNF-alpha protein 
      expression levels were suppressed upon GC treatment in RAW264.7 cells. Our 
      findings suggest that GC has a strong anti-inflammatory effect in NASH, and this 
      effect can be attributed to the suppression of KC activity in the liver.
CI  - Copyright (c) 2021 Xin Xin et al.
FAU - Xin, Xin
AU  - Xin X
AUID- ORCID: 0000-0003-4899-9127
AD  - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University 
      of Traditional Chinese Medicine, Shanghai 201203, China.
FAU - Jin, Yue
AU  - Jin Y
AUID- ORCID: 0000-0002-0426-5933
AD  - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University 
      of Traditional Chinese Medicine, Shanghai 201203, China.
FAU - Wang, Xin
AU  - Wang X
AUID- ORCID: 0000-0003-4348-1767
AD  - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University 
      of Traditional Chinese Medicine, Shanghai 201203, China.
FAU - Cai, Beiyu
AU  - Cai B
AUID- ORCID: 0000-0001-6437-7649
AD  - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University 
      of Traditional Chinese Medicine, Shanghai 201203, China.
FAU - An, Ziming
AU  - An Z
AUID- ORCID: 0000-0001-6570-2415
AD  - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University 
      of Traditional Chinese Medicine, Shanghai 201203, China.
FAU - Hu, Yi-Yang
AU  - Hu YY
AUID- ORCID: 0000-0001-9127-7002
AD  - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University 
      of Traditional Chinese Medicine, Shanghai 201203, China.
AD  - Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 
      201203, China.
AD  - Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional 
      Chinese Medicine, Ministry of Education, Shanghai 201203, China.
FAU - Feng, Qin
AU  - Feng Q
AUID- ORCID: 0000-0002-4641-1636
AD  - Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University 
      of Traditional Chinese Medicine, Shanghai 201203, China.
AD  - Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 
      201203, China.
AD  - Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional 
      Chinese Medicine, Ministry of Education, Shanghai 201203, China.
LA  - eng
PT  - Journal Article
DEP - 20210513
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (Cytokines)
RN  - 0 (Iridoids)
RN  - 0 (Lipopolysaccharides)
RN  - 145295QLXY (geniposide)
RN  - 318ADP12RI (Chlorogenic Acid)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Animals
MH  - China
MH  - Chlorogenic Acid/metabolism/*pharmacology
MH  - Cytokines/drug effects/metabolism
MH  - Drug Therapy, Combination/methods
MH  - Iridoids/metabolism/*pharmacology
MH  - Kupffer Cells/drug effects/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Liver/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Non-alcoholic Fatty Liver Disease/*drug therapy/metabolism
MH  - RAW 264.7 Cells
PMC - PMC8140849
COIS- The authors declare no potential conflicts of interest.
EDAT- 2021/06/08 06:00
MHDA- 2021/09/30 06:00
PMCR- 2021/05/13
CRDT- 2021/06/07 06:05
PHST- 2020/12/03 00:00 [received]
PHST- 2021/02/20 00:00 [revised]
PHST- 2021/05/05 00:00 [accepted]
PHST- 2021/06/07 06:05 [entrez]
PHST- 2021/06/08 06:00 [pubmed]
PHST- 2021/09/30 06:00 [medline]
PHST- 2021/05/13 00:00 [pmc-release]
AID - 10.1155/2021/6615881 [doi]
PST - epublish
SO  - Biomed Res Int. 2021 May 13;2021:6615881. doi: 10.1155/2021/6615881. eCollection 
      2021.