PMID- 32702445
OWN - NLM
STAT- MEDLINE
DCOM- 20200917
LR  - 20200917
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 257
DP  - 2020 Sep 15
TI  - Naringin ameliorates type 2 diabetes mellitus-induced steatohepatitis by 
      inhibiting RAGE/NF-kappaB mediated mitochondrial apoptosis.
PG  - 118118
LID - S0024-3205(20)30869-9 [pii]
LID - 10.1016/j.lfs.2020.118118 [doi]
AB  - AIMS: Recent findings have instituted the role of hyperglycemia-related AGE/RAGE 
      and NF-kappaB in instigating reactive oxygen species (ROS) mediated mitochondrial 
      dysfunction and apoptosis of hepatocyte, which leads to steatohepatitis. 
      Naringin, a flavanone glycoside found to possess myriads of pharmacological 
      benefits along with its antioxidant and anti-inflammatory properties. 
      Consequently, we aimed to decipher the effect of naringin on RAGE/NF-kappaB mediated 
      mitochondrial apoptosis in type 2 diabetes mellitus (T2DM)-induced 
      steatohepatitis. MAIN METHODS: Hepatic HepG2 cells were cultured in palmitic acid 
      medium with and without naringin. Lipid content was examined by Oil Red O and 
      Nile Red staining. Cellular apoptosis was determined by Annexin V-FITC/PI 
      staining. An experimental T2DM-induced steatohepatitis was developed in Sprague 
      Dawley rats by high-fat diet (HFD) for 12 weeks. The naringin was administrated 
      orally at a dose of 100 mg/kg, daily for eight weeks. Glucose and insulin 
      tolerance test was performed. Liver sections were stained by hematoxylin-eosin 
      and picrosirius red. The mRNA and protein expression of RAGE and NF-kappaB were 
      determined by qPCR, Immunofluorescence, and Immunoblotting. Mitochondrial 
      membrane potential (MMP), cellular and mitochondrial ROS were measured by FACS. 
      KEY FINDINGS: Palmitic acid encountered HepG2 cells and HFD fed rats exhibited 
      hyperlipidemia, insulin resistance, abnormal aminotransferases, steatosis, and 
      fibrosis. Besides, the level of AGEs, RAGE, NF-kappaB, and oxidative stress were 
      exacerbated. Moreover, MMP, cellular and mitochondrial ROS were altered in 
      diabetic rats. Nevertheless, the naringin treatment ameliorated the 
      steatohepatitis by improving the levels of aforementioned parameters. 
      SIGNIFICANCE: Collectively, these findings suggested anti-steatohepatitis 
      potential of naringin in diabetics.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Syed, Anees Ahmed
AU  - Syed AA
AD  - Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, 
      Sitapur Road, Lucknow 226031, India; Academy of Scientific and Innovative 
      Research (AcSIR), New Delhi, India.
FAU - Reza, Mohammad Irshad
AU  - Reza MI
AD  - Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, 
      Sitapur Road, Lucknow 226031, India.
FAU - Shafiq, Mohammed
AU  - Shafiq M
AD  - Pharmacology Division, CSIR-Central Drug Research Institute, Sitapur Road, 
      Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New 
      Delhi, India.
FAU - Kumariya, Sanjana
AU  - Kumariya S
AD  - Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, 
      Sitapur Road, Lucknow 226031, India.
FAU - Singh, Pragati
AU  - Singh P
AD  - Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, 
      Sitapur Road, Lucknow 226031, India.
FAU - Husain, Athar
AU  - Husain A
AD  - Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, 
      Sitapur Road, Lucknow 226031, India; Academy of Scientific and Innovative 
      Research (AcSIR), New Delhi, India.
FAU - Hanif, Kashif
AU  - Hanif K
AD  - Pharmacology Division, CSIR-Central Drug Research Institute, Sitapur Road, 
      Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New 
      Delhi, India.
FAU - Gayen, Jiaur R
AU  - Gayen JR
AD  - Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute, 
      Sitapur Road, Lucknow 226031, India; Pharmacology Division, CSIR-Central Drug 
      Research Institute, Sitapur Road, Lucknow 226031, India; Academy of Scientific 
      and Innovative Research (AcSIR), New Delhi, India. Electronic address: 
      jr.gayen@cdri.res.in.
LA  - eng
PT  - Journal Article
DEP - 20200720
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Antioxidants)
RN  - 0 (Flavanones)
RN  - 0 (Insulin)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - N7TD9J649B (naringin)
SB  - IM
MH  - Animals
MH  - Antioxidants/*therapeutic use
MH  - Apoptosis/*drug effects
MH  - Diabetes Mellitus, Experimental/complications
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Fatty Liver/*drug therapy/etiology/pathology
MH  - Flavanones/*therapeutic use
MH  - Fluorescent Antibody Technique
MH  - Glucose Tolerance Test
MH  - Hep G2 Cells/drug effects
MH  - Humans
MH  - Insulin/blood
MH  - Liver/pathology
MH  - Male
MH  - Mitochondria/*drug effects
MH  - NF-kappa B/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptor for Advanced Glycation End Products/*metabolism
OTO - NOTNLM
OT  - Mitochondrial apoptosis
OT  - NF-kappaB
OT  - Naringin
OT  - RAGE
OT  - Steatohepatitis
OT  - Type 2 diabetes mellitus
COIS- Declaration of competing interest All authors declared that there is no conflict 
      of interest.
EDAT- 2020/07/24 06:00
MHDA- 2020/09/18 06:00
CRDT- 2020/07/24 06:00
PHST- 2020/06/27 00:00 [received]
PHST- 2020/07/10 00:00 [revised]
PHST- 2020/07/15 00:00 [accepted]
PHST- 2020/07/24 06:00 [pubmed]
PHST- 2020/09/18 06:00 [medline]
PHST- 2020/07/24 06:00 [entrez]
AID - S0024-3205(20)30869-9 [pii]
AID - 10.1016/j.lfs.2020.118118 [doi]
PST - ppublish
SO  - Life Sci. 2020 Sep 15;257:118118. doi: 10.1016/j.lfs.2020.118118. Epub 2020 Jul 
      20.