PMID- 35643302
OWN - NLM
STAT- MEDLINE
DCOM- 20220616
LR  - 20230330
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 927
DP  - 2022 Jul 15
TI  - Chloroquine modulates the sulforaphane anti-obesity mechanisms in a high-fat diet 
      model: Role of JAK-2/ STAT-3/ SOCS-3 pathway.
PG  - 175066
LID - S0014-2999(22)00327-2 [pii]
LID - 10.1016/j.ejphar.2022.175066 [doi]
AB  - The phytochemical sulforaphane (SFN) has been studied for its potential 
      anti-obesity effect, but neither its molecular targets nor its interaction with 
      the antimalarial drug chloroquine (CQ) has been fully delineated. Therefore, 
      high-fat diet (HFD) obese rats were randomly allocated into one of five groups 
      and were left untreated or gavaged orally with SFN (0.5 or 1 mg/kg), CQ 
      (5 mg/kg), or their combination (0.5/5 mg/kg) for six successive weeks to assess 
      their potential interaction and the enrolled mechanisms. SFN effectively reduced 
      the HFD-induced weight gain, blood glucose, and serum leptin levels, and improved 
      lipid profile. On the molecular level, SFN inhibited the lipogenesis-related 
      enzymes, namely sterol regulatory element-binding protein (SREBP)-1c, fatty acid 
      synthase (FAS), and acetyl-CoA carboxylase (ACC) in both liver and visceral white 
      adipose tissue (vWAT) of HFD obese rats. SFN also turned off the inflammatory 
      pathway conserved Janus kinase/signaling transducers and activators of 
      transcription/suppressor of cytokine signaling (JAK-2/STAT-3/SOCS-3) in these 
      tissues, as well as the inflammatory markers nuclear factor-kappa (NF-kappa) B and 
      interleukin (IL)-22 in serum. In contrast, SFN downregulated the gene expression 
      of microRNA (miR-200a), while significantly increasing the autophagic parameters; 
      viz., beclin-1, autophagy-related protein (ATG)-7, and microtubule-associated 
      protein 2 light chain 3 (LC3-II) in both liver and vWAT. On most of the 
      parameters mentioned above, treatment with CQ solely produced a satisfactory 
      effect and intensified the low dose of SFN in the combination regimen. These 
      findings demonstrated the beneficial effects of using CQ as an add-on 
      anti-obesity medicine to SFN.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Ashmawy, Ahmed I
AU  - Ashmawy AI
AD  - Department of Pharmacology & Therapeutics, Faculty of Pharmacy, Pharos University 
      in Alexandria, Alexandria, Egypt.
FAU - El-Abhar, Hanan S
AU  - El-Abhar HS
AD  - Department of Pharmacology, Toxicology & Biochemistry, Faculty of Pharmacy, 
      Future University in Egypt, Cairo, Egypt.
FAU - Abdallah, Dalaal M
AU  - Abdallah DM
AD  - Department of Pharmacology & Toxicology, Faculty of Pharmacy, Cairo University, 
      Cairo, Egypt. Electronic address: dalaal.abdallah@pharma.cu.edu.eg.
FAU - Ali, Mennatallah A
AU  - Ali MA
AD  - Department of Pharmacology & Therapeutics, Faculty of Pharmacy, Pharos University 
      in Alexandria, Alexandria, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20220526
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Isothiocyanates)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Socs3 protein, rat)
RN  - 0 (Stat3 protein, rat)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 0 (Sulfoxides)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 886U3H6UFF (Chloroquine)
RN  - EC 2.7.10.2 (Jak2 protein, rat)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - GA49J4310U (sulforaphane)
SB  - IM
EIN - Eur J Pharmacol. 2023 May 15;947:175683. PMID: 36997461
MH  - Animals
MH  - *Chloroquine/pharmacology
MH  - *Diet, High-Fat
MH  - *Isothiocyanates/pharmacology
MH  - *Janus Kinase 2/metabolism
MH  - Liver/metabolism
MH  - Obesity/drug therapy/etiology/metabolism
MH  - Random Allocation
MH  - Rats
MH  - *STAT3 Transcription Factor/metabolism
MH  - Sterol Regulatory Element Binding Protein 1/metabolism
MH  - *Sulfoxides/pharmacology
MH  - *Suppressor of Cytokine Signaling 3 Protein/metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Chloroquine
OT  - Inflammation
OT  - JAK-2/STAT-3/ SOCS-3
OT  - Obesity
OT  - Sulforaphane
EDAT- 2022/06/02 06:00
MHDA- 2022/06/18 06:00
CRDT- 2022/06/01 09:24
PHST- 2022/02/06 00:00 [received]
PHST- 2022/05/22 00:00 [revised]
PHST- 2022/05/23 00:00 [accepted]
PHST- 2022/06/02 06:00 [pubmed]
PHST- 2022/06/18 06:00 [medline]
PHST- 2022/06/01 09:24 [entrez]
AID - S0014-2999(22)00327-2 [pii]
AID - 10.1016/j.ejphar.2022.175066 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2022 Jul 15;927:175066. doi: 10.1016/j.ejphar.2022.175066. Epub 
      2022 May 26.