PMID- 37895841
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231030
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 16
IP  - 10
DP  - 2023 Sep 27
TI  - Dapagliflozin/Hesperidin Combination Mitigates Lipopolysaccharide-Induced 
      Alzheimer's Disease in Rats.
LID - 10.3390/ph16101370 [doi]
LID - 1370
AB  - Alzheimer's disease (AD) is the most common form of neurodegenerative disorders 
      worldwide. Its pathologic features include massive neuroinflammation with 
      abnormal deposition of beta-amyloid peptide in the cerebral tissues leading to 
      degeneration of the brain neurons. Adverse effects associated with the 
      traditional drugs used for the treatment of this pathological condition have 
      directed the research efforts towards searching for alternative effective agents 
      with minimal adverse effects. The aim of this study was to elucidate the 
      potential ameliorative effects of dapagliflozin and/or hesperidin on Alzheimer's 
      disease (AD) induced by lipopolysaccharide (LPS) injection in rats. In a rodent 
      model of AD, the effect of dapagliflozin with or without hesperidin on the 
      biochemical parameters and the behavioral tests as well as the histopathological 
      parameters was determined. Each of dapagliflozin and hesperidin restored the 
      behavioral tests to the reference values, augmented the antioxidant defense 
      mechanisms, ameliorated the neuronal inflammatory responses, combatted the 
      changes in Toll-like receptor-4 (TLR-4)/High-mobility group box 1 (HMGB1) protein 
      signaling and receptors of advanced glycation end products (RAGE) levels, and 
      restored the balance between the apoptotic signals and autophagy in the 
      hippocampal tissues. Additionally, both agents exhibited an outstanding ability 
      to combat LPS-induced perturbations in the histopathological and electron 
      microscopic image of the brain tissues. These favorable effects were 
      significantly encountered in the group treated with dapagliflozin/hesperidin 
      combination when compared versus animals treated with either dapagliflozin or 
      hesperidin. In conclusion, inhibition of the hippocampal HMGB1/TLR4/RAGE 
      signaling, the pro-inflammatory axis, and apoptosis alongside augmentation of the 
      antioxidant defenses and autophagy can be regarded as beneficial effects by which 
      dapagliflozin/hesperidin combination may combat LPS-triggered AD.
FAU - Abd Elmaaboud, Maaly A
AU  - Abd Elmaaboud MA
AD  - Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, 
      Egypt.
FAU - Estfanous, Remon S
AU  - Estfanous RS
AD  - Anatomy and Embryology Department, Faculty of Medicine, Tanta University, Tanta 
      31527, Egypt.
FAU - Atef, Aliaa
AU  - Atef A
AD  - Department of Pathology, Faculty of Medicine, Tanta University, Tanta 31527, 
      Egypt.
FAU - Kabel, Ahmed M
AU  - Kabel AM
AUID- ORCID: 0000-0002-5101-8011
AD  - Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, 
      Egypt.
FAU - Alnemari, Khalid A
AU  - Alnemari KA
AD  - Taif Medical Center, Taif 26526, Saudi Arabia.
FAU - Naguib, Tamer M
AU  - Naguib TM
AUID- ORCID: 0000-0001-6676-3180
AD  - Anesthesia and ICU Department, Faculty of Medicine, Tanta University, Tanta 
      31527, Egypt.
FAU - Alsufyani, Shuruq E
AU  - Alsufyani SE
AUID- ORCID: 0000-0002-5567-6169
AD  - Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, 
      P.O. Box 11099, Taif 21944, Saudi Arabia.
FAU - Darwish, Hany W
AU  - Darwish HW
AD  - Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud 
      University, Riyadh 11451, Saudi Arabia.
FAU - Arab, Hany H
AU  - Arab HH
AUID- ORCID: 0000-0002-4195-6901
AD  - Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, 
      P.O. Box 11099, Taif 21944, Saudi Arabia.
AD  - Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, 
      Egypt.
LA  - eng
GR  - RSPD2023R812/King Saud University, Riyadh, Saudi Arabia/
PT  - Journal Article
DEP - 20230927
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC10609711
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - apoptosis
OT  - autophagy
OT  - dapagliflozin
OT  - hesperidin
OT  - inflammatory cascade
OT  - lipopolysaccharide
OT  - oxidative stress
OT  - rats
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/28 11:44
MHDA- 2023/10/28 11:45
PMCR- 2023/09/27
CRDT- 2023/10/28 01:24
PHST- 2023/07/29 00:00 [received]
PHST- 2023/09/19 00:00 [revised]
PHST- 2023/09/24 00:00 [accepted]
PHST- 2023/10/28 11:45 [medline]
PHST- 2023/10/28 11:44 [pubmed]
PHST- 2023/10/28 01:24 [entrez]
PHST- 2023/09/27 00:00 [pmc-release]
AID - ph16101370 [pii]
AID - pharmaceuticals-16-01370 [pii]
AID - 10.3390/ph16101370 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2023 Sep 27;16(10):1370. doi: 10.3390/ph16101370.