Review
Isorhamnetin: A review of pharmacological effects

https://doi.org/10.1016/j.biopha.2020.110301Get rights and content
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Highlights

  • The pharmacological effects of isorhamnetin are reviewed comprehensively.

  • Isorhamnetin is mainly contained in Hippophae rhamnoides and Ginkgo biloba.

  • Isorhamnetin protects cardio-cerebral vessels and nerves.

  • Investigations on the mechanism of action of isorhamnetin are limited.

  • The research on the target of isorhamnetin is missing.

Abstract

Isorhamnetin is one of the most important active ingredients in the fruits of Hippophae rhamnoides L. and the leaves of Ginkgo biloba L., which possesses extensive pharmacological activities. At present, there have been numerous investigations on isorhamnetin, which has the effects of cardiovascular and cerebrovascular protection, anti-tumor, anti-inflammatory, anti-oxidation, organ protection, prevention of obesity, etc. The related mechanisms involve the regulation of PI3K/AKT/PKB, NF-κB, MAPK and other signaling pathways as well as the expression of related cytokines and kinases. Isorhamnetin has a high value of development and application. However, the investigations on its mechanism of action are limited and lack of detailed scientific validation. The manuscript reviewed the pharmacological effects of isorhamnetin and related mechanisms of action for the development of its medicinal properties further.

Abbreviations

NF-κB
nuclear factor-κB
PI3K
phosphatidylinositol 3-kinase
PKB/
AKT protein kinase B
MAPK
mitogen-activated protein kinases
HO-1
heme oxygenase
Nrf2
nuclear factor erythroid-2-related factor 2
ARE
antioxidant response element
VSMC
vascular smooth muscle cells
ox-LDL
oxidized low density lipoprotein
HDL
high density lipoprotein
VLDL
very low density lipoprotein
LDL
low density lipoprotein
IP3
inositol 1, 4, 5-trisphosphate
NO
netrogen monoxide
FAS
tumor necrosis factor receptor superfamily, member 6
FASL
FAS ligand
LDH
lactate dehydrogenase
CFb
cardic fibroblast
AngII
angiotensin II
TGF-β
transforming growth factor-β
Smad
mothers against decapentaplegic
amyloid β-protein
AD
Alzheimer’s disease
BDNF
brain-derived neurotrophic factor
VDC
voltage-dependent calcium channel
ROC
receptor-operated calcium channels
GC
guanylate cyclase
GMP
cyclic guanosine monophosphatec
PGI2
prostacyclin 2
ATP
adenosine-triphosphate
COX
cyclooxygenase
ADP
adenosine diphosphate
PAF
platelet activating factor
RBC
red blood cells
GLUT-4
glucose transporter type 4
JAK
Janus kinase
STAT
signal transducer and activator of transcription
PMOP
postmenopausal osteoporosis
RANK
receptor activator of NF-κB
RANKL
RANK ligand
NFATc1
nuclear factor of activated T-cells 1
TRAP
tartrate acid phosphatase
OPG
osteoprotegerin
OC
osteocalcin
ERK
extracellular regulated protein kinases
P38
protein 38
JNK
c-Jun N-terminal kinase
MEK
mitogen-activated protein kinase kinase
RAS
rat sarcoma
Bcl-2
B-cell lymphoma-2
Bax
Bcl-2 associated X protein
PANC-1
pancreatic cancer cell line
ATM
ataxia-telangiectasia mutation
CHK2
checkpoint kinase 2
AST
aspartate transaminase
ALT
alanine aminotransfease
ALI
acute lung injury
LPS
lipopolysaccharide
IκBa
inhibitor of nuclear factor-κB
PXR
progestational hormone X receptor
IBD
inflammatory bowel disease
TLR4
Toll-like receptors 4
TNF-α
tumor necrosis factor-α
IL
interleukin
iNOS
inducible nitric oxide synthase
SMA
smooth muscle actin
EMT
epithelial mesenchymal transformation
ERS
endoplasmic reticulum stress
PKCε
protein kinase C ε
IFN-γ
interferon-γ
DPPH
1,1- diphenyl-2- picrylhydrazyl
ABTS
diammonium 2, 2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate)
RPE
retinal pigment epithelial
HIF-1α
hypoxia inducible factor 1α
GSH
glutathione
MPO
myeloperoxidase
AKI
acute kidney injury
IR
ischemia reperfusion
AMPK
adenosine 5′-monophosphate-activated protein kinase
CAMKK2
recombinant calcium/ calmodulin dependent protein kinase kinase 2
AA
arachidonic acid
HSC
hepatic stellate cells
PAI-1
plasminogen Activator Inhibitor 1
PPAR
peroxisome proliferators-activated receptors
ConA
concanavalin A
AFH
acute fulminant hepatitis
APAP
paracetamol
XO
xanthine oxidase
UA
uric acid
MFS
Miaoyao Fanggan sachet
DCs
dendritic cells
BMDCs
bone marrow-derived dendritic cells
CD
costimulatory molecules
CCR7
chemokine receptor 7
Hlα
alpha hemolysin
S. aureus
Staphylococcus aureus
PGE2
prostaglandin E2
HETE
Hydroxyeicosatetraenoic acid
5-HT
5-hydroxytryptamine
SDTNBI
substructure-drug-target network-based inference
MC1R
melanocortin receptor 1
MITF
microphthalmia associated transcription factor
TYR
tyrosinase
TYRP1
tyrosinase-related protein 1
DCT
dopachrome tautomerase
PPARA
peroxisome proliferative activated receptor alpha
PPARD
peroxisome proliferative activated receptor delta
PPARG
peroxisome proliferative activated receptor gamma
ALOX12
arachidonate 12-lipoxygenase
ALOX15
arachidonate 15-lipoxygenase
CBR1
carbonyl reductase 1
OFI
opuntia ficus-indica
NAFLD
nonalcoholic fatty liver disease
UV
ultraviolet

Keywords

Isorhamnetin
Flavonoids
Effect
Mechanism
Therapy

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1

These authors contributed equally to this work.