Monoamine oxidase (MAO) is an important enzyme in the metabolism of a wide range of endogenous monoamine neurotrasmitters such as noradrenaline, dopamine, and serotonin (5-HT), and also catalyzes as well the removal of exogenous amines. Paeonol, originated from the traditional Chinese medicine, is a naturally occuring MAO inhibitor with IC50 values of 54.6 μM and 42.5 μM for MAO-A and MAO-B, respectively[7]. Paeonol dose- and time- dependently induced not only antiproliferation activity and apoptosis but also autophagy via blocking the Akt/mTOR pathway in A2780 and SKOV3 cells. In addition, combination treatment with Paeonol and an autophagy inhibitor (3-methyladenine and hydroxychloroquine) showed significant synergetic effects on inhibiting cell viability and promoting apoptosis in vitro and in the A2780 xenograft model, without severe side effects[8]. Paeonol at 50 and 100μM prevented IL-1β-induced inflammatory response by inhibiting numerous factors of osteoarthritis(OA), including IL-6, TNF-a, NOX2, PTGS2, NUCB2/nesfatin-1, ICAM-1, VCAM-1, MMP-3/13, degradation of type II collagen, and NF-kB activation through the rescue of IkBa in human primary chondrocytes[9].
Paeonol/丹皮酚 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HCT116 cells
7.8125, 15.625, 31.25, 62.5, 125, 250 and 500 µg/ml
12, 24, 48 and 72 hours
To assess the inhibitory effect of Paeonol on HCT116 cell viability, the results showed that Paeonol significantly inhibited the proliferation of HCT116 cells in a dose- and time-dependent manner.
Int J Mol Med. 2020 Aug;46(2):675-684.
SKOV3 cells
1.2 mM
24 and 48 hours
To evaluate the inhibitory effect of Paeonol on cell proliferation, results showed that Paeonol significantly inhibited the proliferation of SKOV3 cells.
Cell Death Dis. 2019 Aug 13;10(8):609.
A2780 cells
1.2 mM
24 and 48 hours
To evaluate the inhibitory effect of Paeonol on cell proliferation, results showed that Paeonol significantly inhibited the proliferation of A2780 cells.
Cell Death Dis. 2019 Aug 13;10(8):609.
NSC-34/hSOD1G93A (MT)
100 µM
24 hours
Evaluate the protective effect of Paeonol against glutamate, LPS, and H2O2-induced cytotoxicity, results showed Paeonol significantly improved cell viability
Antioxidants (Basel). 2022 Jul 18;11(7):1392.
NSC-34/hSOD1WT (WT)
100 µM
24 hours
Evaluate the protective effect of Paeonol against glutamate, LPS, and H2O2-induced cytotoxicity, results showed Paeonol significantly improved cell viability
Antioxidants (Basel). 2022 Jul 18;11(7):1392.
Cardiomyocytes
50 µM
24 hours
Paeonol promotes Mfn2-mediated mitochondrial fusion, restores mitochondrial function and cell viability, and inhibits Dox-induced cardiomyocyte apoptosis and oxidative stress.
J Adv Res. 2023 May;47:151-162.
Primary microglial cells
0.5 to 1 mM
24 hours
Paeonol inhibited lipopolysaccharide-induced nitrite release and reduced the secretion of tumor necrosis factor-alpha and interleukin-1β.
Neural Regen Res. 2013 Jun 25;8(18):1637-43.
RAW 264.7 cells
25, 50 µM
24 hours
Evaluate the effect of paeonol on LPS-induced MAPK protein expression in RAW 264.7 cells. Results showed that paeonol significantly reduced the protein expression levels of COX-2 and NF-κB and affected the phosphorylation of p-p38.
Biomolecules. 2022 Nov 3;12(11):1634.
RAW 264.7 cells
6.3, 12.5, 25, 50 µM
24 hours
Evaluate the effect of paeonol on LPS-induced IL-6 and TNF-α production in RAW 264.7 cells. Results showed that paeonol inhibited the release of IL-6 and TNF-α in a concentration-dependent manner.
Biomolecules. 2022 Nov 3;12(11):1634.
GMI-R1 cells
4 µM
24 hours
Paeonol promotes the transformation of LPS-treated GMI-R1 microglia from the M1 phenotype to the M2 phenotype.
CNS Neurosci Ther. 2023 Sep;29(9):2666-2679.
Human primary umbilical vein endothelial cell (HUVEC)
10 µM
24 hours
To evaluate the effect of Paeonol on HUVEC cell viability, results showed that Paeonol treatment significantly enhanced HUVEC viability.
Drug Des Devel Ther. 2023 May 24;17:1567-1582.
Aspergillus flavus
0.625 mg/mL
24 hours
Paeonol significantly destroyed both the outer amorphous layer and the inner fibrous layer of A. flavus cell walls, leading to thinner cell walls and chaotic cytoplasm.
Foods. 2021 Dec 1;10(12):2951.
Human umbilical vein/vascular endothelial cell line (HUVEC-C)
10 µM
24 hours, 48 hours, 72 hours
To evaluate the effect of Paeonol on HUVEC-C cell numbers, results showed that Paeonol treatment significantly increased cell numbers.
Drug Des Devel Ther. 2023 May 24;17:1567-1582.
RAW264.7 macrophages
32, 64, 128 µg/mL
3 hours pretreatment or 4 hours treatment
To assess the anti-infection activity and mechanism of paeonol against P. aeruginosa infection in vitro, results showed paeonol downregulated the expression of QS-related virulence genes and reduced PAO1-induced cell damage
Front Immunol. 2022 May 24;13:896874.
BV-2 microglial cells
10 or 30 µM
30 min pretreatment followed by 24 hours stimulation
To investigate the effects of Paeonol on ATP-induced cell migratory activity. Results showed that Paeonol effectively reduced ATP-enhanced migratory activity.
Int J Mol Sci. 2015 Apr 21;16(4):8844-60.
BV-2 microglial cells
3, 10, or 30 µM
30 min pretreatment followed by 24 hours stimulation
To investigate the inhibitory effects of Paeonol on LPS/IFN-γ-induced inflammatory responses. Results showed that Paeonol significantly inhibited the release of NO and the expressions of iNOS and COX-2.
Int J Mol Sci. 2015 Apr 21;16(4):8844-60.
Primary cardiomyocytes
25, 50, 100, 200 µM
48 hours
To evaluate the effects of Paeonol on mitochondrial fusion and function in high glucose-treated cardiomyocytes. Results showed that 100 μmol/L Paeonol significantly increased mitochondrial volume, decreased mitochondrial number, inhibited mitochondrial oxidative stress, and improved ATP production and mitochondrial respiratory capacity.
Redox Biol. 2021 Oct;46:102098.
SW1353 cells
3, 10, 30 µM
48 hours
Evaluate the effect of Paeonol on the viability of SW1353 cells, showing no effect on cell viability at 3–30 μM
Int J Mol Sci. 2014 Jul 2;15(7):11760-72.
JJ012 cells
3, 10, 30 µM
48 hours
Evaluate the effect of Paeonol on the viability of JJ012 cells, showing no effect on cell viability at 3–30 μM
Int J Mol Sci. 2014 Jul 2;15(7):11760-72.
NSC-34/hSOD1G93A (MT)
347 nM
5 min
Evaluate the uptake characteristics of [3H]Paeonol, results showed time-, concentration-, and pH-dependent uptake
Antioxidants (Basel). 2022 Jul 18;11(7):1392.
NSC-34/hSOD1WT (WT)
347 nM
5 min
Evaluate the uptake characteristics of [3H]Paeonol, results showed time-, concentration-, and pH-dependent uptake
Antioxidants (Basel). 2022 Jul 18;11(7):1392.
RAW 264.7 cells
6.3, 12.5, 25, 50 µM
6 hours
Evaluate the effect of paeonol on LPS-induced mRNA expression of IL-6, IL-1β, and TNF-α in RAW 264.7 cells. Results showed that paeonol reduced the mRNA expression levels of these inflammatory cytokines in a concentration-dependent manner.
Biomolecules. 2022 Nov 3;12(11):1634.
Organotypic hippocampal slice cultures
0.5 and 1 mM
72 hours
Paeonol pretreatment markedly blocked lipopolysaccharide-induced hippocampal cell death and inhibited the release of nitrite and interleukin-1beta.
Neural Regen Res. 2013 Jun 25;8(18):1637-43.
3T3-L1 cells
1000 µM
8 days
Paeonol inhibits the differentiation of 3T3-L1 cells into mature adipocytes and reduces lipid accumulation.
Nutrients. 2020 Jan 24;12(2):309.
Paeonol/丹皮酚 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
ICR mice
LPS-induced neuroinflammation model
Intraperitoneal injection
10 or 30 mg/kg
Once daily for three consecutive days, followed by a single LPS injection
To investigate the effects of Paeonol on LPS-induced motor coordination dysfunction and microglial activation. Results showed that Paeonol significantly improved motor coordination in LPS-injected mice and reduced microglial activation.
Int J Mol Sci. 2015 Apr 21;16(4):8844-60.
Sprague-Dawley rats
Chronic constrictive injury (CCI) model
Intragastric administration
100 mg/kg
Twice daily for 21 days
Paeonol alleviates neuropathic pain by modulating microglial M1 and M2 polarization via the RhoA/p38MAPK signaling pathway.
CNS Neurosci Ther. 2023 Sep;29(9):2666-2679.
Wistar rats
Hepatic ischemia/reperfusion injury model
Oral
100 mg/kg
Once daily for 7 days
To evaluate the protective effect of paeonol against hepatic ischemia/reperfusion injury, results showed that paeonol attenuated liver injury by inhibiting oxidative stress, inflammation, and apoptosis.
Antioxidants (Basel). 2022 Aug 29;11(9):1687
Sprague-Dawley rats
Dox-induced cardiotoxicity model
Oral gavage
150 mg/kg
Once daily for two weeks
Paeonol activates the PKCε-Stat3-Mfn2 signaling pathway to promote mitochondrial fusion, alleviating Dox-induced cardiotoxicity and myocardial injury.
J Adv Res. 2023 May;47:151-162.
BALB/c mice
IMQ-induced psoriasis-like skin inflammation model
Oral
20 mg/kg and 40 mg/kg
Once daily for 7 days
To evaluate the therapeutic effect of compound B12 on IMQ-induced psoriasis-like skin inflammation. Results showed that compound B12 significantly alleviated skin inflammation symptoms and PASI score.
J Orthop Translat. 2024 Nov 24;50:1-13
BALB/c mice
IMQ-induced psoriasis-like skin inflammation model
Oral
20 mg/kg and 40 mg/kg
Once daily for 7 days
To evaluate the therapeutic effect of compound B12 on IMQ-induced psoriasis-like skin inflammation. Results showed that compound B12 significantly alleviated skin inflammation symptoms and PASI score.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):817-831
SPF mice
PAO1 acute infection model
Intragastric administration
25, 50, 100 mg/kg
3 consecutive days
To evaluate the anti-infection activity of paeonol in vivo, results showed paeonol decreased the bacterial load in the lung and inhibited the mRNA expression of inflammation cytokines
Front Immunol. 2022 May 24;13:896874.
BALB/c mice
Lincomycin-induced antibiotic-associated diarrhea model
Oral
25, 50, 100 mg/kg
Twice daily for 7 days
Evaluate the effect of paeonol on lincomycin-induced diarrhea in mice. Results showed that paeonol significantly improved diarrhea symptoms, reduced weight loss and water intake, and decreased serum levels of TNF-α and IL-4.
Biomolecules. 2022 Nov 3;12(11):1634.
ApoE−/− mice
Murine carotid artery catheter guide wires injury model
Intraperitoneal injection
30 mg/kg
Pretreated for 7 consecutive days, continued treatment after surgery until tissue collection
To evaluate the effect of Paeonol on vascular stenosis after vascular injury, results showed that Paeonol treatment significantly suppressed vascular neointima formation.
Drug Des Devel Ther. 2023 May 24;17:1567-1582.
BALB/c nude mice
A2780 xenograft model
Intraperitoneal injection
40 mg/kg
Once every 2 days, total of 6 times (12 days)
To evaluate the antitumor activity of Paeonol in vivo, results showed that Paeonol significantly inhibited tumor growth, and the effect was enhanced when combined with the autophagy inhibitor HCQ.
Cell Death Dis. 2019 Aug 13;10(8):609.
Sprague-Dawley rats
Diabetic cardiomyopathy model
Oral gavage
75, 150, 300 mg/kg
Once daily for 12 weeks
To evaluate the protective effects of Paeonol on diabetic cardiomyopathy. Results showed that Paeonol (150 or 300 mg/kg/day) significantly improved cardiac function, reduced myocardial hypertrophy and fibrosis, inhibited cardiomyocyte apoptosis and oxidative stress, and promoted mitochondrial fusion and functional recovery.
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