(+)-Pinocembrin 5, 7- dihydroxy flavanone) is the most abundant chiral flavonoid found in propolis, exhibiting antioxidant, antimicrobial and anti-inflammatory properties. Pinocembrin inhibits HDC activity and histamine in IgE-sensitized RBL-2H3 in response to dinitrophenol (DNP)-bovine serum albumin (BSA) stimulation. In addition, Pinocembrin mitigated the damage in the mitochondrial membrane, formation of cytoplasmic granules and degranulation as indicated by lower β-hexoseaminidase level[3]. Pinocembrin ameliorates diabetic nephropathy when there is no kidney damage but when it is already present, pinocembrin accelerates kidney damage[4]. Pinocembrin can reduce nerve damage in the ischemic area and reduce mitochondrial dysfunction and the degree of oxidative stress. Pinocembrin can be absorbed rapidly in the body and easily cross the blood-brain barrier. In addition, the absorption/elimination process of pinocembrin occurs rapidly and shows no serious accumulation in the body[5]. In vivo, pinocembrin dose-dependently reduced lesion volume by ∼47.5% and reduced neurologic deficits of mice at 72h after collagenase-induced ICH (intracerebral hemorrhage). The optimal dose of pinocembrin (5mg/kg) suppressed microglial activation as evidenced by decreases in CD68-positive microglia and reduced proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6[6].
Pinocembrin/乔松素 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Primary microglia
1, 3, 10 µM
1 hour pretreatment followed by 24 hours LPS stimulation
Pinocembrin dose-dependently inhibited the secretion of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and reduced NO production in LPS-stimulated primary microglia.
Brain Behav Immun. 2017 Mar;61:326-339.
BV-2 cells
1, 3, 10 µM
1 hour pretreatment followed by 24 hours LPS stimulation
Pinocembrin dose-dependently inhibited the secretion of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and reduced NO production in LPS-stimulated BV-2 cells. Additionally, 10 μM Pinocembrin significantly decreased iNOS expression.
Brain Behav Immun. 2017 Mar;61:326-339.
Keloid fibroblasts
0 to 80 µM
1, 3, 5, 7, and 9 days
To evaluate the effect of pinocembrin on the proliferation of keloid fibroblasts, results showed that pinocembrin dose-dependently inhibited cell proliferation
Biomolecules. 2021 Aug 19;11(8):1240.
SH-SY5Y cells
1.0 µM, 3.0 µM, 10.0 µM
24 hours
To investigate the effect of pinocembrin on cell viability and ROS generation. Results showed that pinocembrin enhanced cell viability but had no significant effect on ROS generation.
BMC Med. 2012 Sep 18;10:105.
U2OS cells
1.0 µM, 3.0 µM, 10.0 µM
24 hours
To investigate the effect of pinocembrin on RAGE expression. Results showed that pinocembrin significantly inhibited the overexpression of RAGE.
BMC Med. 2012 Sep 18;10:105.
BV2 cells
1, 3, 10 µM
24 hours
To evaluate the protective effects of Pinocembrin on BV2 cells treated with intermittent hypoxia (IH). Results showed that Pinocembrin significantly increased cell survival, inhibited NLRP3 inflammasome activation, and enhanced BNIP3-mediated mitophagy.
J Neuroinflammation. 2020 Nov 11;17(1):337.
Y-79 retinoblastoma cells
5 µM
24 hours
Assess the effect of Pinocembrin on TGF-β1-induced invasion and migration abilities of Y-79 cells, showing significant inhibition of invasion and migration
Cell Biosci. 2014 Aug 12;4:41.
Y-79 retinoblastoma cells
0-5 µM
24 hours
Evaluate the cytotoxicity of Pinocembrin on Y-79 cells, showing no cytotoxicity at concentrations ranging from 0-5 μM
Cell Biosci. 2014 Aug 12;4:41.
Mouse primary dermal fibroblasts
20, 40, and 80 µM
24 hours
To evaluate the effect of pinocembrin on TGF-β1-induced proliferation of mouse primary dermal fibroblasts, results showed that pinocembrin significantly inhibited cell proliferation
Biomolecules. 2021 Aug 19;11(8):1240.
SH-SY5Y cells
3, 10, 30 µM
24 hours
To evaluate the protective effect of pinocembrin on SH-SY5Y cells under oxygen-glucose deprivation (OGD) conditions. Results showed that pinocembrin significantly increased the expression levels of Reelin, apoER2, and p-dab1 after OGD injury.
Drug Des Devel Ther. 2020 Sep 4;14:3577-3587.
Cardiac myofibroblasts
25 µM
4 hours
Pinocembrin inhibited collagen secretion and fibrosis
Mol Med. 2021 Sep 6;27(1):100.
Bone marrow macrophages (BMMs)
0, 1, 5, 10, 20, 50 µM
48 hours
Assess the cytotoxicity of PIN on BMMs, showing no significant cytotoxicity at concentrations of 20 μM or lower.
J Orthop Translat. 2024 Mar 27;45:197-210.
Bone marrow macrophages (BMMs)
2.5 and 5 µM
60 minutes
Assess the effect of PIN on RANKL-induced intracellular ROS production, showing a significant reduction in ROS levels.
J Orthop Translat. 2024 Mar 27;45:197-210.
Endothelial cells (ECs)
40 µM
7 days
To evaluate the protective effect of pinocembrin against AGE-induced cytotoxicity. Results showed that pinocembrin restored cell cycle distribution and viability, and significantly reduced AGE-induced oxidative stress.
Cells. 2019 Apr 26;8(5):385.
HUVECs
10, 20, 65 µM
8 hours
To evaluate the effect of Pinocembrin on the ability of HUVECs to form tubular structures. The results showed that Pinocembrin exhibited antiangiogenic activity both in solution and microencapsulated forms.
Transferred to new plates daily until experiment endpoint (e.g., Day 5 for thermal stress, Day 5 for oxidative stress)
Evaluate anti-aging effects of Pinocembrin derivatives (e.g., pb-3): 1) Enhanced thermotolerance and oxidative stress resistance (prolonged median survival time); 2) Reduced lipofuscin accumulation; 3) Decreased intracellular ROS levels; 4) Activated SOD-3 expression and DAF-16 nuclear translocation via DAF-16/FOXO pathway; 5) No lifespan extension in daf-16, hsp-16.2, daf-2, and age-1 mutants, indicating dependency on these genetic pathways.
Drug Des Devel Ther. 2021 Oct 5;15:4177-4193
Wistar rats
Vascular dementia model induced by permanent bilateral common carotid artery ligation
Intravenous injection via tail vein
1, 3, 10 mg/kg
Once daily until the end of the experiment (day 56 post-surgery)
To evaluate the effect of pinocembrin on cognitive function in rats with vascular dementia. Results showed that pinocembrin significantly improved learning and memory deficits, reduced hippocampal neuronal damage, and upregulated the expression of proteins related to the Reelin-dab1 signaling pathway.
Drug Des Devel Ther. 2020 Sep 4;14:3577-3587.
Sprague-Dawley rats
Electrocoagulation-induced thrombotic focal ischemic rat model
Intravenous injection via tail vein
10 mg/kg
Single administration, observed for 24 hours
Pinocembrin significantly decreased the infarct volume, ameliorated t-PA-induced hemorrhagic transformation, and protected the blood-brain barrier. Metabolomics analysis revealed that pinocembrin had significant intervention effects on metabolites significantly altered after t-PA thrombolysis.
Acta Pharmacol Sin. 2021 Aug;42(8):1223-1234
C57BL/6J mice
Chronic unpredictable mild stress (CUMS) model
Oral gavage
10 mg/kg
Once daily for 3 weeks
Pinocembrin alleviated CUMS-induced depressive-like behaviors by ameliorating neuroinflammation and apoptosis.
Mol Med. 2020 May 27;26(1):53
Gallus gallus
Chick chorioallantoic membrane (CAM) model
Direct contact with vascularized region
10, 20, 65 μM
3 days
To evaluate the antiangiogenic activity of Pinocembrin in the chick chorioallantoic membrane model. The results showed that Pinocembrin significantly reduced the number of blood vessels.
Pharmaceutics. 2022 Feb 22;14(3):484.
C57BL/6 mice
Experimental autoimmune encephalomyelitis (EAE) model
Intraperitoneal injection
20 and 40 mg/kg
Daily, starting from the first sign of disease
Pinocembrin significantly ameliorated the disease severity of EAE, reduced the demyelination area and inflammatory cell infiltration.
Neurosci Bull. 2021 Sep;37(9):1314-1324
C57BL/6J mice
OVX-induced osteoporosis model
Intraperitoneal injection
20 mg/kg
Once daily for six weeks
Evaluate the therapeutic effect of PIN on osteoporosis induced by estrogen deficiency, showing significant reductions in serum TRAcP and CTX-1 levels and improvements in bone microstructure and biomechanical properties.
J Orthop Translat. 2024 Mar 27;45:197-210.
Kunming mice
Aβ25-35-induced Alzheimer's disease model
Oral
20 mg/kg, 40 mg/kg
Once daily for 8 days
To investigate the effect of pinocembrin on cognitive function and neuronal protection. Results showed that pinocembrin improved cognitive function, preserved the ultrastructural neuropil and decreased neurodegeneration of the cerebral cortex.
BMC Med. 2012 Sep 18;10:105.
C57BL/6 mice
Bleomycin-induced skin fibrosis model
Intradermal injection
20, 40, and 80 μM
Once daily for 3 weeks
To evaluate the effect of pinocembrin on bleomycin-induced skin fibrosis, results showed that pinocembrin significantly alleviated skin fibrosis
Biomolecules. 2021 Aug 19;11(8):1240.
C57BL/6J mice
Intermittent hypoxia (IH) model
Intraperitoneal injection
40 mg/kg
Every 2 days for 21 days
To evaluate the protective effects of Pinocembrin on intermittent hypoxia (IH)-induced neuroinflammation and cognitive dysfunction. Results showed that Pinocembrin significantly improved spatial learning and memory ability, reduced neuronal apoptosis and hippocampal inflammation, and enhanced BNIP3-mediated mitophagy.
J Neuroinflammation. 2020 Nov 11;17(1):337.
C57BL/6 mice
Collagenase-induced ICH model
Intravenous injection via tail vein
5 mg/kg
Starting at 2 h after ICH, twice daily until euthanasia
Pinocembrin dose-dependently reduced lesion volume (47.5% reduction at 5 mg/kg), ameliorated neurologic deficits, and reduced brain edema. Additionally, Pinocembrin suppressed microglial activation, decreased proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and reduced the number of M1-like microglia.
Brain Behav Immun. 2017 Mar;61:326-339.
Sprague-Dawley rats
Post-infarct heart failure model
Intravenous injection
5 mg/kg
Every other day for 2 weeks
Pinocembrin improved cardiac function and remodeling by activating Nrf2/HO-1 signaling pathway, reducing fibrosis and apoptosis, and promoting angiogenesis
Mol Med. 2021 Sep 6;27(1):100.
Sprague-Dawley rats
Chronic ischaemic heart failure model
Tail vein injection
5 mg/kg
Daily for 2 months
Pinocembrin ameliorated arrhythmias in rats with chronic ischaemic heart failure, reduced the incidence and duration of ventricular fibrillation, and improved cardiac autonomic nerve remodeling.
Ann Med. 2021 Dec;53(1):830-840
Sprague-Dawley rats
Anxiety disorder model induced by empty bottle stimulation
Tail vein injection
5 mg/kg
Daily administration for the last 2 weeks
Pinocembrin significantly improved anxiety-like behaviors, alleviated electrophysiological and structural remodeling, and reduced AF susceptibility
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