Pinocembrin

Pinocembrin inhibits lipopolysaccharide-induced inflammatory mediators production in BV2 microglial cells through suppression of PI3K/Akt/NF-κB pathway.[Pubmed: 26049009]

Eur J Pharmacol. 2015 Jun 3;761:211-216.

Pinocembrin, one of the primary flavonoids from Pinus heartwood and Eucalyptus, has been reported to have anti-inflammatory and antioxidant activity.
METHODS AND RESULTS:
This study was designed to evaluate the inhibitory effects of Pinocembrin on inflammatory mediators production in LPS-stimulated BV2 microglial cells. The results showed that Pinocembrin dose-dependently inhibited LPS-induced inflammatory mediators TNF-α, IL-1β, NO and PGE2 production. Pinocembrin also inhibited LPS-induced iNOS and COX-2 expression. Moreover, Pinocembrin inhibited LPS-induced PI3K, Akt phosphorylation, and NF-κB activation, which were required for inflammatory mediators production. Furthermore, treatment of Pinocembrin induced nuclear translocation of Nrf2 and expression of HO-1.
CONCLUSIONS:
In conclusion, our data indicated that Pinocembrin inhibited LPS-induced inflammatory mediators production by suppressing PI3K/Akt/NF-κB signaling pathway.

Pinocembrin: An antifungal compound secreted by leaf glands of eastern cottonwood.[Reference: WebLink]

Phytopathology, 1982, 72(7):877-80.

Pinocembrin: An antifungal compound secreted by leaf glands of eastern cottonwood

Pinocembrin attenuates hippocampal inflammation, oxidative perturbations and apoptosis in a rat model of global cerebral ischemia reperfusion.[Pubmed: 25560584]

Pharmacol Rep. 2015 Feb;67(1):115-22.

Pinocembrin is a major flavonoid molecule isolated from honey and propolis. It has versatile pharmacological and biological activities including antimicrobial, anti-inflammatory, antioxidant, and anticancer activities as well as neuroprotective effects against cerebral ischemic injury. The purpose of the current study was to determine the possible mechanisms of neuroprotection elicited by Pinocembrin with specific emphasis on chronic prophylactic use before the induction of global cerebral ischemia reperfusion.
METHODS AND RESULTS:
Global cerebral ischemia-reperfusion (I/R) was induced by bilateral carotid artery occlusion for 15min followed by 60min reperfusion period. Animals were randomly allocated into 3 groups (n=28): Sham operated, I/R control and rats treated with Pinocembrin (10mg/kg, po) daily for 7 days then I/R was induced 1h after the last dose of Pinocembrin. After reperfusion rats were killed by decapitation, brains were removed and both hippocampi separated and the following biochemical parameters were estimated; lactate dehydrogenase activity, oxidative stress markers (lipid peroxides, nitric oxide and reduced glutathione), inflammatory markers (myeloperoxidase, tumor necrosis factor-alpha, nuclear factor kappa-B, interleukin-6 and interleukin-10), apoptotic biomarkers (caspase 3 and cytochrome C), neurotransmitters (glutamate, gamma aminobutyric acid) and infarct size were assessed. Pinocembrin ameliorated damage induced by I/R through suppressing oxidative stress, inflammatory and apoptotic markers as well as mitigating glutamate and lactate dehydrogenase activity. One of the more significant findings to emerge from this study is that Pinocembrin normalized the infarct size elevated by I/R.
CONCLUSIONS:
Pinocembrin showed a neuroprotective effects through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Pinocembrin protects the brain against ischemia-reperfusion injury and reverses the autophagy dysfunction in the penumbra area.[Pubmed: 25271424]

Molecules. 2014 Sep 30;19(10):15786-98.

The aim of this study was to investigate the effects of Pinocembrin on brain ischemia/reperfusion (I/R) injury and the potential involvement of autophagy activity changes in the penumbra area in the mechanisms of Pinocembrin activity.
METHODS AND RESULTS:
Focal cerebral I/R model was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by 24 h reperfusion. Pinocembrin was administered intravenously at different doses (1, 3, and 10 mg/kg, respectively) at the onset of reperfusion. Neurological function, brain infarction and brain swelling ratio were evaluated. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and immunohistochemical analysis (Caspase-3) were used to evaluate apoptosis in the penumbra cortex. Two key proteins of autophagy, LC3B and Beclin1, were detected by western blot. The results showed that Pinocembrin-treatment could significantly reduce neurological deficit scores, infarct volume, cerebral edema and improve pathological lesion in the I/R rats. Pinocembrin-treatment could also reduce the number of TUNEL-positive and Caspase-3-positive neurons, and upregulate the expression of LC3B and Beclin1 in penumbra area.
CONCLUSIONS:
These results suggested that Pinocembrin could protect the brain against I/R injury, and the possible mechanisms might be attributed to inhibition of apoptosis and reversed autophagy activity in penumbra area.

Pinocembrin suppresses TGF-β1-induced epithelial-mesenchymal transition and metastasis of human Y-79 retinoblastoma cells through inactivating αvβ3 integrin/FAK/p38α signaling pathway.[Pubmed: 25949790]

Cell Biosci. 2014 Aug 12;4:41.

Pinocembrin is the most abundant flavonoid in propolis. In this study, we investigated the antimetastatic effect of Pinocembrin on TGF-β1-induced epithelial-mesenchymal transition (EMT) and metastasis of human Y-79 retinoblastoma cells.
METHODS AND RESULTS:
Firstly, the results showed that Pinocembrin significantly suppresses the TGF-β1-induced abilities of the invasion and migration of Y-79 cells under non-cytotoxic concentration. Pinocembrin decreased TGF-β1-induced expression of vimentin, N-cadherin, αv and β3 integrin in Y-79 cells. Molecular data also showed Pinocembrin inhibits the activation of focal adhesion kinase (FAK) and p38α signal involved in the downregulation of enzyme activities, protein and messenger RNA levels of matrix metalloproteinase-2/9 (MMP-2/-9) induced by TGF-β1. Next, Pinocembrin also strongly inhibited the degradation of inhibitor of kappaBα (IκBα) and the nuclear levels of nuclear factor kappa B (NF-κB). Also, a dose-dependent inhibition on the binding ability of NF-κB was further observed under Pinocembrin treatment.
CONCLUSIONS:
Presented results indicated that Pinocembrin inhibits TGF-β1-induced epithelial-mesenchymal transition (EMT) and metastasis of Y-79 cells by inactivating the αvβ3 integrin/FAK/p38α signaling pathway. Thus, our findings point to the anticancer potential of Pinocembrin against retinoblastoma cells.

Pinocembrin improves cognition and protects the neurovascular unit in Alzheimer related deficits.[Pubmed: 24468471]

Neurobiol Aging. 2014 Jun;35(6):1275-85.

Amyloid-β (Aβ) peptides accumulate in the brain and initiate a cascade of pathologic events in Alzheimer's disease. The receptor for advanced glycation end products (RAGE) has been implicated to mediate Aβ-induced perturbations in the neurovascular unit (NVU). We demonstrated that Pinocembrin exhibits neuroprotection through inhibition of the Aβ and/or RAGE pathway, but the therapeutic role and mechanism involved are not ascertained.
METHODS AND RESULTS:
Here, we report that a 3-month treatment with Pinocembrin prevents the cognition decline in APP/PS1 transgenic mice without altering Aβ burden and oxidative stress. Instead, Pinocembrin is effective in conferring neurovascular protection through maintenance of neuropil ultrastructure, reduction of glial activation and levels of inflammatory mediators, preservation of microvascular function, improving the cholinergic system by conserving the ERK-CREB-BDNF pathway, and modulation of RAGE-mediated transduction. Furthermore, in an in vitro model, Pinocembrin provides the NVU protection against fibrillar Aβ????, accompanied by regulation of neurovascular RAGE pathways.
CONCLUSIONS:
Our findings indicate that Pinocembrin improves cognition, at least in part, attributable to the NVU protection, and highlights Pinocembrin as a potential therapeutic strategy for the prevention and/or treatment of Alzheimer's disease.