PMID: 

Biotech Histochem. 2019 Jan ;94(1):10-25. Epub 2018 Aug 13. PMID: 30101628

Abstract Title: 

Paeonol exhibits anti-tumor effects by apoptotic and anti-inflammatory activities in 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis.

Abstract: 

We investigated the preventive potential of paeonol on 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis. Oral tumors were developed in the buccal pouches of Syrian golden hamsters using topical application of 0.5% DMBA three times/week for 10 weeks. DMBA treated hamsters developed hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. The animals also exhibited increased lipid oxidation, decreased antioxidant status and altered levels of detoxification agents. Paeonol treatment of DMBA treated hamsters for 14 weeks decreased tumor incidence, volume and burden Paeonol treatment also increased antioxidant activity and decreased lipid oxidation to near normal levels. Histomorphology and the expression patterns of mutant p53, cyclo-oxygenase (COX-2) and caspase-9 were investigated in the oral buccal mucosa. Paeonolexhibited protective effects against DMBA induced oral carcinogenesis owing to its antitumor, antioxidant, anti-inflammatory and apoptosis inducing properties.

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PMID: 

Evid Based Complement Alternat Med. 2018 ;2018:3063145. Epub 2018 Aug 15. PMID: 30186353

Abstract Title: 

Paeonol Ameliorates Ovalbumin-Induced Asthma through the Inhibition of TLR4/NF-B and MAPK Signaling.

Abstract: 

Asthma is a chronic inflammatory disease of the airways, with complex signaling pathways involved in its pathogenesis. It was reported that paeonol attenuated airway inflammation of ovalbumin (OVA)-induced mice. Therefore, it is of importance to further investigate the underlying mechanism. BALB/c mice were challenged with OVA for the asthma model, which was validated by the changed levels of IL-4, IFN-, and IgE. The elevation of IL-4 and the decreasing of IFN-were significantly in middle (p

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PMID: 

Biochimie. 2019 Jan ;156:129-137. Epub 2018 Sep 10. PMID: 30213522

Abstract Title: 

Paeonol attenuates ligation-induced periodontitis in rats by inhibiting osteoclastogenesis via regulating Nrf2/NF-κB/NFATc1 signaling pathway.

Abstract: 

Paeonol is a natural phenolic compound in Moutan Cortex with multiple biological functions, such as anti-inflammatory and anti-oxidant activity. Recent evidence has proven that persistent inflammation, oxidative stress, along with nuclear factor E2-related factor 2 (Nrf2) signaling dysfunction in periodontium are the possible causes of alveolar bone resorption, and ultimately lead to periodontitis. The present study was designed to explore the protective effects of paeonol on ligation-induced periodontitis in rats, and investigate the possible mechanism. We found that treatment with paeonol (40, 80 mg/kg, intraperitoneal injection) for 7 days remarkably decreased the expression of receptor activator of nuclear factor kappa-B ligand increased the expression of osteoprotegrin and inhibited the formation of osteoclasts. This function of paeonol might be correlated with its ability to reduce inflammatory factors (IL-1β, IL-6 and TNF-α) and alleviate oxidative stress (SOD, MDA, GSH and ROS) in gingival tissues. Besides, paeonol increased Nrf2 activity. Silence of Nrf2 using specific siRNA diminished the inhibitory effect of paeonol on NF-κB p65 activation and downstream expression, suggesting that Nrf2 was essential for protective effect of paeonol. These results showed that paeonol protected against periodontitis-aggravated osteoclastogenesis and alveolar bone lesion via regulating Nrf2/NF-κB/NFATc1 signaling pathway.

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PMID: 

Hum Exp Toxicol. 2019 May ;38(5):510-518. Epub 2018 Dec 24. PMID: 30580614

Abstract Title: 

Mechanisms underlying gastroprotective effect of paeonol against indomethacin-induced ulcer in rats.

Abstract: 

Paeonol, a natural phenolic compound, possesses diverse beneficial effects including antioxidant and anti-inflammatory effects. Gastric ulcer is still the most prevalent irritant illness among the gastrointestinal diseases. The present study explored the protective effect of paeonol at two dose levels in indomethacin (IND)-induced gastric ulcer in rats. Forty-eight male Wistar rats were arranged into six groups: control, paeonol-treated, IND-treated, IND/paeonol (low and high doses)-treated, and ranitidine-treated groups. The oxidative status was evaluated by determining malondialdehyde level, superoxide dismutase activity, reduced glutathione content as well as hemoxygenase-1 (HO-1) gene expressions, and the antioxidant protein; NAD(P)H quinone oxidoreductase 1 (NQO1) immunostaining. The pro-inflammatory genes nuclear factorκB (NF-κB) and interleukin 1β (IL-1β) were estimated together with the proapoptotic gene of caspase 3. IND caused multiple gastric ulcers with evident oxidative damage and elevated pro-inflammatory and proapoptotic markers. Paeonol protected significantly, in a dose-dependent manner, the gastricmucosa from ulcerative lesion of IND similar to the reference drug ranitidine. Paeonol pretreatment diminished gastric oxidative stress and restored the gastric antioxidant capacity by elevating gastric gene expression of HO-1 and protein expression of NQO1. Paeonol also reduced NF-κB, IL-1β, andcaspase 3 gene expressions. In conclusion, paeonol offered a gastroprotection dependent on its antioxidant, anti-inflammatory, and antiapoptotic effects.

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PMID: 

Front Pharmacol. 2018 ;9:1105. Epub 2018 Nov 20. PMID: 30515094

Abstract Title: 

Paeonol Attenuated Inflammatory Response of Endothelial Cells via Stimulating Monocytes-Derived Exosomal MicroRNA-223.

Abstract: 

Paeonol, an active compound isolated from the radix of, has been shown to have anti-atherosclerosis effects by regulating blood cells' function and protecting vascular cells injury. Besides, emerging evidences has proven that exosomes might play a pivotal role in intercellular communication by transmiting proteins and microRNAs from cell to cell. However, the relationship between monocytes-derived exosomal microRNA-223 and vascular inflammation injury along with paeonol' effects are still not clear.Our study aimed to explain whether paeonol's protective effect on inflammatory response is related to the regulation of exosomal microRNA-223 in the VECs.ApoEmice were fed with high fat diet to replicate the AS model. HE staining and immunohistochemistry was used to detect inflammatory response of aorta. The expression of IL-1β and IL-6 were detected by ELISA. Western blot was used to detect the expression of STAT3, pSTAT3, ICAM-1 and VCAM-1. qRT-PCR was used to detect miR-223 expression. Exosomes were extracted from THP-1 cells by differential centrifugation and observed by transmission electron microscope. Observationof exosomes uptake into HUVECs was realized by laser microscopy. miR-223 target gene was detected by double luciferase gene report test.experiments confirmed that paeonol restricted atherosclerosis development and increased miR-223 expression, inhibited STAT3 pathway in ApoEmice., miR-223 showed robust presence in THP-1 cells and undetectable in HUVECs. And we had observed that miR-223 could be internalized from THP-1 cells into HUVECs taking exosomes as a carrier. Paeonol obviously increased miR-223 expression in co-cultured HUVECs and exosomes in concentration dependent manner, compared to LPS group. In addition, paeonol relieved inflammatory secretion, adhesion and STAT3 expression in HUVECs, which could be inverted after miR-223 inhibitor transfection into THP-1 cells.Paeonol could increase the expression of miR-223 in THP-1 derived exosomes and in HUVECs after uptake of exosomes, whereas decrease the expression of STAT3, p-STAT3 in HUVECs. Ultimately paeonol decreased the expression of IL-1β, IL-6, ICAM-1, VCAM-1 in HUVECs and alleviated adhesion of THP-1 cells to HUVECs.

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PMID: 

Oxid Med Cell Longev. 2018 ;2018:1098617. Epub 2018 Nov 7. PMID: 30524649

Abstract Title: 

Beneficial Effects Exerted by Paeonol in the Management of Atherosclerosis.

Abstract: 

Atherosclerosis, a chronic luminal stenosis disorder occurred in large and medium arteries, is the principle pathological basis of cardiovascular diseases with the highest morbidity and mortality worldwide. In oriental countries, traditional Chinese medicine Cortex Moutan has been widely used for the treatment of atherosclerosis-related illnesses for thousands of years. Paeonol, a bioactive monomer extracted from Cortex Moutan, is an important pharmacological component responsible for the antiatherosclerotic effects. Numerous lines of findings have established that paeonol offers beneficial roles against the initiation and progression of atherosclerotic lesions through inhibiting proatherogenic processes, such as endothelium damage, chronic inflammation, disturbance of lipid metabolism, uncontrolled oxidative stress, excessive growth, and mobilization of vascular smooth muscle cells as well as abnormality of platelet activation. Investigations identifying the atheroprotective effects of paeonol present substantial evidence for potential clinical application of paeonol as a therapeutic agent in atherosclerosis management. In this review, we summarize the antiatherosclerotic actions by which paeonol suppresses atherogenesis and provide newly insights into its atheroprotective mechanisms and the future clinical practice.

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PMID: 

Oncol Lett. 2019 Feb ;17(2):1761-1767. Epub 2018 Nov 19. PMID: 30675235

Abstract Title: 

Paeonol-mediated apoptosis of hepatocellular carcinoma cells by NF-κB pathway.

Abstract: 

The aim of the study was to investigate the effect of paeonol on the apoptosis of hepatocellular carcinoma cells and to explore the possible mechanism of its effect. During the experiment, the human hepatoma (Huh7) cell line was cultured and treated with different concentrations of paeonol. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the effects of paeonol at different concentrations on the proliferation of Huh7 cells after 24 h, and the optimal concentration of paeonol was selected for follow-up experiments. Huh7 cells were divided into the blank control group (C group), parthenolide [(an inhibitor of nuclear factorκ-light-chain-enhancer of activated B cells (NF-κB)] group (CE group), paeonol group (PO group), and paeonol + tumor necrosis factor-α (TNF-α) (an activator of NF-κB) group (PN group). The effect of paeonol on the apoptosis of Huh7 cells was detected via flow cytometry and Hoechst staining, respectively. The expression levels of NF-κB and protein apoptosis inhibitor-5 (p-API-5) were detected by semi-quantitative polymerase chain reaction (PCR) and western blot analysis, respectively, and the activity of NF-κB in cells was measured by NF-κB p65/50. After determination of the effects ofpaeonol at different concentrations on Huh7 cells by MTT assay, it was found that paeonol at the concentration of 200-800 µM could inhibit the proliferation of Huh7 cells (P

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PMID: 

Pharmazie. 2019 02 1 ;74(2):101-106. PMID: 30782259

Abstract Title: 

Paeonol ameliorates lipopolysaccharides-induced acute lung injury by regulating TLR4/MyD88/ NF-κB signaling pathway.

Abstract: 

Paeonol has been found to hold analgesic, antipyretic and anti-allergic activities. Here, we investigated the protective effect of paeonol on acute lung injury (ALI) induced by lipopolysaccharides (LPS) and explored the underlying mechanisms on TLR4/MyD88/NF-κB signaling pathway. C57BL/6 mice were randomly divided into control (normal saline, NS, 0.2 mL/d), LPS (NS, 0.2 mL/d), LPS + dexamethasone (DXMS) (5 mg/kg/d), LPS + paeonol (50, 25, 12.5 mg/kg/d) groups. The results of the lung tissue scores scale and HE staining showed that paeonol could attenuate the infiltration of inflammatory cells and the thickening of alveolar wall significantly. The result of W/D ratio showed that paeonol could also prevent pulmonary edema, as well as inhibit significantly the levels of TNF-α, IL-1β and IL-6 in serum and proteins expression and mRNA. In addition,paeonol can also downregulate the expression or phosphorylation of TLR4, MyD88 and NF-κB. In general, our findings showed that the protective effect of paeonol on LPS-induced ALI by regulating TLR4/MyD88/NF-κB signaling pathway. This study provides evidence for the application of paeonol in treating ALI.

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PMID: 

Front Pharmacol. 2019 ;10:261. Epub 2019 Mar 19. PMID: 30941042

Abstract Title: 

Paeonol Ameliorates Glucose and Lipid Metabolism in Experimental Diabetes by Activating Akt.

Abstract: 

Our previous study proved that paeonol (Pae) could lower blood glucose levels of diabetic mice. There are also a few reports of its potential use for diabetes treatment. However, the role of Pae in regulating glucose and lipid metabolism in diabetes remains largely unknown. Considering the critical role of serine/threonine kinase B (Akt) in glucose and lipid metabolism, we explored whether Pae could improve glucose and lipid metabolism disorders via Akt. Here, we found that Pae attenuated fasting blood glucose, glycosylated serum protein, serum cholesterol and triglyceride (TG), hepatic glycogen, cholesterol and TG in diabetic mice. Moreover, Pae enhanced glucokinase (GCK) and low-density lipoprotein receptor (LDLR) protein expressions, and increased the phosphorylation of Akt. In insulin-resistant HepG2 cells, Pae increased glucose uptake and decreased lipid accumulation. What's more, Pae elevated LDLR and GCK expressions as well as Akt phosphorylation, which was consistent with theresults. Knockdown and inhibition experiments of Akt revealed that Pae regulated LDLR and GCK expressions through activation of Akt. Finally, molecular docking assay indicated the steady hydrogen bond was formed between Pae and Akt2. Experiments above suggested that Pae ameliorated glucose and lipid metabolism disorders and the underlying mechanism was closely related to the activation of Akt.

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PMID: 

Immunopharmacol Immunotoxicol. 2019 Jun ;41(3):438-445. Epub 2019 May 23. PMID: 31119954

Abstract Title: 

Paeonol alleviates CCl-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-β/Smad3 signaling.

Abstract: 

Paeonol is a natural phenolic component isolated from the root bark of peony with multiple pharmacological activities. We investigated the anti-fibrotic effect and underlying mechanism of paeonol.Twenty-four male C57BL/6J mice were divided into 4 groups ( = 6 in each group), injected with CClto induce liver fibrosis and administrated with paeonol according to the regimen. The serum activity of ALT and AST, and H&E staining were to assess liver injury. Sirius and Masson staining, and hydroxyproline content were to evaluate the degree of liver fibrosis. TNF-α, IL-6, TGF-β, MDA, GSH-PX, SOD, and CAT were detected to reflect inflammation and oxidative stress. RT-qPCR and Western blot analysis to assess the activation of HSCs and TGF-β/Smad3 signaling.Paeonol ameliorated liver injury and liver fibrosis, reflected by the decrease of ALT, AST, less lesion in H&E staining, mitigated fibrosis in Sirius and Masson staining, lessened content of hydroxyproline. Paeonol attenuated the level of IL-6 and TNF-α, and elevated the activity of GSH-PX, SOD, and CAT with reducing the level of MDA. The expression of col 1a, α-SMA, vimentin, and desmin were down-regulated and TGF-β/Smad3 signaling pathway was inhibited.These data demonstrated that paeonol could alleviate CCl-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-β/Smad3 signaling.

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