PMID: 

Molecules. 2012 Apr 20 ;17(4):4672-83. Epub 2012 Apr 20. PMID: 22522397

Abstract Title: 

Effect of paeonol on antioxidant and immune regulatory activity in hepatocellular carcinoma rats.

Abstract: 

The study investigated the immunity and antioxidant potential of paeonol by employing a hepatocellular carcinoma (HCC) rat model. Three doses of paeonol (20, 40, 60 mg/kg b.w. orally) were administrated to diethylnitrosamine (DEN)-induced HCC rats. Results showed that paeonol significantly reduced the serum AST, ALT, ALP, GGT, AFU and liver MDA levels, increased serum WBC, TP, ALB, A/G, TNF-α and IFN-γ and liver antioxidant enzymes activities (SOD, CAT, GSH-Px, GR) in HCC rats. Altogether, these results suggest that the paeonol could effectively decrease oxidative injury and improve immunity function in HCC rats.

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PMID: 

J Ethnopharmacol. 2013 Mar 27 ;146(2):543-51. Epub 2013 Jan 26. PMID: 23357312

Abstract Title: 

Paeonol suppresses oxidized low-density lipoprotein induced endothelial cell apoptosis via activation of LOX-1/p38MAPK/NF-κB pathway.

Abstract: 

Paeonol is an active compound isolated from traditional Chinese medicine, and has been shown to have anti-atherosclerosis, anti-inflammatory, antioxidant effects. The present investigation was undertaken to determine the suppression effects of paeonol on oxidized low-density lipoprotein (ox-LDL) induced endothelial cell line HUVEC apoptosis and to uncover some of the underlying mechanisms of these effects. Cell viability and lactate dehydrogenase (LDH) were measured to evaluate the cell injuries. Apoptosis was evaluated by Hoechst 33342 staining and flow cytometry. Intracellular reactive oxygen species (ROS) generation was detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA). Real-time PCR was used to confirm the expression of LOX-1 mRNA. Western blotting was used to evaluate the protein expression of LOX-1 and Bcl-2, as well as caspase-3 cleavage, p38-mitogen-activated protein kinase (p38MAPK) phosphorylation. NF-κB nuclear translocation was detected by Western blotting and immunofluorescence. Caspase-3 activity was measured using a colorimetric protease assay kit. The results showed that ox-LDL significantly decreased cell viability and increased the LDH release, as well as the apoptotic rate (P

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PMID: 

Fundam Clin Pharmacol. 2014 Jun ;28(3):268-76. Epub 2013 Feb 17. PMID: 23413967

Abstract Title: 

Paeonol suppresses lipopolysaccharide-induced inflammatory cytokines in macrophage cells and protects mice from lethal endotoxin shock.

Abstract: 

Paeonol (2'-hydroxy-4'-methoxyacetophenone) is the main phenolic compound of the radix of Paeonia suffruticosa which has been used as traditional Chinese medicine. In this study, we primarily investigated the anti-inflammatory effects and the underlying mechanisms of paeonol in RAW macrophage cells; and based on these effects, we assessed the protective effects of paeonol on lipopolysaccharide-induced endotoxemia in mice. The in vitro study showed that paeonol regulated the production of TNF-α, IL-1β, IL-6, and IL-10 via inactivation of IκBα, ERK1/2, JNK, and p38 MAPK. In mouse model of lipopolysaccharide-induced endotoxemia, pro- and anti-inflammatory cytokines are significantly regulated, and thus the survival rates of lipolysaccharide-challenged mice are improved by paeonol (150,200, or 250 mg/kg). Therefore, paeonol has a beneficial activity against lipopolysaccharide-induced inflammation in RAW 264.7 cell and mouse models.

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PMID: 

J Gastroenterol Hepatol. 2013 Jul ;28(7):1223-33. PMID: 23425217

Abstract Title: 

Paeonol inhibits hepatic fibrogenesis via disrupting nuclear factor-κB pathway in activated stellate cells: in vivo and in vitro studies.

Abstract: 

BACKGROUND AND AIMS: Hepatic fibrosis represents a major cause of morbidity and mortality worldwide. The present study was to evaluate the antifibrogenesis effect of paeonol and involved mechanisms.METHODS: The degree of liver injury was evaluated biochemically by measuring serum and fibrotic markers and pathological examination. Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and trypan blue staining. Cytotoxic effects were determined using lactate dehydrogenase release assay. Cell cycle was determined using single dyeing methods of propidium iodide (PI) by flow cytometry. Apoptosis was confirmed using double-staining of annexin V/PI and Hoechst. Western blot, immunofluorescence and real-time polymerase chain reaction were used to explore the molecular mechanisms.RESULTS: Treatment with paeonol significantly protected the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase, improving the histological architecture of the liver, and by inhibiting activation of hepatic stellate cells (HSCs) in vivo. Interestingly, paeonol had no apparent cytotoxic effects but could markedly inhibit primary HSC proliferation and induced HSC cell cycle arrest at the G2/M checkpoint. These effects were caused by paeonol suppression of phosphorylation of cycle protein cdc2 and of CDK2. Moreover, that paeonol triggered mitochondrial apoptosis pathway and led to activation of caspase cascades in HSCs was found. Mechanistic investigations revealed that the nuclear factor-κB (NF-κB) pathway inhibition resulted in the earlier events. Furthermore, paeonol altered the expression of some marker proteins relevant to HSCs activation.CONCLUSION: Paeonol could inhibit HSC proliferation and induce mitochondrial apoptosis via disrupting NF-κB pathway, which might be the mechanisms of paeonol reduction of liver fibrosis.

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PMID: 

Acta Histochem. 2013 Oct ;115(8):835-9. Epub 2013 Jun 13. PMID: 23768958

Abstract Title: 

Paeonol induces apoptosis in human ovarian cancer cells.

Abstract: 

Paeonol is a broad-spectrum antitumor agent, which is widely used in the treatment of various tumors in Asia. However, the effect of paeonol on ovarian cancer remains unclear. The purpose of this study was to investigate the effect of paeonol on ovarian cancer cells and its possible mechanism. Results measured by MTT (methyl thiazoyltetrazolium) assay showed that cell viability was markedly reduced in a dosage-dependent manner, when treated with paeonol for 24 h. Flow cytometry and Hoechst staining results indicated that the rate of apoptosis in the paeonol pretreatment group was higher than the control group. After co-culture with paeonol, cleaved Caspase 3 protein levels increased while survivin protein levels decreased. In conclusion, our findings indicate that paeonol can induce apoptosis of ovarian cancer cells via activation of Caspase 3 and down-regulation of survivin, and therefore is potentially an effective chemotherapeutic agent for ovarian cancer.

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PMID: 

Neurosci Lett. 2013 Aug 9 ;549:63-8. Epub 2013 Jun 19. PMID: 23791853

Abstract Title: 

Neuroprotective effect of paeonol on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat.

Abstract: 

Diabetic encephalopathy (DE) has been characterized by the impaired cognition and the abnormalities of neurochemistry and neurostructure. The study was conducted to evaluate the neuroprotective effect of paeonol on STZ-induced DE rats. Paeonol of 25, 50, 100mg/kg (p.o.) could decrease the latency time and path length, and enhance significantly the spent time in the target quadrant and platform crossings in Morris water maze test. The treatment with paeonol could also increase significantly Na(+)-K(+)-ATP enzyme and ChAT activities, as well as decreasing significantly AchE activity in hippocampal tissue. Immunohistochemistry and TUNEL staining showed that paeonol could attenuate apoptosis of neurons and caspase 3 expression, improve two neurotrophic factors BDNF and IGF expressions, and also ameliorate Aβ deposition in the hippocampus and cerebral cortex. In conclusion, the present study demonstrated diabetic rats treated with paeonol could ameliorate the cognition deficits. These findings indicated paeonol might act as a beneficial agent for the prevention and treatment of DE.

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PMID: 

Neural Regen Res. 2013 Jun 25 ;8(18):1637-43. PMID: 25206460

Abstract Title: 

Paeonol attenuates inflammation-mediated neurotoxicity and microglial activation.

Abstract: 

Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. The root of Paeonia lactiflora Pall has been considered useful for the treatment of various disorders in traditional oriental medicine. Paeonol, found in the root of Paeonia lactiflora Pall, has a wide range of pharmacological functions, including anti-oxidative, anti-inflammatory and neuroprotective activities. The objective of this study was to examine the efficacy of paeonol in the repression of inflammation-induced neurotoxicity and microglial cell activation. Organotypic hippocampal slice cultures and primary microglial cells from rat brain were stimulated with bacterial lipopolysaccharide. Paeonol pretreatment was performed for 30 minutes prior to lipopolysaccharide addition. Cell viability and nitrite (the production of nitric oxide), tumor necrosis factor-alpha and interleukin-1beta products were measured after lipopolysaccharide treatment. In organotypic hippocampal slice cultures, paeonol blocked lipopolysaccharide-related hippocampal cell death and inhibited the release of nitrite and interleukin-1beta. Paeonol was effective in inhibiting nitric oxide release from primary microglial cells. It also reduced the lipopolysaccharide-stimulated release of tumor necrosis factor-alpha and interleukin-1β from microglial cells. Paeonol possesses neuroprotective activity in a model of inflammation-induced neurotoxicity and reduces the release of neurotoxic and proinflammatory factors in activated microglial cells.

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PMID: 

Evid Based Complement Alternat Med. 2013 ;2013:310989. Epub 2013 Sep 19. PMID: 24171038

Abstract Title: 

Paeonol, a major compound of moutan cortex, attenuates Cisplatin-induced nephrotoxicity in mice.

Abstract: 

Cisplatin is an effective chemotherapeutic agent that is used for the treatment of a variety of cancers; however, its nephrotoxicity limits the use of this drug. In the present study, we examined whether paeonol, a major compound of Moutan Cortex, has protective effects on cisplatin-induced acute renal failure in mice. To accomplish this, Balb/c mice (6 to 8 wk of age, weighing 20 to 25 g) were administered, Moutan Cortex (300 mg/kg) or paeonol (20 mg/kg) once a day. At day 4, mice received cisplatin (30, 20, or 10 mg/kg) intraperitoneally. The paeonol-treated group showed marked attenuation of serum creatine and blood urea nitrogen levels aswell as reduced levels of proinflammatory cytokines and nitric oxide when compared to the control group. In addition, the paeonol-treated group showed prolonged survival and marked attenuation of renal tissue injury. Taken together, these results demonstrated that paeonol can prevent the renal toxic effects of cisplatin.

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PMID: 

Acta Pharmacol Sin. 2014 Apr ;35(4):483-8. Epub 2014 Feb 24. PMID: 24562307

Abstract Title: 

Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release.

Abstract: 

AIM: Paeonol (2'-hydroxy-4'-methoxyacetophenone) from Cortex moutan root is a potential therapeutic agent for atherosclerosis. This study sought to investigate the mechanisms underlying anti-inflammatory effects of paeonol in rat vascular endothelial cells (VECs) in vitro.METHODS: VECs were isolated from rat thoracic aortas. The cells were pretreated with paeonol for 24 h, and then stimulated with ox-LDL for another 24 h. The expression of microRNA-21 (miR-21) and PTEN in VECs was analyzed using qRT-PCR. The expression of PTEN protein was detected by Western blotting. TNF-α release by VECs was measured by ELISA.RESULTS: Ox-LDL treatment inhibited VEC growth in dose- and time-dependent manners (the value of IC50 was about 20 mg/L at 24 h). Furthermore, ox-LDL (20 mg/L) significantly increased miR-21 expression and inhibited the expression of PTEN, one of downstream target genes of miR-21 in VECs. In addition, ox-LDL (20 mg/L) significantly increased the release of TNF-α from VECs. Pretreatment with paeonol increased the survival rate of ox-LDL-treated VECs in dose- and time-dependent manners. Moreover, paeonol (120 μmol/L) prevented ox-LDL-induced increases in miR-21 expression and TNF-α release, and ox-LDL-induced inhibition in PTEN expression. A dual-luciferase reporter assay showed that miR-21 bound directly to PTEN's 3'-UTR, thus inhibiting PTEN expression. In ox-LDL treated VECs, transfection with a miR-21 mimic significantly increased miR-21 expression and inhibited PTEN expression, and attenuated the protective effects of paeonol pretreatment, whereas transfection with an miR-21 inhibitor significantly decreased miR-21 expression and increased PTEN expression, thus enhanced the protective effects of paeonol pretreatment.CONCLUSION: miR-21 is an important target of paeonol for its protective effects against ox-LDL-induced VEC injury, which may play critical roles in development of atherosclerosis.

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PMID: 

Am J Chin Med. 2014 ;42(2):361-74. PMID: 24707868

Abstract Title: 

Effect of paeonol on tissue destruction in experimental periodontitis of rats.

Abstract: 

We evaluated the effects of paeonol, a phenolic compound of Moutan Cortex, on the tissue inflammation and destruction in experimental periodontitis of rats. The maxillary palatal bony surfaces of 18 rats received injections of lipopolysaccharide (LPS, 5 mg/mL), PBS or LPS-plus-paeonol (40 mg/kg, intra-peritoneal injection) for three days. Five days later, the osteoclasts were examined and compared after tartrate-resistant acid phosphatase staining. In another 36 rats, the experimental periodontitis was induced by placing the ligatures around the maxillary second and mandibular first molars. Seven days later, the periodontal destruction and inflammation in rats with paeonol (40 mg/kg or 80 mg/kg) and those who had no ligature or without paeonol were compared by dental radiography, micro-computerized tomography (micro-CT), and histology. Gingival mRNA expressions of pre-inflammatory cytokines, including IL-1β' IL-6 and TNF-α were also examined. Compared to the effect of the LPS positive control, the paeonol injection significantly reduced the induced osteoclast formation. In ligature-induced periodontitis, the periodontal bone supporting ratio was significantly higher in the ligature-plus-paeonol groups compared to that of the ligature group, although they were still less than those in the non-ligature group. By micro-CT and by histology/histometry, a consistent anti-destructive effect was observed when paeonol was added. Moreover, less amount of inflammatory cell-infiltrated connective tissuearea, connective tissue attachment, and mRNA expressions of pro-inflammatory cytokines were presented in the ligature-plus-paeonol groups than those in the ligature group. These results suggested that paeonol might have a protective potential on gingival tissue inflammation and alveolar bone loss during the process of periodontitis by inhibiting pro-inflammatory cytokines.

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