PMID: 

Inflammation. 2019 Dec 10. Epub 2019 Dec 10. PMID: 31823179

Abstract Title: 

p-Coumaric Acid Attenuates IL-1β-Induced Inflammatory Responses and Cellular Senescence in Rat Chondrocytes.

Abstract: 

Osteoarthritis (OA) is a common chronic inflammatory joint disease characterized by cartilage degradation. p-Coumaric acid (PCA), a dietary phenolic compound, has exerted anti-inflammatory and anti-oxidative activities in various diseases. However, the effects of PCA on OA have not been reported. In the present study, we aimed to investigate the effects of PCA on interleukin-1β(IL-1β)-induced inflammatory responses and cellular senescence in rat chondrocytes. Our results revealed that PCA remarkably downregulated IL-1β-induced inflammatory factors such as COX2 and iNOS and cartilage-degrading enzymes like matrix metalloproteinases (MMP1, MMP3, and MMP13) and aggrecanases (ADAMTS4 and ADAMTS5) in chondrocytes. The IL-1β-induced degradation of cartilage matrix (collagen II and aggrecan) could also be suppressed by PCA. Besides, PCA treatment effectively inhibited the IL-1β-induced p16INK4a protein expression and SAβ-gal activities in vitro. Mechanism analysis showed that PCA suppressed IL-1β-induced activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) pathways. In vivo, we also found that PCA could alleviate the development of OA in a rat model. Altogether, our findings implicate that p-coumaric acid attenuates IL-1β-induced inflammatory responses and cellular senescence via inhibition of the MAPK and NF-κB signaling pathway in chondrocytes, and p-coumaric acid may be a promising candidate for the treatment of osteoarthritis.

read more

PMID: 

Nefrologia. 2019 Dec 28. Epub 2019 Dec 28. PMID: 31892486

Abstract Title: 

Antioxidant effect of p-coumaric acid on interleukin 1-β and tumor necrosis factor-α in rats with renal ischemic reperfusion.

Abstract: 

BACKGROUND AND AIMS: Renal ischemia-reperfusion occurs in some clinical conditions such as kidney surgery that can leads to acute renal failure. The aim of this study was to investigate the effect of p-coumaric acid (CA) on ischemia reperfusion (I/R) injury.METHODS: Thirty rats were randomly divided into five groups; control, CA (100mg/kg), I/R, propylene glycol (10%)+I/R and CA+I/R, (n=6 each). CA and propylene glycol were administered orally for 2 weeks. Then, the rats were subjected to bilateral renal ischemia for 45min and followed by reperfusion for 24h. All rats were killed and kidney function tests, tissue malondialdehyde and activity of antioxidant enzymes were determined. Histopathological evaluations were also performed. In addition, renal expression of the tumor necrosis factor-α and interleukin-1β were determined using enzyme-linked immunosorbent assay and immunohistochemistry.RESULTS: CA significantly improved the Cr and BUN levels in CA+I/R group compared to I/R group (p

read more

PMID: 

Biomed Pharmacother. 2019 Dec ;120:109205. Epub 2019 Oct 18. PMID: 31634777

Abstract Title: 

Ferulic acid, a natural polyphenol, protects against osteoporosis by activating SIRT1 and NF-κB in neonatal rats with glucocorticoid-induced osteoporosis.

Abstract: 

Osteoporosis is a chronic disease whose symptoms include a reduction in bone strength, osteopenia, and damage to the bone microstructure. Ferulic acids are natural polyphenols present in various fruits that suppress the fusion and apoptosis of mature osteoclasts. Rats were divided into sham, control (osteoporosis), 10 mg/kg body weight ferulic acid, 20 mg/kg body weight ferulic acid, and 30 mg/kg body weight ferulic acid treatment groups. Osteoporosis was induced in neonatal by administration of dexamethasone (glucocorticoids). Bone mineral density (BMD), osteocalcin and alkaline phosphatase (ALP) levels,bone mechanical parameters, and mRNA and protein levels of sirtuin1 (SIRT1) and nuclear factor kappa-B (NF-κB) in the osteoporotic neonatal rats were assessed. Histopathological analysis was also conducted. Treatment with 20 and 30 mg/kg body weight ferulic acid increased BMD by 25% and 141.7%, respectively, but reduced ALP and osteocalcin levels. Furthermore, treatment with 20 or 30 mg/kg body weight ferulic acid significantly reduced the pixel intensity and significantly increased the peak load and ultimate stiffness. Ferulic acid significantly increased the mRNA and protein levels of SIRT1 and reduced those of NF-κB. Finally, the histopathological analysis showed that ferulic acid increased BMD. In summary, ferulic acid exhibited protective effects against osteoporosis in neonatal rats.

read more

PMID: 

Phytother Res. 2019 Dec 4. Epub 2019 Dec 4. PMID: 31802562

Abstract Title: 

Amelioration of insulin resistance using the additive effect of ferulic acid and resveratrol on vesicle trafficking for skeletal muscle glucose metabolism.

Abstract: 

Dysregulation of vesicle trafficking in muscle is one of the factors responsible for the pathogenesis of insulin resistance (IR). Ferulic acid (FER) and resveratrol (RSV) are known to have hypoglycemic property. In this study, differentiated L6 myotubes were induced with palmitate as a model of IR. Chemical ablation of muscle vesicles was used to investigate how FER and RSV influence glucose utilization. Results showed that both FER and RSV elicit glucose uptake and promote glycogen synthesis in insulin-resistant muscle cells. Mechanistic studies further showed that FER markedly enhances the transferrin receptor-containing endosomal compartment activities via phosphoinositide 3-kinase (PI3K)/atypical protein kinase C-dependent pathway, while RSV facilitates glucose transporter storage vesicles (GSV) trafficking via an exercise-like effect of conventional protein kinase C/5'-adenosine monophosphate-activated protein kinase (AMPK) modulation. Therefore, these two phenolic compounds promoted glucose transport through two separate routes, and they had an additive effect on the increase of glucose uptake in insulin-resistant muscle cells. These findings provide a basis for the understanding of the antidiabetic potential of RSV and FER combination.

read more

PMID: 

Sci Rep. 2020 Jan 23 ;10(1):1063. Epub 2020 Jan 23. PMID: 31974389

Abstract Title: 

The dual role of curcumin and ferulic acid in counteracting chemoresistance and cisplatin-induced ototoxicity.

Abstract: 

Platinum-based agents, such as cisplatin, form the mainstay of currently used chemotherapeutic regimens for several malignancies; however, the main limitations are chemoresistance and ototoxic side effects. In this study we used two different polyphenols, curcumin and ferulic acid as adjuvant chemotherapeutics evaluating (1) in vivo their antioxidant effects in protecting against cisplatin ototoxicity and (2) in vitro the transcription factors involved in tumor progression and cisplatin resistance. We reported that both polyphenols show antioxidant and oto-protective activity in the cochlea by up-regulating Nrf-2/HO-1 pathway and downregulating p53 phosphorylation. However, only curcumin is able to influence inflammatory pathways counteracting NF-κB activation. In human cancer cells, curcumin converts the anti-oxidant effect into a pro-oxidant and anti-inflammatory one. Curcumin exerts permissive and chemosensitive properties by targeting the cisplatin chemoresistant factors Nrf-2, NF-κB and STAT-3 phosphorylation. Ferulic acid shows a biphasic response: it is pro-oxidant at lower concentrations and anti-oxidant at higher concentrations promoting chemoresistance. Thus, polyphenols, mainly curcumin, targeting ROS-modulated pathways may be a promising tool for cancer therapy. Thanks to their biphasic activity of antioxidant in normal cells undergoing stressful conditions and pro-oxidant in cancer cells, these polyphenols probably engage an interplay among the key factors Nrf-2, NF-κB, STAT-3 and p53.

read more

PMID: 

Med Sci Monit. 2020 Jan 27 ;26:e920095. Epub 2020 Jan 27. PMID: 31983729

Abstract Title: 

Ferulic Acid Induces Apoptosis of HeLa and Caski Cervical Carcinoma Cells by Down-Regulating the Phosphatidylinositol 3-Kinase (PI3K)/Akt Signaling Pathway.

Abstract: 

BACKGROUND Ferulic acid is an antioxidant phenolic compound derived from plants, which has effects on cancer cells. This study aimed to investigate the effects of ferulic acid on HeLa and Caski human cervical carcinoma cells and the molecular mechanisms involved. MATERIAL AND METHODS HeLa and Caski human cervical carcinoma cells were grown in culture and treated with increasing doses of ferulic acid. The MTT assay was used to evaluate cell viability. Flow cytometry was performed with 4',6-diamidino-2-phenylindole (DAPI) and Annexin V staining for cell apoptosis. The expression of myeloid leukemia cell differentiation-1 (Mcl-1) protein and MCL-1 mRNA were determined by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS Ferulic acid significantly reduced HeLa and Caski cell viability in the concentration range of 4-20µM (P

read more

PMID: 

Cardiovasc Hematol Disord Drug Targets. 2019 Jun 18. Epub 2019 Jun 18. PMID: 31237217

Abstract Title: 

The effects of chrysin on serum corticosterone levels and brain oxidative injury induced by immobilization in rat.

Abstract: 

The current study was designed to investigate the effects of chrysin (CH) on serum corticosterone level. We also investigated depression-like behavior induced by chronic restraint stress in rats. The rats were kept in restrainers for 1 hour daily for 21 consecutive days. Then, the animals were daily injected with either vehicle or CH (10, 20, 30µg/kg) for 21 days. Our findings showed that the serum corticosterone levels significantly increased in rats submitted to the restraint stress versus non-stressed animals (p

read more

PMID: 

Neurochem Int. 2019 10 ;129:104496. Epub 2019 Jun 25. PMID: 31247243

Abstract Title: 

Chrysin ameliorates cerebral ischemia/reperfusion (I/R) injury in rats by regulating the PI3K/Akt/mTOR pathway.

Abstract: 

In this study, the effects of chrysin on cerebral ischemia by establishing middle cerebral artery occlusion (MCAO) in rat were investigated. In vivo experiments, the rats were orally administrated with clopidogrel or chrysin once daily for 7 days before the experimental of ischemia and the rats were divided into 5 groups: the sham group, the I/R group, I/R + clopidogrel group, I/R + chrysin (10 mg/kg), I/R + chrysin (20 mg/kg) group. Chrysin significantly ameliorated the I/R rats, evaluated by TTC staining, determination of brain wet to dry weight ratio and neurological deficits. Moreover, in serum and brain tissues of the I/R rats, chrysin also could effectively suppress the release of inflammatory cytokines, including levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, chrysin could improve the SOD activity in the I/R rats. Mechanically, chrysin could activate the PI3K/Akt/mTORpathway, inhibited inflammation and apoptosis. In oxygen-glucose deprivation and recovery (OGD/R)-induced SH-SY5Y cells in vitro. Chrysin markedly decreased the levels of TNF-α, IL-6 and IL-1β in supernatant of OGD/R-induced SH-SY5Y cells via activating PI3K/Akt/mTOR pathway. In conclusion, our study demonstrated that chrysin might be a potential therapeutic agent for cerebral ischemia.

read more

PMID: 

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2019 May 28 ;44(5):522-527. PMID: 31303615

Abstract Title: 

[Effects of chrysin on the apoptosis in oral squamous carcinoma KB cell line and the underlying mechanisms].

Abstract: 

To investigate the effect of chrysin on apoptosis of oral squamous carcinoma KB cell line and the possible mechanisms, and to provide new ideas for the treatment of oral cancer.
 Methods: Oral cancer KB cells were treated with different concentrations of chrysin (1, 2, 4, 8, 16, and 32 μmol/L) for 24 h. Cell proliferation was detected by MMT assay; apoptosis was detected by flow cytometry; the activity of caspase-3/7 was detected by chemiluminescent assay; mitochondrialmembrane potential in KB cells was determined by JC-1 assay; and Western blotting was used to determine the activation of protein kinase B (AKT) and phosphoinositide-3-kinase (PI3K).
 Results: Chrysin inhibited the proliferation of KB cells in a concentration-dependent manner, accompanied by increase in apoptosis of KB cells, activation of caspase-3/7, decrease in mitochondrial membrane potential, and suppression of the phosphorylation of AKT and PI3K.
 Conclusion: The effect of chrysin on KB cell apoptosis may be related to mitochondrial dysfunction and inhibition of PI3K/AKT pathway.

read more

PMID: 

Food Funct. 2019 Aug 1 ;10(8):4566-4576. Epub 2019 Jul 17. PMID: 31314039

Abstract Title: 

Effect of chrysin on changes in intestinal environment and microbiome induced by fructose-feeding in rats.

Abstract: 

Intake of fructose-containing sugars is epidemiological and experimentally linked to metabolic syndrome (MS). We recently verified that the dietary polyphenol chrysin was able to abolish some of the metabolic changes induced by fructose-feeding in the rat. Because the role of the intestine upon fructose-induced MS is poorly understood, we decided to investigate the influence of fructose, in vivo, on the intestinal environment and the ability of chrysin to interfere with the putative observed changes. For this, adult male Sprague-Dawley rats were treated for 18 weeks as follows: (A) tap water (CONT), (B) tap water and chrysin (100 mg kgday) (CHRY), (C) 10% fructose in tap water (FRUCT), and (D) 10% fructose in tap water and chrysin (100 mg kgday) (FRUCT + CHRY). Our findings show that the relative expression of SGLT1 and GLUT2 mRNA were not affected by fructose-feeding and/or chrysin. In contrast, GLUT5 mRNA expression was markedly increased in fructose-fed animals, and this effect was reduced by chrysin. However, the apparent permeability toC-FRUCT was markedly and similarly decreased in FRUCT, CHRY and FRUCT + CHRY rats. Jejunal villus width and crypt depth were significantly higher in FRUCT and FRUCT + CHRYS rats, respectively. Finally, chrysin did not alter gut microbiota composition, but fructose significantly increased Lactobacillus and E. coli. Moreover, FRUCT + CHRY rats had an increase on the Firmicutes to Bacteroidetes ratio. This is the first report showing that chrysin is able to interfere with the effects of fructose at the intestinal level, which may contribute to the fructose-induced MS features.

read more