PMID: 

Eur J Cancer Prev. 2019 Nov ;28(6):472-482. PMID: 30407216

Abstract Title: 

Supplementation of p-coumaric acid exhibits chemopreventive effect via induction of Nrf2 in a short-term preclinical model of colon cancer.

Abstract: 

Suppression of colorectal cancer by means of chemoprevention is gaining great attention owing to promising outcomes with less adverse effects in preclinical and clinical trials. The present study aims to explore the mechanism of chemoprevention by p-coumaric acid (p-CA) in a short-term preclinical model of colon cancer. 1,2-dimethylhydrazine-administered rats supplemented with p-CA showed downregulation of the expression of colonic proteins, namely, cyclin B1, cdc2 and mdm2, which regulate cell cycle, and immediate early response genes, namely, c-fos, c-jun and c-myc, which regulate cell proliferation. Apoptosis induction was also observed in the colon of p-CA-supplemented rats as assessed by the Bax/Bcl-2 ratio. Immunohistochemistry, immunoblotting and real-time polymerase chain reaction analysis revealed that supplementation of p-CA improved the in-vivo detoxification potential by modulating the cytoplasmic-to-nuclear ratio of nuclear factor erythroid 2-related factor 2, favouring the induction of genes responsible for cytoprotection and detoxification. The outcome of these findings suggests that p-CA inhibited polyp formation by improving the process of detoxification and apoptosis in the colon of 1,2-dimethylhydrazine-administered rats.

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PMID: 

Respir Physiol Neurobiol. 2019 02 ;260:95-104. Epub 2018 Nov 14. PMID: 30447305

Abstract Title: 

Prophylactic effect and mechanism of p-coumaric acid against hypoxic cerebral edema in mice.

Abstract: 

Our previous study found that the anti-hypoxia effect of Tibetan turnip (Brassica rapa ssp. rapa) is directly related to its p-Coumaric acid (CA) and glucoside (pCoumaric acid-beta-d-glucopyranoside, CAG) contents. The present study aimed to investigate the role and mechanism of CA against hypoxic cerebral edema. Male mice were randomly divided into one normoxia group and three hypoxia groups, which were gavaged with sterilized water, CA, or dexamethasone, respectively, once daily for 4 days. The mice were then exposed to normoxia or hypoxia (9.5% O) for 24 h. The results showed that the brain water content (BWC) and blood-brain-barrier permeability were significantly lower in the CA treatment group than in the hypoxia vehicle group. Mice in the CA treatment group showed good blood-brain-barrier integrity; increased Na-K-ATPase activity and mitochondrial membrane potential; decreased oxidative stress and inflammation; and increased occludin protein levels. Prophylactic administration of CA and dexamethasone exerted similar effects against hypoxic cerebral edema. The mechanism involved improving the integrity of the blood-brain-barrier, and inhibiting oxidative stress and inflammation.

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PMID: 

Biomed Pharmacother. 2019 Mar ;111:579-587. Epub 2018 Dec 31. PMID: 30599319

Abstract Title: 

Protective effects of p-coumaric acid against oxidant and hyperlipidemia-an in vitro and in vivo evaluation.

Abstract: 

Dietary phenols are antioxidants with diverse physiological functions that are beneficial for human health. The objective of this research work was to investigate antioxidant activity of p-coumaric acid (p-CA) using four in vitro methods, the protective effects against oxidative stress in PC12 cells, and hypolipidemic effects on High fat-diet (HFD) mice model. The p-CA exhibited moderate antioxidant activity in the selected in vitro assay. The highest chelating activity of p-CA at 50 μg/mL was found to be 52.22%. Pretreatment with p-CA significantly enhanced cell viability of PC12 cell and suppressed AAPH-induced intracellular ROS generation and AAPH-induced LDH release. The hypolipidemic effects of p-CA (100 mg/kg BW) was directly linked to the increased expression of nuclear factor erythroid 2-related factor (Nrf2) by 2.0-fold, Glutathione peroxidase (Gpx) by 3.8-fold, Superoxide dismutase (SOD-1) by 1.6-fold, Heme oxygenase (HO-1) by 1.72-fold and NAD(P)H Quinone Dehydrogenase 1 (NQO-1) by 1.5-fold compared with HFD group. In addition to these effects, p-CA decreased total cholesterol and atherosclerosis index levels, and increased catalase (CAT) level in serum, total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) levels in liver as compared HFD group. Administration of p-CA also promoted the recovery of hyperlipidemia steatohepatitis in mice by ameliorating lipid peroxidation. These results suggested that p-CA is a potent antioxidant with potential therapeutic efficacy for treating hyperlipidemia symptoms.

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PMID: 

Phytother Res. 2019 Apr ;33(4):989-997. Epub 2019 Jan 29. PMID: 30693991

Abstract Title: 

Anti-inflammatory effects of chemical components from Ginkgo biloba L. male flowers on lipopolysaccharide-stimulated RAW264.7 macrophages.

Abstract: 

Ginkgo biloba L., well known as living fossil, have various pharmacological activities. Eighteen compounds were isolated from Ginkgo male flowers including a novel matsutake alcohol glycoside, Ginkgoside A (1), and 17 known compounds-calaliukiuenoside (2), benzylalcohol O-α-l-arabinopyranosyl-(1 → 6)-β-d-glucopyranoside (3), amentoflavone (4), sciadopitysin (5), bilobetin (6), isoginkgetin (7), olivil 4-O-β-d-glucopyranoside (8), dihydrodehydrodiconiferyl alcohol-4-O-β-d-glucoside (9), (+)-cyclo-olivil-6-O-β-d-glucopyranoside (10), (-)-isolariciresinol 4-O-β-d-glucopyranoside (11), coniferin (12), trans-cinnamic acid-4-O-β-d-glucopyranoside (13), p-coumaryl alchol glucoside (14), stroside B (15), methylconiferin (16), cis-p-coumaric acid 4-O-β-d-glucopyranoside (17), and cis-coniferin (18). Thirteen of these compounds had not previously found in Ginkgo. All extractive fractions and isolated compounds were evaluated for their anti-inflammatory ability in the lipopolysaccharide-induced RAW264.7 macrophages. The ethanol extract of Ginkgo flowers and the chloroform and ethyl acetate fractions can significantly decrease nitric oxide (NO), interleukin-6 (IL-6), and prostaglandin E(PGE) production at 100 μg/ml. The most effective compounds, bilobetin (6) and isoginkgetin (7), elevated the NO inhibition ratios to 80.19% and 82.37% at 50 μM, respectively. They also exhibited significant dose-dependent inhibitory effects on tumor necrosis factor-α, IL-6, PGE, inducible NO synthase mRNA, and cyclooxygenase-2 mRNA levels. So they can be promising candidates for the development of new anti-inflammatory agents.

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PMID: 

Diabetes Metab Syndr Obes. 2020 ;13:53-63. Epub 2020 Jan 8. PMID: 32021351

Abstract Title: 

The Renoprotective Effects of Naringenin (NGN) in Gestational Pregnancy.

Abstract: 

Introduction: Gestational diabetes mellitus (GDM) is defined as glucose intolerance that is first diagnosed during pregnancy, a condition risking the health of both the mother and the baby. Naringenin (NGN) has been demonstrated to have multiple therapeutic functions, while it is also considered to exhibit antidiabetic properties. The present study aimed to investigate the protective effects of NGN in pregnant diabetic rats.Methods: GDM was induced by feeding the rats with a high-fat diet for 5 weeks, followed by intraperitoneal injection of streptozotocin (35 mg/kg). The fasting blood glucose were determined with a glucometer and the 24-h urine protein (24-UPro) were determined by the sulfonyl salicylic acid method. The pathological morphological changes and apoptosis of glomeruli cells of kidney tissue using hematoxylin and eosin (H&E) staining and TUNEL analysis. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum T-AOC, the activity of SOD, the levels of GSH-Px, CAT and MDA, TNF-α, IL-6, TGF-β, ICAM-1.The expression of related genes were measured by RT-qPCR and Western blot analyses.Results: In the NGN-treated group, it was observed that the general status of the rats was improved, while the levels of blood glucose and 24-UPro were significantly decreased. In addition, the histopathological changes in renal tissues and renal cell apoptosis were significantly improved upon treatment with NGN. The expression levels of oxidative stress and inflammation-associated factors also differed signifigcantly between the model and NGN-treated groups. Upon treatment with NGN, the levels of peroxisome proliferator-activated receptorα were significantly increased, while the activity of enzymes involved in the oxidative metabolism of fatty acids was significantly decreased.Conclusion: These preliminary experimental findings demonstrate that NGN has a certain renoprotective effect on GDM, which provides a novel therapeutic option for this condition.

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PMID: 

Inflammation. 2019 Dec ;42(6):1939-1950. PMID: 31267276

Abstract Title: 

p-Coumaric Acid Attenuates Lipopolysaccharide-Induced Lung Inflammation in Rats by Scavenging ROS Production: an In Vivo and In Vitro Study.

Abstract: 

Lipopolysaccharide (LPS), known as lipoglycans and endotoxins found in the cell wall of some type of Gram-negative bacteria, causes acute lung inflammation (ALI). p-Coumaric acid (p-CA) possesses anti-inflammatory and anti-oxidative activities. The main purpose of our research was to explore the effect of p-CA on LPS-induced inflammation. In part I, 32 rats were divided into four groups: Control, LPS (5 mg/kg), p-CA (100 mg/kg), and LPS + p-CA to investigate acute lung inflammation caused by LPS. In part II, the effect of LPS-stimulated inflammatory response on A549 cells was investigated. The dosage of LPS and p-CA which used in this part was 1 μg/ml and 20 mM, respectively. ALI rats showedan elevation in antioxidant activity, TNF-alpha, IL-6, MDA, inflammatory parameters, and Nrf2 gene expression. Although pre-treatment with p-CA could return these changes approximately to normal condition in all two-part studies (in vivo and in vitro). The results of in vivo and in vitro study showed that LPS induced lung inflammation. Pre-treatment with p-CA causes modulating of oxidative stress in inflammatory condition in lung injury and A549 cell.

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PMID: 

J Periodontal Res. 2019 Dec ;54(6):690-701. Epub 2019 Jul 21. PMID: 31328274

Abstract Title: 

Oral supplementation with p-coumaric acid protects mice against diabetes-associated spontaneous destruction of periodontal tissue.

Abstract: 

OBJECTIVE: Dietary bioactive materials having anti-inflammatory and antioxidant potentials are able to inhibit diabetes-associated periodontal complications. Although numerous studies indicate that administration of p-coumaric acid (p-CA) ameliorates diabetes and diabetes-related complications, the roles of p-CA on periodontal tissue destruction in diabetic mice and the possible mechanisms therein are not completely understood. In this study, we evaluated whether supplementation with p-CA protects mice against diabetes-associated spontaneous periodontal destruction and also explored the associated mechanism therein using in vivo and in vitro experimental systems.MATERIALS AND METHODS: C57BL/6 male mice were divided into sham, streptozotocin (STZ), and STZ+CA groups (n = 5/group). Sham group was intraperitoneally injected with sodium buffer, whereas other two groups were injected with the buffer containing 160 mg/kg of STZ. STZ-induced diabetic mice received oral gavage with p-CA (50 mg/kg) (STZ+CA group) or with buffer only (STZ group) daily for 6 weeks. The effect of p-CA on diabetes-associated spontaneous periodontal destruction was evaluated using μCT analysis, hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, and immunohistochemical staining methods. The efficacies of p-CA on cell proliferation, osteoblast differentiation, reactive oxygen species (ROS) accumulation, and antioxidant-related marker expression were examined using human periodontal ligament fibroblasts (hPLFs) cultured under high glucose condition.RESULTS: Streptozotocin group exhibited periodontal tissue destruction along with increased inflammation, oxidative stress, and osteoclast formation, as well as with decreased osteogenesis. However, oral administration with p-CA protected mice against STZ-induced periodontal destruction by inhibiting inflammation and osteoclastic activation. STZ+CA group also showed higher expression of antioxidant and osteogenic markers in periodontal tissue than did STZ group. Treatment with high glucose concentration (30 mmol/L) impaired proliferation and osteoblast differentiation of hPLFs along with cellular ROS accumulation, whereas these impairments were almost completely disappeared by supplementation with p-CA.CONCLUSION: These findings demonstrate that supplementation with p-CA inhibits diabetes-associated spontaneous destruction of periodontal tissue by enhancing anti-inflammatory, anti-osteoclastogenic, and antioxidant defense systems in STZ-treated mice.

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PMID: 

Biochem Biophys Res Commun. 2019 Oct 1 ;517(4):655-661. Epub 2019 Aug 13. PMID: 31416617

Abstract Title: 

p-Coumaric acid inhibits the Listeria monocytogenes RecA protein functions and SOS response: An antimicrobial target.

Abstract: 

Bacterial RecA plays an important role in the evaluation of antibiotic resistance via stress-induced DNA repair mechanism; SOS response. Accordingly, RecA became an important therapeutic target against antimicrobial resistance. Small molecule inhibitors of RecA may prevent adaptation of antibiotic resistance mutations and the emergence of antimicrobial resistance. In our study, we observed that phenolic compound p-Coumaric acid as potent RecA inhibitor. It inhibited RecA driven biochemical activities in vitro such as ssDNA binding, strand exchange, ATP hydrolysis and RecA coprotease activity of E. coli and L. monocytogenes RecA proteins. The mechanism underlying such inhibitory action of p-Coumaric acid involves its ability to interfere with the DNA binding domain of RecA protein. p-Coumaric acid also potentiates the activity of ciprofloxacin by inhibiting drastic cell survival of L. monocytogenes as well as filamentation process; the bacteria defensive mechanism in response to DNA damage. Additionally, it also blocked the ciprofloxacin induced RecA expression leading to suppression of SOS response in L. monocytogenes. These findings revealed that p-Coumaric acid is a potent RecA inhibitor, and can be used as an adjuvant to the existing antibiotics which not only enhance the shelf-life but also slow down the emergence of antibiotic resistance in bacteria.

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PMID: 

Iran J Basic Med Sci. 2019 Aug ;22(8):949-955. PMID: 31579452

Abstract Title: 

p-Coumaric acid protects cardiac function against lipopolysaccharide-induced acute lung injury by attenuation of oxidative stress.

Abstract: 

Objectives: Acute lung injury (ALI) has a high mortality rate and is characterized by damage to pulmonary system giving rise to symptoms such as histological alteration, lung tissue edema and production of proinflammatory cytokine. p-Coumaric acid (p-CA), as a phenolic compound, that is found in many types of fruits and vegetables has been reported to exhibit a therapeutic effect in several inflammatory disorders. The aim of our study was evaluation of pretreatment with p-CA against heart dysfunction, oxidative stress and nuclear factor-erythroid 2 -related factor 2 (Nrf2) modifications following lipopolysaccharide (LPS)-induced acute lung inflammation.Materials and Methods: The rats were divided into four groups (n=8): Control, LPS (5 mg/kg, it), p-CA (100 mg/kg, IP), and LPS+pCA. Inflammatory response and oxidative stress were evaluated by measurement of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) levels in heart tissue. For evaluation of the effect of LPS on cardiac response, electrocardiography (ECG) and hemodynamic parameters were recorded.Results: A significant increase in lipid peroxidation (

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PMID: 

Life Sci. 2019 Dec 1 ;238:116965. Epub 2019 Oct 17. PMID: 31629762

Abstract Title: 

P-Coumaric acid alleviates experimental diabetic nephropathy through modulation of Toll like receptor-4 in rats.

Abstract: 

AIMS: Diabetic nephropathy (DN) is responsible for the occurrence of 30-47% of the incident cases of end-stage renal disease (ESRD) worldwide. DN is a chronic inflammatory disorder, which results from hyperglycemia-induced alterations and leads to renal fibrosis and ESRD. Toll like receptor-4 (TLR-4) participates in regulation of inflammatory response through controlling of innate immune system. P-Coumaric Acid (P-CA) is a natural hydroxycinnamic acid derivative and is widely present in vegetables, fruits, mushrooms and cereals. This study aimed to explore the renoprotective effect of P-CA, as anti-inflammatory and antioxidant natural compound, against experimental DN.METHODS: DN was induced by single intraperitoneal injection of streptozotocin (45 mg/kg) in rats. In kidney homogenate, levels of TLR-4, interleukin-6 (IL-6) and transforming growth factor β1 (TGFβ1) were measured using ELISA technique. Also, kidney collagen content was determined colorimetrically.KEY FINDINGS: Oral administration of P-CA (100 mg/kg) for 8 weeks significantly alleviated the DN. P-CA significantly reduced serum concentrations of glucose, creatinine, blood urea nitrogen (BUN) and reduced protein content in urine. Also, P-CA significantly increased superoxide dismutase (SOD) activity and significantly reduced kidney contents of malondialdehyde (MDA), TLR-4, IL-6, TGFβ1 and collagen when compared with DN group. Moreover, P-CA significantly improved DN-induced histopathological abnormalities.SIGNIFICANCE: P-CA confers protection against the progression of DN. This renoprotective effect can be attributed to its ability to decrease the generation of inflammatory and fibrotic cytokines in addition to restoring oxidant/antioxidant balance through its ability to down-regulate TLR-4 activation.

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