A Review of the Health Protective Effects of Phenolic Acids against a Range of Severe Pathologic Conditions (Including Coronavirus-Based Infections).

Phenolic acids comprise a class of phytochemical compounds that can be extracted from various plant sources and are well known for their antioxidant and anti-inflammatory properties. A few of the most common naturally occurring phenolic acids (i.e., caffeic, carnosic, ferulic, gallic, p-coumaric, rosmarinic, vanillic) have been identified as ingredients of edible botanicals (thyme, oregano, rosemary, sage, mint, etc.). Over the last decade, clinical research has focused on a number of in vitro (in human cells) and in vivo (animal) studies aimed at exploring the health protective effects of phenolic acids against the most severe human diseases. In this review paper, the authors first report on the main structural features of phenolic acids, their most important natural sources and their extraction techniques. Subsequently, the main target of this analysis is to provide an overview of the most recent clinical studies on phenolic acids that investigate their health effects against a range of severe pathologic conditions (e.g., cancer, cardiovascular diseases, hepatotoxicity, neurotoxicity, and viral infections-including coronaviruses-based ones).

Neuroprotective and Anti-Inflammatory Effects of Evernic Acid in an MPTP-Induced Parkinson's Disease Model.

Oxidative stress, mitochondrial dysfunction, and neuroinflammation are strongly associated with the pathogenesis of Parkinson's disease (PD), which suggests that anti-oxidative and anti-inflammatory compounds might provide an alternative treatment for PD. Here, we evaluated the neuroprotective effects of evernic aid (EA), which was screened from a lichen library provided by the Korean Lichen Research Institute at Sunchon National University. EA is a secondary metabolite generated by lichens, including Ramalina, Evernia, and Hypogymnia, and several studies have described its anticancer, antifungal, and antimicrobial effects. However, the neuroprotective effects of EA have not been studied. We found that EA protected primary cultured neurons against 1-methyl-4-phenylpyridium (MPP+)-induced cell death, mitochondrial dysfunction, and oxidative stress, and effectively reduced MPP+-induced astroglial activation by inhibiting the NF-κB pathway. In vivo, EA ameliorated MPTP-induced motor dysfunction, dopaminergic neuronal loss, and neuroinflammation in the nigrostriatal pathway in C57BL/6 mice. Taken together, our findings demonstrate that EA has neuroprotective and anti-inflammatory effects in PD models and suggest that EA is a potential therapeutic candidate for PD.

Isolation and characterization of anti-inflammatory and analgesic compounds from Uapaca staudtii Pax (Phyllanthaceae) stem bark.

ETHNOPHARMACOLOGICAL RELEVANCE: Uapaca species including Uapacastaudtii Pax (Phyllanthaceae) are used in West Africa ethnomedicine to treat diverse ailments including pile, rheumatism, oedema and wound healing. However, the anti-inflammatory and analgesic potential as well as constituents of the Uapacastaudtii stem bark has not been investigated. AIM OF THE STUDY: The study was designed to evaluate the anti-inflammatory, analgesic, and antioxidant activities of extract and fractions ofU. staudtii stem bark, and to isolate the bioactive constituents. MATERIALS AND METHODS: The anti-inflammatory, analgesic and antioxidant activities of the ethanol extract, dichloromethane, ethyl acetate, butanol, and aqueous fractions of U. staudtii stem bark, as well as protocatechuic acid and betulinic acid isolated from the bioactive ethyl acetate fraction were evaluated in different mice models of inflammation and pain; furthermore, antioxidant assays were carried out. Chemical structures of isolated compounds were established based on spectroscopic studies and comparison with literature data. RESULTS: The ethanol extract and ethyl acetate fraction exhibited good anti-inflammatory, analgesic, and antioxidant capacity in all studied models, comparable with those of the standard drugs used. Protocatechuic acid also gave significant (p < 0.05) anti-inflammatory (83%and 88% inhibition for egg-albumin induced and xylene induced oedema, respectively), analgesic (56% inhibition and 22 s of pain suppression for acetic acid-induced and hot plate-induced pain, respectively), and antioxidant effects (97% inhibition and absorbance of 2.516 at 100 µg/mL for DPPH and FRAP assay, respectively) in all the models, whereas betulinic acid only exhibited significant (p < 0.05) anti-inflammatory and antioxidant activity. CONCLUSIONS: The result supports the medicinal uses of the U. staudtii stem bark in the management of pain and inflammatory disease. This is the first report on the biological activities and characterization of compounds inU. staudtii, and presence of protocatechuic acid in Uapaca genus.

Effects of Corchorus olitorius and protacatechuic acid on diabetic rat testis tissue / Efectos de Corchorus olitorius y ácido protocatéquico en el tejido testicular de rata diabética

SUMMARY: The aim of this study is to investigate the effects of Protocatechuic acid and Corchorus olitorius on streptozotocin (STZ) induced diabetic rat testis tissue. Randomly selected Wistar Albino rats were divided into five groups as; Diabetes Mellitus, Diabetes Mellitus treated with Corchorus Olitorus (STZ+CO), Diabetes Mellitus treated with Protacatechuic acid (STZ+PCA), Corchorus olitorius (CO), Protocatechuic acid (PCA) and Control. Diabetic model was generated by intraperitoneal injection of 60 mg/kg Streptozotosin. After 48 hours of the STZ injection, blood samples were collected from tail vein in order to measure blood glycose levels. Over 250 mg/dL accepted as diabetic subjets and fed with 250 mg/kg Corchorus olitorius or 20 mg/kg PCA by oral gavage for three weeks. At the end of the experiment, right testes were removed and fixed in 10 % neutral formaldehyde for paraffine embedding. Sections were stained by HE, Masson trichrome, PAS and TUNEL for microscopic evaluation. Control, PCA-only and Corchorus olitorius-only treated group testes tissues showed a normal tissue organization, when degeneration in seminiferous tubules, the vacuolization, seperations in spermatogenic cell series, outpouring of cell groups in the lumen, vesicular body formation, liquid accumulation in the interstitial region and edema were observed in STZ induced diabetic models and untreated groups. Besides, higher amount of TUNEL (+) stained cells were determined in STZ group. On the other hand, blood glucose level and number of TUNEL (+) stained cells were decreased as a result of PCA and Corchorus olitorius treatment. Because of the reduction of blood glucose level and apoptotic cell numbers, PCA and Corchorus olitorius decreace the complications of diabetes mellitus induced rat testis.

RESUMEN: El objetivo de este estudio fue investigar los efectos del ácido protocatéquico y Corchorus olitorius sobre el tejido testicular de rata diabética inducida por estreptozotocina (STZ). Las ratas Wistar Albino fueron seleccionadas al azar y se dividieron en cinco grupos; Diabetes Mellitus, Diabetes Mellitus tratada con Corchorus olitorius (STZ + CO), Diabetes Mellitus tratada con ácido protocatéquico (STZ + PCA), Corchorus olitorius (CO), ácido protocatéquico (PCA) y Control. El modelo diabético se generó por inyección intraperitoneal de 60 mg/kg de estreptozotosina. Después de 48 horas de la inyección de STZ, se recogieron muestras de sangre de la vena de la cola para medir los niveles de glucosa. Niveles mayores a 250 mg/dL fueron considerados como especímenes diabéticos y alimentados con Corchorus olitorius de 250 mg/kg o PCA de 20 mg/kg por sonda oral durante tres semanas. Al final del experimento, se extirparon los testículos derechos y se fijaron en formaldehído neutro al 10 % para la inclusión en parafina. Las secciones se tiñeron con HE, tricromo de Masson, PAS y TUNEL para evaluación microscópica. Los tejidos de los testículos de los grupos control, tratados solo con PCA y con Corchorus olitorius mostraron una organización tisular normal. En cambio en modelos diabéticos inducidos por STZ y grupos no tratados se observó degeneración en los túbulos seminíferos, vacuolización, separaciones en series de células espermatogénicas, efusión de grupos celulares en la luz, formación del cuerpo vesicular, acumulación de líquido en la región intersticial y edema. Además, se determinó una mayor cantidad de células teñidas con TUNEL (+) en el grupo STZ. Por otro lado, el nivel de glucosa en sangre y el número de células teñidas con TUNEL (+) disminuyeron como resultado del tratamiento con PCA y Corchorus olitorius. Debido a la reducción del nivel de glucosa en sangre y el número de células apoptóticas, se observó que PCA y Corchorus olitorius disminuyen las complicaciones de los testículos de rata inducidos por diabetes mellitus.

Protocatechuic acid supplement alleviates allergic airway inflammation by inhibiting the IL-4Rα-STAT6 and Jagged 1/Jagged2-Notch1/Notch2 pathways in allergic asthmatic mice.

OBJECTIVE AND DESIGN: To clarify the effects of dietary supplementation of protocatechuic acid (PCA) and in-depth mechanisms on allergic asthma in ovalbumin (OVA)-induced mice. MATERIALS: Female BALB/c mice were randomly divided into three groups (n = 10 in each group): control group, OVA-induced allergic asthma group, and OVA plus PCA group. TREATMENT: Dietary supplementation of PCA was achieved by adding 50 mg/kg PCA to AIN 93G diet for 25 days. METHODS: Peripheral blood cells, pulmonary inflammatory cell infiltration, the levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), the mRNA levels of Th2-related genes in the lungs, and the protein expressions of the IL-4Rα-STAT6 and the Jagged1/Jagged2-Notch1/Notch2 signaling pathways were measured. RESULTS: Significantly reduced inflammatory cells infiltration and mucosal hypersecretion in the lung tissues, repaired levels of interleukin IL-4, IL-5, and IL-13 in the BALF, and decreased mRNA expression of IL-4, IL-5, and GATA3 were observed in OVA plus PCA group. Moreover, PCA treatment down-regulated the protein levels of IL-4Rα-STAT6 and Jagged1/Jagged2-Notch1/Notch2 signaling pathways. CONCLUSIONS: Dietary supplement of PCA alleviated allergic asthma partly through suppressing the IL-4Rα-STAT6 and Jagged1/Jagged2-Notch1/Notch2 signaling pathways in mice. Our study provided the theoretic basis of PCA used as functional food in preventing allergic asthma.

Black Raspberries and Protocatechuic Acid Mitigate DNFB-Induced Contact Hypersensitivity by Down-Regulating Dendritic Cell Activation and Inhibiting Mediators of Effector Responses.

Contact hypersensitivity (CHS) is the most common occupational dermatological disease. Dendritic cells (DCs) mediate the sensitization stage of CHS, while T-cells facilitate the effector mechanisms that drive CHS. Black raspberry (Rubus occidentalis, BRB) and BRB phytochemicals possess immunomodulatory properties, but their dietary effects on CHS are unknown. We examined the effects of diets containing BRB and protocatechuic acid (PCA, a constituent of BRB and an anthocyanin metabolite produced largely by gut microbes), on CHS, using a model induced by 2,4-dinitrofluorobenze (DNFB). Mice were fed control diet or diets supplemented with BRB or PCA. In vitro bone-marrow derived DCs and RAW264.7 macrophages were treated with BRB extract and PCA. Mice fed BRB or PCA supplemented diets displayed decreased DNFB-induced ear swelling, marked by decreased splenic DC accumulation. BRB extract diminished DC maturation associated with reduced Cd80 expression and Interleukin (IL)-12 secretion, and PCA reduced IL-12. Dietary supplementation with BRB and PCA induced differential decreases in IL-12-driven CHS mediators, including Interferon (IFN)-γ and IL-17 production by T-cells. BRB extracts and PCA directly attenuated CHS-promoting macrophage activity mediated by nitric oxide and IL-12. Our results demonstrate that BRB and PCA mitigate CHS pathology, providing a rationale for CHS alleviation via dietary supplementation with BRB or BRB derived anthocyanins.

Administration of a mixture of triterpenoids from yeyachun and phenolic acids from danshen ameliorates carbon tetrachloride-induced liver fibrosis in mice by the regulation of intestinal flora.

yeyachun and danshen exist as Chinese patent medicine, Xuemai Tong, and are clearly effective at alleviating liver fibrosis (LF). Previous studies have indicated that triterpenoids from yeyachun (EFT), and phenolic acids from danshen (SMP) are effective in the treatment of LF. The regulation of intestinal flora is an effective method for treating LF. The aim of this study was to investigate the effect of a mixture of EFT and SMP on carbon tetrachloride (CCl4) induced LF. Our results showed the mixture significantly decreased liver damage and fibrosis index, and maintained liver tissue composition, compared to the model group. Moreover, the imbalance of symptoms of intestinal flora was improved. The mixture also caused changes to metabolites of gut flora. Furthermore, the expression of CD68 in liver tissues from the treated groups was significantly decreased when compared to the model group. However, no significant difference was observed from microstructure of gut tissues and LPS concentrations in the serum between mixture treated mice and model mice. This study suggests that the mixture of EFT and SMP had a significant effect on CCl4 induced LF, and the mechanism of this action, at least in part, involved the regulation of intestinal flora and their metabolites.

Fruits of Terminalia chebula Retz.: A review on traditional uses, bioactive chemical constituents and pharmacological activities.

Fruits of Terminalia chebula Retz. (Combretaceae) are widely used as crude drugs in various traditional medicine systems. The aim of this article is to review the available scientific information regarding the traditional uses, bioactive chemical constituents and the pharmacological activities of T. chebula. Numerous researches conducted on T. chebula have confirmed the presence of wide range of the phytochemicals such as flavonoids, tannins, phenolic acids and other bioactive compounds. T. chebula is also widely studied regarding its pharmacological activities such as antioxidant, hepatoprotective, neuroprotective, cytotoxic, antidiabetic, anti-inflammatory activities among others. However, more in vivo and clinical studies for mechanism-based pharmacological evaluation should be conducted in future to provide stronger scientific evidences for their traditional uses.

A green tea-triggered genetic control system for treating diabetes in mice and monkeys.

Cell-based therapies are recognized as the next frontier in medicine, but the translation of many promising technologies into the clinic is currently limited by a lack of remote-control inducers that are safe and can be tightly regulated. Here, we developed therapeutically active engineered cells regulated by a control system that is responsive to protocatechuic acid (PCA), a metabolite found in green tea. We constructed multiple genetic control technologies that could toggle a PCA-responsive ON/OFF switch based on a transcriptional repressor from Streptomyces coelicolor We demonstrated that PCA-controlled switches can be used for guide RNA expression-mediated control of the CRISPR-Cas9 systems for gene editing and epigenetic remodeling. We showed how these technologies could be used as implantable biocomputers in live mice to perform complex logic computations that integrated signals from multiple food metabolites. Last, we used our system to treat type 1 and type 2 diabetes in mice and cynomolgus monkeys. This biocompatible and versatile food phenolic acid-controlled transgenic device opens opportunities for dynamic interventions in gene- and cell-based precision medicine.

Protocatechuic Acid-Mediated miR-219a-5p Activation Inhibits the p66shc Oxidant Pathway to Alleviate Alcoholic Liver Injury.

Alcohol abuse has become common worldwide and has been recognized as a major cause of chronic alcoholic liver disease (ALD). ALD encompasses a complex process that includes a broad scope of hepatic lesions, ranging from steatosis to cirrhosis. In particular, reactive oxygen species (ROS) are mainly involved. Numerous studies have shown that p66shc plays a significant role in ALD. Protocatechuic acid (PCA), a dihydroxybenzoic acid that is naturally found in green tea, vegetables, and fruits, has efficient free radical scavenging effects. In this study, we aimed to assess the protective effect of PCA on ALD and to evaluate the microRNA- (miRNA-) p66shc-mediated reduction of ROS formation in ALD. Our results demonstrated that PCA treatment significantly decreased p66shc expression and downstream ROS formation in ALD. miR-219a-5p, which was identified by bioinformatics and experimental analysis, was enhanced by PCA and subsequently suppressed p66shc expression. Importantly, p66shc played an essential role in the protection of PCA-stimulated miR-219a-5p overexpression. Overall, these findings show that PCA-stimulated miR-219a-5p expression mitigates ALD by reducing p66shc-mediated ROS formation. This study may contribute to the development of therapeutic interventions for ALD.

Protocatechuic acid attenuates angiotensin II-induced cardiac fibrosis in cardiac fibroblasts through inhibiting the NOX4/ROS/p38 signaling pathway.

Cardiac fibrosis plays a crucial role in the pathogenesis of myocardial infarction (MI). It has been found that differentiation of cardiac fibroblasts (CFs) into myofibroblasts is a major event in the process of cardiac fibrosis. In the present study, we aimed to investigate the effects of protocatechuic acid (PCA), a cardiac protective agent, on the CFs differentiation in vitro. The results showed that PCA exhibited inhibitory effects on the cell proliferation and migration in angiotensin II (Ang II)-induced CFs. PCA treatment suppressed the Ang II-induced expression of α-smooth muscle actin (α-SMA), which is a hallmark of myofibroblasts. In addition, the production of extracellular matrix (ECM) proteins, including type I collagen (Col I) and connective tissue growth factor (CTGF), were significantly decreased in the PCA-treated CFs. The Ang II-induced increased levels of matrix metalloproteinase (MMP)-2, and MMP-9 were reduced by PCA. Furthermore, PCA resulted in decrease in reactive oxygen species (ROS) generation, as well as the expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme 4 (NOX4) and p-p38 in Ang II-induced CFs. These findings showed that PCA treatment prevented the Ang II-induced cardiac fibrosis by inhibiting the NOX4/ROS/p38 signaling pathway in vitro, suggesting that PCA might be a therapeutic agent for MI.

Monoaminergic system is implicated in the antidepressant-like effect of hyperoside and protocatechuic acid isolated from Impatiens glandulifera Royle in mice.

We have recently demonstrated that the hydroethanolic extracts of Impatiens glandulifera Royle (Balsaminaceae) have antianxiety effect in mice. The present study was aimed to investigate an antidepressant activity of hyperoside (HYP) and protocatechuic acid (PCA), two polyphenols isolated from the aerial parts of this plant, using the forced swimming test (FST) and tail suspension test (TST) in mice. The implication of the monoaminergic system in this effect was assessed and brain-derived neurotrophic factor (BDNF) expression was measured. At doses 1.875, 3.75 and 7.5 mg/kg, HYP and PCA significantly reduced immobility in the FST and TST, without affecting locomotor activity of mice. Pretreatment with p-chlorophenylalanine (PCPA 100 mg/kg, a serotonin synthesis inhibitor) or α-methyl-DL-tyrosine (AMPT 100 mg/kg, a catecholamine synthesis inhibitor) was able to prevent antidepressant-like effect of HYP and PCA (3.75 mg/kg). Sub-effective doses of fluoxetine (5 mg/kg) or reboxetine (2 mg/kg) were capable of potentiating the effect of a sub-effective dose of HYP (0.94 mg/kg) in the FST. Co-administration of sub-effective dose of PCA (0.94 mg/kg) and reboxetine (2 mg/kg) resulted in reducing immobility in the FST. The antidepressant-like effect of HYP and PCA was also prevented by the administration of sulpiride (50 mg/kg), a D2 antagonist. In addition, HYP (3.75 and 7.5 mg/kg) and PCA (7.5 mg/kg) improved the expression of hippocampal BDNF of mice subjected to TST. Altogether, our findings suggest that HYP and PCA exert antidepressant-like effects in mice, which was possibly mediated by monoaminergic system and the upregulation of BDNF level.

Phenolic acid profiling and antiglycation studies of leaf and fruit extracts of tyrosine primed Momordica charantia seeds for possible treatment of diabetes mellitus.

The increasing risk of variety of fatal diseases including diabetes mellitus is imposing serious challenge to chemist, biologists and clinicians. Due to the side effects of the chemotherapy, worldwide it is thinking that phyto-medicine are more effective to cope continuously increasing risk of fatal diseases without any side effect. Seed priming is a strategic pre-sowing semi-bioengineering technique which has ability to improve the growth rate and biologically active compounds in short time. Among seed priming techniques, tyrosine seed priming most frequently used because amino acids provide best growth media for nutritional food crops. Seeds of Momordica charantia were subjected to the pre-sowing tyrosine solution. Different growth parameters including growth emergence rate, seedling vigor, growth and weight of root, shoot and leaf were studied. The results showed positive effect on Momordica charantia seed growth and phenolic acids production i.e. ferulic acid - 43.95 ppm and sinapic acid - 18.39 ppm. The antiglycation assay showed 23.45±1.23% antiglycation activity of primed-seed fruit extract as compare to control seed fruit extract (0.87±0.03%). On the basis of the results, it is concluded that tyrosine primed seed fruit extract could effectively be further tested for pre-clinical and clinical studies to manage diabetes mellitus disease.

Potential Antinociceptive Effects of Chinese Propolis and Identification on Its Active Compounds.

Propolis is an important bee product which has been applied to the treatment of several diseases. The aim of this study was to understand the material basis of Chinese propolis on pain relief; different Chinese propolis fractions (40W, 40E, 70E, and 95E raw propolis extracted followed by 40%, 70%, or 95% ethanol) were prepared, and their antinociceptive effects were evaluated. By analyzing using UPLC-Q-TOF-MS, we showed that 40W was rich in phenolic acids, like caffeic acid, while 40E, 70E, and 95E have relatively high levels in flavonoids, like galangin, pinocembrin, and chrysin. Notably, chrysin amounts in 70E and 95E are much higher than those in 40E fraction. Antinociceptive effects by these propolis fractions were evaluated in mice using acetic acid-induced writhing test, hot plate test, and tail immersion test, respectively. We noticed that only 40E fraction showed a significant reduction on acetic acid-induced writhing test. Importantly, in the hot plate test, all groups showed their effectiveness, except for the 70E group. We also noticed that 40W, 40E, and 95E administration caused an increase in the tail withdrawal latency of the mice. These data suggested that the different antinociceptive effects of different fractions from Chinese propolis extracts are directly link to their flavonoid composition.

Phenolic acid and flavonoid-rich fraction of Sasa quelpaertensis Nakai leaves prevent alcohol induced fatty liver through AMPK activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Sasa quelpaertensis Nakai is an edible dwarf bamboo cultivated mainly in Jeju Island, South Korea and its leaf displays various health-promoting properties including antioxidant scavenging. AIM OF THE STUDY: In this study, we aimed at elucidating its hepatoprotective effect against alcohol-induced fatty liver. METHODS: In in vitro study, we evaluated the cytotoxicity and hepatoprotective effect of different solvent fractions (aqua, butanol, chloroform, ethyl acetate and hexane) of 80% EtOH extract of S. quelpaertensis Nakai leaf. In vivo experiment performed using binge alcohol consumption model. RESULTS: Although all five fractions (0-1000 µg/mL) were non-cytotoxic to HepG2 cells, only ethyl acetate fraction (SQEA), rich in phenolic acids such as p-coumaric acid and flavonoids particularly myristin, showed hepatoprotective effect against EtOH (400 mM) in HepG2 cells. Furthermore, SQEA significantly decreased the ethanol induced cell death and enhanced the cell proliferation. In in vivo experiment using binge consumption model (5 g of EtOH/kg body weight in every 12 h for 3 times), SQEA treatment (10, 50 and 100 mg/kg) markedly reduced the alcohol induced histopathological changes and serum EtOH content, and reversed the reduction of glutathione level in ethanol challenged livers. Further, it suppressed the expression of cytochrome P450 2E1 (CYP2E1). In particular, SQEA activated AMP activated protein kinase (AMPK) pathway, and decreased the expression of tumor necrosis factor receptor-1 (TNFR1), which attenuated lipogenesis via decreased expression of fatty acid synthase (FAS). Inhibited lipogenesis due to SQEA treatment directed towards decreased perilipin-2 expression. These results indicate that SQEA has hypolipidemic effect which is mediated by decreased oxidative stress, increased fatty acid oxidation response and decreased lipogenesis. CONCLUSION: Our results suggest the possibility of developing SQEA as a natural hepatoprotective agent potent in attenuating alcohol-induced fatty liver.

Effects of Protocatechuic Acid (PCA) on Global Cerebral Ischemia-Induced Hippocampal Neuronal Death.

Global cerebral ischemia (GCI) is one of the main causes of hippocampal neuronal death. Ischemic damage can be rescued by early blood reperfusion. However, under some circumstances reperfusion itself can trigger a cell death process that is initiated by the reintroduction of blood, followed by the production of superoxide, a blood⁻brain barrier (BBB) disruption and microglial activation. Protocatechuic acid (PCA) is a major metabolite of the antioxidant polyphenols, which have been discovered in green tea. PCA has been shown to have antioxidant effects on healthy cells and anti-proliferative effects on tumor cells. To test whether PCA can prevent ischemia-induced hippocampal neuronal death, rats were injected with PCA (30 mg/kg/day) per oral (p.o) for one week after global ischemia. To evaluate degenerating neurons, oxidative stress, microglial activation and BBB disruption, we performed Fluoro-Jade B (FJB), 4-hydroxynonenal (4HNE), CD11b, GFAP and IgG staining. In the present study, we found that PCA significantly decreased degenerating neuronal cell death, oxidative stress, microglial activation, astrocyte activation and BBB disruption compared with the vehicle-treated group after ischemia. In addition, an ischemia-induced reduction in glutathione (GSH) concentration in hippocampal neurons was recovered by PCA administration. Therefore, the administration of PCA may be further investigated as a promising tool for decreasing hippocampal neuronal death after global cerebral ischemia.

Antihypertensive and antioxidant effects of protocatechuic acid in deoxycorticosterone acetate-salt hypertensive rats.

Protocatechuic acid (PCA) is a natural antioxidant with beneficial cardiovascular properties. In this study, the effect of supplementation with PCA was investigated in deoxycorticosterone acetate (DOCA)-salt hypertension. Male Wistar rats received DOCA (25 mg/kg, s.c.) twice weekly and 1% NaCl in drinking water and simultaneously treated with PCA (50, 100 and 200 mg/kg, p.o.) for 4 weeks. Systolic blood pressure (SBP) was detected using tail-cuff method. Electrolytes including Na+, K+ and chloride, catalase activity, glutathione, total antioxidant capacity, malondialdehyde (MDA) and hydroperoxides concentration were measured in serum samples. Body and organs weight, water intake and, kidney and heart histopathology were also evaluated. Administration of PCA reversed the changes caused by DOCA-salt approximately at all doses. At the lowest dose, PCA significantly decreased SBP (132.5 ±â€¯4.0 vs 152.3 ±â€¯4.5 mmHg, P < .05), serum sodium (138.5  ±â€¯1.52 vs 141 ±â€¯1.50, P < .05) and chloride level (101.6 ±â€¯1.47 vs 110 ±â€¯1.39, P < .01) and raised serum potassium level (3.8 ±â€¯0.09 vs 3.1 ±â€¯0.17, P < .05) compared with DOCA-salt hypertensive rats. PCA increased serum catalase activity, total antioxidant capacity and glutathione concentration and reduced MDA and hydroperoxides levels. PCA also improved organ weight changes, reduced water intake and moderately prevented histopathological changes of kidney and heart upon DOCA-salt administration. The present study indicates the antihypertensive and antioxidant effects of PCA against DOCA-salt hypertension.

Dietary phenolic acids reverse insulin resistance, hyperglycaemia, dyslipidaemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats.

This study investigated the influence of caffeic, ferulic, gallic and protocatechuic acids on high-fructose diet-induced metabolic syndrome in rats. Oral administration of the phenolic acids significantly reversed high-fructose diet-mediated increase in body mass index and blood glucose. Furthermore, phenolic acids restored high-fructose diet-mediated alterations in metabolic hormones (insulin, leptin and adiponectin). Similarly, elevated tumour necrosis factor-α, interleukin-6 and -8 were significantly lowered. Administration of phenolic acids restored High-fructose diet-mediated increase in the levels of lipid parameters and indices of atherosclerosis, cardiac and cardiovascular diseases. High-fructose diet-mediated decrease in activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase) and increase in oxidative stress biomarkers (reduced glutathione, lipid peroxidation products, protein oxidation and fragmented DNA) were significantly restored by the phenolic acids. The result of this study shows protective influence of caffeic acid, ferulic acid, gallic acid and protocatechuic acid in high-fructose diet-induced metabolic syndrome.

Preventive and Therapeutic Potentials of Anthocyanins in Diabetes and Associated Complications.

Diet is an essential factor affecting the development of and risk for diabetes mellitus. In search of preventative and therapeutic strategies, the potential role of certain foods and their bioactive compounds to prevent the pathogenesis associated with metabolic diseases is to be considered. Human consumption of anthocyanins is among the highest of all flavonoids. Epidemiological studies have suggested that the consumption of anthocyanins lowers the risk of diabetes and diabetic complications. Anthocyanins are important natural bioactive pigments responsible for red to blue colour of fruits, leaves, seeds, stems and flowers, which are present in a variety of plant species particularly in berries and cherries. A large number of bioactive anthocyanins, such as cyanidin, malvidin, delphinidin, pelargonidin, peonidin, petunidin and their metabolites have shown multiple biological activities with apparent effects on glucose absorption, glucose uptake, insulin secretion and sensitivity, on the enzymes involved in glucose metabolism, gene expressions, inflammatory mediators, glucose transporters in progression of diabetes and associated complications, such as diabetic retinopathy, nephropathy, neuropathy and diabetic vascular diseases. The versatility of the anthocyanins provides a promising approach for diabetes management than synthetic drugs. Here we summarize the effect of several anthocyanins on many in vitro, in vivo and clinical studies and also reveal the mechanisms which could prevent or reverse the underlying mechanisms of diabetic pathologies including promotion of antioxidant, antihyperlipidemic, anti-inflammatory and anti-apoptotic activities.

Bypassing human CoQ10 deficiency.

Primary disorders of the human coenzyme Q10 (CoQ10) biosynthesis pathway are a known cause of severe pediatric diseases. So far, oral administration of CoQ10 is the only treatment strategy for affected individuals. However, the real benefit of CoQ10 supplementation remains questionable and clinical studies regarding efficiency are lacking. Here we provide an outlook on novel treatment approaches using CoQ precursor compounds. These metabolic bypass strategies might be a promising alternative for oral CoQ10 supplementation regimens.