Protective Effects Of Protocatechuic Acid Research Articles

The protective effects of protocatechuic acid against natural and chemical toxicants: cellular and molecular mechanisms.

Protocatechuic acid (PCA) is a water-soluble polyphenol compound that is extracted from certain fruits and plants or obtained from glucose fermentation. Several in vivo and in vitro studies have determined that PCA has protective effects against the toxicity of natural and chemical toxicants. We searched these articles in PubMed, Google Scholar, and Scopus with appropriate keywords from inception up to August 2023. Forty-nine studies were found about protective effects of PCA against drug toxicity, metal toxicity, toxins, chemical toxicants, and some other miscellaneous toxicants. PCA indicates these protective effects by suppression of oxidative stress, inflammation, and apoptosis. PCA reduces reactive oxygen/nitrogen species (RONS) and enhances the level of antioxidant parameters mainly through the activation of the Nrf-2 signaling pathway. PCA also decreases the levels of inflammatory mediators via downregulating the TLR-4-mediated IKBKB/NF-κB and MAPK/Erk signaling pathways. In addition, PCA inhibits apoptosis by lowering the expression of Bax, caspase-3, and caspase-9 along with enhancing the level of the antiapoptotic protein Bcl-2. Further evaluation, especially in humans, is necessary to confirm PCA as a potential therapeutic approach to intervene in such toxicities.

Protective Effect of Protocatechuic Acid on Oxidative Damage and Cognitive Impairment in Pb-Induced Rats.

Protocatechuic acid (PCA), a class of water-soluble phenolic acid abundant in the human diet, has been shown to be of great nutritional interest and to have medicinal value. However, the protective effects against lead (Pb)-induced body injury have not been elucidated. In this study, we explored the protective effect of PCA on Pb-induced oxidative damage and cognitive impairment in rats. The results showed that PCA could reduce the Pb content in rat bodies (blood, bone, brain, liver, and kidney) after Pb exposure. Moreover, PCA may inhibit Pb-induced oxidative damage by increasing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreasing the level of malondialdehyde (MDA) in the brain, liver, and kidney. In addition, PCA may alleviate Pb-induced learning and memory impairment by upregulating neurotransmitter levels; maintaining the normal function of N-methyl-D-aspartate receptors (NMDARs); and promoting Ca2+ influx, thus activating signaling molecules, related protein kinases, and transcription factors in the cAMP-PKA-CREB pathway. In general, PCA could reduce oxidative stress and ameliorate the learning and memory deficits in Pb-treated rats, indicating that PCA may be an effective preventive agent and treatment or plumbism.

High affinity of protocatechuic acid to human serum albumin and modulatory effects against oxidative stress and inflammation in alveolar epithelial cells: Modulation of pulmonary fibrosis

Protocatechuic acid (PCA), C7H6O4, has been shown to possess potential antioxidant properties. But its interaction with the main plasma carrier protein, human serum albumin (HSA), as well as its antioxidant mechanism remains largely unknown. It has been shown that induced pulmonary fibrosis can be modulated through mitigating epithelial apoptosis mediated by the prohibition of oxidative stress. Therefore, in this study, the interaction of PCA and HSA was explored by spectroscopy, calorimetry (DSC), as well as molecular docking studies. Also, the protective effects of PCA against lipopolysaccharide (LPS)-induced cytotoxicity and oxidative stress were evaluated by MTT, ROS, ELISA, real-time PCR, and western blot assays. It was shown that under the interaction of HSA with PCA a spontaneous interaction occurs with the contribution of hydrophobic forces, which results in the formation of a stable complex. Cellular assays showed that PCA reduced LPS-induced cytotoxicity in human type II alveolar epithelial cells (AECs) through mitigation of ROS production, release and gene expression of TNf-α and IL-1β as pro-inflammatory mediators, and caspase-3 gene and protein as an apoptotic factor. Also, it was shown that PCA can reduce the expression of NF-κB at the protein level, indicating a possible inhibition of pulmonary fibrosis via regulating the NF-κB signaling pathway. In conclusion, PCA could be a promising therapeutic agent for the control of oxidative stress in AECs which is an important factor in redox modulatory therapy, while its pharmacodynamics can be modulated by interaction with HSA.

Abstract P127: Protective Effects Of Protocatechuic Acid In Murine Model Of UUO-induced Renal Injury

Chronic kidney disease (CKD) is a global public health problem, affecting millions of people worldwide. CKD can result from obstructive nephropathy; a condition that arises from urinary flow obstruction in the kidneys, leading to renal inflammation and injury. Protocatechuic acid (PCA) is a natural phenolic compound that showed a promising protective effect in cardiovascular diseases. In the current study, we investigated the reno-protective effects of PCA in mice model of unilateral ureteral obstruction (UUO). Male C57BL/6J mice (10-12 weeks old) were divided into 4 groups (n=6-8/group). Sham control, Sham/P (sham plus PCA (50 mg/kg IP daily for two weeks), UUO, and UUO plus PCA. Induction of UUO significantly decreased creatinine clearance (CrCl) and increased pulse wave velocity (PWV), a marker of arterial stiffness, relative to sham control (CrCl; sham control: 60.6 ± 14 vs. UUO: 24.5 ± 6.0 ml/day and PWV; sham control: 1.58 ± 0.1 vs. UUO: 3.35 ± 0.22 m/s). Immuno-histochemical analysis revealed that KIM-1 expression, a marker of tubular injury, was elevated in UUO mice vs. sham control and PCA reduced this elevation, however there was no significance difference in urinary KIM-1 excretion. Moreover, UUO significantly increased renal oxidative stress and inflammation as evidenced by elevation in renal TBARs, IL-6, active caspase-1 and active MMP2 compared to sham control (TBARs; sham control: 8.3 ± 0.9 vs. UUO: 30.5 ± 3.33 nmol/mg protein, renal IL-6; sham control: 1 ± 0.07 vs. UUO: 24.35 ± 8.55 pg/mg protein, active caspase-1; sham control: 1.7 x 10 3 ± 95 vs. UUO: 2.79 x 10 3 ± 145 cpm/μg protein and MMP2; sham control: 1.6 ± 0.4 vs. UUO: 6 ± 0.6 ng/μg protein). PCA treatment significantly improved the UUO-induced decline in creatinine clearance (52.5 ± 10.2 ml/day) and attenuated UUO-induced elevation in renal PWV (1.95 ± 0.1 m/s). Furthermore, PCA treatment significantly decreased renal TBARs (5.2 ± 1.12 nmol/mg protein), IL-6 (5.39 ± 1.4 pg/mg protein) and active MMP2 (1.1 ± 0.3 ng/μg protein) in UUO-induced renal injury. Collectively, these data suggests that PCA provides renal protection in murine model of UUO via reduction of renal oxidative stress, inflammation and fibrosis.

Protective Effect of Protocatechuic Acid in Genotoxicity-Induced by Carbon Tetrachloride: A Preliminary Study

Carbon tetrachloride (CCl4) is commonly utilized as a solvent, a refrigerant, and a dry-cleaning agent. However, its genotoxic effect has been well documented. The present work was designed to assess the genotoxic effect of carbon tetrachloride in the bone marrow of rats. The safety and the possible protective effect of protocatechuic acid (PCA) in the genotoxicity induced by carbon tetrachloride (CCl4) were evaluated using a micronucleus assay. Rats were divided into six groups where groups I and II served as the control. Group III was exposed to CCl4 only at 3mL/kg intraperitoneally. Groups IV and V rats were pretreated with PCA at 10mg/kg and 20 mg/kg respectively before administering CCl4. Group VI received PCA only (20mg/kg) for 7 consecutive days. At the end of the experiment, a micronucleus assay was carried out. There was a significant MnPCE in the bone marrow of CCl4-treated rats as compared with control (p<0.05). The administration of PCA at the doses of 10 and 20mg/kg significantly reduced the MnPCE when compared with the group treated with CCl4 (3ml/kg) only (p<0.05). The data provided in this study considered PCA to be relatively safe, non-genotoxic and can modulate the genetic damage involved in CCl4 toxicity by decreasing the frequency of micronucleated cells.

Protective effects of protocatechuic acid against doxorubicin- and arsenic trioxide-induced toxicity in cardiomyocytes.

Some chemotherapeutic drugs are associated with an increased risk of cardiotoxicity in patients. Protocatechuic acid (PCA) is a phenolic acid with valuable cardiovascular, chemo-preventive, and anticancer activities. Recent studies have shown the cardioprotective effects of PCA in several pathological conditions. This investigation aimed to assess the possible protective effects of PCA on cardiomyocytes against toxicities caused by anti-neoplastic agents, doxorubicin (DOX), and arsenic trioxide (ATO). H9C2 cells were exposed to DOX (1 μM) or ATO (35 μM) after 24 h pretreatment with PCA (1-100 μM). MTT and lactate dehydrogenase (LDH) tests were used to define cell viability or cytotoxicity. Total oxidant and antioxidant capacities were evaluated by measuring hydroperoxides and ferric-reducing antioxidant power (FRAP) levels. Expression of the TLR4 gene was also quantitatively estimated by real-time polymerase chain reaction. PCA showed a proliferative effect on cardiomyocytes and significantly enhanced cell viability and reduced cytotoxicity of DOX and ATO during MTT and LDH assays. Pretreatment of cardiomyocytes with PCA significantly decreased hydroperoxide levels and elevated FRAP value. Moreover, PCA meaningfully decreased TLR4 expression in DOX-and ATO-treated cardiomyocytes. In conclusion, antioxidant and cytoprotective activities were found for PCA versus toxicities caused by DOX and ATO in cardiomyocytes. However, further in vivo investigations are recommended to assess its clinical value for the prevention and treatment of cardiotoxicity induced by chemotherapeutic agents.

Protective effects of protocatechuic acid on growth performance, intestinal barrier and antioxidant capacity in broilers challenged with lipopolysaccharide

‘Prohibition of the antibiotic uses’ aggravates the problem of intestinal diseases in poultry, and nutritional regulation has become a research hotspot, such as supplementation with active ingredients derived from plants. This research was conducted to investigate the effects of protocatechuic acid (PCA) on growth, intestinal barrier, and antioxidant capacity of broilers injected with lipopolysaccharide (LPS). Four hundred and eighty 1-day-old yellow feather broilers were randomly allocated to four groups, each with six replicates of 20 broilers. The treatments were basal diet + saline injection (CON) or LPS injection (CON-LPS), and diets with 300 or 600 mg/kg PCA supplementation + LPS injection (P300, P600). Birds were injected intramuscularly on 17th and 19th day of age, then sampled on day 21. The LPS injection significantly decreased BW and average daily gain of broilers, and compared with birds in CON-LPS, PCA supplementation increased (P < 0.05) those variables; moreover, 300 mg/kg PCA also decreased the feed-to-gain ratio. No differences were observed in relative weights of immune organs (P > 0.05). LPS decreased the villus height/crypt depth ratio (V/C) in jejunum of broilers, while PCA (P300 and P600) increased (P < 0.05) the jejunal villus height and V/C compared with birds in CON-LPS. LPS challenge increased jejunal malondialdehyde (MDA) concentration and decreased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities in plasma (P < 0.05); compared with birds in CON-LPS, jejunal and plasmal GSH-Px activity (P300 and P600) and jejunal T-SOD activity (P300) were decreased (P < 0.05), and hepatic MDA concentration (P600) was increased (P < 0.05). LPS significantly decreased the transcript abundances of OCLN, ZO-1, JAM2, MUC2, SOD1, CAT and GPX in jejunal mucosa of birds, and supplementation with PCA attenuated the decrease in OCLN, JAM2, and MUC2 expression compared with birds in CON-LPS; moreover, 600 mg/kg PCA offset the deduction in SOD1, CAT and GPX expression. In conclusion, dietary supplementation with PCA could improve antioxidant status and attenuate the damage in intestinal barrier and loss in growth performance of LPS-challenged broilers, and 600 mg/kg PCA showed more improved effects on antioxidant capacity.

Effects of protocatechuic acid against cisplatin-induced neurotoxicity in rat brains: an experimental study

Aims/Objectives: Cisplatin (CIS) is widely used in the treatment of various malignant tumors. The aim of study is to determine the potential protective effects of protocatechuic acid (PCA) on the brain in neurotoxicity induced by CIS in rats.Materials and methods: Forty rats were divided into four groups: 1-Control group: 2- PCA group: PCA was administered orally at a dose of 100 mg/kg/day for 5 weeks. 3-CIS group: 5 mg/kg/week of CIS was administered intraperiteonally 4-PCA + CIS group: The rats were given PCA orally daily for 5 weeks and CIS of 5 mg/kg/week. The brain tissues were used for histopathological examinations and for total antioxidant capacity (TAC), total oxidative state (TOS), oxidative stress index (OSI), tumornecrosis factor-alpha (T NF-α), interleukin 6 (IL-6) Interleukin 1 beta (IL-1β), acetylcholinesterase (AChE), glutamate, gamma aminobutyric acid (GABA), dopamine analyzes in ELISA. WBC, RBC, hemoglobin and hematocrit levels were measured.Results: PCA + CIS group compared to CIS group TOS, OSI, T NF-α, IL-6, IL-1β, AChE, glutamate, WBC levels decreased significantly, while TAC and GABA levels increased statistically significant. With this study, P CA corrected the deterioration in the oxidant / antioxidant status, suppressed neuro-inflammation, decreased AChE activity, partially normalized neurotransmitters, and decreased the increased WBC count. Necrosis seen in the CIS group in histopathological examinations was never seen in the PCA + CIS group.Conclusions: PCA may provide therapeutic benefit when used in conjunction with CIS.

Protocatechuic acid protects hepatocytes against hydrogen peroxide-induced oxidative stress

Oxidative stress is a main cause of tissue damage and highly associated with incidence of human chronic diseases. Among the major target organs attacked by reactive oxygen species (ROS) is the liver. Protocatechuic acid (PCA) is a phenolic compound found in green tea, acai oil and some mushroom species that possesses strong antioxidative and anti-inflammatory activity and may have benefits as a natural phytochemical for prevention of human diseases. However, the protective effect of PCA on hydrogen peroxide (H2O2)-induced oxidative stress specifically in the liver has not yet been investigated. The current study aims to observe if PCA possesses protective activity against H2O2-induced oxidative stress in HepG2 human liver cancer cells. Relative to untreated control cells, treatment of HepG2 cells with PCA reduced H2O2-induced cell death and mitigated H2O2-induced production of ROS; furthermore, it mitigated the H2O2-induced increase of caspase-3/7 enzyme activity, expression of cleaved poly(ADP-ribose) polymerase (PARP), expression of endoplasmic reticulum (ER) stress genes including activating transcription factor 4 (ATF4), serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α (IRE1α) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). These findings indicate that PCA effectively protects hepatic cells from H2O2-induced oxidative stress and cell death.

The protective effect of protocatechuic acid on hepatotoxicity induced by cisplatin in mice

Cisplatin is one of the most potent anti-cancer drugs used for the treatment of various solid tumors, yet it has several side effects that may limit its clinical use. Hepatotoxicity is one of the most serious side effects as it may lead to liver failure. Several mechanisms including oxidative stress, inflammation, and apoptosis have been examined in cisplatin-induced hepatotoxicity. Protocatechuic acid (Proto) which is naturally occurring phenolic acid has shown different biological activity as antioxidant, anti-inflammatory, and anti-apoptotic. In this study, we investigate the protective effect of Proto at two doses 100 and 150 mg/kg on hepatotoxicity induced by a single injection of 10 mg/kg cisplatin in female albino mice.The present study demonstrates for the first time that Proto administration (100 and 150 mg/Kg) significantly attenuates cisplatin-induced changes in liver function [increase serum albumin and decrease liver injury markers ALT, AST, GGT, and bilirubin]. This was associated with marked hepatic antioxidant effects [decrease MDA and NO levels, increase GSH and SOD activity]. Moreover, Proto reduced cisplatin-induced apoptosis in the liver through decreasing caspase-3, annexin-V, and BAX. Both doses suppressed cisplatin-induced expression of iNOS and NF-ᴋB p65 subunit and pro-inflammatory cytokines (IL-6 and TNF-α). Also, Proto improved histopathological examination of the liver. The present findings reveal that the antioxidant, anti-inflammatory, and anti-apoptotic effects of Proto are the main mechanisms by which Proto can ameliorate cisplatin-induced liver injury.

Effect of protocatechuic acid against renal ischemia reperfusion damage on extracellular matrix integrity and related signal pathways

Abstract Objective In this study, possible protective effects of protocatechuic acid (PCA) against experimentally-induced acute renal ischemia/reperfusion (I/R) damage in rats, on matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and the associated signal transduction pathways were investigated. Methods A total of 3–4 month-old, 200–250 g Sprague Dawley rats were divided into groups of five (n=7). A right kidney nephrectomy surgery was conducted to all groups under anesthesia. Rats were administered polyethylene glycol 1 h prior to ischemia (Group I, II) and PCA (Group III, IV, V) intraperitoneally. Forty five minutes before the ischemia during 24 h reperfusion on all rats except those in Group I. At the end of the experiment, blood urea nitrogen (BUN), creatinine values and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme levels were investigated in blood serum. MMP-2 and MMP-9 gene expression levels were determined by RT-PCR, and p38 and p-p38 protein expression levels Western blotting method. Renal tissue was examined histologically and immunohistochemically. Results It is assumed that 80 and 120 mg/kg of PCA might have a protective effect against oxidative stress damage caused by renal I/R. Conclusion In our study, PCA has been shown to modulate the increased expression of MMP-2 and MMP-9 mRNA along with increased oxidative stress during renal I/R, as well as oxidative damage-induced p38 protein expression. It was determined that particularly 120 mg kg−1 PCA reduced the renal I/R injury at a rate of 35–45%.

Protective effects of protocatechuic acid against cognitive impairment in an amyloid beta-induced Alzheimer's disease mouse model

In this study, we investigated the protective effects of protocatechuic acid (PA) against cognitive impairment in an amyloid-beta (Aβ)-induced Alzheimer's disease (AD) mouse model. PA was administered orally for 14 days at 100 and 200 mg/kg/day. To examine effects on cognition, we conducted behavior tests including the T-maze test, novel object recognition, and the Morris water maze test. In addition, we measured lipid peroxidation, nitric oxide (NO) production, and inflammation-related protein expression in mice tissues. The PA-administered group showed more use of novel routes, better novel object recognition, and learning and memory ability compared to the Aβ25-35-injected mice in the behavior tests. The results indicated that the administration of higher PA protected against cognitive impairment. In addition, the PA-administered groups showed significantly decreased lipid peroxidation and NO production in the brain, kidney, and liver tissues. Furthermore, the PA-administered groups showed attenuated Aβ25-35-induced neuroinflammation by downregulating inflammatory mediators, inducible nitric oxide synthase and cyclooxygenase-2 in the brain. The results of the present study suggest that PA may be a protective agent against AD.

Protective Effect of Protocatechuic Acid, Phenolic Compound of Momordica Charantia, against Oxidative Stress and Neuroinflammation in C6 Glial Cell

Protective Effect of Protocatechuic Acid, Phenolic Compound of <i>Momordica Charantia</i>, against Oxidative Stress and Neuroinflammation in C6 Glial Cell

Protective Effect of Protocatechuic Acid, Phenolic Compound of Momordica Charantia, against Oxidative Stress and Neuroinflammation in C6 Glial Cell

Protective Effect of Protocatechuic Acid, Phenolic Compound of <i>Momordica Charantia</i>, against Oxidative Stress and Neuroinflammation in C6 Glial Cell

Hepatorenal protective effects of protocatechuic acid in rats administered with anticancer drug methotrexate

The efficacy of methotrexate (MTX) as an anticancer drug is limited by some adverse effects including hepatic and renal toxicities. The present study investigated the possible protective effect of protocatechuic acid (PCA), a phenolic phytochemical widely present in several edible vegetables and fruits, on hepatorenal toxicity associated with MTX treatment in rats. Male Wistar rats were randomly assigned to five groups (n = 10), namely control, MTX alone (20 mg/kg), PCA alone (50 mg/kg), and rats that were coadministered MTX and PCA at 25 and 50 mg/kg. The MTX was administered as a single intraperitoneal dose on the first day, whereas PCA treatment lasted 7 days. Results indicated that PCA significantly (p < 0.05) abrogated MTX-mediated elevation in indices of hepatorenal toxicity. Furthermore, PCA protected against MTX-induced decreases in glutathione level and antioxidant enzyme activities as well as the increase in reactive oxygen and nitrogen species and lipid peroxidation in the liver and kidney of the treated rats. Administration of PCA markedly abated MTX-induced increases in interleukin-1β, tumor necrosis factor alpha, and caspase 3 activity in the rats. The biochemical data on the hepatorenal protective effects of PCA were well supported by the histological data. Collectively, PCA protected against MTX-induced hepatorenal toxicity via antioxidant, anti-inflammatory, and antiapoptotic mechanisms.

Protective effects of protocatechuic acid against seizure-induced neuronal death in the pilocarpine-induced status epilepticus rat model (P2.279)

Protective effects of protocatechuic acid against seizure-induced neuronal death in the pilocarpine-induced status epilepticus rat model (P2.279)

Protective effect of protocatechuic acid against inflammatory stress induced in human dermal fibroblasts

BackgroundProtocatechuic acid (PCA) is an anthocyanin metabolite with a high antioxidant property. It is also known for having anticancer and anti-inflammatory capacities with diverse medicinal activities. As one of the active ingredients in plant sources, PCA has been studied and has revealed various mechanisms, but effects on cosmetology are not sufficient. This paper suggests the effects of PCA on cosmeceutical via antioxidant and senescence-inhibiting activities.MethodsPrior to demonstrating PCA efficacy, we performed cell viability of PCA of 0–100 μM with or without lipopolysaccharide (LPS) using water-soluble tetrazolium salt (WST-1). Then, to evaluate the antioxidant capacity, especially excessive generated reactive oxygen species (ROS), researchers carried out ROS scavenging activity of PCA through 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence intensity. Cellular senescence was assessed by senescence-associated β-galactosidase (SA-β-gal)-positive value, and extracellular matrix (ECM)-associated gene expression, collagen type I, alpha 1 chain (COL1A1), and matrix metalloproteinase-1 (MMP1) were estimated through quantitative real-time polymerase chain reaction (qRT-PCR).ResultsPCA has not shown cellular toxicity under 100 μM, with or without LPS. The results demonstrated that PCA exerted an antioxidant effect on LPS-treated human dermal fibroblasts (HDFs), via ROS scavenging activity. Furthermore, PCA has shown the senescence attenuating efficacy in HDFs through reducing senescent cells and regulating COL1A1 and MMP1 gene expression.ConclusionThis work suggests the potential benefits of PCA against LPS-induced excessive ROS generation and cellular senescence, for the first time.

Protective Effects of Protocatechuic Acid on Seizure-Induced Neuronal Death.

Protocatechuic acid (PCA) is a type of phenolic acid found in green tea and has been shown to have potent antioxidant and anti-inflammatory properties. However, the effect of PCA on pilocarpine seizure-induced neuronal death in the hippocampus has not been evaluated. In the present study, we investigated the potential therapeutic effects of PCA on seizure-induced brain injury. Epileptic seizure was induced by intraperitoneal (i.p.) injection of pilocarpine (25 mg/kg) in adult male rats, and PCA (30 mg/kg) was injected into the intraperitoneal space for three consecutive days after the seizure. Neuronal injury and oxidative stress were evaluated three days after a seizure. To confirm whether PCA increases neuronal survival and reduced oxidative injury in the hippocampus, we performed Fluoro-Jade-B (FJB) staining to detect neuronal death and 4-hydroxynonenal (4HNE) staining to detect oxidative stress after the seizure. In the present study, we found that, compared to the seizure vehicle-treated group, PCA administration reduced neuronal death and oxidative stress in the hippocampus. To verify whether a decrease of neuronal death by PCA treatment was due to reduced glutathione (GSH) concentration, we measured glutathione with N-ethylmaleimide (GS-NEM) levels in hippocampal neurons. A seizure-induced reduction in the hippocampal neuronal GSH concentration was preserved by PCA treatment. We also examined whether microglia activation was affected by the PCA treatment after a seizure, using CD11b staining. Here, we found that seizure-induced microglia activation was significantly reduced by the PCA treatment. Therefore, the present study demonstrates that PCA deserves further investigation as a therapeutic agent for reducing hippocampal neuronal death after epileptic seizures.

Protective Effect of Protocatechuic Acid on TNBS-Induced Colitis in Mice Is Associated with Modulation of the SphK/S1P Signaling Pathway.

(1) Background: The present study aimed to investigate whether beneficial effects of protocatechuic acid (PCA) are associated with inhibition of the SphK/S1P axis and related signaling pathways in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) model of inflammatory bowel disease; (2) Methods: Colitis was induced in male Balb/c mice by intracolonic administration of 2 mg of TNBS. PCA (30 or 60 mg/kg body wt) was given intraperitoneally daily for five days; (3) Results: Administration of PCA prevented the macroscopic and microscopic damage to the colonic mucosa, the decrease in body weight gain and the increase in myeloperoxidase activity induced by TNBS. PCA-treated mice exhibited a lower oxidized/reduced glutathione ratio, increased expression of antioxidant enzymes and Nrf2 and reduced expression of proinflammatory cytokines. Following TNBS treatment mRNA levels, protein concentration and immunohistochemical labelling for SphK1 increased significantly. S1P production and expression of S1P receptor 1 and S1P phosphatase 2 were significantly elevated. However, there was a decreased expression of S1P lyase. Furthermore, TNBS-treated mice exhibited increased phosphorylation of AKT and ERK, and a higher expression of pSTAT3 and the NF-κB p65 subunit. PCA administration significantly prevented those changes; (4) Conclusions: Data obtained suggest a contribution of the SphK/S1P system and related signaling pathways to the anti-inflammatory effect of PCA.

Ameliorative Effect of Chronic Supplementation of Protocatechuic Acid Alone and in Combination with Ascorbic Acid in Aniline Hydrochloride Induced Spleen Toxicity in Rats.

Background. Present study was designed to evaluate the protective effects of protocatechuic acid alone and in combination with ascorbic acid in aniline hydrochloride induced spleen toxicity in rats. Materials and Methods. Male Wistar rats of either sex (200–250 g) were used and divided into different groups. Spleen toxicity was induced by aniline hydrochloride (100 ppm) in drinking water for a period of 28 days. Treatment group received protocatechuic acid (40 mg/kg/day, p.o.), ascorbic acid (40 mg/kg/day, p.o.), and combination of protocatechuic acid (20 mg/kg/day, p.o.) and ascorbic acid (20 mg/kg/day, p.o.) followed by aniline hydrochloride. At the end of treatment period serum and tissue parameters were evaluated. Result. Rats supplemented with aniline hydrochloride showed a significant alteration in body weight, spleen weight, feed consumption, water intake, hematological parameters (haemoglobin content, red blood cells, white blood cells, and total iron content), tissue parameters (lipid peroxidation, reduced glutathione, and nitric oxide content), and membrane bound phosphatase (ATPase) compared to control group. Histopathology of aniline hydrochloride induced spleen showed significant damage compared to control rats. Treatment with protocatechuic acid along with ascorbic acid showed better protection as compared to protocatechuic acid or ascorbic acid alone in aniline hydrochloride induced spleen toxicity. Conclusion. Treatment with protocatechuic acid and ascorbic acid in combination showed significant protection in aniline hydrochloride induced splenic toxicity in rats.