Therapeutic Effect Of Ferulic Acid Research Articles

Ferulic acid alleviates sciatica by inhibiting peripheral sensitization through the RhoA/p38MAPK signalling pathway

BackgroundNonsteroidal anti-inflammatory drugs are used to relieve sciatica, but their effects are not satisfactory. PurposeThis study aimed to explore the therapeutic effects of ferulic acid on sciatica. MethodsThirty-two SD rats were randomly divided into 4 groups, i.e., sham operation group, chronic constriction injury (CCI) group, mecobalamin group, and ferulic acid group. We conducted behavioural tests, ELISA, PCR, Western blots, and immunofluorescence analysis. Specific inhibitors were used in cell experiments to explore the related mechanisms. ResultsThermal hyperalgesia was induced after CCI operation, and ferulic acid relieved thermal hyperalgesia. In addition, ferulic acid decreased the IL1β, IL6, TNF-α, and CRP mRNA levels; the IBA-1, iNOS, IL1β, RhoA, RhoA-GTP, COX2, Rock1, TRPV1, TRPA1, and p-p38MAPK levels in dorsal root ganglion (DRG) neurons; and the LPS, CRP, substance P (SP), and prostaglandin E2 (PGE2) levels in serum, and these levels were higher in the CCI group. In the cell experiments, LPS induced M1 polarization of GMI-R1 cells via the RhoA/Rock pathway. Ferulic acid attenuated LPS-induced M1 polarization by decreasing the levels of M1 polarization markers, including IL1β, IL6, TNF-α, iNOS, and CD32, and increased M2 polarization by increasing the levels of M2 polarization markers, including CD206 and Arg-1. LPS treatment clearly increased the iNOS, IL1β, RhoA, Rock1, Rock2 and p-p38 MAPK levels and reduced Arg-1 expression, and ferulic acid reversed these changes. ConclusionFerulic acid can inhibit peripheral sensitization by reducing the levels of inflammatory factors, TRPA1 and TRPV1 through the RhoA/p38 MAPK pathway to alleviate sciatica.

Antioxidant Properties of Ferulic Acid on cardiovascular diseases

Background: As a dietary phytochemical, Ferulic acid (FA) is caused by metabolism between phenylalanine and tyrosine with physiological functions like anti-inflammatory, anti-diabetic, anticancer, antioxidant, antimicrobial and cardioprotective properties. This study aims to investigate FA protective effects on cardiovascular diseases.Methods: We covered references like these, web-based scientific databases, PubMed publications, ScienceDirect and Springer. Recent patent on FA therapeutic function in treatment of cardiovascular diseases potential was evaluated.Results: Studies showed that foods rich in FA prevent hypertension. FA, a free radical scavenger, is an enzyme inhibitor which catalyzes free radical generation and enhances scavenger enzyme activity. As a potent scavenger of free radicals, it dilutes oxidative stress, and reduces elevated blood-pressure by improving endothelial function and increasing bioavailability of this oxide in arterial vasculature. FA can enhance angiogenesis and wound healing.Conclusion: In this review, protective function of FA, an antioxidant compound in some nutrition such as fruits, vegetables, and grains, was discussed in terms of its relationship with cardiovascular diseases. Despite numerous data on FA, its effects on human is not recognized; further clinical studies about therapeutic effects of FA on patients with vascular diseases are required.

Ferulic acid as anticarcinogenic agent against 1,2-dimethylhydrazine induced colon cancer in rats

ObjectivesThe aim of the study was to assess the beneficial effect of ferulic acid (FA) compared to 5-flurouracil (5FU) on colon cancer caused by 1,2-dimethylhydrazine (DMH). MethodRats were divided into four groups (Control, FA, 5FU and DMH groups). The DMH group was injected subcutaneously once a week for 15 weeks. FA group was orally administered three times per week for 4 weeks with dose of 50 mg/kg. The 5FU group was intraperitoneally injected once per week with dose of 50 mg/kg for 4 weeks. ResultsHistopathological, immunohistochemical and molecular studies have been undertaken. The mucosa of the induced colon cancer was significant infiltrated by mononuclear cells and hemorrhage. Also, there was improper shape of the crypts with partial loss of polarity. The muscularis mucosa was infiltrated by pleomorphic cells. The mucosa and submucosa have indeed been invaded by a gland-like set of cells, congested blood vessels with extravagance of mononuclear cells, which are concentrated in the mucosa that fills the corium of the connective tissue. Moreover, colon sections of the DMH treated rats showed intensive immunoreactivity to Ki67, CK20 and weak immunoreactivity to P53 and Caspase-3. Moreover, FA could significantly (p < 0.01) upregulate P53 by approximately 5 fold. ConclusionsFindings of the present study indicated a significant therapeutic effect of ferulic acid against colon cancer by inhibiting proliferation and promoting apoptosis.

MicroRNA-9 mediated the protective effect of ferulic acid on hypoxic-ischemic brain damage in neonatal rats.

Neonatal hypoxic-ischemic brain damage (HIBD) is prone to cognitive and memory impairments, and there is no effective clinical treatment until now. Ferulic acid (FA) is found within members of the genus Angelica, reportedly shows protective effects on neuronal damage. However, the protective effects of FA on HIBD remains unclear. In this study, using the Morris water maze task, we herein found that the impairment of spatial memory formation in adult rats exposed to HIBD was significantly reversed by FA treatment and the administration of LNA-miR-9. The expression of miRNA-9 was detected by RT-PCR analyses, and the results shown that miRNA-9 was significantly increased in the hippocampus of neonatal rats following HIBD and in the PC12 cells following hypoxic-ischemic injury, while FA and LNA-miR-9 both inhibited the expression of miRNA-9, suggesting that the therapeutic effect of FA was mainly attributed to the inhibition of miRNA-9 expression. Indeed, the silencing of miR-9 by LNA-miR-9 or FA similarly attenuated neuronal damage and cerebral atrophy in the rat hippocampus after HIBD, which was consistent with the restored expression levels of brain-derived neurotrophic factor (BDNF). Therefore, our findings indicate that FA treatment may protect against neuronal death through the inhibition of miRNA-9 induction in the rat hippocampus following hypoxic-ischemic damage.

Ferulic Acid Modulates Dysfunctional Metabolic Pathways and Purinergic Activities, While Stalling Redox Imbalance and Cholinergic Activities in Oxidative Brain Injury.

The neuroprotective activities of phenolics have been demonstrated in several studies, with their antioxidant properties playing an influential role. In this study, the therapeutic effect of ferulic acid was investigated on oxidative stress, purinergic and cholinergic enzymatic activities, and dysregulated metabolic pathways in oxidative brain injury. Ferulic acid significantly elevatedthe reduced glutathione (GSH) level, superoxide dismutase and catalase activities, and concomitantly depleted malondialdehyde and nitric oxide level. It also inhibited the activities of acetylcholinesterase and butyrylcholinesterase, and increased the activities of ATPase. LC-MS analysis of the metabolites revealed restoration of most depleted metabolites, with concomitant generation of dihydroferulic acid 4-O-glucuronide, diadenosine heptaphosphate, cis-4-decenoic acid, ganglioside GT3 (d18:0/23:0), phosphatidylinositol-3,4,5-trisphosphate, and phosphoribosyl-ATP on treatment with ferulic acid. Pathway analysis of the identified metabolites revealed reactivation of oxidative-inactivated pathways, with concomitant activation of histidine and inositol phosphate metabolic pathways. There was no cytotoxicity on incubation of ferulic acid with HT22 cells. Molecular docking studies revealed a high affinity for acetylcholinesterase, with a binding energy of - 7.4kcal/mol. In silico simulation analysis predicted permeability of ferulic acid across blood brain barrier (BBB) and an oral LD50 calculated value of 1772mg/kg, with a toxicity class of 4. These results indicate the antioxidative and protective effects of ferulic acid in oxidative brain injury.

Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-β/Smad signaling pathway [Corrigendum

Purpose Liver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis in vitro and in vivo. Materials and methods Human hepatic stellate cell line (HSC) LX-2 was used for in vitro assays. Transforming growth factor β1 (TGF-β1) was used to induce hepatic fibrosis in LX-2 cells. Western blot was used to detect protein levels of collagen I, fibronectin, α-smooth muscle actin (SMA), p-Smad2, p-Smad3, p-p38, and p-JNK. Gene expression was measured by RT-qPCR. Fluorescence staining was used to determine localization of Smad4. CCl4-induced hepatic fibrosis in SD rats was used as an in vivo model. Histological features were detected by hematoxylin and eosin staining. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hexadecenoic acid (HA), and hydroxyproline (Hyp) were measured by ELISA. Results TGF-β1 treatment significantly increased levels of collagen I, fibronectin, α-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells. Ferulic acid improved TGF-β1-induced hepatic fibrosis via regulation of the TGF-β1/Smad pathway. Consistent with in vitro data, CCl4 caused severe hepatic fibrosis in SD rats, as determined by ALT, AST, HA, and Hyp upregulation. Protein levels of p-Smad2 and p-Smad3 in liver tissues were significantly increased following treatment with CCl4. All CCL4-induced changes were markedly attenuated by ferulic acid treatment. Conclusion Ferulic acid potently improved hepatic fibrosis via inhibition of the TGF-β1/Smad pathway in vitro and in vivo. These findings provided evidence for potential use of ferulic acid to treat or prevent liver fibrosis.

Effects of ferulic acid on proliferation, invasion and apoptosis of osteosarcoma cells

Objective To explore the therapeutic effect of ferulic acid on osteosarcoma and its specific therapeutic mechanism. Methods Osteosarcoma 143B cell lines were divided into 4 groups. The cells treated with 50 mmol/L ferulic acid were the low dose group, the cells treated with 100 mmol/L ferulic acid were the middle dose group, and the cells treated with 200 mmol/L ferulic acid were the high dose group. Cell viability was measured by methyl thiazol tetrazolium (MTT), apoptosis and cell cycle were detected by flow cytometry, and B lymphoma-2 gene (bcl-2), bcl-2 related X protein (bax), cyclin-dependent kinase 2, 4, 6 (CDK2, CDK4, CDK6) were detected by Western blotting. The expression of CDK2, CDK4, CDK6. Finally, the invasive ability of each group was detected by Transwell. Results After treatment with ferulic acid, the apoptosis rate of 143B cells was significantly increased, the survival rate was significantly decreased, the cell invasion inhibition ratewas significantly increased [control group 0%, low dose group (23.14±2.85)%, medium dose group (50.26±3.73)%, high dose group (72.15±4.58)%, P<0.05], G0/G1 phase cell ratio was significantly increased [control group (40.52±6.58)%, low dose group (52.26±5.72)%, middle dose group (70.26±6.85)%, high dose group (82.98±8.52)%, P<0.05], the expression of bcl-2, CDK2, CDK4, CDK6 was significantly decreased, and the expression of bax protein was significantly increased, and these changes were dose-dependent with ferulic acid. Conclusion Ferulic acid can treat osteosarcoma by regulating the apoptosis of osteosarcoma cells, which is dose dependent. Key words: Ferulic acid; Osteosarcoma; Apoptosis

Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-β/Smad signaling pathway.

PurposeLiver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis in vitro and in vivo.Materials and methodsHuman hepatic stellate cell line (HSC) LX-2 was used for in vitro assays. Transforming growth factor β1 (TGF-β1) was used to induce hepatic fibrosis in LX-2 cells. Western blot was used to detect protein levels of collagen I, fibronectin, α-smooth muscle actin (SMA), p-Smad2, p-Smad3, p-p38, and p-JNK. Gene expression was measured by RT-qPCR. Fluorescence staining was used to determine localization of Smad4. CCl4-induced hepatic fibrosis in SD rats was used as an in vivo model. Histological features were detected by hematoxylin and eosin staining. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hexadecenoic acid (HA), and hydroxyproline (Hyp) were measured by ELISA.ResultsTGF-β1 treatment significantly increased levels of collagen I, fibronectin, α-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells. Ferulic acid improved TGF-β1-induced hepatic fibrosis via regulation of the TGF-β1/Smad pathway. Consistent with in vitro data, CCl4 caused severe hepatic fibrosis in SD rats, as determined by ALT, AST, HA, and Hyp upregulation. Protein levels of p-Smad2 and p-Smad3 in liver tissues were significantly increased following treatment with CCl4. All CCL4-induced changes were markedly attenuated by ferulic acid treatment.ConclusionFerulic acid potently improved hepatic fibrosis via inhibition of the TGF-β1/Smad pathway in vitro and in vivo. These findings provided evidence for potential use of ferulic acid to treat or prevent liver fibrosis.

Ferulic acid, a dietary polyphenol suppresses osteoclast differentiation and bone erosion via the inhibition of RANKL dependent NF-κB signalling pathway

AimsBone erosion induced by enhanced osteoclast formation is a debilitating pathological phenomenon in rheumatoid arthritis (RA). Recent finding has revealed that ferulic acid is associated with reduced osteoclast differentiation and bone erosion. However, the underlying mechanism through which ferulic acid inhibited osteoclast differentiation and bone erosion still remains to be elucidated. This study assessed the therapeutic effects of ferulic acid on osteoclast differentiation and bone erosion by targeting RANKL dependent NF-κB pathway. Main methodsRAW 264.7 monocyte/macrophage cells were left untreated/treated with 25, 50 and 100 μM ferulic acid prior to stimulation with/without RANKL and M-CSF. Osteoclast differentiation and formation was assessed by SEM and TRAP analysis whereas its functional activity of bone erosion was determined by pit formation assay. Crucial transcription factors (NF-κBp-65, NFATc1 and c-Fos) and osteoclast specific genes (TRAP, MMP-9 and Cathepsin K) were evaluated by quantitative RT-PCR. Further, the protein level expression of NF-κBp-65, NFAtc1, c-Fos and MMP-9 was assessed using western blot analysis. Key findingsOur results demonstrated that ferulic acid significantly attenuated RANKL induced osteoclast differentiation as evidenced from SEM and TRAP staining analysis. A remarkable decrease in the bone resorption activity of osteoclasts was also noticed upon ferulic acid treatment. In addition, the down-regulation of RANKL induced NF-κB activation and its associated downstream factors like NFATc1, c-Fos, TRAP, Cathepsin K and MMP-9 was also observed upon ferulic acid treatment. SignificanceThus, our findings evidence the anti-stimulatory and anti-resorptive role of ferulic acid via the inhibition of RANKL dependent NF-κB signalling pathway.

The Potential Therapeutic Effect of Ferulic Acid in Mitigating Oxidative Stress Induced by γ-Irradiation in Male Rats

THE TESTIS is considered as one of the most sensitive organs in the body to ionizing radiation because of the rapidly dividing germinal epithelium. Seminal oxidative stress (OS) causes damage of the sperm plasma membrane and loss of its DNA integrity, therefore, the need for an effective therapeutic agent is evident. The present study investigated the mechanism(s) of potential therapeutic effect of ferulic acid (FA) on radiation-induced testicular damage.

Ferulic acid is nephrodamaging while gallic acid is renal protective in long term treatment of chronic kidney disease

The long term therapeutic effect of ferulic acid (FA) and gallic acid (GA) in treatment of chronic kidney disease (CKD) has been lacking. Doxorubicin (DR, Adriamycin)-induced CKD rat model was established for this study. DR significantly reduced levels of serum albumin, GOT, GPT, RBC, TNF-α, and urinary creatinine and elevated serum cholesterol, TG, BUN, creatinine, uric acid, WBC, platelet count, and IL-6. In DRCKD rats, FA and GA significantly increased kidney weight and glomerular volume. FA reduced glomerular filtration rate but GA did not. FA enhanced more collagen deposition than GA in renal cortex and glomeruli. Both FA and GA showed crucial hyperlipidemic activity. The inhibitory effects of FA and GA on MMP-2 were very comparable. GA suppressed MMP-2 more effectively than FA in DRCKD rats. Both FA and GA induced SOD elevation and MDA elimination. In DRCKD rats, Western blot analysis indicated that FA further up-regulated CD34, α-SMA, tissue pDGFR, p-PDGFR, and TGF-β; and down-regulated p-PI3K, and p-Akt. Since both PDGF-BB and TGF-β are considered to induce kidney prefibrosis stage, GA was proved to be more beneficial in this regard. GA tends to protect the CKD while FA is not recommended for the long term CKD therapy.

Therapeutic effect of ferulic acid, an ethereal fraction of ethanolic of seed of Syzygium cumini against streptozotocin-induced diabetes in male rat

Diabetic therapeutic and antioxidative effects of an ethereal fraction of the ethanolic extract of the seed of Syzygium cumini was studied in streptozotocin (STZ)-induced diabetic rats. Diabetes resulted in a significant elevation in the fasting blood glucose level and in the activity of hepatic glucose-6-phosphatase. There was diminution in the levels of glycogen in the liver and skeletal muscle along with diminution in the activities of hepatic glucose-6-phosphate dehydrogenase, catalase and peroxidase in diabetic rats when compared with controls. Hepatic levels of thiobarbituric acid reactive substance (TBARS) and conjugated dienes (CD) were elevated in respect to control. Oral coadministration of the above fraction to diabetic rats resulted in significant protection in all these parameters. Histological studies of the pancreas showed a qualitative diminution in the area and volume of the islet's of Langerhans, but coadministration of the specific fraction resulted in a significant recovery of the islet's of Langerhans. Chromatography study revealed that the used fraction was ferulic acid (FA). Treatment with FA in normoglycemic rats did not show any significant change in the levels of the selected biosensors. The possible hypothesis for the therapeutic effect of FA against diabetes may be due to its pancreatic beta-cell regenerative effect and/or due to its antioxidant properties.