Network pharmacology-based research into the mechanism of ferulic acid on acute lung injury through enhancing transepithelial sodium transport.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferulic acid (FA) has shown potential therapeutic applications in treating lung diseases. However, the underlying mechanisms by which FA ameliorates acute lung injury (ALI) have not been distinctly elucidated. AIM OF THE STUDY: The project aims to observe the therapeutic effects of FA on lipopolysaccharide-induced ALI and to elucidate its specific mechanisms in regulating epithelial sodium channel (ENaC), which majors in alveolar fluid clearance during ALI. MATERIALS AND METHODS: In this study, the possible pathways of FA were determined through network pharmacology analyses. The mechanisms of FA in ALI were verified by in vivo mouse model and in vitro studies, including primary alveolar epithelial type 2 cells and three-dimensional alveolar organoid models. RESULTS: FA ameliorated ALI by improving lung pathological changes, reducing pulmonary edema, and upregulating the α/γ-ENaC expression in C57BL/J male mice. Simultaneously, FA was observed to augment ENaC levels in both three-dimensional alveolar organoid and alveolar epithelial type 2 cells models. Network pharmacology techniques and experimental data from inhibition or knockdown of IkappaB kinase ß (IKKß) proved that FA reduced the phosphorylation of IKKß/nuclear factor-kappaB (NF-κB) and eliminated the lipopolysaccharide-inhibited expression of ENaC, which could be regulated by nuclear protein NF-κB p65 directly. CONCLUSIONS: FA could enhance the expression of ENaC at least in part by inhibiting the IKKß/NF-κB signaling pathway, which may potentially pave the way for promising treatment of ALI.

Absorbed Bioactive Compounds Replicate Guanxin II-Induced Endothelium-Associated in/ex vivo Vasodilation.

OBJECTIVE: To develop an interference-free and rapid method to elucidate Guanxin II (GX II)'s representative vasodilator absorbed bioactive compounds (ABCs) among enormous phytochemicals. METHODS: The contents of ferulic acid, tanshinol, and hydroxysafflor yellow A (FTA) in GX II/rat serum after the oral administration of GX II (30 g/kg) were detected using ultra-performance liquid chromatography-mass spectrometry. Totally 18 rats were randomly assigned to the control group (0.9% normal saline), GX II (30 g/kg) and FTA (5, 28 and 77 mg/kg) by random number table method. Diastolic coronary flow velocity-time integral (VTI), i.e., coronary flow or coronary flow-mediated dilation (CFMD), and endothelium-intact vascular tension of isolated aortic rings were measured. After 12 h of exposure to blank medium or 0.5 mmol/L H2O2, endothelial cells (ECs) were treated with post-dose GX II of supernatant from deproteinized serum (PGSDS, 300 µL PGSDS per 1 mL of culture medium) or FTA (237, 1539, and 1510 mg/mL) for 10 min as control, H2O2, PGSDS and FTA groups. Nitric oxide (NO), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), superoxide dismutase (SOD), malondialdehyde (MDA) and phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated endothelial nitric oxide synthase (p-eNOS) were analyzed. PGSDS was developed as a GX II proxy of ex vivo herbal crude extracts. RESULTS: PGSDS effectively eliminates false responses caused by crude GX II preparations. When doses equaled the contents in GX II/its post-dose serum, FTA accounted for 98.17% of GX II -added CFMD and 92.99% of PGSDS-reduced vascular tension. In ECs, FTA/PGSDS was found to have significant antioxidant (lower MDA and higher SOD, P<0.01) and endothelial function-protective (lower VEGF, ET-1, P<0.01) effects. The increases in aortic relaxation, endothelial NO levels and phosphorylated PI3K/Akt/eNOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester (L-NA, eNOS inhibitor) and wortmannin (PI3K/AKT inhibitor), respectively, indicating an endothelium-dependent vasodilation via the PI3K/AKT-eNOS pathway (P<0.01). CONCLUSION: This study provides a strategy for rapidly and precisely elucidating GX II's representative in/ex vivo cardioprotective absorbed bioactive compounds (ABCs)-FTA, suggesting its potential in advancing precision ethnomedicine.

P-coumaric Acid: Advances in Pharmacological Research Based on Oxidative Stress.

P-coumaric acid is an important phenolic compound that is mainly found in fruits, vegetables, grains, and fungi and is also abundant in Chinese herbal medicines. In this review, the pharmacological research progress of p-coumaric acid in recent years was reviewed, with emphasis on its role and mechanism in oxidative stress-related diseases, such as inflammation, cardiovascular diseases, diabetes, and nervous system diseases. Studies have shown that p-coumaric acid has a positive effect on the prevention and treatment of these diseases by inhibiting oxidative stress. In addition, p-coumaric acid also has anti-tumor, antibacterial, anti-aging skin and other pharmacological effects. This review will provide reference and inspiration for further research on the pharmacological effects of p-coumaric acid.

Elucidation the mechanism of the active ingredient imperatorin promoting drug absorption in cell model.

Imperatorin (IMP) is the main bioactive furanocoumarin of Angelicae dahuricae radix, which is a well-known traditional Chinese medicine. The purpose of this study was to elucidate the role of IMP in promoting absorption and the possible mechanism on the compatible drugs of Angelicae dahuricae radix. The influence of IMP on drugs' intestinal absorption was conducted by the Caco-2 cell model. The mechanism was studied by investigating the transcellular transport mode of IMP and its influence on P-glycoprotein (P-gp)-mediated efflux, protein expression of P-gp and tight junction, and cell membrane potential. The result showed IMP promoted the uptake of osthole, daidzein, ferulic acid, and puerarin and improved the transport of ferulic acid and puerarin in Caco-2 cells. The absorption-promoting mechanism of IMP might involve the reduction of the cell membrane potential, decrease of P-gp-mediated drug efflux and inhibition of the P-gp expression level in the cellular pathway, and the loosening of the tight junction protein by the downregulation of the expression levels of occludin and claudin-1 in the paracellular pathway. This study provides new insights into the understanding of the improved bioavailability of Angelicae dahuricae radix with its compatible drugs.

System biology mediated assessment of molecular mechanism for sinapic acid against breast cancer: via network pharmacology and molecular dynamic simulation.

Sinapic acid is a hydroxycinnamic acid widespread in the plant kingdom, known to be a potent anti-oxidant used for the treatment of cancer, infections, oxidative stress, and inflammation. However, the mode of action for its chemotherapeutic properties has yet not been unleashed. Hence, we aimed to identify potential targets to propose a possible molecular mechanism for sinapic acid against breast cancer. We utilized multiple system biology tools and databases like DisGeNET, DIGEP-Pred, Cytoscape, STRING, AutoDock 4.2, AutoDock vina, Schrodinger, and gromacs to predict a probable molecular mechanism for sinapic acid against breast cancer. Targets for the disease breast cancer, were identified via DisGeNET database which were further matched with proteins predicted to be modulated by sinapic acid. In addition, KEGG pathway analysis was used to identify pathways; a protein-pathway network was constructed via Cytoscape. Molecular docking was performed using three different algorithms followed by molecular dynamic simulations and MMPBSA analysis. Moreover, cluster analysis and gene ontology (GO) analysis were performed. A total of 6776 targets were identified for breast cancer; 95.38% of genes predicted to be modulated by sinapic acid were common with genes of breast cancer. The 'Pathways in cancer' was predicted to be modulated by most umber of proteins. Further, PRKCA, CASP8, and CTNNB1 were predicted to be the top 3 hub genes. In addition, molecular docking studies revealed CYP3A4, CYP1A1, and SIRT1 to be the lead proteins identified from AutoDock 4.2, AutoDock Vina, and Schrodinger suite Glide respectively. Molecular dynamic simulation and MMPBSA were performed for the complex of sinapic acid with above mentioned proteins which revealed a stable complex throughout simulation. The predictions revealed that the mechanism of sinapic acid in breast cancer may be due to regulation of multiple proteins like CTNNB1, PRKCA, CASP8, SIRT1, and cytochrome enzymes (CYP1A1 & CYP3A4); the majorly regulated pathway was predicted to be 'Pathways in cancer'. This indicates the rationale for sinapic acid to be used in the treatment of breast cancer. However, these are predictions and need to be validated and looked upon in-depth to confirm the exact mechanism of sinapic acid in the treatment of breast cancer; this is future scope as well as a drawback of the current study.

Analysis of Inhibitory Behaviour of Ferulic Acid and p-Coumaric Acid on Saccharomyces Cerevisiae Cells.

Metabolomics has been widely used to identify changes in relevant differential metabolites. The metabolites of Saccharomyces cerevisiae cells supplemented with ferulic acid and p-coumaric acid were prepared and extracted. Untargeted metabolomics analysis of saccharomyces cerevisiae metabolites was performed. In addition, GNPS, Respect and MassBank databases were used to search and compare the information in the whole database. It was found that 100 and 92 different metabolites were significantly changed (P value < 0.05,VIP value > 1,) in Saccharomyces cerevisiae cells treated with ferulic acid and p-coumaric acid respectively. Including isothiocyanate, L-threonine, adenosine, glycerin phospholipid choline, niacinamide and palmitic acid. These metabolites with significant differences were enriched by KEGG pathway using MetPA database.

Molecular mechanism of ferulic acid and its derivatives in tumor progression.

Cancer is a significant disease that poses a major threat to human health. The main therapeutic methods for cancer include traditional surgery, radiotherapy, chemotherapy, and new therapeutic methods such as targeted therapy and immunotherapy, which have been developed rapidly in recent years. Recently, the tumor antitumor effects of the active ingredients of natural plants have attracted extensive attention. Ferulic acid (FA), (3-methoxy-4-hydroxyl cinnamic), with the molecular formula is C10H10O4, is a phenolic organic compound found in ferulic, angelica, jujube kernel, and other Chinese medicinal plants but is also, abundant in rice bran, wheat bran, and other food raw materials. FA has anti-inflammatory, analgesic, anti-radiation, and immune-enhancing effects and also shows anticancer activity, as it can inhibit the occurrence and development of various malignant tumors, such as liver cancer, lung cancer, colon cancer, and breast cancer. FA can cause mitochondrial apoptosis by inducing the generation of intracellular reactive oxygen species (ROS). FA can also interfere with the cell cycle of cancer cells, arrest most cancer cells in G0/G1 phase, and exert an antitumor effect by inducing autophagy; inhibiting cell migration, invasion, and angiogenesis; and synergistically improving the efficacy of chemotherapy drugs and reducing adverse reactions. FA acts on a series of intracellular and extracellular targets and is involved in the regulation of tumor cell signaling pathways, including the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT), B-cell lymphoma-2 (Bcl-2), and tumor protein 53 (P53) pathways and other signaling pathways. In addition, FA derivatives and nanoliposomes, as platforms for drug delivery, have an important regulatory effect on tumor resistance. This paper reviews the effects and mechanisms of antitumor therapies to provide new theoretical support and insight for clinical antitumor therapy.

The efficacy of sodium ferulate combination therapy in coronary heart disease: A systematic review and meta-analysis.

BACKGROUND: Sodium ferulate (SF), a derivative of ferulic acid, is one of the active constituents in medicinal plants thought to be useful in fighting cardiovascular diseases. However, there still lacks a systematic review of the efficacy and safety of SF in treating coronary heart disease (CHD). It is therefore the purpose of this study to comprehensively review all clinical randomized controlled trials (RCTs) of SF in CHD to assess its efficacy and safety. METHODS: All analysis is based on 8 databases as of February 2023, which includes 35 outcomes of RCTs that investigate the effect of SF combination therapy in CHD. The present study evaluates the quality and bias of selected literature by the Jadad scale and Cochrane Collaboration's tools, and also the quality of evidence by GRADE Profiler. Furthermore, it applies sensitivity analysis to assess the high heterogeneity impact of outcomes and conducted subgroup analysis to estimate the influence factors in these studies. The study protocol was set documented, and published beforehand in PROSPERO (Registration No.CRD42022348841). RESULTS: The meta-analysis of 36 studies (with 3207 patients) shows that SF combined with conventional drugs has improved clinical effectiveness for patients with CHD [RR: 1.21 (95% CI 1.17,1.26); p < 0.00001]. Statistically significant results of meta-analyses are also seen in electrocardiography (ECG) efficacy, frequency of angina attacks, endothelium-dependent flow-mediated vasodilation (FMD), nitric oxide (NO), endothelin (ET), whole Blood low shear rate (LS), platelet aggregation test (PAgT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL6), triglyceride (TG). Adverse events are reported in 6 RCTs. By GRADE approaches, 2 outcomes (clinical efficacy, CRP) indicate a moderate quality of evidence, 17 outcomes indicate low quality of evidence, with the other 16 very low-quality. CONCLUSION: SF combination therapy has a better curative effect than conventional therapy. However, due to items with low-quality evidence demonstrated in the study, the presence of clinical heterogeneity, and imprecision in partial outcome measures, all these led to limitations in the evidence of this study. Thus, the conclusion needs to be further verified by more in-depth research.

Almond [Prunus dulcis (Mill.) DA Webb] Processing Residual Hull as a New Source of Bioactive Compounds: Phytochemical Composition, Radical Scavenging and Antimicrobial Activities of Extracts from Italian Cultivars ('Tuono', 'Pizzuta', 'Romana').

In this study we developed a new extract, by the use of conventional solid-solvent extraction and a food-grade hydroalcoholic solvent, rich in phenolic and triterpenoid components from almon hull to be employed as functional ingredient in food, pharma and cosmetic sectors. Two autochthonous Sicilian cultivars ('Pizzuta' and 'Romana') and an Apulian modern cultivar ('Tuono') have been tested for the production of the extract. Results showed that the two Sicilian varieties, and in particular the 'Romana' one, present the best characteristics to obtain extracts rich in triterpenoids and hydroxycinnamic acids, useful for the production of nutraceutical supplements. About triterpenoids, the performance of the hydroalcoholic extraction process allowed to never go below 46% of recovery for 'Pizzuta' samples, with significantly higher percentages of recovery for 'Tuono' and 'Romana' extracts (62.61% and 73.13%, respectively) while hydroxycinnamic acids were recovered at higher recovery rate (84%, 89% and 88% for 'Pizzuta', 'Romana' and 'Tuono' extracts, respectively). Invitro antioxidant and antimicrobial activities exerted by the extracts showed promising results with P. aeruginosa being the most affected strain, inhibited up to the 1/8 dilution with 'Romana' extract. All the three tested extracts exerted an antimicrobial action up to 1/4 dilutions but 'Romana' and 'Pizzuta' extracts always showed the greatest efficacy.

Coumaric acid from M. polymorphum extracts reverses the activated state of hepatic stellate cells (GRX) and inhibits their proliferation by decreasing the p53/p21 pathway.

Coumaric acid is a phenolic compound found in medicinal plants. Its use has been reported in the treatment of inflammatory diseases, prevention of alterations induced by oxidative stress, as well as acetaminophen-induced hepatotoxicity. Thus, this study evaluated coumaric acid as a potential treatment for liver fibrosis. Cell proliferation was assessed by the trypan blue exclusion technique and the cytotoxicity of coumaric acid was performed using an LDH assay. Mechanisms of cell apoptosis were evaluated by flow cytometry. The expression of genes associated with apoptosis, cell cycle control, and fibrosis was assessed by qPCR. The production of lipid droplets was quantified by oil red staining. The experiments performed showed that the treatment with coumaric acid was able to reduce cell proliferation without causing cell cytotoxicity or apoptosis. Coumaric acid was able to inhibit the expression of cyclin D1 and CDK's (CDK2, CDK4, and CDK6), increasing p53 and p21, which could lead to cell cycle arrest. Treatment with coumaric acid was also able to revert the activated phenotype of GRX cells to their quiescent state. Thus, our results suggest that coumaric acid has a potential therapeutic effect against liver fibrosis.

Ferulic acid enhances insulin secretion by potentiating L-type Ca2+ channel activation.

OBJECTIVE: To investigate the effect of ferulic acid, a natural compound, on pancreatic beta cell viability, Ca2+ channels, and insulin secretion. METHODS: We studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca2+ channels and insulin secretion, respectively. RESULTS: Ferulic acid did not affect cell viability during exposures up to 72 h. The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca2+ channel current, shifting its activation curve in the hyperpolarizing direction with a decreased slope factor, while the voltage dependence of inactivation was not affected. On the other hand, ferulic acid have no effect on T-type Ca2+ channels. Furthermore, ferulic acid significantly increased insulin secretion, an effect inhibited by nifedipine and Ca2+-free extracellular fluid, confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca2+ influx through L-type Ca2+ channel. Our data also suggest that this may be a direct, nongenomic action. CONCLUSION: This is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca2+ channel current in pancreatic ß cells by enhancing its voltage dependence of activation, leading to insulin secretion.

Neuroprotective Properties of Ferulic Acid in Preclinical Models of Alzheimer's Disease: A Systematic Literature Review.

BACKGROUND: Alzheimer's disease (AD) is one of the most common diseases in the elderly, with a high incidence of dementia. The pathogenesis of AD is complex, and there is no unified conclusion and effective treatment in the clinic. In recent years, with the development of traditional Chinese medicine (TCM), researchers put forward the idea of prevention and treatment of AD based on TCM according to the characteristics of multi- target of TCM. Ferulic acid (FA), also known as 3-methoxy-4-hydroxycinnamic acid, is an active ingredient in TCM that inhibits ß-amyloid (Aß) aggregation and has antioxidant and anti-inflammatory effects. FA derivatives have been reported to have low toxicity, high biological activity, and high blood-brain barrier permeability. However, the multitarget of FA in the treatment of AD has not been systematically elucidated. OBJECTIVES: In this systematic review, we aimed to comprehensively assess the neuroprotective effects of FA and its derivatives on in vitro and in vivo AD models. METHODS: We searched PubMed, Chinese National Knowledge Infrastructure (CNKI), Baidu Academic, and Wanfang databases for relevant pre-clinical studies until November 2021. RESULTS: We identified studies that evaluated the efficacy of FA and its derivatives using relevant keywords. 864 studies were included, of which 129 were found in PubMed, 111 in CNKI, 454 in Baidu Academic, and 170 in Wanfang. Due to duplication between databases, and after applying the exclusion and inclusion criteria, 43 articles were selected. Thereafter, the abstracts of the 43 articles were reviewed. Finally, 21 articles were included in this review, including 11 in vivo, 5 in vitro, and 5 in vivo and in vitro studies. CONCLUSION: Previous studies have shown that FA or its derivatives have multiple therapeutic effects on AD models and can improve the symptoms of AD and resistance of AD cell models. FA and its derivatives have anti-Aß aggregation, antioxidant, antiinflammatory, and other effects and are potential drugs for the multi-targeted treatment of AD. The result of our study showed that FA and its derivatives have significant therapeutic effects on animal and cell models of AD, suggesting that they may be potential therapeutic drugs for patients with AD.

Sinapic Acid Alleviates Acute Pancreatitis in Association with Attenuation of Inflammation, Pyroptosis, and the AMPK/NF-[Formula: see text]B Signaling Pathway.

Among the diseases of the digestive system, the incidence of acute pancreatitis (AP) has increased. Although the AP is primarily self-limited, mortality remains high when it progressed to severe acute pancreatitis (SAP). Despite significant advances in new drug development, treatments for AP are not ideal. Here, we discovered a novel hydroxycinnamic acid, sinapic acid (SA), which is widely distributed in plants and is an effective treatment for AP. Using in vitro and in vivo models, we demonstrated that pretreatment with SA ameliorated cerulein-induced pancreatic damage and inflammation and inhibited the activation of Caspase-1 and Caspase-11, which mediate pyroptosis of pancreatic acinar cells during AP. These effects may occur through the inhibition of AMPK phosphorylation and downregulation of NF-[Formula: see text]B. Our findings demonstrate the therapeutic effects and reveal the underlying mechanisms of SA, which warrants its further study as an effective treatment for AP.

Phytochemicals from Red Onion, Grown with Eco-Sustainable Fertilizers, Protect Mammalian Cells from Oxidative Stress, Increasing Their Viability.

Red onion, a species of great economic importance rich in phytochemicals (bioactive compounds) known for its medicinal properties, was fertilized with sulphur-bentonite enriched with orange residue or olive pomace, with the aim of producing onion enriched in health beneficial compounds. There is a worldwide great demand of minimally processed food or food ingredients with functional properties because of a new awareness of how important healthy functional nutrition is in life. Phytochemicals have the capacity to regulate most of the metabolic processes resulting in health benefits. Red onion bioactive compound quantity and quality can vary according to cultivation practices. The main aims of the current research were to determine the chemical characteristics of the crude extracts from red onion bulbs differently fertilized and to evaluate their biological activity in normal and oxidative stress conditions. The lyophilized onion bulbs have been tested in vitro on two cellular models, i.e., the H9c2 rat cardiomyoblast cell line and primary human dermal fibroblasts, in terms of viability and oxygen radical homeostasis. The results evidenced different phytochemical compositions and antioxidant activities of the extracts obtained from red onions differently fertilized. Sulphur-bentonite fertilizers containing orange waste and olive pomace positively affected the red onion quality with respect to the red onion control, evidencing that sulphur-bentonite-organic fertilization was able to stimulate plant a secondary metabolism inducing the production of phytochemicals with healthy functions. A positive effect of the extracts from red onions treated with fertilizers-in particular, with those containing orange waste, such as the reduction of oxidative stress and induction of cell viability of H9c2 and human fibroblasts-was observed, showing a concentration- and time-dependent profile. The results evidenced that the positive effects were related to the phenols and, in particular, to chlorogenic and p-coumaric acids and to the flavonol kaempferol, which were more present in red onion treated with low orange residue than in the other treated ones.

Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer's Disease: A Narrative Review.

Alzheimer's disease (AD) is a progressive degenerative disorder of the central nervous system, characterized by neuroinflammation, neurotransmitter deficits, and neurodegeneration, which finally leads to neuronal death. Emerging evidence highlighted that hyperglycemia and brain insulin resistance represent risk factors for AD development, thus suggesting the existence of an additional AD form, associated with glucose metabolism impairment, named type 3 diabetes. Owing to the limited pharmacological options, novel strategies, especially dietary approaches based on the consumption of polyphenols, have been addressed to prevent or, at least, slow down AD progression. Among polyphenols, ferulic acid is a hydroxycinnamic acid derivative, widely distributed in nature, especially in cereal bran and fruits, and known to be endowed with many bioactivities, especially antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy. Considering the importance of ferulic acid as a bioactive molecule and its widespread distribution in foods and medicinal plants, the aim of the present narrative review is to provide an overview on the existing preclinical and clinical evidence about the neuroprotective properties and mechanisms of action of ferulic acid, also focusing on its ability to modulate glucose homeostasis, in order to support a further therapeutic interest for AD and type 3 diabetes.

Ferulic acid- and gallic ester-acylated pectin: Preparation and characterization.

In this study, pectin was modified with ferulic acid (Fa), trans-ferulic acid (trans-Fa), methyl gallate (MG), and ethyl gallate (EG) via the enzymatic method using aqueous/organic phases to enhance its physiochemical and bio-active properties. Results revealed that lipase might catalyze the hydrolysis of the ester bond within pectin in aqueous phase and prompt the transesterification between the hydroxyl group in the para position in Fa/trans-Fa or the 2'-OH group of MG/EG and the carboxylic group of pectin in the organic phase. The graft ratio was 21.00%, 21.67%, 13.24%, and 11.93% for the Fa-, trans-Fa-, MG-, and EG-modified pectin, respectively. In addition, compared with native pectin, the modified pectin exhibited improved apparent viscosity and emulsion activity. Moreover, the clearance of 1,1-diphenyl-2-picryl hydrazine (DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) was effectively enhanced for the modified pectin. Furthermore, the modified pectin exhibited strong antibacterial activity against Escherichia coli and Staphylococcus aureus while no cytotoxic effects based on the results of cell culture experiments. Our results provide a theoretical basis for the expansion of pectin applications in the food and pharmaceutical industries.

Ferulic Acid Protects Human Lens Epithelial Cells against Ionizing Radiation-Induced Oxidative Damage by Activating Nrf2/HO-1 Signal Pathway.

Ionizing radiation- (IR-) induced oxidative stress has been recognized as an important mediator of apoptosis in lens epithelial cells (LECs) and also plays an important role in the pathogenesis of IR-induced cataract. Ferulic acid (FA), a phenolic phytochemical found in many traditional Chinese medicine, has potent radioprotective and antioxidative properties via activating nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway. The goals of this study were to determine the protective effect of FA against IR-induced oxidative damage on human lens epithelial cells (HLECs) and to elucidate the role of Nrf2 signal pathway. HLECs were subjected to 4 Gy X-ray radiation with or without pretreatment of FA. It was found that FA pretreatment protected HLECs against IR-induced cell apoptosis and reduced levels of ROS and MDA caused by radiation in a dose-dependent manner. IR-dependent attenuated activities of antioxidant enzymes (SOD, CAT, and GPx) and decreased ratio of reduced GSH/GSSG were increased by pretreatment of FA. FA inhibited IR-induced increase of Bax and cleaved caspase-3 and the decrease of Bcl-2 in a dose-dependent manner. Furthermore, FA provoked Nrf2 nuclear translocation and upregulated mRNA and protein expressions of HO-1 in a dose-dependent manner. These findings indicated that FA could effectively protect HLECs against IR-induced apoptosis by activating Nrf2 signal pathway to inhibit oxidative stress, which suggested that FA might have a therapeutic potential in the prevention and alleviation of IR-induced cataract.

Production of Bioactive Substances to Alleviates Hangover and Ethanol-Induced Liver Damage through Fermentation of Oenanthe javanica Using Lactiplantibacillus plantarum.

The purpose of this study is to evaluate the effect of the bioconversion products of Oenanthe javanica extract fermented by Lactiplantibacillus plantarum (OEFL) on relieving hangovers and improving liver function. In addition, the bioactive substance of the OEFL, which alleviates hangover and ethanol-induced liver damage, was identified and its bioactive property was verified through in vivo experiments. In major substances analysis using high-performance liquid chromatography, OEFL produced 9.5-fold higher p-coumaric acid than the O. Javanica extract (OE). In addition, considering that quinic acid, which is not present in the OE, was produced in the OEFL it was confirmed that chlorogenic acid was decomposed into quinic acid by bioconversion. In the in vivo experiment using Sprague-Dawley rats, the OEFL and p-coumaric acid diets reduced blood ethanol, acetaldehyde, GPT, and ALP concentrations, increasing blood albumin concentrations compared to ethanol-administered groups, demonstrating that OEFL and p-coumaric acid, the main substance in the OEFL, improved ethanol-induced liver damage. Furthermore, the OEFL and its main bioactive substance, p-coumaric acid, alleviated liver fibrosis by downregulating TGF-ß, SMAD-2, SMAD-4, α-SMA, and upregulating MMP-1. Therefore, OEFL is expected to be used as a functional food or pharmaceutical material as it has been confirmed to effectively relieve hangovers, prevent liver damage, and delay liver fibrosis in ethanol-induced liver damages.

Main active components of Si-Miao-Yong-An decoction (SMYAD) attenuate autophagy and apoptosis via the PDE5A-AKT and TLR4-NOX4 pathways in isoproterenol (ISO)-induced heart failure models.

Heart failure (HF), the main cause of death in patients with many cardiovascular diseases, has been reported to be closely related to the complicated pathogenesis of autophagy, apoptosis, and inflammation. Notably, Si-Miao-Yong-An decoction (SMYAD) is a traditional Chinese medicine (TCM) used to treat cardiovascular disease; however, the main active components and their relevant mechanisms remain to be discovered. Based on our previous ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) results, we identified angoriside C (AC) and 3,5-dicaffeoylquinic acid (3,5-DiCQA) as the main active components of SMYAD. In vivo results showed that AC and 3,5-DiCQA effectively improved cardiac function, reduced the fibrotic area, and alleviated isoproterenol (ISO)-induced myocarditis in rats. Moreover, AC and 3,5-DiCQA inhibited ISO-induced autophagic cell death by inhibiting the PDE5A/AKT/mTOR/ULK1 pathway and inhibited ISO-induced apoptosis by inhibiting the TLR4/NOX4/BAX pathway. In addition, the autophagy inhibitor 3-MA was shown to reduce ISO-induced apoptosis, indicating that ISO-induced autophagic cell death leads to excess apoptosis. Taken together, the main active components AC and 3,5-DiCQA of SMYAD inhibit the excessive autophagic cell death and apoptosis induced by ISO by inhibiting the PDE5A-AKT and TLR4-NOX4 pathways, thereby reducing myocardial inflammation and improving heart function to alleviate and treat a rat ISO-induced heart failure model and cell heart failure models. More importantly, the main active components of SMYAD will provide new insights into a promising strategy that will promote the discovery of more main active components of SMYAD for therapeutic purposes in the future.

Salvianolic acid B and ferulic acid synergistically promote angiogenesis in HUVECs and zebrafish via regulating VEGF signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Induced vascular growth in the myocardium has been widely acknowledged as a promising intervention strategy for patients with ischemic coronary artery disease. Yet despite long-term efforts on gene, protein or cell-based pro-angiogenic therapies, the clinical translation remains challenging. Noticeably, multiple medicinal herbs have long-term documented effects in promoting blood circulation. Salvia miltiorrhiza and Ligusticum stratum are two representative traditional Chinese medicine herbs with suggested roles in enhancing organ blood supply, and Guanxinning Tablet (GXNT), a botanical drug which is formulated with these two herbs, exhibited significant efficacy against angina pectoris in clinical practices. AIM OF THE STUDY: This study aimed to examine the pro-angiogenic activity of GXNT and its major components, as well as to explore their pharmacological mechanism in promoting angiogenesis. MATERIALS AND METHODS: In vitro, the pro-angiogenic effects of GXNT and its major components were examined on human umbilical vein endothelial cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch assay, and endothelial cell tube formation assay. In vivo, the pro-angiogenic effects were examined on the ponatinib-induced angiogenesis defective zebrafish model. The active compounds were identified through phenotype-based screening in zebrafish, and their pharmacological mechanism was explored in both in vitro and in vivo models by immunofluorescent staining, cell cycle analysis, quantitative PCR and whole embryo in-situ hybridization. RESULTS: We demonstrated strong pro-angiogenic effects of GXNT in both human umbilical vein endothelial cells and zebrafish model. Moreover, through phenotype-based screening in zebrafish for active compounds, pro-angiogenic effects was discovered for salvianolic acid B (Sal B), a major component of Salvia miltiorrhiza, and its activity was further enhanced when co-administered with ferulic acid (FA), which is contained in Ligusticum stratum. On the cellular level, Sal B and FA cotreatment increased endothelial cell proliferation of sprouting arterial intersomitic vessels in zebrafish, as well as largely restored G1-S cell cycle progression and cyclin D1 expression in angiogenic defective HUVECs. Through quantitative transcriptional analysis, increased expression of vegfr2 (kdr, kdrl) and vegfr1 was detected after GXNT or SalB/FA treatment, together with upregulated transcription of their ligands including vegf-a, vegf-b, and pgfb. Bevacizumab, an anti-human VEGF-A monoclonal antibody, was able to significantly, but not completely, block the pro-angiogenic effects of GXNT or SalB/FA, suggesting their multi-targeting properties. CONCLUSIONS: In conclusion, from a traditional Chinese medicine with effects in enhancing blood circulation, we demonstrated the synergistic pro-angiogenic effects of Sal B and FA via both in vitro and in vivo models, which function at least partially through regulating the expression of VEGF receptors and ligands. Future studies are warranted to further elaborate the molecular interaction between these two compounds and the key regulators in the process of neovascularization.