Gallic Acid Research Articles

Network pharmacology and in vivo experiment-based strategy for investigating the mechanism of chronic prostatitis/chronic pelvic pain syndrome in QianLieJinDan tablets

BackgroundChronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease that is prone to recurrence. It typically leads to varying degrees of pelvic pain and discomfort, as well as symptoms related to the urinary system in affected patients. QianLieJinDan tablets (QLJD), a traditional Chinese medicine, have shown promising therapeutic effects on CP/CPPS in clinical practice, but the underlying mechanisms of QLJD in treating CP/CPPS have not been determined. ObjectiveTo reveal the phytochemical characterization and multitarget mechanism of QLJD on CP/CPPS. MethodsThe concentrations of the components of QLJD were determined using UHPLC-Q Exactive Orbitrap-MS. Utilizing network pharmacology approaches, the potential components, targets, and pathways involved in the treatment of CP/CPPS caused by QLJD were screened. Molecular docking calculations were employed to assess the affinity between the components of the QLJD and potential targets, revealing the optimal molecular conformation and binding site. Finally, the therapeutic efficacy and potential underlying mechanisms of QLJD were investigated through pharmacological experiments. ResultsIn this study, a total of 35 components targeting 29 CP-related genes were identified, among which quercetin, baicalin, icariin, luteolin, and gallic acid were the major constituents. Enrichment analysis revealed that the potential targets were involved mainly in the regulation of cytokines, cell proliferation and apoptosis, and the oxidative stress response and were primarily associated with the cytokine‒cytokine receptor interaction pathway, the IL-17 signaling pathway, the Th17 cell differentiation pathway, and the JAK-STAT signaling pathway. In vivo experiments demonstrated that QLJD effectively attenuated the infiltration of CD3+ T cells and the expression of ROS in a CP/CPPS model rat prostate tissue. Furthermore, through the inhibition of IL-6 and STAT3 expression, QLJD reduced the differentiation of Th17 cells, thereby ameliorating pathological injury and prostatic index in prostate tissue. ConclusionThe potential of QLJD as an anti-CP/CPPS agent lies in its ability to interfere with the expression of IL-6 and STAT3, inhibit Th17 cell differentiation, reduce inflammatory cell infiltration in rat prostate tissue, and alleviate oxidative stress damage through its multi-component, multi-target, and multi-pathway effects.

Mechanistic approach of tannery wastewater and sulfadiazine mutual toxicity in wheat (Triticum aestivum L.) and mitigation through exogenous application of gallic acid.

Excessive release of chromium (Cr) from the tanning industry and antibiotics from livestock caused severe hazards to humans. Gallic acid (GA 10 mM) alleviated alone/combined SDZ 30 mg kg−1 and TWW 40, 60, and 100% stress in wheat. GA (10 mM) decreased the TSP 12 and 13%, TFAA 8 and 10%, TSS 14 and 16%, RS 18 and 16%, and NRS 11 and 9% in shoots and grains under SDZ + TWW (30 mg kg−1+100%), compared without foliar. GA (10 mM) declined the MDA 20 and 31, EL 13 and 36%, H2O2 17 and 15%, O2•- 10 and 11% in leaves and roots, under combined SDZ + TWW (30 mg kg−1+100%), compared without foliar. GA (10 mM) improved the POD 106 and 30%, SOD 145 and 31%, CAT 78, and 35%, APX 100 and 25% in leaves and roots under combined SDZ + TWW (30 mg kg−1+100%), compared without foliar application. Considerably GA (10 mM) reduced total Cr 18, CrIII 20, and CrVI 50% in roots and shoots 19, 41, and 48%, and grains 15, 27, and 29% respectively, under combined SDZ + TWW (30 mg kg−1+100%) stress, compared without foliar. Overall, GA boosted the wheat growth, physiology, and defence system by inhibiting the combined SDZ + Cr toxicity.

Mechanism of action of Taohong Siwu decoction in the alleviation of primary dysmenorrhea.

As one of the most common gynecological disorders, PD significantly impacts the quality of life for women. TSD, a well-known traditional Chinese medical prescription, has gained popularity for its use in treating gynecological cold coagulation and blood stasis syndromes such as PD. However, the lack of comprehensive data hinders our understanding of its molecular mechanism. The objective of the present study is to investigate the therapeutic effects of TSD on PD and elucidate its plausible mechanism. HPLC was employed to confirm the presence of the principal metabolites of TSD. The rat model of PD was induced by OT exposure following IWM and EB pretreatment, and subsequently treated with TSD via gastric gavage. The effects and potential mechanisms of TSD on PD rats were explored, encompassing general behavior, morphological alterations in the uterus and ovaries, biochemical indicators in the uterus and serum, and levels of proteins related to the PI3K/AKT signaling pathway. Gallic acid, hydroxysafflower yellow A, albiflorin, paeoniflorin, and ferulic acid were determined to be the primary active metabolites of TSD. The pharmacological studies yielded results indicating the successful establishment of the PD model in rats. Additionally, TSD demonstrated its ability to protect PD rats by ameliorating general behavior, mitigating pathological damage to uterine and ovarian tissues, and modulating the expression levels of correlated factors (PGE2, PGF2α, Ca2+, TXB2, IL-6, TNF-α, NO, and COX-2) as well as p-PI3K/PI3K and p-AKT/AKT proteins. TSD exhibited protective effects against PD in rats through its interaction with multiple targets including P13K/AKT signaling pathway, indicating that TSD holds therapeutic potential for PD treatment and providing evidence supporting the rational utilization of TSD.

Protective effects of gallic acid against nickel-induced kidney injury: impact of antioxidants and transcription factor on the incidence of nephrotoxicity

Nickel (Ni) is a common metal with a nephrotoxic effect, damaging the kidneys. This study investigated the mechanism by which gallic acid (GA) protects mice kidneys against renal damage induced by Nickel oxide nanoparticles (NiO-NPs). Forty male Swiss albino mice were randomly assigned into four groups, each consisting of ten mice (n = 10/group): Group I the control group, received no treatment; Group II, the GA group, was administrated GA at a dosage of 110 mg/kg/day body weight; Group III, the NiO-NPs group, received injection of NiO-NPs at a concentration of 20 mg/kg body weight for 10 consecutive days; Group IV, the GA + NiO-NPs group, underwent treatment with both GA and NiO-NPs. The results showed a significant increase in serum biochemical markers and a reduction in antioxidant activities. Moreover, levels of 8-hydroxy-2’-deoxyguanosine (8-OH-dG), phosphorylated nuclear factor kappa B (p65), and protein carbonyl (PC) were significantly elevated in group III compared with group I. Furthermore, the western blot analysis revealed significant high NF-κB p65 expression, immunohistochemistry of the NF-κB and caspase-1 expression levels were significantly increased in group III compared to group I. Additionally, the histopathological inspection of the kidney in group III exhibited a substantial increase in extensive necrosis features compared with group I. In contrast, the concomitant coadministration of GA and NiO-NPs in group IV showed significant biochemical, antioxidant activities, immunohistochemical and histopathological improvements compared with group III. Gallic acid has a protective role against kidney dysfunction and renal damage in Ni-nanoparticle toxicity.

Impact of Drying Method and Solvent Extraction on Ethiopian Verbascum sinaiticum (Qetetina) Leaves: Metabolite Profiling and Evaluation of Antioxidant Capacity

The aim of this study was to evaluate the effects of different drying methods on bioactive compounds and to analyze their composition in Verbascum sinaiticum (V. sinaiticum) leaf extracts using UHPLC-ESI-QTOF-MS/MS. V. sinaiticum is traditionally used as an herbal medicine, yet it has undergone limited scientific investigations regarding its secondary metabolites. V. sinaiticum leaves were dried using oven dryers at 50 °C, 60 °C, and 70 °C, as well as a freeze dryer. The leaves were then extracted using 50% and 70% aqueous ethanol and 100% aqueous solutions. The results showed that the highest contents of TPC and TFC were observed when 70% aqueous ethanol was used during freeze drying, reaching 181.73 mg GAE/g dw and 78.57 mg CE/g dw, respectively. The strongest correlations were observed between the TFC and DPPH radical scavenging activity (0.9082), followed by TPC and ABTS assays (0.8933) and TPC and DPPH (0.8272). In the FTIR analysis, freeze drying exhibited a lower intensity of the phenolic -OH functional groups, contrasting with significant denaturation observed during oven drying at 70 °C. Metabolite analysis identified 29 compounds in V. sinaiticum leaves, further confirming the presence of 14 phenolic and flavonoid compounds, including kaempferol, catechin, gallic acid, and myricetin derivatives, consistent with the experimentally observed antioxidant capacity. This study highlights the impact of drying methods on the bioactive composition of V. sinaiticum and underscores its potential as a source of antioxidants for food, nutraceutical, and pharmaceutical applications.

Sulfur dioxide generating pads containing different concentrations of sodium metabisulfite maintains postharvest quality of ‘Hicaznar’ pomegranate

This study investigated the effects of different sulfur dioxide (SO2) generating pads containing different concentrations of sodium metabisulfite (Na2S2O5) on the storage of ‘Hicaznar’ pomegranate fruit. For this purpose, the pomegranates were harvested at optimal harvest maturity (total soluble solids (TSS): 17.70 %, titratable acidity (TA): 1.57 % citric acid). The first, second and third groups were treated with SO2 generating pads containing different concentrations of Na2S2O5 (1.5, 3.0 and 4.5 g). The fourth group was control which received no treatment. The SO2 generating pads were placed on top of the fruit with butter paper containing holes were kept between the fruit and pads. All the treatments were packaged under modified atmosphere packages (MAP) and stored at 6 °C and 90–95 % relative humidity (RH). The fruit samples for quality analysis were taken at 45, 90, 120, 150 and 180 days (d) of cold storage (CS). Post removal, the samples from each treatment were kept at 20 °C for additional 3 d to determine shelf life (SL) performance of fruit. Extending storage duration showed increase in weight loss, h° values, total flavonoid content, carbon dioxide (CO2) levels and decay index while decrease in L*, C* values, appearance and taste scores, TSS content, TA, total phenolic content, total antioxidant activity, total anthocyanin, ascorbic acid, organic acids (citric, malic, succinic and oxalic acids) contents, phenolic compounds (gallic, protocatechuic and chlorogenic acid), oxygen (O2) levels and SO2 production in MAP. SO2 generating pads reduced weight loss and decay index. The highest taste value was recorded in 3.0 g SO2 generating pads. The highest h° value was in 1.5 g SO2 generating pads while the greatest total anthocyanin content in CS was in 3.0 and 4.5 g with maximum total anthocyanin content in SL was recorded in 1.5 and 4.5 g SO2 generating pads. SO2 generating pads exhibited maximum total phenolic content, total antioxidant activity and gallic acid content as compared to control. There were no SO2 residues in pomegranate arils throughout the storage. It can be concluded that SO2 generating pads can be a potential tool to preserve the postharvest quality of ‘Hicaznar’ pomegranate for 180 d of CS.

Comparison of Extraction Techniques for Determining Bioactive Compounds and Antioxidant Activity of Spirulina platensis

Spirulina platensis (S. platensis) is a high-nutrient blue-green algae that has been used as a food supplement for a long time. It contains carbohydrates, lipids, proteins, vitamins, minerals, and bioactive compounds essential for basic human nutrition. It is known to have anti-cancer, antioxidant, anti-inflammatory, neuroprotective, hepatoprotective, and hypocholesterolemic properties due to the bioactive compounds it contains. In this study, the effects of freeze-thawing, a rapid freezing (-20°C) and thawing (4°C) process, and ultrasonically assisted extraction techniques on the color, antioxidant capacity, total phenolic content, and phenolic composition of Spirulina platensis extracts were investigated. The antioxidant capacity of the extracts obtained was determined by two different methods, DPPH (2,2-diphenyl-1-picryl hydrazyl) and ABTS (2,2-azinobis (3-ethylbenzothiazollin-6-sulfonic acid)). The sugar profile was determined by HPLC-RID and phenolic composition was determined by HPLC-ESI-DAD-MS/MS. The antioxidant activity and total phenolic content of samples prepared by the freeze-thawing were higher than those prepared by ultrasonic-assisted conventional extraction technique. In addition to ferulic acid 4-O-glucuronide and brevifolin carboxylate, an isocoumarin derivative, as the dominant phenolic compound in S. platensis extracts, a total of 10 phenolic compounds including catechin isomer, resveratrol C-hexoside, myricetin, ferulic acid, gallic acid, phloroglucinol, and lutein were detected. Glucose was the predominant sugar in both samples. The total sugar content was higher in the freeze-thawed samples (217.92 mg/100 g DW) than in the ultrasonic-assisted conventional extraction technique (182.91 mg/100 g DW). S. platensis has a significant amount of antioxidants, valuable secondary metabolites, and potential commercial applications and medicinal properties, but releasing these compounds is difficult due to the cell wall. This study was carried out to determine how different extraction techniques alter the release of bioactive compounds.

Chemical composition and discrimination with volatile profiles of Yongchuan Xiuya green tea with different baking treatments

AbstractThis study aimed to explore the effects of different baking treatments on the quality of Yongchuan Xiuya (YCXY) green tea. It was found that a long time baking at low temperature was beneficial to keep green colour, faint scent, mellow and fresh taste quality, whereas baking under high temperature was adverse to the quality. Baking treatments slightly regulated (−)‐epigallocatechin, (−)‐epicatechin, (−)‐gallocatechin gallate, total chlorophyll and carotenoid. As the baking temperature rose, the content of tea polyphenols, gallic acid, catechins, caffeine, soluble sugar and polyphenols/amino acids ratio obviously decreased. A total of 40 kinds of volatiles were detected in these six tea samples. A model for aroma type discrimination was successfully established based on partial least squares‐discriminant analysis (PLS‐DA). Ten kinds of volatile substances were the key characteristic markers for the faint scent, chestnut aroma and high‐fired aroma types of YCXY green tea. 1‐hexanol, hotrienol and dimethyl sulfide were furtherly used to discriminant aroma type based on Fisher discriminant analysis (FDA).

Phytochemical Analysis and Antioxidant Effects of Prunella vulgaris in Experimental Acute Inflammation.

Prunella vulgaris (PV) is one of the most commonly used nutraceuticals as it has been proven to have anti-inflammatory and antioxidant properties. The aim of this study was to evaluate the phytochemical composition of PV and its in vivo antioxidant properties. A phytochemical analysis measuring the total phenolic content (TPC), the identification of phenolic compounds by HPLC-DAD-ESI, and the evaluation of the in vitro antioxidant activity by the DPPH assay of the extract were performed. The antioxidant effects on inflammation induced by turpentine oil were experimentally tested in rats. Seven groups with six animals each were used: a control group, the experimental inflammation treatment group, the experimental inflammation and diclofenac sodium (DS) treatment group, and four groups with their inflammation treated using different dilutions of the extract. Serum redox balance was assessed based on total oxidative status (TOS), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), total thiols, and an oxidative stress index (OSI) contents. The TPC was 0.28 mg gallic acid equivalents (GAE)/mL extract, while specific representatives were represented by caffeic acid, p-coumaric acid, dihydroxybenzoic acid, gentisic acid, protocatechuic acid, rosmarinic acid, vanillic acid, apigenin-glucuronide, hesperidin, kaempferol-glucuronide. The highest amount (370.45 μg/mL) was reported for hesperidin, which is a phenolic compound belonging to the flavanone subclass. The antioxidant activity of the extracts, determined using the DPPH assay, was 27.52 mmol Trolox/mL extract. The PV treatment reduced the oxidative stress by lowering the TOS, OSI, NO, and MDA and by increasing the TAC and thiols. In acute inflammation, treatment with the PV extract reduced oxidative stress, with lower concentrations being more efficient and having a better effect than DS.

Ultraviolet-C Light and Peracetic Acid Extend the Shelf Life of Fresh and Frozen Strawberries

The postharvest life of strawberries is short, and disinfection processes for fresh-cut and frozen strawberries are needed to address the risk posed by foodborne pathogens in this kind of product. For this, a process involving immersion in a 40 mg L−1 peracetic acid (PA) solution accompanied by the use of an emerging technology, ultraviolet-C for 2 min, was studied for its impact on strawberry quality and microbial load as a novel alternative method to chlorine sanitation. The shelf life of the washed strawberries was evaluated in fresh (whole or fresh-cut) product for 11 days at 4 °C and in product that had been frozen for 12 months at –20 °C (air or modified atmosphere, 20% CO2, 5% O2, and 75% N2). After washing, total aerobic mesophylls, yeast, and mold decreased by 0.5–1.0 log units and these counts remained low during storage. The fresh and fresh-cut fruits’ firmness (2.3 ± 0.5 N at day 11) and lightness (expressed by L*, averaging 31.0 ± 0.1) were maintained. Although antioxidant activity, expressed by the amount of radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), decreased during storage in fresh-cut samples, total ferric reducing antioxidant power (FRAP), total phenolic content, and total anthocyanin content were maintained in all the formats during storage (averaging 1.33 ± 0.04 g kg−1 ascorbic acid equivalents, 0.212 ± 0.01 g kg−1 gallic acid equivalents, and 0.03 ± 0.01 g kg−1 pelargonidine-3-glucoside). An increase in red color (from 32.1 to 39.3 a* values) and a loss of firmness of up to 46.8% was observed after the first month of frozen storage with no changes in the nutritional quality. Considering the sanitizing effect of water UV-C with peracetic acid (WUVPA) and the results obtained in the present study, the addition of this process in the production chain of strawberries could be an effective method to maintain the shelf life of the fruits, especially for fresh-cut strawberries.

MOLECULAR DOCKING AND ADMET BASED MINING OF NATURAL COMPOUNDS FROM PTEROCARPUS MARSUPIUM AGAINST PRIME TARGETS OF DIABETES MELLITUS

In the Ayurvedic system of medicine, Pterocarpus marsupium Linn bark extract is used for the treatment of diabetes. It has a rich profile of chemical constituents. However, phytochemicals with antidiabetic activity are not reported yet. To comprehend more about this plant’s antidiabetic mechanism of action, 26 reported phytochemicals, namely, pterostilbene, marsupsin/ carpusin, 7-O-α-L-rhamnopyranosyloxy4′-methoxy-5-hydroxy isoflavone, (-)-epicatechin, pterosupin, liquiritigenin, vijayoside, pteroside, propterol-b, beta-eudesmol, pseudobaptigenin, isoliquiritigenin, garbanzol, 5-de-oxykaempferol, catechol, gallic acid, 3,4-dihydroxybenzoic acid, naringetol, 4-hydroxybenzaldehyde, trans-stilbene, 3,7,4’-trihydroxyflavone, 7,4’-dihydroxyflavone, (2S)-7-hydroxyflavanone, oleanolic acid, lupeol and marsupol/ebanol, were subjected to molecular docking studies using six targets of diabetes, namely, C and N-terminal subunits of human maltase-glucoamylase, glucagon like peptide-1, N-terminal sucraseisomaltase, human peroxisome proliferator-activated receptor –α and ϒ. The docking studies were carried out using PyRx and AutoDock Vina 1.1.2 software. Compounds with optimum binding affinity were subjected to evaluate drug likeliness and toxicity using SwissADME and admetSAR web tools. Vijayoside was found to have maximum affinity (-8.5 Kcal mol-1) with N-terminal subunit of human maltaseglucoamylase. The binding energies of O-α-L-rhamnopyranosyloxy-4'-methoxy-5-hydroxy isoflavone was found to be maximum with C-terminal (-10.0 Kcal mol-1). Danugliprion, a standard, was found to have maximum binding affinity (-11.4 Kcal mol-1) with glucagon-like peptide-1. Pteroside was found to bind favorably (-7.5 Kcal mol-1) with N-terminal sucrase-isomaltase.7-O-α-L-rhamnopyranosyloxy4′-methoxy-5-hydroxy isoflavone has exhibited stable interactions with other receptors (-10.2 and -8.2 Kcal mol-1 for human peroxisome proliferator-activated receptor–α and ϒ). These three phytochemicals also exhibited druggability properties. Further in vitro and in vivo studies may fully validate the results.

Exploring Varied (Green) Extraction Methods to Optimize Galia Melon Peel Antioxidant Potential

Cucumis melo L. (C. melo), commonly known as the melon, is a widely cultivated tropical fruit associated with nutritional benefits and bioactive properties. With global production reaching 40 million tons annually, the fruit processing industry generates significant waste, primarily peels, totaling 8 to 20 million tons yearly. These organic by-products are rich in bioactive compounds such as antioxidants, offering health benefits such as a reduced risk of cancer and cardiovascular diseases, as well as of diabetes and neurogenerative diseases, offering an opportunity for sustainable utilization. C. melo by-products have demonstrated various health benefits, including anti-inflammatory, analgesic, and antioxidant properties, attributed mainly to polyphenols. Recognizing the potential of melon waste, this study systematically explored different extraction methods, including stirring (ST), ultrasound (US), and pulsed electric field (PEF) methods, while considering factors such as extraction time, temperature, and solvent composition. The primary goal was to identify the most effective extraction procedures and optimal conditions for maximizing the yield of total polyphenols and antioxidant capacity (using the FRAP and DPPH methods) from C. melo peel by-products. According to the results, the optimum conditions include ST as the extraction method, an ethanolic solvent with a strength of 50%, a 150 min extraction duration, and an 80 °C extraction temperature. The maximum values of total polyphenols that can be observed are 3.75 mg gallic acid equivalents (GAE)/g of dry weight (dw) and 25.77 μmol ascorbic acid equivalents (AAE)/g dw and 34.44 μmol AAE/g dw from FRAP and DPPH antioxidant assays, respectively. The polyphenols identified were the following: gallic acid, neochlorogenic acid, catechin, chlorogenic acid, epicatechin, and kaempferol. By securing the maximum isolation of bioactive content and antioxidant activity, the research will contribute to sustainable waste management by reducing waste and developing value-added products.

Unraveling Shikimate Dehydrogenase Inhibition by 6-Nitroquinazoline-2,4-diol and Its Impact on Soybean and Maize Growth

The shikimate pathway is crucial for the biosynthesis of aromatic amino acids in plants and represents a promising target for developing new herbicides. This work aimed to identify inhibitors of shikimate dehydrogenase (SDH), a key enzyme of the shikimate pathway that catalyzes the conversion of 3-dehydroshikimate to shikimate. Virtual screening and molecular dynamic simulations were performed on the SDH active site of Arabidopsis thaliana (AtSDH), and 6-nitroquinazoline-2,4-diol (NQD) was identified as a potential inhibitor. In vitro assays showed that NQD decreased the activity of AtSDH by reducing Vmax while keeping KM unchanged, indicating non-competitive inhibition. In vivo, hydroponic experiments revealed that NQD reduced the root length of soybean and maize. Additionally, NQD increased the total protein content and certain amino acids. Soybean roots uptake NQD more efficiently than maize roots. Furthermore, NQD reduced shikimate accumulation in glyphosate-treated soybean roots, suggesting its potential to restrict the flow of metabolites along the shikimate pathway in soybean. The simultaneous treatment of maize seedlings with glyphosate and NQD accumulated gallic acid in the roots, indicating that NQD inhibits SDH in vivo. Overall, the data indicate that NQD inhibits SDH both in vitro and in vivo, providing valuable insights into the potential development of herbicides targeting SDH.

LMD and LC-MS-based chemical constituents and pharmacological effects assessment for two different processing methods of the root of Paeonia lactiflora Pall.

The plant of Paeonia lactiflora Pall. belongs to Ranunculaceae, and its root can be divided into two categories according to different processing methods, which included that one was directly dried without peeling the root of the P. lactiflora (PR), and the other was peeled the root of the P. lactiflora (PPR) after boiled and dried. To evaluate the difference of chemical components, UPLC-ESI-Q-Exactive Focus-MS/MS and UPLC-QQQ-MS were applied. The distribution of chemical components in different tissues was located by laser microdissection (LMD), especially the different ingredients. A total of 86 compounds were identified from PR and PPR. Four kind of tissues were isolated from the fresh root of the P. lactiflora (FPR), and 54 compounds were identified. Especially the content of gallic acid, albiflorin, and paeoniflorin with high biological activities were the highest in the cork, but they were lower in PR than that in PPR, which probably related to the process. To illustrate the difference in pharmacological effects of PR and PPR, the tonifying blood and analgesic effects on mice were investigated, and it was found that the tonifying blood and analgesic effects of PPR was superior to that of PR, even though PR had more constituents. The material basis for tonifying blood and analgesic effect of the root of P. lactiflora is likely to be associated with an increase in constituents such as paeoniflorin and paeoniflorin lactone after boiled and peeled. The study was likely to provide some theoretical support for the standard and clinical application.

Gallic Acid Can Promote Low-Density Lipoprotein Uptake in HepG2 Cells via Increasing Low-Density Lipoprotein Receptor Accumulation.

Gallic acid (GA) is a type of polyphenolic compound that can be found in a range of fruits, vegetables, and tea. Although it has been confirmed it improves non-alcoholic fatty liver disease (NAFLD), it is still unknown whether GA can improve the occurrence of NAFLD by increasing the low-density lipoprotein receptor (LDLR) accumulation and alleviating cholesterol metabolism disorders. Therefore, the present study explored the effect of GA on LDLR and its mechanism of action. The findings indicated that the increase in LDLR accumulation in HepG2 cells induced by GA was associated with the stimulation of the epidermal growth factor receptor-extracellular regulated protein kinase (EGFR-ERK1/2) signaling pathway. When the pathway was inhibited by EGFR mab cetuximab, it was observed that the activation of the EGFR-ERK1/2 signaling pathway induced by GA was also blocked. At the same time, the accumulation of LDLR protein and the uptake of LDL were also suppressed. Additionally, GA can also promote the accumulation of forkhead box O3 (FOXO3) and suppress the accumulation of hepatocyte nuclear factor-1α (HNF1α), leading to the inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) mRNA expression and protein accumulation. This ultimately results in increased LDLR protein accumulation and enhanced uptake of LDL in cells. In summary, the present study revealed the potential mechanism of GA's role in ameliorating NAFLD, with a view of providing a theoretical basis for the dietary supplementation of GA.

Unravelling and reconstructing the biosynthetic pathway of bergenin

Bergenin, a rare C-glycoside of 4-O-methyl gallic acid with pharmacological properties of antitussive and expectorant, is widely used in clinics to treat chronic tracheitis in China. However, its low abundance in nature and structural specificity hampers the accessibility through traditional crop-based manufacturing or chemical synthesis. In the present work, we elucidate the biosynthetic pathway of bergenin in Ardisia japonica by identifying the highly regio- and/or stereoselective 2-C-glycosyltransferases and 4-O-methyltransferases. Then, in Escherichia coli, we reconstruct the de novo biosynthetic pathway of 4-O-methyl gallic acid 2-C-β-D-glycoside, which is the direct precursor of bergenin and is conveniently esterified into bergenin by in situ acid treatment. Moreover, further metabolic engineering improves the production of bergenin to 1.41 g L−1 in a 3-L bioreactor. Our work provides a foundation for sustainable supply of bergenin and alleviates its resource shortage via a synthetic biology approach.

Study on the Antifungal Activity of Gallic Acid and Its Azole Derivatives against Fusarium graminearum.

The wheat scab caused by Fusarium graminearum (F. graminearum) has seriously affected the yield and quality of wheat in China. In this study, gallic acid (GA), a natural polyphenol, was used to synthesize three azole-modified gallic acid derivatives (AGAs1-3). The antifungal activity of GA and its derivatives against F. graminearum was studied through mycelial growth rate experiments and field efficacy experiments. The results of the mycelial growth rate test showed that the EC50 of AGAs-2 was 0.49 mg/mL, and that of AGAs-3 was 0.42 mg/mL. The biological activity of AGAs-3 on F. graminearum is significantly better than that of GA. The results of field efficacy tests showed that AGAs-2 and AGAs-3 significantly reduced the incidence rate and disease index of wheat scab, and the control effect reached 68.86% and 72.11%, respectively. In addition, preliminary investigation was performed on the possible interaction between AGAs-3 and F. graminearum using density functional theory (DFT). These results indicate that compound AGAs-3, because of its characteristic of imidazolium salts, has potential for use as a green and environmentally friendly plant-derived antifungal agent for plant pathogenic fungi.

Exploring the anti‐inflammatory ingredients and potential of golden buckwheat (Fagopyrum dibotrys) on the TLR4/NLRP3 pathway in acute lung injury

AbstractGolden buckwheat, also called Fagopyrum dibotrys (D. Don) H. Hara, is a plant of the genus Buckwheat in the buckwheat family. The aim of this study was to screen the bioactive ingredients of golden buckwheat extract and investigate the protective effect on acute lung injury (ALI). The ethyl acetate extract (EAE) was identified as the active fraction in LPS‐induced RAW264.7 cells, with gallic acid, proanthocyanidin B2, and epicatechin at 0.0563%, 0.3707%, and 0.3868%, respectively. At the same time, 20 compounds (mainly flavonoids and organic acids) were identified by UPLC‐Q‐Exactive Orbitrap‐HRMS in EAE. Furthermore, the EAE reduced lung histopathology scores in mice with ALI, decreased the dry‐to‐wet weight ratio of lung tissue, and significantly inhibited the concentrations of IL‐1β, TNFα, and IL‐6 in bronchoalveolar lavage fluid (BALF). It also reduced the number of leukocytes, decreased the activity of MPO in lung tissue, and inhibited the levels of TLR4/NLRP3 pathway mRNA and protein in lung tissue. Our study indicated that golden buckwheat as a source of functional food prevents or treats associated lung diseases by modulating the activation of the TLR4/NLRP3 signaling pathway.

Utilization of some fruit rinds in small ruminant feeding: nutritional characteristics determination.

Every year, thousands of tons of fruit wastes are produced worldwide while most of them remain unused and are released into the environment. Incorporation of these wastes to feedstuffs reduces competition between food and feed, and reduces environmental risks or methane yield in ruminants. Nevertheless, no comprehensive research was available on the nutritional properties of rinds of different fruits in small ruminant feeding. Hence, this research investigates the nutritional potential of some fruit's rinds (Kiwi, Tangerine, Grapefruit, Sweet lemon, Sour lemon, Banana, Mango, Orange, Apple, Peach, and Persimmon) by in vitro ruminal-microbial and standard laboratory methods. Persimmon rind had the higher total phenolic contents (TPC, 22mg gallic acid equivalents/g dry matter: DM) than the other treatments (P < 0.0001). The ether extract (EE), neutral detergent fiber (NDF), acid detergent fiber (ADF), and ash contents of banana rind were greater (P < 0.0001), however its DM, relative feed value (RFV), and non-fiber carbohydrates (NFC) were lower than the other treatments (P < 0.0001). A different range of minerals was observed among fruit rinds along with a higher content of potassium (42.5g/kg DM) and manganese (49mg/kg DM) in banana rind (P < 0.0001). Persimmon (45.7ml/200mg DM) and sweet lemon (75.7ml/200mg DM) rinds recorded the lowest and highest potential gas production, respectively (P < 0.0001). Persimmon exhibited a lower percentage of methane (11.5%) rather than other rinds (P < 0.0001). The total volatile fatty acids (TVFA) and metabolizable energy (ME) in sweet lemon, and dry matter digestibility (DMD) and organic matter digestibility (OMD) in tangerine were greater compared with other rinds. The rind of the banana exhibited the highest amounts of titratable acidity (283 mEq×10- 3), acid-buffering capacity (200 mEq×10- 3), and acid-base buffering capacity (260 mEq×10- 3) (P < 0.0001). In conclusion, the present rinds differed in chemical-nutritional characteristics. These rinds may feed as a substitute for conventional forages in the diets of small ruminants on a large scale throughout the year; however, these in vitro findings need to be scientifically validated under in vivo experiments.

Profiling and optimized extraction of bioactive polyphenolic compounds from young, red-fleshed apple using eco-friendly deep eutectic solvents

Red-fleshed apple cultivars with an enhanced content of polyphenolic compounds have attracted increasing interest due to their promising health benefits. Here, we have analysed the polyphenolic content of young, red-fleshed apples (RFA) and optimised extraction conditions of phenolics by utilising natural deep eutectic solvents (NDES). We also compare the antioxidant, neuroprotective and antimicrobial activities of NDES- and methanol-extracted phenolics from young RFA. High-performance liquid chromatography coupled to high-resolution mass spectrometry (HPLC-HRMS) was used for phenolics identification and quantification. Besides young RFA, ripe red-fleshed, young and ripe white-fleshed apples were analysed, revealing that young RFA possess the highest phenolic content (2078.4 ± 4.0 mg gallic acid equivalent/100 g), and that ripe white-fleshed apples contain the least amount of phenolics (545.0 ± 32.0 mg gallic acid equivalent/100 g). The NDES choline chloride-glycerol containing 40 % w/w H2O gave similar yields at 40 °C as methanol. In addition, the polyphenolics profile, and bioactivities of the NDES extract from young RFA were comparable that of methanol extracts. Altogether, our data show that NDES extracts of young RFA are a promising source of bioactive polyphenolics with potential applications in diverse sectors, e.g., for functional food production, smart material engineering and natural therapies.