Prenanthes purpurea and 3,5-DiCQA Alleviate Cellular Stress in H2O2-Induced Neurotoxicity: An In Vitro Comparative Study.

Oxidative stress exerts multiple disruptive effects on cellular morphology and function and is a major detriment to age-related and pathological neurodegenerative processes. The present study introduces an evaluative and comparative investigation of the antioxidant and cytoprotective properties of a Prenanthes purpurea extract and its major constituent 3,5-dicaffeoylquinic acid (DiCQA) in an in vitro model of H2O2-induced neurotoxicity. Using validated in vitro and in silico approaches, we established the presence and concentration dynamics of cellular protection in a 24 h pretreatment regimen with the natural products. The conducted cytotoxicity studies and the automated Chou-Talalay analysis for studying drug interactions demonstrated a strong antagonistic effect of the tested substances against oxidative stimuli in an "on demand" manner, prevailing at the higher end of the concentration range. These findings were further supported by the proteomic characterization of the treatment samples, accounting for a more distinct neuroprotection provided by the pure polyphenol 3,5-DiCQA.

Gastrointestinal digestion of yerba mate, rosemary and green tea extracts and their subsequent colonic fermentation by human, pig or rat inocula.

Polyphenolic compounds are common constituents of human and animal diets and undergo extensive metabolism by the gut microbiota before entering circulation. In order to compare the transformations of polyphenols from yerba mate, rosemary, and green tea extracts in the gastrointestinal tract, simulated gastrointestinal digestion coupled with colonic fermentation were used. For enhancing the comparative character of the investigation, colonic fermentation was performed with human, pig and rat intestinal microbiota. Chemical analysis was performed using a HPLC system coupled to a diode-array detector and mass spectrometer. Gastrointestinal digestion diminished the total amount of phenolics in the rosemary and green tea extracts by 27.5 and 59.2 %, respectively. These reductions occurred mainly at the expense of the major constituents of these extracts, namely rosmarinic acid (-45.7 %) and epigalocatechin gallate (-60.6 %). The yerba mate extract was practically not affected in terms of total phenolics, but several conversions and isomerizations occurred (e.g., 30 % of trans-3-O-caffeoylquinic acid was converted into the cis form). The polyphenolics of the yerba mate extract were also the least decomposed by the microbiota of all three species, especially in the case of the human one (-10.8 %). In contrast, the human microbiota transformed the polyphenolics of the rosemary and green extracts by 95.9 and 88.2 %, respectively. The yerba mate-extract had its contents in cis 3-O-caffeoylquinic acid diminished by 78 % by the human microbiota relative to the gastrointestinal digestion, but the content of 5-O-caffeoylquinic acid (also a chlorogenic acid), was increased by 22.2 %. The latter phenomenon did not occur with the rat and pig microbiota. The pronounced interspecies differences indicate the need for considerable caution when translating the results of experiments on the effects of polyphenolics performed in rats, or even pigs, to humans.

Integrated metabolomic and transcriptomic analysis reveals biosynthesis mechanism of flavone and caffeoylquinic acid in chrysanthemum.

BACKGROUND: Chrysanthemum morifolium 'HangBaiJu', a popular medicinal and edible plant, exerts its biological activities primarily through the presence of flavones and caffeoylquinic acids (CQAs). However, the regulatory mechanism of flavone and CQA biosynthesis in the chrysanthemum capitulum remains unclear. RESULTS: In this study, the content of flavones and CQAs during the development of chrysanthemum capitulum was determined by HPLC, revealing an accumulation pattern with higher levels at S1 and S2 and a gradual decrease at S3 to S5. Transcriptomic analysis revealed that CmPAL1/2, CmCHS1/2, CmFNS, CmHQT, and CmHCT were key structural genes in flavones and CQAs biosynthesis. Furthermore, weighted gene co-expression correlation network analysis (WGCNA), k-means clustering, correlation analysis and protein interaction prediction were carried out in this study to identify transcription factors (TFs) associated with flavone and CQA biosynthesis, including MYB, bHLH, AP2/ERF, and MADS-box families. The TFs CmERF/PTI6 and CmCMD77 were proposed to act as upstream regulators of CmMYB3 and CmbHLH143, while CmMYB3 and CmbHLH143 might form a complex to directly regulate the structural genes CmPAL1/2, CmCHS1/2, CmFNS, CmHQT, and CmHCT, thereby controlling flavone and CQA biosynthesis. CONCLUSIONS: Overall, these findings provide initial insights into the TF regulatory network underlying flavones and CQAs accumulation in the chrysanthemum capitulum, which laid a theoretical foundation for the quality improvement of C. morifolium 'HangBaiJu' and the high-quality development of the industry.

Potential Risk of Caffeoylquinic Acids, the Main Polyphenol Components in Coffee, on the Health of Piglets.

As the main coffee polyphenols, caffeoylquinic acids (CQAs) are abundant in coffee-derived products and have the potential to act as novel feed additives for animals. However, research on the side effects of dietary CQAs supplementation is scarce, especially in young animals. Here, we explore the safety of CQAs derived from green coffee beans. Results showed that ingesting 50, 125, 250, and 500 mg/kg of dietary CQAs for 55 days is associated with greater final body weight, average daily gain, and feed efficiency in piglets compared with the control group (P < 0.05). CQAs also increased the apparent digestibility of dry matter, crude protein, and gross energy at a dose over 50 mg/kg (P < 0.05). Interestingly, CQAs supplementation with 500 mg/kg increased the white blood cell count (P < 0.05). Moreover, CQAs supplementation at a dose over 50 mg/kg decreased the serum total cholesterol concentration but increased the immunoglobulin M level in serum (P < 0.05). Importantly, CQAs supplementation had no side effects on organ histopathology and organ weight (P > 0.05). These results suggest that CQAs could serve as a secure and effective additive to improve growth performance without negatively affecting the organs of piglets.

Design of chitosan colon delivery micro/nano particles for an Achillea millefolium extract with antiproliferative activity against colorectal cancer cells.

In this study, chitosan low molecular weight (LCH) and chitosan medium molecular weight (MCH) were employed to encapsulate a yarrow extract rich in chlorogenic acid and dicaffeoylquinic acids (DCQAs) that showed antiproliferative activity against colon adenocarcinoma cells. The design of CH micro/nanoparticles to increase the extract colon delivery was carried out by using two different techniques: ionic gelation and spray drying. Ionic gelation nanoparticles obtained were smaller and presented higher yields values than spray-drying microparticles, but spray-drying microparticles showed the best performance in terms of encapsulation efficiency (EE) (> 94%), also allowing the inclusion of a higher quantity of extract. Spray-drying microparticles designed using LCH with an LCH:extract ratio of 6:1 (1.25 mg/mL) showed a mean diameter of 1.31 ± 0.21 µm and EE values > 93%, for all phenolic compounds studied. The release profile of phenolic compounds included in this formulation, at gastrointestinal pHs (2 and 7.4), showed for most of them a small initial release, followed by an increase at 1 h, with a constant release up to 3 h. Chlorogenic acid presented the higher release values at 3 h (56.91% at pH 2; 44.45% at pH 7.4). DCQAs release at 3 h ranged between 9.01- 40.73%, being higher for 1,5- and 3,4-DCQAs. After gastrointestinal digestion, 67.65% of chlorogenic and most DCQAs remained encapsulated. Therefore, spray-drying microparticles can be proposed as a promising vehicle to increase the colon delivery of yarrow phenolics compounds (mainly chlorogenic acid and DCQAs) previously described as potential agents against colorectal cancer.

Molecular Mechanisms of Anticarcinogenic Potential of Hydrocotyle umbellata and Its Major Components.

Despite the development of several anticancer treatments, there remains a need for new drugs that can overcome resistance and reduce side effects. While the medicinal herb Hydrocotyle umbellata (H. umbellata) has been used to relieve pain and inflammation, its antitumor properties have not yet been explored. In this study, we investigated the anticarcinogenic potential of H. umbellata extract (HUE) and its major components, as well as the underlying molecular mechanisms. Our results showed that HUE inhibited the growth of various tumor cell lines, including B16F10, without affecting non-cancer cells. Furthermore, HUE was effective in treating and preventing tumor growth in mice. Our mechanistic studies revealed that HUE inhibited cellular respiration, thereby reducing tumor cell proliferation. When combined with 2-deoxy-D-glucose, HUE demonstrated an enhanced anticancer effect by increasing the rate apoptosis. Analysis of the ethyl acetate and n-butanol fractions of HUE identified 1,3,4-trihydroxy-2-butanyl-α-d-glucopyranoside and caffeoylquinic acid derivatives as the major components responsible for the observed anticancer effects. In conclusion, our findings suggest that HUE and its two major components have the potential to be developed as effective therapeutic agents for a wide range of tumors by targeting cancer cell metabolism.

3,4,5-tri-O-caffeoylquinic acid attenuates influenza A virus induced inflammation through Toll-like receptor 3/7 activated signaling pathway.

BACKGROUND: 3,4,5-tri-O-caffeoylquinic acid (3,4,5-TCQA), a natural polyphenolic acid, has been shown to be effective against influenza A virus (IAV) infection. Although it was found to inhibit the neuraminidase of IAV, it may also perturb other cellular functions, as polyphenolic acids have shown antioxidant, anti-inflammatory and other activities. PURPOSE: This study aimed to investigate the effect of 3,4,5-TCQA at a cell level, which is critical for protecting host cell from IAV infection. STUDY DESIGN AND METHODS: We explored the effect of 3,4,5-TCQA on H292 cells infected or un-infected with Pr8 IAV. The major genes and related pathway were identified through RNA sequencing. The pathway was confirmed by qRT-PCR and western blot analysis. The anti-inflammatory activity was evaluated using nitric oxide measurement assay. RESULTS: We showed that 3,4,5-TCQA downregulated the immune response in H292 cells, and reduced the cytokine production in Pr8-infected cells, through Toll-like receptor (TLR) signaling pathway. In addition, 3,4,5-TCQA showed anti-inflammatory activity in LPS-activated RAW264.7 cells. CONCLUSION: Collectively, our results indicated that 3,4,5-TCQA suppressed inflammation caused by IAV infection through TLR3/7 signaling pathway. This provides a new insight into the antiviral mechanism of 3,4,5-TCQA.

Quinic acid alleviates high-fat diet-induced neuroinflammation by inhibiting DR3/IKK/NF-κB signaling via gut microbial tryptophan metabolites.

With the increasing of aging population and the consumption of high-fat diets (HFD), the incidence of Alzheimer's disease (AD) has skyrocketed. Natural antioxidants show promising potential in the prevention of AD, as oxidative stress and neuroinflammation are two hallmarks of AD pathogenesis. Here, we showed that quinic acid (QA), a polyphenol derived from millet, significantly decreased HFD-induced brain oxidative stress and neuroinflammation and the levels of Aß and p-Tau. Examination of gut microbiota suggested the improvement of the composition of gut microbiota in HFD mice after QA treatment. Metabolomic analysis showed significant increase of gut microbial tryptophan metabolites indole-3-acetic acid (IAA) and kynurenic acid (KYNA) by QA. In addition, IAA and KYNA showed negative correlation with pro-inflammatory factors and AD indicators. Further experiments on HFD mice proved that IAA and KYNA could reproduce the effects of QA that suppress brain oxidative stress and inflammation and decrease the levels of of Aß and p-Tau. Transcriptomics analysis of brain after IAA administration revealed the inhibition of DR3/IKK/NF-κB signaling pathway by IAA. In conclusion, this study demonstrated that QA could counteract HFD-induced brain oxidative stress and neuroinflammation by regulating inflammatory DR3/IKK/NF-κB signaling pathway via gut microbial tryptophan metabolites.

3,5-DCQA as a Major Molecule in MeJA-Treated Dendropanax morbifera Adventitious Root to Promote Anti-Lung Cancer and Anti-Inflammatory Activities.

(1) Background: Phytochemicals are crucial antioxidants that play a significant role in preventing cancer. (2) Methods: We explored the use of methyl jasmonate (MeJA) in the in vitro cultivation of D. morbifera adventitious roots (DMAR) and evaluated its impact on secondary metabolite production in DMAR, optimizing concentration and exposure time for cost-effectiveness. We also assessed its anti-inflammatory and anti-lung cancer activities and related gene expression levels. (3) Results: MeJA treatment significantly increased the production of the phenolic compound 3,5-Di-caffeoylquinic acid (3,5-DCQA). The maximum 3,5-DCQA production was achieved with a MeJA treatment at 40 µM for 36 h. MeJA-DMARE displayed exceptional anti-inflammatory activity by inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS) in LPS-induced RAW 264.7 cells. Moreover, it downregulated the mRNA expression of key inflammation-related cytokines. Additionally, MeJA-DMARE exhibited anti-lung cancer activity by promoting ROS production in A549 lung cancer cells and inhibiting its migration. It also modulated apoptosis in lung cancer cells via the Bcl-2 and p38 MAPK pathways. (4) Conclusions: MeJA-treated DMARE with increased 3,5-DCQA production holds significant promise as a sustainable and novel material for pharmaceutical applications thanks to its potent antioxidant, anti-inflammatory, and anti-lung cancer properties.

Di-caffeoylquinic acid: a potential inhibitor for amyloid-beta aggregation.

Alzheimer's disease (AD) remains a challenging neurodegenerative disorder with limited therapeutic success. Traditional Chinese Medicine (TCM), as a promising new source for AD, still requires further exploration to understand its complex components and mechanisms. Here, focused on addressing Aß (1-40) aggregation, a hallmark of AD pathology, we employed a Thioflavin T fluorescence labeling method for screening the active molecular library of TCM which we established. Among the eight identified, 1,3-di-caffeoylquinic acid emerged as the most promising, exhibiting a robust binding affinity with a KD value of 26.7 nM. This study delves into the molecular intricacies by utilizing advanced techniques, including two-dimensional (2D) 15N-1H heteronuclear single quantum coherence nuclear magnetic resonance (NMR) and molecular docking simulations. These analyses revealed that 1,3-di-caffeoylquinic acid disrupts Aß (1-40) self-aggregation by interacting with specific phenolic hydroxyl and amino acid residues, particularly at Met-35 in Aß (1-40). Furthermore, at the cellular level, the identified compounds, especially 1,3-di-caffeoylquinic acid, demonstrated low toxicity and exhibited therapeutic potential by regulating mitochondrial membrane potential, reducing cell apoptosis, and mitigating Aß (1-40)-induced cellular damage. This study presents a targeted exploration of catechol compounds with implications for effective interventions in AD and sheds light on the intricate molecular mechanisms underlying Aß (1-40) aggregation disruption.

Efficacy of 2 botanical aphicides, chicoric and 3,5-dicaffeoylquinic acids, on aphids susceptible and resistant to synthetic insecticides.

Dicaffeoyltartaric acid (diCT) and 3,5-dicaffeoylquinic acid (3,5-diCQ) are described for their aphicidal properties on several aphid species. Intending to valorize diCT and 3,5-diCQ as biocontrol products and because of the high adaptive capacities of aphids to xenobiotics, we sought to determine the existence of adaptation first in Myzus persicae (Sulzer) (Hemiptera: Aphididae) and then other aphids. Resistance of aphids to these biopesticides could be promoted by (i) the existence of resistance to synthetic insecticides that may confer cross-resistance and (ii) the presence of these compounds in wild plants likely which may have led to pre-existing adaptation in aphids. We assessed the resistance levels to diCT and 3,5-diCQ in 7 lab strains (including some resistant to synthetic aphicides) and 7 wild populations of M. persicae using biotests. The activities of detoxification enzymes contributing to insecticide resistance were also measured. Additionally, we followed the same method to characterize susceptibility to these caffeic derivatives in wild populations of Nasonovia ribisnigri (Mosley) (Hemiptera: Aphididae), Brevicoryne brassicae(Linnaeus) (Hemiptera: Aphididae) and, Aphis craccivora(Koch) (Hemiptera: Aphididae). Our results show variability in susceptibility to diCT between populations of M. persicae, but resistance ratios (RR) were low (RR = 3.59). We found no cross-resistance between synthetic insecticides and diCT. Carboxylesterase and glutathione-S-transferase did not seem to be involved in its detoxification. A clone of A. craccivora collected from peanut, a species rich in diCT, was not susceptible to either diCT or 3,5-diCQ, suggesting a common molecular target for these 2 molecules and the existence of a high-effect resistance mechanism. These active botanical substances remain good candidates for M. persicae biocontrol in agriculture.

Light-Emitting Diodes and Liquid System Affect the Caffeoylquinic Acid Derivative and Flavonoid Production and Shoot Growth of Rhaponticum carthamoides (Willd.) Iljin.

Plant in vitro cultures can be an effective tool in obtaining desired specialized metabolites. The purpose of this study was to evaluate the effect of light-emitting diodes (LEDs) on phenolic compounds in Rhaponticum carthamoides shoots cultured in vitro. R. carthamoides is an endemic and medicinal plant at risk of extinction due to the massive harvesting of its roots and rhizomes from the natural environment. The shoots were cultured on an agar-solidified and liquid-agitated Murashige and Skoog's medium supplemented with 0.1 mg/L of indole-3-acetic acid (IAA) and 0.5 mg/L of 6-benzyladenine (BA). The effect of the medium and different treatments of LED lights (blue (BL), red (RL), white (WL), and a combination of red and blue (R:BL; 7:3)) on R. carthamoides shoot growth and its biosynthetic potential was observed. Medium type and the duration of LED light exposure did not affect the proliferation rate of shoots, but they altered the shoot morphology and specialized metabolite accumulation. The liquid medium and BL light were the most beneficial for the caffeoylquinic acid derivatives (CQAs) production, shoot growth, and biomass increment. The liquid medium and BL light enhanced the content of the sum of all identified CQAs (6 mg/g DW) about three-fold compared to WL light and control, fluorescent lamps. HPLC-UV analysis confirmed that chlorogenic acid (5-CQA) was the primary compound in shoot extracts regardless of the type of culture and the light conditions (1.19-3.25 mg/g DW), with the highest level under R:BL light. BL and RL lights were equally effective. The abundant component was also 3,5-di-O-caffeoylquinic acid, accompanied by 4,5-di-O-caffeoylquinic acid, a tentatively identified dicaffeoylquinic acid derivative, and a tricaffeoylquinic acid derivative 2, the contents of which depended on the LED light conditions.

Caffeoylquinic acid profiling: comparative analysis in yerba mate, Indian camphorweed, and stevia extracts with emphasis on the influence of brewing conditions and cold storage in yerba mate infusion.

Herbal infusions exhibit diverse pharmacological effects, such as antioxidant, anti-inflammatory, anticancer, antihypertensive, and antineurodegenerative activities, which can be attributed to the high content of phenolic compounds (e.g., caffeoylquinic acids (CQAs)). In this study, we used ultraperformance liquid chromatography to determine the content of CQAs in the methanolic extracts of model herbs, namely, yerba mate (Ilex paraguariensis), stevia (Stevia rebaudiana), and Indian camphorweed (Pluchea indica (L.) Less.). The results revealed that yerba mate had the highest total CQA content (108.05 ± 1.12 mg/g of dry weight). Furthermore, we evaluated the effect of brewing conditions and storage at 4 °C under dark and light conditions on the antioxidant property and total phenolic and CQA contents of a yerba mate infusion. The analysis of the yerba mate infusions prepared with different steeping times, dried leaf weights, and water temperatures revealed that the amount of extracted CQAs was maximized (∼175 mg/150 mL) when 6 g of dried leaves were steeped in hot water for 10 min. A total of 10-day refrigerated storage resulted in no significant changes in the antioxidant activity and total phenolic and CQA contents of an infusion kept in a brown container (dark). However, the antioxidant properties and total phenolic and CQA contents were negatively affected when kept in a clear container, suggesting the detrimental effect of light exposure. Our study provides practical recommendations for improving the preparation and storage of herbal infusions, thus catering to the needs of consumers, food scientists, and commercial producers. Moreover, it is the first study of the influence of light exposure on the content of crucial quality attributes within plant-based beverages.

Coffee leaf extract inhibits advanced glycation end products and their precursors: A mechanistic study.

Excessive accumulation of advanced glycation end products (AGEs) in the body is associated with diabetes and its complications. In this study, we aimed to explore the potential and mechanism of coffee leaf extract (CLE) in inhibiting the generation of AGEs and their precursors in an in vitro glycation model using bovine serum albumin and glucose (BSA-Glu) for the first time. High-performance liquid chromatography analysis revealed that CLE prepared with ultrasound pretreatment (CLE-U) contained higher levels of trigonelline, mangiferin, 3,5-dicaffeoylquinic acid, and γ-aminobutyric acid than CLE without ultrasound pretreatment (CLE-NU). The concentrations of these components, along with caffeine and rutin, were dramatically decreased when CLE-U or CLE-NU was incubated with BSA-Glu reaction mixture. Both CLE-U and CLE-NU exhibited a dose-dependent inhibition of fluorescent AGEs, carboxymethyllysine, fructosamine, 5-hydroxymethylfurfural, 3-deoxyglucosone, glyoxal, as well as protein oxidation products. Notably, CLE-U exhibited a higher inhibitory capacity compared to CLE-NU. CLE-U effectively quenched fluorescence intensity and increased the α-helix structure of the BSA-Glu complex. Molecular docking results suggested that the key bioactive compounds present in CLE-U interacted with the arginine residues of BSA, thereby preventing its glycation. Overall, this research sheds light on the possible application of CLE as a functional ingredient in combating diabetes by inhibiting the generation of AGEs.

Valorization of Pineapple (Ananas comosus) By-Products in Milk Coffee Beverage: Influence on Bioaccessibility of Phenolic Compounds.

The industrial processing of pineapples generates a substantial quantity of by-products, including shell, crown, and core. Bromelain, a proteolytic enzyme found naturally in pineapple, including its by-products, may positively influence the bioaccessibility of phenolics from milk coffee. Therefore, this study aimed to assess how the inclusion of extracts from pineapple by-products, namely shell, crown and core, could impact the bioaccessibility of coffee phenolics when combined with milk. After measuring the proteolytic activity of pineapple by-products, the standardized in vitro digestion model of INFOGEST was employed to evaluate changes in total phenolic content, total antioxidant capacity, and individual phenolic compounds in different coffee formulations. The results showed that incorporating extracts from the crown or core in both black and milk coffee increased the bioaccessibility of total phenolics (from 93 to 114% to 105-129%) and antioxidants (from 54 to 56% to 84-87%), while this effect was not observed for the shell. Moreover, adding core extracts also enhanced the bioaccessibility of caffeoylquinic acids and gallic acid in milk coffee (from 0.72 to 0.85% and 109-155%, respectively). Overall, the findings of this study highlight that bromelain from pineapple core may have a favorable effect on the recovery of phenolic compounds in milk coffee, possibly due to its ability to cleave proteins. These outcomes point out that industrial by-products can be transformed into economic value by being reintroduced into the production process through suitable treatment instead of disposal.

Characterization and Quantification of the Major Bioactive Compounds in Mexican Purple Tomatoes.

The present work carries out a quantitative analysis of the major bioactive compounds found in the native Mexican purple tomatoes. Total phenolic content ranged from 7.54 to 57.79 mg TPC/g DM, total flavonoid content ranged from 1.89 to 16.93 mg TFC/g DM, total anthocyanin content ranged from 0.29 to 2.56 mg TAC/g DM, and total carotenoid content ranged from 0.11 to 0.75 mg TCC/ g DM. In addition, 14 phenolic acids were identified, among which caffeoylquinic acid derivatives were the most abundant compounds with chlorogenic acid concentration up to 9.680 mg/g DM, together with flavonoids, such as rutin and quercetin-hexoxide. The qualitative analysis also showed the presence of 9 acylated anthocyanins and 2 carotenoids with significant functional features. As for anthocyanins, their chemical structures disclosed special structural features: glycosylated anthocyanins exhibited cis-trans hydroxycinnamic moieties and petunidin-3-(trans-p-coumaroyl)-rutinoside-5-glucoside was reported to be the main anthocyanin, whitin the range of concentrations between 0.160 and 1.143 mg/g DM.

Combination of Artemisia selengensis Turcz leaves polysaccharides and dicaffeoylquinic acids could be a potential inhibitor for hyperuricemia.

Caffeioyl quinic acids and polysaccharides from Artemisia selengensis Turcz are considered potential bioactive substances for hyperuricemia (HUA) treatment. While the mechanism of multi-component combined intervention of polysaccharides and dicaffeoylquinic acids (diCQAs) is not yet clear. In this study, we investigated the effect of A. selengensis Turcz leaves polysaccharides (APS) on the HUA treatment with diCQAs in vitro by direct inhibition of XOD activities and in vivo by using animal model. The results showed that APS had almost no inhibitory effect on XOD activities in vitro, but the inhibitory activity of diCQAs on XOD was affected by changes in inhibition type and inhibition constant. Compared to APS and diCQAs alone, high-dose APS and diCQAs in combination (ADPSh) could significantly reduce the production of uric acid (16.38 % reduction compared to diCQAs group) and oxidative stress damage. Additionally, this combined therapy showed promise in restoring the gut microbiota balance and increasing the short-chain fatty acids levels. The results suggested that APS and diCQAs in combination could be a potential inhibitor for HUA treatment.

Caffeoylquinic Acid Mitigates Neuronal Loss and Cognitive Decline in 5XFAD Mice Without Reducing the Amyloid-ß Plaque Burden.

Background: Caffeoylquinic acid (CQA), which is abundant in coffee beans and Centella asiatica, reportedly improves cognitive function in Alzheimer's disease (AD) model mice, but its effects on neuroinflammation, neuronal loss, and the amyloid-ß (Aß) plaque burden have remained unclear. Objective: To assess the effects of a 16-week treatment with CQA on recognition memory, working memory, Aß levels, neuronal loss, neuroinflammation, and gene expression in the brains of 5XFAD mice, a commonly used mouse model of familial AD. Methods: 5XFAD mice at 7 weeks of age were fed a 0.8% CQA-containing diet for 4 months and then underwent novel object recognition (NOR) and Y-maze tests. The Aß levels and plaque burden were analyzed by enzyme-linked immunosorbent assay and immunofluorescent staining, respectively. Immunostaining of markers of mature neurons, synapses, and glial cells was analyzed. AmpliSeq transcriptome analysis and quantitative reverse-transcription-polymerase chain reaction were performed to assess the effect of CQA on gene expression levels in the cerebral cortex of the 5XFAD mice. Results: CQA treatment for 4 months improved recognition memory and ameliorated the reduction of mature neurons and synaptic function-related gene mRNAs. The Aß levels, plaque burden, and glial markers of neuroinflammation seemed unaffected. Conclusions: These findings suggest that CQA treatment mitigates neuronal loss and improves cognitive function without reducing Aß levels or neuroinflammation. Thus, CQA is a potential therapeutic compound for AD, improving cognitive function via as-yet unknown mechanisms independent of reductions in Aß or neuroinflammation.

Quinic acid regulated TMA/TMAO-related lipid metabolism and vascular endothelial function through gut microbiota to inhibit atherosclerotic.

BACKGROUND: Quinic acid (QA) and its derivatives have good lipid-lowering and hepatoprotective functions, but their role in atherosclerosis remains unknown. This study attempted to investigate the mechanism of QA on atherogenesis in Apoe-/- mice induced by HFD. METHODS: HE staining and oil red O staining were used to observe the pathology. The PCSK9, Mac-3 and SM22a expressions were detected by IHC. Cholesterol, HMGB1, TIMP-1 and CXCL13 levels were measured by biochemical and ELISA. Lipid metabolism and the HMGB1-SREBP2-SR-BI pathway were detected by PCR and WB. 16 S and metabolomics were used to detect gut microbiota and serum metabolites. RESULTS: QA or low-frequency ABX inhibited weight gain and aortic tissue atherogenesis in HFD-induced Apoe-/- mice. QA inhibited the increase of cholesterol, TMA, TMAO, CXCL13, TIMP-1 and HMGB1 levels in peripheral blood of Apoe-/- mice induced by HFD. Meanwhile, QA or low-frequency ABX treatment inhibited the expression of CAV-1, ABCA1, Mac-3 and SM22α, and promoted the expression of SREBP-1 and LXR in the vascular tissues of HFD-induced Apoe-/- mice. QA reduced Streptococcus_danieliae abundance, and promoted Lactobacillus_intestinalis and Ileibacterium_valens abundance in HFD-induced Apoe-/- mice. QA altered serum galactose metabolism, promoted SREBP-2 and LDLR, inhibited IDOL, FMO3 and PCSK9 expression in liver of HFD-induced Apoe-/- mice. The combined treatment of QA and low-frequency ABX regulated microbe-related Glycoursodeoxycholic acid and GLYCOCHENODEOXYCHOLATE metabolism in HFD-induced Apoe-/- mice. QA inhibited TMAO or LDL-induced HCAECs damage and HMGB1/SREBP2 axis dysfunction, which was reversed by HMGB1 overexpression. CONCLUSIONS: QA regulated the gut-liver lipid metabolism and chronic vascular inflammation of TMA/TMAO through gut microbiota to inhibit the atherogenesis in Apoe-/- mice, and the mechanism may be related to the HMGB1/SREBP2 pathway.

Profile of Phenolic Compounds and Antioxidant Activity of Celery (Apium graveolens) Juices Obtained from Pulp after α-Amylase Treatment from Aspergillus oryzae.

The purpose of this study was to determine the content of certain phenolic compounds, antioxidant activity, pressing efficiency, extract content, and sugars in celeriac juices obtained from the pulp after α-amylase treatment from Aspergillus oryzae. The test material consisted of peeled and unpeeled celery pulp kept at a temperature of 25 °C with and without the enzyme for a period of 30 and 60 min. The juices obtained from them were analyzed for the content of selected phenolic acids and flavonoids using the UPLC-PDA-ESI-MS/MS method, for antioxidant activity measured using the ABTS˙+ and DPPH˙ method, and for the total polyphenol content using the F-C method. Additionally, the juice pressing efficiency, the extract content using the refractometer method, and the sugar content using the HPLC method were checked. Significantly higher antioxidant activity, pressing yield, and average content of caffeic acid glucoside, quinic acid, kaempferol-3,7-di-O-glucoside, and chrysoeriol-7-O-apiosylglucoside were obtained in juices from peeled celery. Maceration of the pulp with amylase resulted in a significant reduction in antioxidant activity compared to control samples. An is-total increase of 17-41% in total flavonoid content was observed in all juices tested after treatment with the enzyme for 30 and 60 min, and the phenolic acid content increased by 4-41% after treatment of the pulp with amylase for 60 min. The 60 min holding of the pulp at 25 °C, including with the enzyme, was shown to decrease the antioxidant activity and the content of quinic acid, ferulic acid, and chrysoriol-7-O-apiose-glucoside in the juices tested compared to the samples held for 30 min, while the content of other phenolic acids and flavonoids increased. In addition, after 60 min of enzymatic maceration, the pressing yield of the juices increased.