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.

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.

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.

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.

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.

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.

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.

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.

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.

Discovery and characterization of novel ATP citrate lyase inhibitors from Acanthopanax senticosus (Rupr. & Maxim.) Harms.

ATP citrate lyase (ACLY) is a key enzyme in glucolipid metabolism, and abnormally high expression of ACLY occurs in many diseases, including cancers, dyslipidemia and cardiovascular diseases. ACLY inhibitors are prospective treatments for these diseases. However, the scaffolds of ACLY inhibitors are insufficient with weak activity. The discovery of inhibitors with structural novelty and high activity continues to be a research hotpot. Acanthopanax senticosus (Rupr. & Maxim.) Harms is used for cardiovascular disease treatment, from which no ACLY inhibitors have ever been found. In this work, we discovered three novel ACLY inhibitors, and the most potent one was isochlorogenic acid C (ICC) with an IC50 value of 0.14 ± 0.04 µM. We found dicaffeoylquinic acids with ortho-dihydroxyphenyl groups were important features for inhibition by studying ten phenolic acids. We further investigated interactions between the highly active compound ICC and ACLY. Thermal shift assay revealed that ICC could directly bind to ACLY and improve its stability in the heating process. Enzymatic kinetic studies indicated ICC was a noncompetitive inhibitor of ACLY. Our work discovered novel ACLY inhibitors, provided valuable structure-activity patterns and deepened knowledge on the interactions between this targe tand its inhibitors.

Aster glehni Extract, Including Caffeoylquinic Acids as the Main Constituents, Induces PPAR ß/δ-Dependent Muscle-Type Change and Myogenesis in Apolipoprotein E Knockout Mice.

To probe the functions of Aster glehni (AG) extract containing various caffeoylquinic acids on dyslipidemia, obesity, and skeletal muscle-related diseases focused on the roles of skeletal muscle, we measured the levels of biomarkers involved in oxidative phosphorylation and type change of skeletal muscle in C2C12 cells and skeletal muscle tissues from apolipoprotein E knockout (ApoE KO) mice. After AG extract treatment in cell and animal experiments, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to estimate the levels of proteins that participated in skeletal muscle type change and oxidative phosphorylation. AG extract elevated protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), phosphorylated 5'-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor beta/delta (PPARß/δ), myoblast determination protein 1 (MyoD), and myoglobin in skeletal muscle tissues. Furthermore, it elevated the ATP concentration. However, protein expression of myostatin was decreased by AG treatment. In C2C12 cells, increments of MyoD, myoglobin, myosin, ATP-producing pathway, and differentiation degree by AG were dependent on PPARß/δ and caffeoylquinic acids. AG extract can contribute to the amelioration of skeletal muscle inactivity and sarcopenia through myogenesis in skeletal muscle tissues from ApoE KO mice, and function of AG extract may be dependent on PPARß/δ, and the main functional constituents of AG are trans-5-O-caffeoylquinic acid and 3,5-O-dicaffeoylquinic acid. In addition, in skeletal muscle, AG has potent efficacies against dyslipidemia and obesity through the increase of the type 1 muscle fiber content to produce more ATP by oxidative phosphorylation in skeletal muscle tissues from ApoE KO mice.

Identification of Peucedanum japonicum Thunb. extract components and their protective effects against dexamethasone-induced muscle atrophy.

BACKGROUND: Peucedanum japonicum Thunb. (PJ) is a vegetable widely consumed in East Asia and is known to have anticancer and anti-inflammatory effects. However, the effect of PJ on muscle atrophy remains elusive. PURPOSE: This study aimed to investigate the effect of PJ and its active compound on dexamethasone (DEX)-induced muscle atrophy. METHODS: We performed qualitative and quantitative analysis of PJ using ultra-performance liquid chromatography-mass spectrometry tandem mass spectrometry (UPLC-MS/MS) and high-performance liquid chromatography (HPLC), respectively. The efficacy of PJ and its main compound 4-caffeoylquinic acid (CQA) on muscle atrophy was evaluated in DEX-induced myotube atrophy and DEX-induced muscle atrophy in mouse myoblasts (C2C12) and C57BL/6 mice, in vitro and in vivo, respectively. RESULTS: The UPLC-MS/MS and HPLC data showed that the concentration of 4-CQA in PJ was 18.845 mg/g. PJ and 4-CQA treatments significantly inhibited DEX-induced myotube atrophy by decreasing protein synthesis and glucocorticoid translocation to the nucleus in C2C12 myotubes. In addition, PJ enhanced myogenesis by upregulating myogenin and myogenic differentiation 1 in C2C12 cells. PJ supplementation effectively increased muscle function and mass, downregulated atrogenes, and decreased proteasome activity in C57BL/6 mice. Additionally, PJ effectively decreased the nuclear translocation of forkhead transcription factor 3 alpha by inhibiting glucocorticoid receptor. CONCLUSION: Overall, PJ and its active compound 4-CQA alleviated skeletal muscle atrophy by inhibiting protein degradation. Hence, our findings present PJ as a potential novel pharmaceutical candidate for the treatment of muscle atrophy.

Protective Effect of Que Zui Tea on d-Galactose-Induced Oxidative Stress Damage in Mice via Regulating SIRT1/Nrf2 Signaling Pathway.

Que Zui tea (QT) is an important herbal tea in the diet of the 'Yi' people, an ethnic group in China, and it has shown significant antioxidant, anti-inflammatory, and hepatoprotective effects in vitro. This study aims to explore the protective effects of the aqueous-ethanol extract (QE) taken from QT against ᴅ-galactose (ᴅ-gal)-induced oxidative stress damage in mice and its potential mechanisms. QE was identified as UHPLC-HRMS/MS for its chemical composition and possible bioactive substances. Thus, QE is rich in phenolic and flavonoid compounds. Twelve compounds were identified, the main components of which were chlorogenic acid, quinic acid, and 6'-O-caffeoylarbutin. Histopathological and biochemical analysis revealed that QE significantly alleviated brain, liver, and kidney damage in ᴅ-gal-treated mice. Moreover, QE remarkably attenuated oxidative stress by activating the Nrf2/HO-1 pathway to increase the expression of antioxidant indexes, including GSH, GSH-Px, CAT, SOD, and T-AOC. In addition, QE administration could inhibit the IL-1ß and IL-6 levels, which suppress the inflammatory response. QE could noticeably alleviate apoptosis by inhibiting the expressions of Caspase-3 and Bax proteins in the brains, livers, and kidneys of mice. The anti-apoptosis mechanism may be related to the upregulation of the SIRT1 protein and the downregulation of the p53 protein induced by QE in the brain, liver, and kidney tissues of mice. Molecular docking analysis demonstrated that the main components of QE, 6'-O-caffeoylarbutin, chlorogenic acid, quinic acid, and robustaside A, had good binding ability with Nrf2 and SIRT1 proteins. The present study indicated that QE could alleviate ᴅ-gal-induced brain, liver and kidney damage in mice by inhibiting the oxidative stress and cell apoptosis; additionally, the potential mechanism may be associated with the SIRT1/Nrf2 signaling pathway.

Bioassay guided isolation of caffeoylquinic acids from the leaves of Ilex pubescens Hook. et Arn. and investigation of their anti-influenza mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Ilex pubescens Hook. et Arn. (Maodongqing, MDQ) is a common herbal tea ingredient in Southern China for heat clearance and anti-inflammation. Our preliminary screening showed that 50% ethanol extract of its leaves has anti-influenza virus activity. In this report, we proceed to identify the active components and clarify the related anti-influenza mechanisms. AIM: We aim to isolate and identify the anti-influenza virus phytochemicals from the extract of the MDQ leaves, and study their anti-influenza virus mechanism. MATERIAL AND METHODS: Plaque reduction assay was used to test the anti-influenza virus activity of fractions and compounds. Neuraminidase inhibitory assay was used to confirm the target protein. Molecular docking and reverse genetics were used to confirm the acting site of caffeoylquinic acids (CQAs) on viral neuraminidase. RESULTS: Eight CQAs, 3,5-di-O-caffeoylquinic acid methyl ester (Me 3,5-DCQA), 3,4-di-O-caffeoylquinic acid methyl ester (Me 3,4-DCQA), 3,4,5-tri-O-caffeoylquinic acid methyl ester (Me 3,4,5-TCQA), 3,4,5-tri-O-caffeoylquinic acid (3,4,5-TCQA), 4,5-di-O-caffeoylquinic acid (4,5-DCQA), 3,5-di-O-caffeoylquinic acid (3,5-DCQA), 3,4-di-O-caffeoylquinic acid (3,4-DCQA), and 3,5-di-O-caffeoyl-epi-quinic acid (3,5-epi-DCQA) were identified from the MDQ leaves, in which Me 3,5-DCQA, 3,4,5-TCQA and 3,5-epi-DCQA were isolated for the first time. All these eight compounds were found to inhibit neuraminidase (NA) of influenza A virus. The results of molecular docking and reverse genetics indicated that 3,4,5-TCQA interacted with Tyr100, Gln412 and Arg419 of influenza NA, and a novel NA binding groove was found. CONCLUSION: Eight CQAs isolated from the leaves of MDQ were found to inhibit influenza A virus. 3,4,5-TCQA was found to interact with Tyr100, Gln412 and Arg419 of influenza NA. This study provided scientific evidence on the use of MDQ for treating influenza virus infection, and laid the foundation for the development of CQA derivatives as potential antiviral agents.

Investigation of the phytochemical composition and remedial effects of southern grape hyacinth (Muscari neglectum Guss. ex Ten.) plant extract against carbon tetrachloride-induced oxidative stress in rats.

We aimed to determine the phytochemical contents of the aerial part M. neglectum aerial part (MAP) and M. neglectum bulb (MB) ethanolic extract of Muscari neglectum and to investigate their protective effects on gastric damage induced by carbon tetrachloride (CCl4) in rats. After the toxicity testing, 42 female Wistar albino rats were divided into 7 groups, Control, MAP, MB, CCl4, CCl4 + MAP, CCl4 + MB, and CCl4 + Silymarin groups. At the end of the experiment, the serum biochemical parameters, antioxidant defense enzymes, and malondialdehyde (MDA) contents in the stomach tissue were evaluated to determine the antioxidant role of the M. neglectum extracts. According to the gas chromatography-mass spectroscopy, fatty acid analysis, octadecadienoic, and 9,12,15 octadecatrienoic fatty acids were found as major fatty acids in the MAP, whereas 9,12 octadecadienoic and octadecanoic acids were the major fatty acids in the MB. According to the liquid chromatography-tandem mass spectrometry, quinic acid, fumaric acid, gentisic acid, caffeic acid, kaempferol, and apigenin were found in the MAP, while quinic acid, fumaric acid, caffeic acid, and kaempferol were found in the MB. The total phenolic and flavonoid contents in the extract were determined in the MAP and MB. The MAP and MB extracts generally caused a statistically significant decrease in the MDA content and increase in the antioxidant parameters in the stomach tissue. It was concluded that MAP and MB extracts may have antioxidant and gastric protective effects due to the phytochemical content of M. neglectum.HighlightsAccording to LC-MS/MS results, quinic acid, fumaric acid, chemferol, apigenin, and caffeic acid were determined as major compounds in M. neglectum extracts.According to GC-MS results, octadecadienoic, octadecatrienoic, and octadecanoic methyl esters were the major fatty acids of the M. neglectum extracts.The M. neglectum extracts regulated the levels of stomach damage and biochemical parameters.The M. neglectum extracts extract might have pharmaceutical-nutritional potential.

Multispectroscopic and Computational Investigations on the Binding Mechanism of Dicaffeoylquinic Acids with Ovalbumin.

Recently, studies on the interactions between ovalbumin (OVA) and polyphenols have received a great deal of interest. This study explored the conformational changes and the interaction mechanism of the binding between OVA and chlorogenic acid (CGA) isomers such as 3,4-dicaffeoylquinic acids (3,4-diCQA), 4,5-dicaffeoylquinic acids (4,5-diCQA), and 3,5-dicaffeoylquinic acids (3,5-diCQA) using multispectroscopic and in silico analyses. The emission spectra show that the diCQAs caused strong quenching of OVA fluorescence under different temperatures through a static quenching mechanism with hydrogen bond (H-bond) and van der Waals (vdW) interactions. The values of binding constants (OVA-3,4-diCQA = 6.123 × 105, OVA-3,5-diCQA = 2.485 × 105, OVA-4,5-diCQA = 4.698 × 105 dm3 mol-1 at 298 K) suggested that diCQAs had a strong binding affinity toward OVA, among which OVA-3,4-diCQA exhibits higher binding constant. The results of UV-vis absorption and synchronous fluorescence indicated that the binding of all three diCQAs to OVA induced conformational and micro-environmental changes in the protein. The findings of molecular modeling further validate the significant role of vdW force and H-bond interactions in ensuring the stable binding of OVA-diCQA complexes. Temperature-dependent molecular dynamics simulation studies allow estimation of the individual components that contribute to the total bound free energy value, which allows evaluation of the nature of the interactions involved. This research can provide information for future investigations on food proteins' physicochemical stability and CGA bioavailability in vitro or in vivo.

Protective effect of D-(-)-quinic acid as food supplement in modulating AMP-activated protein kinase signalling pathway activation in HFD induced obesity.

BACKGROUND: Dietary quinic acid given as the nutritional supplement, which may leads to tryptophan and nicotinamide production in the intestinal tract and NAD+ precursor which can prevent from the negative consequences of high fat diet (HFD) consumption. OBJECTIVE: The present study was designed to assess in vivo and in vitro effect of D-(-)-Quinic acid in high-fat diet induced hyperlipidemia in mice. MATERIAL AND METHODS: Thirty six albino mice were randomly divided in six groups and each group had six mice. Group I, controlled mice given normal pellet diet, Group-II mice, administered with high fat diet (HFD), Group-III mice given standard drug, Atorvastatin (20 mg/kg, p.o.) along with HFD to mice and Group IV, V and VI mice received D-(-)-Quinic acid at a dose of 75, 150 and 300 mg/kg, respectively in separate group along with HFD to mice. After completion of trial (49 days) the animals were sacrificed and evaluated for body weight, organ fat pad weight, and changes in weight of liver, heart and kidney and also for biochemical parameters, expression of adipogenic and inflammation markers in adipose tissues, and histology examination of liver tissue. RESULTS: In vitro testing results showed, D-(-)-Quinic acid potentially inhibit α-glucosidase enzyme activity as compared to acarbose. The D-(-)-Quinic acid showed significant hypolipidemic activity by decreasing the increased level of cholesterol, triglyceride level, LDL, VLDL and other hepatic parameters like SGOT and SGPT in serum. D-(-)-Quinic acid reduces the mRNA expression level of PPAR-γ2, TNF-α, IL-1ß and IL-6 in adipose tissue in hyperlipidemic mice.

The Q-system: A Versatile Repressible Binary Expression System.

Binary expression systems are useful genetic tools for experimentally labeling or manipulating the function of defined cells. The Q-system is a repressible binary expression system that consists of a transcription factor QF (and the recently improved QF2/QF2w), the inhibitor QS, a QUAS-geneX effector, and a drug that inhibits QS (quinic acid). The Q-system can be used alone or in combination with other binary expression systems, such as GAL4/UAS and LexA/LexAop. In this review chapter, we discuss the past, present, and future of the Q-system for applications in Drosophila and other organisms. We discuss the in vivo application of the Q-system for transgenic labeling, the modular nature of QF that allows chimeric or split transcriptional activators to be developed, its temporal control by quinic acid, new methods to generate QF2 reagents, intersectional expression labeling, and its recent adoption into many emerging experimental species.

Ameliorative role of Cyanus depressus (M.Bieb.) Soják plant extract against diabetes-associated oxidative-stress-induced liver, kidney, and pancreas damage in rats.

In this original article, we aimed to assess the ameliorative role of Cyanus depressus (CD) plant ethanolic extract treatment of streptozotocin (STZ)-induced liver, kidney, and pancreas damage in rats. The rats were divided into five groups (n = 7): control, CD, Diabetes mellitus (DM), DM + CD, and DM + glibenclamide (Gly). The DM groups were injected with a single dose of 50 mg/kg STZ intraperitoneally (i.p.). While the CD and DM + CD groups received 400 mg/kg/day intragastrically for 21 days, the DM + Gly group received 3 mg/kg/day of Gly intragastrically throughout the experiment. Statistically significance was accepted as p < .05. According to our liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) data, quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid were the major compounds, in descending order. Weekly blood glucose, serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and urea, malondialdehyde (MDA) (liver and pancreas), and blood glycosylated hemoglobin % (HbA1c %) were significantly decreased, whereas finally live body weights (LBWs), reduced glutathione (GSH), glutathione S-transferase (GST) and catalase (CAT) (pancreas), and pancreatic islet diameter and area were increased significantly in the CD-treated diabetic group. Moreover, CD administration was found to be effective in the protection of the histology of the liver, kidneys, and pancreatic islets in the STZ-induced rats. Consequently, we concluded that CD administration reduces hyperglycemia, oxidative stress, and histopathology in STZ-induced experimental rats by improving antioxidant defenses. PRACTICAL APPLICATIONS: Today, the prevalence of diabetes is increasing rapidly throughout the world and it causes complications such as kidney damage, blindness, amputations, and cardiovascular diseases. Despite medical technological advances, people's interest in medicinal herbal products is gradually increasing. Biochemical and histopathological findings showed that the use of the plant CD at the determined dose (400 mg/kg/day) in rats with DM by STZ had strong antioxidant and antidiabetic effects. CD may have a drug potential in preventing DM and its complications because of its phytochemical content including some phenolic acids such as quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid. Isolation of bioactive compounds from CD and investigation of their therapeutic effects could be planned as further studies.