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.

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.

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.

Development of solid-state fermentation process of spent coffee grounds for the differentiated obtaining of chlorogenic, quinic, and caffeic acids.

BACKGROUND: Spent coffee grounds (SCGs) are a good source of chlorogenic acid (CGA), which can be hydrolyzed to quinic acid (QA) and caffeic acid (CA). These molecules have antioxidant and neuroprotective capacities, benefiting human health. The hydrolysis of CGA can be done by biotechnological processes, such as solid-state fermentation (SSF). This work evaluated the use of SSF with Aspergillus sp. for the joint release of the three molecules from SCGs. RESULTS: Hydroalcoholic extraction of the total phenolic compounds (TPCs) from SCGs was optimized, obtaining 28.9 ± 1.97 g gallic acid equivalent (GAE) kg-1 SCGs using 0.67 L ethanol per 1 L, a 1:9 solid/liquid ratio, and a 63 min extraction time. Subsequently, SSF was performed for 30 days, achieving the maximum yields for CGA, QA, and TPCs on the 16th day: 7.12 ± 0.01 g kg-1 , 4.68 ± 0.11 g kg-1 , and 54.96 ± 0.49 g GAE kg-1 respectively. CA reached its maximum value on the 23rd day, at 4.94 ± 0.04 g kg-1 . The maximum antioxidant capacity was 635.7 mmol Trolox equivalents kg-1 on the 14th day. Compared with unfermented SCGs extracts, TPCs and CGA increase their maximum values 2.3-fold, 18.6-fold for CA, 14.2 for QA, and 6.4-fold for antioxidant capacity. Additionally, different extracts' profiles were obtained throughout the SSF process, allowing us to adjust the type of enriched extract to be produced based on the SSF time. CONCLUSION: SSF represents an alternative to produce extracts with different compositions and, consequently, different antioxidant capacities, which is a potentially attractive fermentation process for different applications. © 2022 Society of Chemical Industry.

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.

Potential Mechanisms Involved in the Protective Effect of Dicaffeoylquinic Acids from Artemisia annua L. Leaves against Diabetes and Its Complications.

Diabetes mellitus is a chronic disease affecting the globe and its incidence is increasing pandemically. The use of plant-derived natural products for diabetes management is of great interest. Polar fraction of Artemisia annua L. leaves has shown antidiabetic activity in vivo. In the present study, three major compounds were isolated from this polar fraction; namely, 3,5-dicaffeoylquinic acid (1); 4,5-dicaffeoylquinic acid (2), and 3,4- dicaffeoylquinic acid methyl ester (3), using VLC-RP-18 and HPLC techniques. The potential protective effects of these compounds against diabetes and its complications were investigated by employing various in vitro enzyme inhibition assays. Furthermore, their antioxidant and wound healing effectiveness were evaluated. Results declared that these dicaffeoylquinic acids greatly inhibited DPPIV enzyme while moderately inhibited α-glucosidase enzyme, where compounds 1 and 3 displayed the most prominent effects. In addition, compound 3 showed pronounced inhibition of α-amylase enzyme. Moreover, these compounds markedly inhibited aldose reductase enzyme and exerted powerful antioxidant effects, among which compound 3 exhibited the highest activity implying a notable potentiality in impeding diabetes complications. Interestingly, compounds 2 and 3 moderately accelerated scratch wound healing. Our findings suggest that these dicaffeoylquinic acids can be promising therapeutic agents for managing diabetes and its complications.

Novel Quinic Acid Glycerates from Tussilago farfara Inhibit Polypeptide GalNAc-Transferase.

The discovery of a bioactive inhibitor tool for human polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts), the initiating enzyme for mucin-type O-glycosylation, remains challenging. In the present study, we identified an array of quinic acid derivatives, including four new glycerates (1-4) from Tussilago farfara, a traditional Chinese medicinal plant, as active inhibitors of GalNAc-T2 using a combined screening approach with a cell-based T2-specific sensor and purified enzyme assay. These inhibitors dose-dependently inhibited human GalNAc-T2 but did not affect O-linked N-acetylglucosamine transferase (OGT), the other type of glycosyltransferase. Importantly, they are not cytotoxic and retain inhibitory activity in cells lacking elongated O-glycans, which are eliminated by the CRISPR/Cas9 gene editing tool. A structure-activity relationship study unveiled a novel quinic acid-caffeic acid conjugate pharmacophore that directs inhibition. Overall, these new natural product inhibitors could serve as a basis for developing an inhibitor tool for GalNAc-T2.

Interactions of Ascorbic Acid, 5-Caffeoylquinic Acid, and Quercetin-3-Rutinoside in the Presence and Absence of Iron during Thermal Processing and the Influence on Antioxidant Activity.

Bioactive compounds in fruit and vegetables influence each other's antioxidant activity. Pure standards, and mixtures of the common plant compounds, namely ascorbic acid, 5-caffeoylquinic acid, and quercetin-3-rutinoside (sum 0.3 mM), in the presence and absence of iron, were analyzed pre- and post-thermal processing in an aqueous solution. Antioxidant activity was measured by total phenolic content (TPC), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (TEAC) radical-scavenging assays. Ionic ferrous iron (Fe2+) and ferric iron (Fe3+) were measured photometrically. For qualification and quantification of reaction products, HPLC was used. Results showed that thermal processing does not necessarily lead to a decreased antioxidant activity, even if the compound concentrations decreased, as then degradation products themselves have an antioxidant activity. In all used antioxidant assays the 2:1 ratio of ascorbic acid and 5-caffeoylquinic acid in the presence of iron had strong synergistic effects, while the 1:2 ratio had strong antagonistic effects. The pro-oxidant iron positively influenced the antioxidant activity in combination with the used antioxidants, while ferrous iron itself interacted with common in vitro assays for total antioxidant activity. These results indicate that the antioxidant activity of compounds is influenced by factors such as interaction with other molecules, temperature, and the minerals present.

Anti-Inflammatory Effect of 4,5-Dicaffeoylquinic Acid on RAW264.7 Cells and a Rat Model of Inflammation.

Anti-inflammatory agents that are safer and more effective than the currently used non-steroidal anti-inflammatory drugs are urgently needed. The dicaffeoylquinic acid (diCQA) isomer 4,5-diCQA exhibits antioxidant activity and various other health-promoting benefits; however, its anti-inflammatory properties require further investigation. This study was conducted to evaluate the anti-inflammatory properties of 4,5-diCQA in vitro and in vivo using RAW264.7 cells and a carrageenan-induced inflammation model, respectively. In RAW264.7 cells, 4,5-diCQA pretreatment significantly inhibited lipopolysaccharide-induced expression of nitric oxide, prostaglandin E2, nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin-1ß, and interleukin-6, without inducing cytotoxicity. The inhibitory effects of 4,5-diCQA were mediated by the suppression of nuclear factor-κB nuclear translocation and mitogen-activated protein kinase (MAPK) phosphorylation. Oral administration of 4,5-diCQA at doses of 5, 10, and 20 mg/kg of the body weight suppressed carrageenan-induced edema and the expression of nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α in a dose-dependent manner. Collectively, our results suggest that 4,5-diCQA exerts anti-inflammatory effects by suppressing activation of the nuclear factor-κB and MAPK pathways in vitro and reducing carrageenan-induced edema in vivo. Therefore, 4,5-diCQA shows potential as a natural alternative to non-steroidal anti-inflammatory drugs.

Neochlorogenic acid anchors MCU-based calcium overload for cancer therapy.

Cancer is a major threat to human health worldwide, yet the clinical therapies remain unsatisfactory. In this study, we found that a Tetrastigma hemsleyanum leaves flavone (TLF) intervention could achieve tumor inhibition. Besides, neochlorogenic acid (NA), which had the highest absorbance peak in the HPLC profile of TLF, showed superior anti-proliferation ability over TLF, and could effectively trigger apoptosis, restrain migration, and facilitate cytoskeleton collapse, suggesting its key role in TLF's anticancer property. Molecular docking analysis suggested that NA was capable of binding with mitochondrial Ca2+ uniporter (MCU), and further experiments confirmed that NA upregulated the MCU level to permit excess calcium ion influx, leading to mitochondrial calcium imbalance, dysfunction, structure alteration, and ROS elevation. Moreover, tumor-bearing mice were applied to further confirm the excellent tumor inhibition ability of NA under Ca2+-abundant conditions. Therefore, this study uncovered that NA could effectively trigger robust MCU-mediated calcium overload cancer therapy, which could be utilized in novel strategies for future cancer treatment.

Hydrothermal Processing and In Vitro Simulated Human Digestion Affects the Bioaccessibility and Bioactivity of Phenolic Compounds in African Pumpkin (Momordica balsamina) Leaves.

The African pumpkin (Momordica balsamina) contains bioactive phenolic compounds that may assist in reducing oxidative stress in the human body. The leaves are mainly consumed after boiling in water for a specific time; this hydrothermal process and conditions of the gastrointestinal tract may affect the presence and bioactivity of phenolics either positively or negatively. In this study, the effects of hydrothermal processing (boiling) and in vitro simulated human digestion on the phenolic composition, bioaccessibility and bioactivity in African pumpkin were investigated in comparison with those of spinach (Spinacia oleracea). A high-resolution ultra-performance liquid chromatography, coupled with diode array detection, quadrupole time-of-flight and mass spectrometer (UPLC-DAD-QTOF-MS) was used to profile phenolic metabolites. Metabolites such as 3-caffeoylquinic acid, 5-caffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid were highly concentrated in the boiled vegetable extracts compared to the raw undigested and all digested samples. The majority of African pumpkin and spinach extracts (non-digested and digested) protected Deoxyribonucleic acid (DNA), (mouse fibroblast) L929 and human epithelial colorectal adenocarcinoma (Caco-2) cells from 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative damage. From these results, the consumption of boiled African pumpkin leaves, as well as spinach, could be encouraged, as bioactive metabolites present may reduce oxidative stress in the body.

Changes in the Antioxidative Activity and the Content of Phenolics and Iridoids during Fermentation and Aging of Natural Fruit Meads.

The aim of the study was to investigate changes in the content of biologically active compounds during the fermentation and aging of natural meads with the addition of three Cornelian cherry juices from three cultivars: 'Koralovyi', 'Podolski' and 'Yantarnyi', in the amount of 10% v/v. After the fermentation process the content of gallic and ellagic acids significantly increased, in relation to wort. Whereas the greatest losses were observed among unstable anthocyanins. The three-month aging process also reduced the content of the analyzed compounds except for ellagic acid, the content of which increased by up to 90%. The content of biologically active compounds, including iridoids and antioxidant phenolics, are constantly changing in the process of fermentation and aging of fruit meads. The studies proved that the addition of Cornelian cherry juice allows significantly enriched classic meads with new biologically active compounds, such as: exceptional iridoids (loganic acid, cornuside, loganine, sweroside), flavonols, phenolic acids and anthocyanins.

A promising strategy for investigating the anti-aging effect of natural compounds: a case study of caffeoylquinic acids.

Caffeoylquinic acids, as plant-derived polyphenols, exhibit multiple biological activities such as antioxidant, anti-inflammatory, and neuroprotective activities. However, only limited information about their effect on longevity is available. In the current study, molecular docking was employed to explore the interactions between six representative caffeoylquinic acids and the insulin-like growth factor-1 receptor (IGFR), which is an important target protein for longevity. The results indicated that all six compounds were embedded well in the active pocket of IGFR, and that 3,5-diCQA exhibited the strongest affinity to IGFR. Moreover, ASP1153, GLU1080, ASP1086, and ARG1003 were the key amino acid residues during the interaction of these 6 compounds with IGFR. Furthermore, the lifespan extension effect of caffeoylquinic acids was evaluated in a Caenorhabditis elegans (C. elegans) model. The results revealed that all the caffeoylquinic acids significantly extended the lifespan of wild-type worms, of which 3,5-diCQA was the most potent compound. Meanwhile, 3,5-diCQA enhanced the healthspan by increasing the body bending and pharyngeal pumping rates and reducing the intestinal lipofuscin level. Further studies demonstrated that 3,5-diCQA induced longevity effects by downregulating the insulin/insulin-like growth factor signaling (IIS) pathway. This study suggested that the combination of molecular docking and genetic analysis of specific worm mutants could be a promising strategy to reveal the anti-aging mechanisms of small molecule natural compounds.

Caffeoylquinic acids: chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity.

Caffeoylquinic acids (CQAs) are specialized plant metabolites we encounter in our daily life. Humans consume CQAs in mg-to-gram quantities through dietary consumption of plant products. CQAs are considered beneficial for human health, mainly due to their anti-inflammatory and antioxidant properties. Recently, new biosynthetic pathways via a peroxidase-type p-coumaric acid 3-hydroxylase enzyme were discovered. More recently, a new GDSL lipase-like enzyme able to transform monoCQAs into diCQA was identified in Ipomoea batatas. CQAs were recently linked to memory improvement; they seem to be strong indirect antioxidants via Nrf2 activation. However, there is a prevalent confusion in the designation and nomenclature of different CQA isomers. Such inconsistencies are critical and complicate bioactivity assessment since different isomers differ in bioactivity and potency. A detailed explanation regarding the origin of such confusion is provided, and a recommendation to unify nomenclature is suggested. Furthermore, for studies on CQA bioactivity, plant-based laboratory animal diets contain CQAs, which makes it difficult to include proper control groups for comparison. Therefore, a synthetic diet free of CQAs is advised to avoid interferences since some CQAs may produce bioactivity even at nanomolar levels. Biotransformation of CQAs by gut microbiota, the discovery of new enzymatic biosynthetic and metabolic pathways, dietary assessment, and assessment of biological properties with potential for drug development are areas of active, ongoing research. This review is focused on the chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity recently reported for mono-, di-, tri-, and tetraCQAs.

Inhibitory mechanism of xanthine oxidase activity by caffeoylquinic acids in vitro.

In this study, the inhibitory activities of eight caffeoylquinic acids (CQAs) against xanthine oxidase (XOD) in vitro were investigated, and the interaction mechanisms between each compound and XOD were studied. HPLC and fluorescence spectra showed that the inhibitory activities of dicaffeoylquinic acids (diCQAs) were higher than that of monocaffeoylquinic acids (monoCQAs), due to the main roles of hydrophobic interaction and hydrogen bond between XOD and diCQAs. Both the binding constant and the lowest binding energy data indicated that the affinities of diCQAs to XOD were stronger than that of monoCQAs. Circular dichroism showed that the structure of XOD was compacted with the increased of α-helix content, resulting in decreased enzyme catalytic activity. Molecular docking revealed that CQAs preferentially bind to the flavin adenine dinucleotide region in XOD. These results provided the mechanisms of CQAs on inhibiting XOD and the further utilization of CQAs as XOD inhibitors to prevent hyperuricemia.

Effect of in vitro gastro-intestinal digestion on the phenolic composition and antioxidant capacity of Burdock roots at different harvest time.

The current study aimed to evaluate how the harvest time affects the phenolic composition in Burdock root flours (BRF) and how these phenolics are influenced by the gastro-intestinal digestive environment. Burdock roots were harvested in 2020 in Jiangsu Province in June (B1), July (B2) and August (B3). The main phenolic, 5-O-caffeoylquinic acid (5-CQA) decreased after in vitro digestion from 1.14 to 0.22 mg/g (B1 < B2 < B3). Total phenolic content of BRF was 61% lower after in vitro digestion whereas 5-CQA bioaccessibility remained at about 60%. Twelve other phenolic compounds were tentatively identified after in vitro digestion. An average reduction in antioxidant capacity of 27% and 10% was observed for DPPH and ABTS, respectively. In conclusion, data demonstrated that phenolic composition, bioaccessibility and antioxidant capacity of Burdock roots harvested at different times were subject to the influence of in vitro gastrointestinal digestion.

Characterization of polyphenol oxidase from purple sweet potato (Ipomoea batatas L. Lam) and its affinity towards acylated anthocyanins and caffeoylquinic acid derivatives.

Biochemical characterization of polyphenol oxidase (PPO) present in purple sweet potato (PSP) is a key step in developing efficient methodologies to control oxidative damage caused by this enzyme to the valuable components of PSP, such as caffeoylquinic acid derivatives and acylated anthocyanins. Thus, this work focused on the assessment of the effects of pH, temperature, and chemical agents on the PPO activity as well as characterization of the PPO substrate specificity towards major phenolic compounds found in PSP. The optimum conditions of enzyme activity were pH 7 and a temperature range of 20-30 °C at which phenolic substrates were oxidized with 72.5-99.8% yield. Zn2+ ions remarkably reduced PPO activity while Cu2+ ions improved enzyme performance. The highest substrate preference was shown for 3,4,5-tri-caffeoylquinic and 3,5-di-caffeoylquinic acid, followed by 5-caffeoylquinic and caffeic acid, 3,4- and 4,5-di-caffeoylquinic acids, peonidin-3-caffeoyl-p-hydroxybenzoyl-sophoroside-5-glucoside. The highest Km values were found for 4,5-feruloyl-caffeoylquinic acid and catechol.

Structure-Based Identification of Natural Products as SARS-CoV-2 Mpro Antagonist from Echinacea angustifolia Using Computational Approaches.

Coronavirus disease-19 (COVID-19) pandemic, caused by the novel SARS-CoV-2 virus, continues to be a global threat. The number of cases and deaths will remain escalating due to the lack of effective therapeutic agents. Several studies have established the importance of the viral main protease (Mpro) in the replication of SARS-CoV-2 which makes it an attractive target for antiviral drug development, including pharmaceutical repurposing and other medicinal chemistry approaches. Identification of natural products with considerable inhibitory potential against SARS-CoV-2 could be beneficial as a rapid and potent alternative with drug-likeness by comparison to de novo antiviral drug discovery approaches. Thereof, we carried out the structure-based screening of natural products from Echinacea-angustifolia, commonly used to prevent cold and other microbial respiratory infections, targeting SARS-CoV-2 Mpro. Four natural products namely, Echinacoside, Quercetagetin 7-glucoside, Levan N, Inulin from chicory, and 1,3-Dicaffeoylquinic acid, revealed significant docking energy (>-10 kcal/mol) in the SARS-CoV-2 Mpro catalytic pocket via substantial intermolecular contacts formation against co-crystallized ligand (<-4 kcal/mol). Furthermore, the docked poses of SARS-CoV-2 Mpro with selected natural products showed conformational stability through molecular dynamics. Exploring the end-point net binding energy exhibited substantial contribution of Coulomb and van der Waals interactions to the stability of respective docked conformations. These results advocated the natural products from Echinacea angustifolia for further experimental studies with an elevated probability to discover the potent SARS-CoV-2 Mpro antagonist with higher affinity and drug-likeness.

Hyaluronidase and degranulation inhibitors from the edible roots of Oenanthe javanica including seric acids F and G that were obtained by heating.

Oenanthe javanica is a vegetable grown in East Asia and Australia in which the roots and aerial parts are boiled together to make certain traditional dishes. Nineteen compounds (1-19) were isolated from O. javanica roots and the chemical structures of 2 new norlignans were determined. The inhibitory effects of the compounds on hyaluronidase and degranulation in RBL-2H3 cells were evaluated to determine antiallergic and antiinflammation activities. Saponins (2-4) and the new norlignan seric acid G (12) were among the active compounds identified. Seric acid G (12), a methoxy derivative of seric acid F (11), was obtained as an interconverting mixture of 3:1 trans-cis isomers. Seric acids F and G (11, 12) were derived from seric acids C (10) and E, respectively, by decarboxylation and dehydration reactions that occurred during heating. It was confirmed by HPLC analysis that all eleven of the O. javanica cultivars contained seric acid C (10).

Identification and Quantitation of Reaction Products from Quinic Acid, Quinic Acid Lactone, and Chlorogenic Acid with Strecker Aldehydes in Roasted Coffee.

To gain comprehensive insight into the interactions of key coffee odorants, like the Strecker aldehydes, acetaldehyde, propanal, methylpropanal, 2- and 3-methylbutanal, and methional, and the nonvolatile fraction of coffee, an untargeted metabolomics approach was applied. Ultra performance liquid chromatography (UPLC)-time of flight (TOF)-mass spectrometry (ESI-) profiling followed by statistical data analysis revealed a marker substance for a coffee beverage spiked with acetaldehyde with an accurate mass of 217.0703 [M - H]-. This compound could be identified as a reaction product of quinic acid (QA) and acetaldehyde linked by acetalization at the cis-diol function of QA. Consequently, the acetalization of aldehydes, QA, 5-O-caffeoyl quinic acid (CQA), and quinic acid γ-lactone (QAL) was investigated by means of model reactions, followed by synthesis, isolation, and structure elucidation via UPLC-TOF-MS and 1D and 2D NMR techniques. UHPLC-MS/MSMRM screening and the quantification of aldehyde adducts in coffee beverages revealed the presence of QA/acetaldehyde, -/propanal, -/methylpropanal, and -/methional reaction products and CQA/acetaldehyde, -/propanal, -/methylpropanal, -/2- and 3-methylbutanal, and -/methional and QAL/acetaldehyde adducts for the first time, in concentrations of 12-270 µg/L for QA/aldehydes, 5-225 µg/L for CQA/aldehydes, and 62-173 µg/L for QAL/acetaldehyde. The sensory characterization of the identified compounds showed bitter taste recognition thresholds of 48-297 µmol/L for CQA adducts and 658 µmol/L for QAL/acetaldehyde, while the QA adducts showed no bitter taste (<2000 µmol/L).