Quercetin Derivatives Research Articles

Structure-based computational screening of 470 natural quercetin derivatives for identification of SARS-CoV-2 Mpro inhibitor.

Coronavirus disease 2019 (COVID-19) is a global pandemic infecting the respiratory system through a notorious virus known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to viral mutations and the risk of drug resistance, it is crucial to identify new molecules having potential prophylactic or therapeutic effect against SARS-CoV-2 infection. In the present study, we aimed to identify a potential inhibitor of SARS-CoV-2 through virtual screening of a compound library of 470 quercetin derivatives by targeting the main protease-Mpro (PDB ID: 6LU7). The study was carried out with computational techniques such as molecular docking simulation studies (MDSS), molecular dynamics (MD) simulations, and molecular mechanics generalized Born surface area (MMGBSA) techniques. Among the natural derivatives, compound 382 (PubChem CID 65604) showed the best binding affinity to Mpro (-11.1 kcal/mol). Compound 382 interacted with LYS5, TYR126, GLN127, LYS137, ASP289, PHE291, ARG131, SER139, GLU288, and GLU290 of the Mpro protein. The SARS-CoV-2 Mpro-382 complex showed acceptable stability during the 100 ns MD simulations. The SARS-CoV-2 Mpro-382 complex also showed an MM-GBSA binding free energy value of -54.0 kcal/mol. The binding affinity, stability, and free energy results for 382 and Mpro were better than those of the native ligand and the standard inhibitors ledipasvir and cobicistat. The conclusion of our study was that compound 382 has the potential to inhibit SARS-Cov-2 Mpro. However, further investigations such as in-vitro assays are recommended to confirm its in-silico potency.

Evaluation of saponin and phenolic profile of quinoa seeds after fungal fermentation

Solid-state fermentation can be an effective method of modelling the bioactive potential of plant materials, but the result is substrate and strain dependent. In this study, edible fungi traditionally used in Asian food fermentations (tempe moulds – Rhizopus oligosporus, R. oryzae and R. chinensis, koji mould – Aspergillus oryzae, oncom mould – Neurospora intermedia, and Mucor indicus) were grown on high-saponin quinoa seeds for 4 days at 30 °C. The sapogenin profile in the substrate was not changed after the fermentation. Whereas, the level and profile of phenolic compounds, as well as the antioxidant activity of the seeds, were diversified. The fermentation with R. chinensis, R. oryzae and A. oryzae caused an increase in soluble quercetin derivatives. Moreover, the concentration of bound phenolics was higher in the quinoa seeds fermented with most Rhizopus strains. The majority of the moulds were also efficient in the decomposition of phytate. Among the strains tested, the most promising results were obtained in the case of R. chinensis and R. oryzae. Further research is required to study their potential for the purpose of the fermentation of cereal and pseudocereal substrates.

Molecular docking analysis of novel quercetin derivatives for combating SARS-CoV-2.

Quercetin belongs to the flavonoid family, which is one of the most frequent types of plant phenolics. This flavonoid compound is a natural substance having a number of pharmacological effects, including anticancer and antioxidant capabilities, as well as being a strong inhibitor of various toxicologically important enzymes. We discuss the potential of newly recently synthesized quercetin-based derivatives to inhibit SARS-CoV-2 protein. ADMET analysis indicated that all of the studied compounds had low toxicities and good absorption and solubility properties. The molecular docking results revealed that the propensity for binding to SARS-CoV-2 main protease is extraordinary. The results are remarkable not only for the binding energy values, which outperform several compounds in prior studies, but also for the number of hydrogen bonds formed. Compound 7a was capable of forming 10 strong hydrogen bonds as well as interact to the protein receptor with a binding energy of -7.79 kcal/mol. Therefore, these compounds should be highlighted in further experimental studies in the context of treating SARS-CoV-2 infection and its effects.

Study of the Chemical Composition of the Fruits of Sea Buckthorh Rockthroom, Growing in the Territory of the Central Black Earth Region

Introduction. The chemical composition of plants is a combination of all primary and secondary metabolites and can be considered as the result of the implementation of genetic information, a «link» between the genotype and phenotype. The complex of biologically active substances (BAS) of most medicinal plants and medicinal herbal preparations derived from them is a multicomponent system that is in interaction, the composition of which is not always fully known. Sea buckthorn is one of the valuable plants with a wide distribution area. Sea buckthorn fruits contain a large number of classes of various BAS. The study of the variability of the chemical composition depending on the climatic conditions of growth, harvesting and drying in order to accumulate and generalize information for the development of unified scientifically based standards for raw material quality indicators is an important area for study.Aim. The purpose of this work was to study the chemical composition of the fruits of sea buckthorn, which grows in the Central Chernozem region.Materials and methods. The raw materials for the analysis were whole fresh fruits of sea buckthorn, harvested in the territory of the Central black earth region of the Russian Federation (Voronezh region). In the work, the TLC method was used to study the composition of various groups of BAS and their identification in extracts from the studied raw materials. In the process of a comprehensive study of the chemical composition of fruits, the determination of carotenoids, flavonoids, tannins, amino acids, hydroxycinnamic acids, anthocyanins, organic acids, sugars, some macroelements and vitamins was carried out.Results and discussion. The fruits of sea buckthorn, growing in the conditions of the Central black earth region, accumulate free amino acids, tannins, organic acids and polysaccharides in significant quantities. The composition of free water-soluble simple sugars, organic acids, B vitamins, as well as the complete amino acid composition was studied in the fruits of sea buckthorn using capillary electrophoresis. A significant content of riboflavin and choline, as well as malic and succinic acids has been established. The results of HPLC analysis showed that flavonoids in the fruits of sea buckthorn growing in the conditions of the Central black earth region are represented by flavonol glycosides – derivatives of quercetin, kaempferol and isorhamnetin. Minor flavolglycosides 3-rutinoside-7-rhamnosides of isorhamnetin, quercetin and kaempferol, 3-sophoroside-7-rhamnosides of quercetin and kaempferol, rutin, 3-glucoside and 3-rhamnoside of isorhamnetin can be used as chemomarkers.Conclusion. The obtained data on the component composition of the phenolic fraction of the fruits of the studied samples of sea buckthorn are similar to the literature data on sea buckthorn of the same species of various varieties harvested in the conditions of the Central zone of the Russian Federation (Moscow region).

Carnivorous Plants from Nepenthaceae and Droseraceae as a Source of Secondary Metabolites

Carnivorous plants are able to attract small animals or protozoa and retain them in their specialized traps. Later, the captured organisms are killed and digested. The nutrients contained in the prey bodies are absorbed by the plants to use for growth and reproduction. These plants produce many secondary metabolites involved in the carnivorous syndrome. The main purpose of this review was to provide an overview of the secondary metabolites in the family Nepenthaceae and Droseraceae, which were studied using modern identification techniques, i.e., high-performance liquid chromatography or ultra-high-performance liquid chromatography with mass spectrometry and nuclear magnetic resonance spectroscopy. After literature screening, there is no doubt that tissues of species from the genera Nepenthes, Drosera, and Dionaea are rich sources of secondary metabolites that can be used in pharmacy and for medical purposes. The main types of the identified compounds include phenolic acids and their derivatives (gallic, protocatechuic, chlorogenic, ferulic, p-coumaric acids, gallic, hydroxybenzoic, vanillic, syringic caffeic acids, and vanillin), flavonoids (myricetin, quercetin, and kaempferol derivatives), including anthocyanins (delphinidin-3-O-glucoside, cyanidin-3-O-glucoside, and cyanidin), naphthoquinones (e.g., plumbagin, droserone, and 5-O-methyl droserone), and volatile organic compounds. Due to the biological activity of most of these substances, the importance of the carnivorous plant as a pharmaceutical crop will increase.

Strawberry Fragaria x ananassa cv. Festival: A Polyphenol-Based Phytochemical Characterization in Fruit and Leaf Extracts.

Berry fruits are an important dietary source of health-promoting antioxidant polyphenols. Interestingly, berry leaves of diverse species, including strawberries, have shown higher bioactive phytochemical content in the leaves than in the fruit. Moreover, the vegetative part of the plants is usually discarded, representing a presumably large source of underutilized bioactive biomass. In this investigation, the polyphenol profiles of tropical highland strawberry (Fragaria x ananassa cv. Festival) leaves and fruits were compared by high-performance liquid chromatography coupled with a diode array detector (UHPLC-DAD) and mass spectrometry (HPLC-MS). The total polyphenol strawberry leaf extracts exhibited a 122-fold-higher total polyphenol content and 13-fold higher antioxidant activity (ORAC) than strawberry fruits, and they showed evidence of possible photoprotective effects against UV damage in human melanoma cells (SK-MEL-28) and in murine embryo fibroblasts (NIH/3T3), together with promising anti-proliferative activities against the same melanoma cells. Seven polyphenols were confirmed by HPLC-DAD in the leaf extracts, with differences depending on fraction solubility. Moreover, three substituted quercetin derivatives, three substituted kaempferol derivatives, two anthocyanins, and catechin were confirmed in the soluble fraction by HPLC-MS. Given their higher total polyphenol content and bioactive activities, underutilized strawberry Festival leaves are a potential source of apparently abundant biomass with prospective bioactive applications.

Regioselective synthesis of quercetin and myricetin derivatives

A regioselective method for the synthesis of esters of quercetin and myricetin at the hydroxy group in the 3 position was developed. As acids participating in the esterification reaction, 2-hydroxybenzoic (salicylic), 4-hydroxybenzoic, 2,6-dihydroxybenzoic, 3,4-dihydroxybenzoic (procatechuic), 3,4,5-trihydroxybenzoic (gallic) acids were used. A new series of quercetin and myricetin esters were obtained.

Apple Pomace as an Ingredient Enriching Wheat Pasta with Health-Promoting Compounds.

The global overproduction of apples is associated with large amounts of post-production waste, for which new forms of utilization should be sought. Therefore, we aimed to enrich wheat pasta with apple pomace in various percentages (10, 20, 30 and 50%). The content of total polyphenols, individual polyphenols (using UPLC-PDA-MS/MS methods) and dietary fibre, chemical composition and physical properties of the resulting pasta were determined. The addition of apple pomace to pasta resulted in increased levels of pro-health compounds: total polyphenols, phenolic acids, quercetin derivatives, flavon-3-ols and dihydrochalcones as well as dietary fibre. Decreases in hardness and maximum cutting energy were also observed in pasta supplemented with apple pomace compared to control pasta. Water absorption capacity was not influenced by the addition of apple pomace, with the exception of pasta made with 50% apple pomace.

Metabolomic Analysis Reveals the Metabolic Diversity of Wild and Cultivated Stellaria Radix (Stellaria dichotoma L. var. lanceolata Bge.)

Stellaria Radix, called Yinchaihu in Chinese, is a traditional Chinese medicine, which is obtained from the dried roots of Stellaria dichotoma L. var. lanceolata Bge. Cultivated yinchaihu (YCH) has become a main source of production to alleviate the shortage of wild plant resources, but it is not clear whether the metabolites of YCH change with the mode of production. In this study, the contents of methanol extracts, total sterols and total flavonoids in wild and cultivated YCH are compared. The metabolites were analyzed by ultra-high performance liquid chromatography-tandem time-of-flight mass spectrometry. The content of methanol extracts of the wild and cultivated YCH all exceeded the standard content of the Chinese Pharmacopoeia. However, the contents of total sterols and total flavonoids in the wild YCH were significantly higher than those in the cultivated YCH. In total, 1586 metabolites were identified by mass spectrometry, and 97 were significantly different between the wild and cultivated sources, including β-sitosterol, quercetin derivatives as well as many newly discovered potential active components, such as trigonelline, arctiin and loganic acid. The results confirm that there is a rich diversity of metabolites in the wild and cultivated YCH, and provide a useful theoretical guidance for the evaluation of quality in the production of YCH.

Chemical characterization of four ancient white wine grapes (Vitis vinifera L.) from the Amalfi coast

Minor grape varieties often possess key traits to produce wines with specific territorial identity. Italy is home to a wide selection of autochthonous grapevines. In 2005, four white grape varieties from the Amalfi coast, Fenile, Ginestra, Pepella and Ripoli were registered in the National Catalogue grapevines. They are all complementary varieties with a rich biodiversity and linked to an ancient wine heritage. Studies on such varieties have not been conducted yet. Here, the metabolite content of the above four grape varieties is described. Ripoli was the richest in quercetin derivatives while very low was the content of kaempferol derivatives; Pepella possessed an equal amount of quercetins and kaempferols; Ginestra and Fenile featured a quercetins abundance twice that of kaempferols. Also, the (+)-catechin content was higher than (–)-epicatechin's; B-type procyanidins occurred in higher concentrations in Pepella and Ripoli than in Fenile and Ginestra. Hydroxycinnamic acids were also identified and quantified. Seeds from each variety were carefully analyzed and flavanols were identified up to decamers along with their galloylation percentage. The obtained data are a tool of variety differentiation and useful to develop appropriate vinification procedures to ameliorate the quality of wines.

Regioselective Synthesis of Quercetin and Myricetin Derivatives.

A regioselective method for the synthesis of esters of quercetin and myricetin at the hydroxy group in the position 3 was developed. As acids participating in the esterification reaction, 2-hydroxybenzoic (salicylic), 4-hydroxybenzoic, 2,6-dihydroxybenzoic, 3,4-dihydroxybenzoic (procatechuic), 3,4,5-trihydroxybenzoic (gallic) acids were used. A new series of quercetin and myricetin esters were obtained.

Phenolic Compounds and Antioxidant Status of Cookies Supplemented with Apple Pomace.

The post-production leftovers after the pressing of apple juice are a rich source of health-promoting compounds, which could be used in the food industry for the manufacture of dietary foods, applicable also for people with celiac disease. This raw material is currently little used, and the cost of its disposal is considerable. Therefore, an attempt was made to enrich gluten-free cookies with different proportions of apple pomace. The content of individual polyphenols determined by the UPLC-PDA-MS/MS method, basic chemical composition, physical properties of cookies with 15%, 30%, 45%, and 60% apple pomace, were evaluated. It was found that apple pomace in gluten-free cookies caused an increase in the content of phenolic acids, quercetin derivatives, flavan-3-ols and dihydrochalcones. An elevation in protein, fat, and minerals was also observed. The growing share of apple pomace caused a significant increase in the content of total fiber, soluble, and insoluble fractions, but resulted in an increase in the hardness and darkening of the cookies while reducing their volume.

Biochemical Evaluation of Antioxidant properties of A Zn-Avicularin Complex Studied in High Fat Diet Fed- Low Dose Streptozotocin Induced Experimental Type 2 Diabetes in Rats

Zinc is an essential trace element next to iron in the human system. Its central role in the synthesis, storage, and functional aspects of insulin is well established. Ever since the insulin-mimetic activity of zinc was recognized, several zinc complexes have been synthesized and studied for their antidiabetic and other pharmacological properties. However, its clinical application is narrow due to poor absorption, toxicity associated with prolonged use. Hence, endeavors are being made for the advancement of zinc complexes with various organic ligands of known therapeutic values to avert the toxicity of zinc. Avicularin, a bioactive flavonol originally isolated from the leaves of Polygonum aviculare Linn., is a quercetin derivative in which the α-L-arabinofuranosyl residue is linked at position 3 of quercetin via a glycosidic linkage. It is non-toxic and reported to possess a wide range of pharmacological properties. Though Avicularin is a glycoside of quercetin, it is hydrophilic while quercetin is lipophilic and hence they may differ in absorption rate. In view of the beneficial and pharmacological properties bestowed with Avicularin, recently we have reported the synthesis, spectral characterization and evaluation of antidiabetic properties of a new Zn-Avicularin complex in HFD fed low dose STZ induced experimental type 2 diabetes in rats. In the present study, an attempt has been made to evaluate the antioxidant properties of the Zn-Avicularin complex by analyzing the levels of oxidative stress markers such as lipid peroxides, hydroperoxides and protein carbonyls in the plasma, pancreas, hepatic and renal tissues. The status of enzymatic antioxidants such as SOD, catalase, Glutathione peroxidase as well as non-enzymatic antioxidants such as vitamin C, vitamin E and ceruloplasmin were assayed. Oral administration of the Zn-Avicularin complex at a concentration of 5mg/kg b.w/rat/day for 30 days significantly ameliorates the hyperglycemia-induced oxidative stress in the diabetic groups of rats and the efficacy was comparable with metformin.

Metabolomics analysis unveils important changes involved in the salt tolerance of Salicornia europaea.

Salicornia europaea is one of the world's salt-tolerant plant species and is recognized as a model plant for studying the metabolism and molecular mechanisms of halophytes under salinity. To investigate the metabolic responses to salinity stress in S. europaea, this study performed a widely targeted metabolomic analysis after analyzing the physiological characteristics of plants exposed to various NaCl treatments. S. europaea exhibited excellent salt tolerance and could withstand extremely high NaCl concentrations, while lower NaCl conditions (50 and 100 mM) significantly promoted growth by increasing tissue succulence and maintaining a relatively stable K+ concentration. A total of 552 metabolites were detected, 500 of which were differently accumulated, mainly consisting of lipids, organic acids, saccharides, alcohols, amino acids, flavonoids, phenolic acids, and alkaloids. Sucrose, glucose, p-proline, quercetin and its derivatives, and kaempferol derivatives represented core metabolites that are responsive to salinity stress. Glycolysis, flavone and flavonol biosynthesis, and phenylpropanoid biosynthesis were considered as the most important pathways responsible for salt stress response by increasing the osmotic tolerance and antioxidant activities. The high accumulation of some saccharides, flavonoids, and phenolic acids under 50 mM NaCl compared with 300 mM NaCl might contribute to the improved salt tolerance under the 50 mM NaCl treatment. Furthermore, quercetin, quercetin derivatives, and kaempferol derivatives showed varied change patterns in the roots and shoots, while coumaric, caffeic, and ferulic acids increased significantly in the roots, implying that the coping strategies in the shoots and roots varied under salinity stress. These findings lay the foundation for further analysis of the mechanism underlying the response of S. europaea to salinity.

Global transcriptome and targeted metabolite analyses of roots reveal different defence mechanisms against Ralstonia solanacearum infection in two resistant potato cultivars.

Ralstonia solanacearum (Rs), the causal agent of bacterial wilt disease in an unusually wide range of host plants, including potato (Solanum tuberosum), is one of the most destructive phytopathogens that seriously reduces crop yields worldwide. Identification of defence mechanisms underlying bacterial wilt resistance is a prerequisite for biotechnological approaches to resistance breeding. Resistance to Rs has been reported only in a few potato landraces and cultivars. Our in vitro inoculation bioassays confirmed that the cultivars 'Calalo Gaspar' (CG) and 'Cruza 148' (CR) are resistant to Rs infection. Comparative transcriptome analyses of CG and CR roots, as well as of the roots of an Rs-susceptible cultivar, 'Désirée' (DES), were carried out two days after Rs infection, in parallel with their respective noninfected controls. In CR and DES, the upregulation of chitin interactions and cell wall-related genes was detected. The phenylpropanoid biosynthesis and glutathione metabolism pathways were induced only in CR, as confirmed by high levels of lignification over the whole stele in CR roots six days after Rs infection. At the same time, Rs infection greatly increased the concentrations of chlorogenic acid and quercetin derivatives in CG roots as it was detected using ultra-performance liquid chromatography - tandem mass spectrometry. Characteristic increases in the expression of MAP kinase signalling pathway genes and in the concentrations of jasmonic, salicylic, abscisic and indoleacetic acid were measured in DES roots. These results indicate different Rs defence mechanisms in the two resistant potato cultivars and a different response to Rs infection in the susceptible cultivar.

Analysis of chemotypes and their markers in leaves of core collections of Eucommia ulmoides using metabolomics.

The leaves of Eucommia ulmoides contain various active compunds and nutritional components, and have successively been included as raw materials in the Chinese Pharmacopoeia, the Health Food Raw Material Catalogue, and the Feed Raw Material Catalogue. Core collections of E. ulmoides had been constructed from the conserved germplasm resources basing on molecular markers and morphological traits, however, the metabolite diversity and variation in this core population were little understood. Metabolite profiles of E. ulmoides leaves of 193 core collections were comprehensively characterized by GC-MS and LC-MS/MS based non-targeted metabolomics in present study. Totally 1,100 metabolites were identified and that belonged to 18 categories, and contained 120 active ingredients for traditional Chinese medicine (TCM) and 85 disease-resistant metabolites. Four leaf chemotypes of the core collections were established by integrated uses of unsupervised self-organizing map (SOM), supervised orthogonal partial least squares discriminant analysis (OPLS-DA) and random forest (RF) statistical methods, 30, 23, 43, and 23 chemomarkers were screened corresponding to the four chemotypes, respectively. The morphological markers for the chemotypes were obtained by weighted gene co-expression network analysis (WGCNA) between the chenomarkers and the morphological traits, with leaf length (LL), chlorophyll reference value (CRV), leaf dentate height (LDH), and leaf thickness (LT) corresponding to chemotypes I, II, III, and IV, respectively. Contents of quercetin-3-O-pentosidine, isoquercitrin were closely correlated to LL, leaf area (LA), and leaf perimeter (LP), suggesting the quercetin derivatives might influence the growth and development of E. ulmoides leaf shape.

Interaction of quercetin and its derivatives with Ca2+-ATPase from sarcoplasmic reticulum: Kinetic and molecular modeling studies.

Sarcoplasmic reticulum Ca2+-ATPases (SERCAs) regulate cellular calcium homeostasis and are targeted for age-related diseases. Among 14 SERCA mRNA splice variants, SERCA1a is specific to adult fast-twitch skeletal muscle. Quercetin derivatives (monochloropivaloylquercetin (CPQ), IC50 = 195.7 µM; 2-chloro-1,4-naphthoquinonequercetin (CHNQ), IC50 = 60.3 µM) were studied for their impact on SERCA1a using molecular modeling and enzyme kinetics. While there were some similarities in kinetic parameters and molecular modeling, the compounds exhibited diverse actions on SERCA1a. Quercetin reduced activity by 48% at 250 μM by binding to the cytosolic ATP-binding pocket with increased ATP affinity. CPQ bound near the Ca2+-binding site, possibly altering the transmembrane domain. CHNQ significantly reduced activity by 94% at 250 μM without binding to substrate sites. It was proposed that CHNQ induced global protein structure changes, inhibiting Ca2+-ATPase activity.

Chemical Composition and Biological Activity of Commelina erecta: An Edible Wild Plant Consumed in Brazil.

In recent years, the interest in products of natural origin has boosted the exploitation and use of plants as food and sources of bioactive compounds, especially wild plants widely used in different cultures for several purposes. Commelina erecta is a wild edible plant (WEP) traditionally used as food and medicine, about which few studies exist. Thus, this study aimed at enhancing the knowledge about its nutritional, chemical and bioactive profile, considering different plant parts and development stages, in order to increase its inclusion in the diet of South American communities. The nutritional profile was found to be similar to other WEP frequently consumed in Brazil. Thirteen phenolic compounds (HPLC-DAD-ESI/MS) were tentatively identified, with apigenin, luteolin and quercetin derivatives being the most abundant. Fructose and oxalic acid were the major sugar and organic acid, respectively, in the aerial parts of C. erecta, and four isoforms of tocopherols were also identified. Regarding the plant's antioxidant activity, the EC50 values varied between 18.4 and 1060 µg/mL in the inhibition of lipid peroxidation assay (TBARS) and between 53 and 115 µg/mL in the oxidative haemolysis inhibition (OxHLIA) assay. The hydroethanolic extract obtained from stems at the flowering stage also presented anti-inflammatory activity. In general, all the extracts evidenced promising antimicrobial activity. Altogether, these results reinforce the traditional use of this plant species as food and medicine to support the diet of needier populations and also promote food sovereignty and sustainability.

Metabolomic analysis reveals stress tolerance mechanisms in common bean (Phaseolus vulgaris L.) related to treatment with a biostimulant obtained from Corynebacterium glutamicum.

Microbial biostimulants have emerged as a sustainable alternative to increase the productivity and quality of important crops. Despite this, the effects of the treatment on plant metabolism are poorly understood. Thus, this study investigated the metabolic response of common bean (Phaseolus vulgaris) related to the treatment with a biostimulant obtained from the extract of Corynebacterium glutamicum that showed positive effects on the development, growth, and yield of crops previously. By untargeted metabolomic analysis using UHPLC-MS/MS, plants and seeds were subjected to treatment with the biostimulant. Under ideal growth conditions, the plants treated exhibited higher concentration levels of glutamic acid, nicotiflorin and glycosylated lipids derived from linolenic acid. The foliar application of the biostimulant under water stress conditions increased the chlorophyll content by 17% and induced the accumulation of flavonols, mainly quercetin derivatives. Also, germination seed assays exhibited longer radicle lengths for seeds treated compared to the untreated control even in the absence of light (13-18% increase, p-value <0.05). Metabolomic analysis of the seeds indicated changes in concentration levels of amino acids (tryptophan, phenylalanine, tyrosine, glutamine, and arginine) and their derivatives. The results point out the enhancement of abiotic stress tolerance and the metabolic processes triggered in this crop associated with the treatment with the biostimulant, giving the first insights into stress tolerance mechanisms in P. vulgaris.

The Potential of Ameliorating COVID-19 and Sequelae From Andrographis paniculata via Bioinformatics.

The current coronavirus disease 2019 (COVID-19) outbreak is alarmingly escalating and raises challenges in finding efficient compounds for treatment. Repurposing phytochemicals in herbs is an ideal and economical approach for screening potential herbal components against COVID-19. Andrographis paniculata, also known as Chuan Xin Lian, has traditionally been used as an anti-inflammatory and antibacterial herb for centuries and has recently been classified as a promising herbal remedy for adjuvant therapy in treating respiratory diseases. This study aimed to screen Chuan Xin Lian's bioactive components and elicit the potential pharmacological mechanisms and plausible pathways for treating COVID-19 using network pharmacology combined with molecular docking. The results found terpenoid (andrographolide) and flavonoid (luteolin, quercetin, kaempferol, and wogonin) derivatives had remarkable potential against COVID-19 and sequelae owing to their high degrees in the component-target-pathway network and strong binding capacities in docking scores. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the PI3K-AKT signaling pathway might be the most vital molecular pathway in the pathophysiology of COVID-19 and long-term sequelae whereby therapeutic strategies can intervene.