Flavonoid Profiles Research Articles

Characterization of Metabolites and Transcriptome of Pepper Accessions from Four Southern Provinces of China

Background/Objectives: Pepper (Capsicum annuum L.) is a widely grown vegetable and spice crop worldwide. This study aims to reveal the differences of metabolites among pepper accessions from different regions and explore candidate genes related to metabolites of pepper. Methods: The metabolome and transcriptome of 36 pepper accessions were determined by widely targeted metabolomics analysis and RNA sequencing technology, and the differential metabolites and differential genes among C. annuum from four important pepper production and consumption provinces of China, Hunan, Guizhou, Yunnan and Sichuan, were analyzed. Results: Flavonoids are the main characteristic metabolites that distinguish pepper accessions from Yun_Gui_Chuan Group and Hunan Group. The aglycones of characteristic flavonoids in each group are different; in Yun_Gui_Chuan Group mainly are luteolin, quercetin, chrysoeriol and isorhamnetin; in Hunan Group mainly are apigenin. Transcriptome data showed that two genes related to flavonoid 3′-monooxygenase differed significantly between the two groups of chili peppers, and we speculated that they may be the core enzymes regulating their flavonoid profile. And an SNP mutation located in gene Cgla06g001871 showed a strong correlation with pepper accessions from Yun_Gui_Chuan Group, which can be used as a DNA marker to identify pepper accessions from Yun_Gui_Chuan Group, and provide strong support for regional specialty variety conservation. In addition, we also analyzed the metabolites related to the taste and nutrition of pepper accessions in the four provinces, and the results showed that the sugar content of pepper accessions from Guizhou was low and the capsaicinoids content of pepper accessions from Sichuan was low, while no significant difference was found in acid and vitamin contents among pepper accessions from the four provinces. Conclusions: The metabolome and transcriptome of 36 pepper accessions from four important pepper production and consumption provinces of China were determined, and the characteristic metabolites and expressed genes of pepper accessions from each province were analyzed.

Impact of fresh-cut onion types and flavonoid profiles on the survival kinetics of foodborne pathogen during refrigerated storage.

This study investigated the effect of onion flavonoid profiles on the growth, survival, and/or death kinetics of foodborne pathogens in fresh-cut onions at 4°C. Fresh-cut white, yellow, red, and sweet onions were inoculated with separate four-strain cocktail(s) of nalidixic acid-adapted Salmonella spp., Escherichia coli O157:H7, and Listeria monocytogenes achieving a 4 to 5 log CFU g-1. The samples were stored in clam shell containers at 4°C and 70±2% relative humidity for 14days. Additionally, flavonoid profiles were determined on uninoculated control samples stored under similar conditions using standard chromatography techniques, with quercetin derivatives identified as the predominant flavonoids. Results indicated significant differences in pathogen reduction and survival across onion types. Salmonella and E. coli O157:H7 populations declined by 2 to 4 log after 14days, while L. monocytogenes populations increased on white and red onions, remained stable on yellow onions, and declined on sweet onions. Red onions contained the highest flavonoid concentrations, followed by sweet, yellow, and white onions. Notably, despite having similar flavonoid levels, sweet onions showed greatest reduction of tested pathogens than red onions, suggesting that factors beyond flavonoid content may contribute to pathogen reduction. These findings provide new insights into the behavior of foodborne pathogens in fresh-cut onions and highlight the potential for flavonoids to influence pathogen survival during refrigerated storage.

Genetic, metabolomic and transcriptomic analyses of the cotton yellow anther trait.

In the fiber industry, cotton (Gossypium hirsutum L.) is an important crop. One of the most important morphology traits of plants is the color of the anthers, is closely related to pollen fertility and stress resistance. Upland cotton anthers appear white, while island cotton and many wild cotton species have yellow anthers. Carotenoids are natural pigments in plants which involved in many metabolic processes, including photosynthesis, photoprotection, photomorphogenesis, growth and development. Here, we characterized the yellow anther trait of G. hirsutum. Carotenoid and flavonoid profiles in the yellow anthers were greatly altered compared to that in the white anthers, indicating that both carotenoids and flavonoids contribute to the yellow anther phenotype. Map-based cloning identified GhYA (GH_A05G4013) encoding a phytoene synthase to be the candidate gene responsible for anther coloration. GhYA is predominantly expressed in anthers, with its expression level gradually decreasing with the development of anthers. Haplotype analysis revealed that white anthers are associated with two haplotypes, with X74 belonging to HAP1. Through evolutionary analysis, it was found that although there are many white anther Germplasm in upland cotton, the two types of white anther haplotypes were mutated from yellow anthers respectively. Comparative transcriptome analysis between the yellow anther and white anther accessions revealed differentially expressed genes related to both the carotenoid and flavonoid biosynthesis pathways, in line with the changed profiles of the two types of metabolites in yellow anthers; meanwhile, it also indicates potential cross-talk between the flavonoid and carotenoid pathways. According to the results, the PSY gene is critical for the regulation of carotenoids accumulation in cotton anthers.

Molecular and biochemical methods for species identification among the genus Cuscuta

Genus Cuscuta (Convolvulaceae) comprises of stem holoparasitic plants that are scientifically highly valuable, as they cause extensive crop damage. They exhibit high morphological similarity, which complicates their species identification. Determining the taxonomical status of obtained specimens from Bulgaria, is crucial for exploring the genetic diversity of the genus and establishing the phylogenetic relationships within the taxon. Thereby different correlations with geographic region and particular environmental conditions can be established. This study employs molecular and biochemical methods, including ITS region sequence analysis of rDNA, RAPD analysis, and HPLC/MS analysis of flavonoids, to identify Cuscuta species and conduct phylogenetic analysis. Overall, a successful identification has been made - while ITS PCR products provide more accurate species identification and phylogenic information, RAPD profiles are convenient for quick identification. Detailed investigation of the RAPD profiles is required due to differences correlating with the habitats of the species. Nevertheless, flavonoid profiles prove themselves as a valuable biochemical marker for species identification. All of the aforementioned methods are suitable and useful for species identification among the genus Cuscuta, depending on the needs and aims of the conducted analysis.

Distinguishing the botanical origins of rare honey through untargeted metabolomics and machine learning interpreting flavonoid profiles.

Distinguishing the botanic origins of monofloral honey is the foremost concern in ensuring its authentication. In this work, an innovative, green, and comprehensive approach was developed to distinguish the botanic origins of four types of rare honey, and the strategy involved in the following aspects: Based on theoretical design, suitable natural deep eutectic solvent (NADES) was screened to extract flavonoids from honey samples; after NADES extracts were directly analyzed by high-resolution mass spectrometry, the discrimination models of monofloral honey were established by untargeted metabolomics combined with machine learning. Based on the comparison of various models, the Random Forest algorithm had higher prediction accuracy for four types of monofloral honey, and characteristic compounds for each rare monofloral honey were screened based on SHapley Additive exPlanations values. This work provides a new perspective on the use of AI technology and green chemistry to control the quality of honey.

Anthocyanin and phenolic landscape of Syzygium cumini extracts via green extraction.

This study determined the anthocyanin and phenolic profile of Syzygium cumini bioactive compounds, including anthocyanins and other flavonoids, alongside diverse phenolic compounds. The study optimized a green extraction technique (ultrasound-assisted enzymatic extraction (UAEE)) to obtain anthocyanin-rich extract from the fruit pulp of S. cumini using the pectinase enzyme. UHPLC-LC/MS, FTIR, and SEM were used to profile the secondary metabolites, functional groups, and surface morphology. Two major anthocyanins, cyanidin and malvidin, and twenty-three non-anthocyanins, including gallic acid, naringenin, myricetin, and kaempferol, were identified in the enzymatic extract of S. cumini. A central-composite design was used to optimize the extraction, analyzing the effects of enzyme concentration (0.01-0.03%), pH (1-3), and ultrasonication time (5-15min) on total anthocyanin content (438.75±29.81mg C3G/100g db), determining the optimal points (0.01%, 2 pH and 10 mins). The optimized extract was further investigated for total phenolic content and antioxidant activities. The study utilized an economical approach to effectively extract maximum anthocyanins from S. cumini fruit for their potential applications as a biocolorant in food products, simultaneously establishing promising health potential through available literature.

Phenolic and Flavonoids Contributions to the Antioxidant, Antidiabetic, and Anticholesterol Activities of Eriobotrya japonica Fruit Extract: An In Vitro Analysis

Eriobotrya japonica has been traditionally used for its medicinal properties. This study investigates its fruit ethanol extract's phenolic and flavonoids profiles and evaluates its antioxidant, antidiabetic, and anticholesterol activities. Eriobotrya japonica fruit ethanol extract was tested for total phenolic and flavonoid content using Folin-Ciocalteu and AlCl3 methods. The antioxidant capacity was assessed by DPPH and metal chelation assays. The antidiabetic action was assessed using α-glucosidase inhibition and the Nelson-Somogyi method, whereas the Liebermann-Burchard method was used to measure anticholesterol. The extract exhibited large quantities of phenolics (38.62 mg GAE/g) and flavonoids (4.23 mg QE/g), demonstrating robust antioxidant activity with IC50 of 55 μg/mL by DPPH method and substantial inhibition (71%) by metal ion chelation. In addition, it exhibited strong antidiabetic effects 2.42 μg/mL in the α-glucosidase inhibition test, and at 10 μg/mL using the Nelson-Somogyi method resulted in a 24.02% yield. The extract demonstrated a significant reduction in cholesterol levels during the process of cholesterol reduction, obtaining a maximum reduction of 47.31% at the highest concentration tested. Ethanol extract of Eriobotrya japonica can be used in treating oxidative stress and diabetes and introduce its potential to reduce cholesterol levels. The high content of phenolic and flavonoids total contributes to its bioactivities, indicating its potential as a functional food ingredient.

Optimization of process parameters in supercritical CO2 extraction of rose essential oil: Evaluation of phenolic, flavonoid, and antioxidant profiles

Optimization of process parameters in supercritical <scp>CO₂</scp> extraction of rose essential oil: Evaluation of phenolic, flavonoid, and antioxidant profiles

Flavonoids analysis in citrus peels by UPLC-Q-TOF-MS/MS and its antioxidant and anti-inflammation activity

Citrus is the world's largest fruit, developed a rich variety resources in a long history of cultivation. Flavonoid is a natural product found widely in citrus plants. In this study, the major flavonoids and relative activities of 9 citrus peels were investigated by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) analysis and antioxidant and anti-inflammatory assays in A549 cell. A total of 51 flavonoids were identified, comprising a variety of subclasses. Notably, Citrus Reticulata Blanco (MJ) and Bu Zhi Huo (CJ) demonstrated distinctive flavonoid profiles. Flavonoid extracts from MJ and Citrus maxima (HY) peels significantly reduced reactive oxygen species (ROS) generation and decreased the levels of cytokines (IL-8, TNF-α, MCP-1, and IL-6) in A549 cells. Furthermore, these extracts up-regulated the expression of Nrf2 and HO-1 and inhibited the phosphorylation of p65 and NF-κB activity. Gray correlation analysis identified (-)-vestitone, dimefline, eupafolin, and trans-cinnamaldehyde as strongly associated with inflammatory markers. The findings suggest that flavonoids extracted from citrus peels possess significant antioxidant and anti-inflammatory activities, highlighting their potential as natural therapeutic agents for combating inflammation.

High-Resolution Tandem Mass Spectrometry for Metabolic Profiling of Ocotea diospyrifolia (Meisn.) Mez Leaves.

Ocotea is an important genus of Lauraceae plant family that comprises over 400 species, many of which pose challenges in taxonomic differentiation due to their complex botanical characteristics. Chemosystematics, and more recently, chemophenetics, have emerged as valuable tools to address these challenges based on their natural products (NPs) composition. O. diospyrifolia (Meisn.) Mez is a poorly studied species with known pharmacological potential. Here, we applied ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS) allied to a curated in-house database with all previous isolated NPs from the Ocotea genus (OcoteaDB), gas phase fragmentations reactions, and biosynthesis. The strategy resulted in compounds annotated in confidence levels 2 (n=27), 3 (n=231), and 4 (n=21) according to the Metabolomics Standards Initiative (MSI). Additional annotations based on fragmentation proposals (n=16) were also included. The study revealed that O. diospyrifolia is a great alkaloid producer, even though different lignoids, which also comes from the shikimate pathway, were annotated. Additionally, the flavonoid profile predominantly consists of flavonol glycosides, complementing prior reports. This study provides the first comprehensive chemical profile of O. diospyrifolia leaves, which corroborates the chemotaxonomy of the species, and also contributes to further characterization studies, as the UHPLC-HRMS data is publicly available.

Integrated Metabolomics and Transcriptomics Provide Key Molecular Insights into Floral Stage-Driven Flavonoid Pathway in Safflower.

Safflower (Carthamus tinctorius L.) is a traditional Chinese medicinal herb renowned for its high flavonoid content and significant medicinal value. However, the dynamic changes in safflower petal flavonoid profiles across different flowering phases present a challenge in optimizing harvest timing and medicinal use. To enhance the utilization of safflower, this study conducted an integrated transcriptomic and metabolomic analysis of safflower petals at different flowering stages. Our findings revealed that certain flavonoids were more abundant during the fading stage, while others peaked during full bloom. Specifically, seven metabolites, including p-coumaric acid, naringenin chalcone, naringenin, dihydrokaempferol, apigenin, kaempferol, and quercetin, accumulated significantly during the fading stage. In contrast, dihydromyricetin and delphinidin levels were notably reduced. Furthermore, key genes in the flavonoid biosynthesis pathway, such as 4CL, DFR, and ANR, exhibited up-regulated expression with safflower's flowering progression, whereas CHI, F3H, and FLS were down-regulated. Additionally, exposure to UV-B stress at full bloom led to an up-regulation of flavonoid content and altered the expression of key flavonoid biosynthetic genes over time. This study not only elucidates the regulatory mechanisms underlying flavonoid metabolism in safflower but also provides insights for maximizing its medicinal and industrial applications.

Effects of exogenous calcium on flavonoid biosynthesis and accumulation in peanut roots under salt stress through multi-omics.

Flavonoids possess antioxidant properties and are crucial in enhancing plant resistance to abiotic stress. Exogenous calcium has been found to regulate the biosynthesis and accumulation of secondary metabolites, including flavonoids. However, the mechanism by which exogenous calcium influences flavonoid regulation in peanut roots under salt stress remains unclear. In this study, four treatment conditions were established: no salt stress, salt stress, exogenous calcium, and a combination of salt stress and exogenous calcium. The peanut root flavonoid profile was comprehensively analyzed using both a broadly targeted metabolomic approach and an absolute quantitative flavonoid metabolome. A total of 168 flavonoids were identified in the broad-target metabolome, while 68 were quantified in the absolute quantification analysis. The findings revealed that salt stress generally increased flavonoid content in peanut roots, while co-treatment with exogenous calcium significantly reduced this accumulation. Additionally, the activities of key enzymes and the expression of genes involved in the flavonoid biosynthesis pathway were upregulated under salt stress, but downregulated following the combined treatment. This study offers valuable insights into the physiological and ecological roles of flavonoids in response to environmental stressors in economically important crops.

Investigating the Phytochemistry and Underlying Glycemic Control Mechanisms of Litchi chinensis Sonn. (Litchi) Peel Ethyl Acetate Extract in a Fructose/Streptozotocin Diabetic Model of Rats.

The glycemic control potential and flavonoid profile of litchi have been documented for its hydroalcoholic extracts, while there is scarce information regarding its ethyl acetate extract. This study investigated the flavonoid profile, as well as the ameliorative potential and possible underlying mechanisms of litchi peel ethyl acetate extract on type 2 diabetes-related pathologies in a fructose/streptozotocin (STZ) model of diabetic rats. Sprague Dawley rats were induced with diabetes by administering 10% fructose for 2 weeks and a single i.p. injection of low-dose (40 mg/kg bw) STZ. Thereafter, the animals were orally administered with a low-dose (150 mg/kg bw) and high-dose (300 mg/kg bw) of the peel extract (LDPE and HDPE, respectively) and metformin (200 mg/kg bw). Compared to untreated diabetic rats (AUC = 1004 mg.h/dL), the HDPE significantly (p < 0.05) improved glucose tolerance (AUC = 847 mg.h/dL), which was statistically comparable (p ˃ 0.05) to the effect of metformin (AUC = 903 mg.h/dL). Serum insulin and pancreatic histology data showed that the STZ-induced pancreatic damage and insulin depletion was improved by the HDPE, which could be linked to the observed ameliorative effect of the extract on pancreatic lipid peroxidation and SOD and catalase activity. The extract further improved liver and muscle glycogen storage, as well as muscle hexokinase activity and Akt phosphorylation, suggesting that the extract exerts glycemic control by enhancing glycogen storage and modulating insulin-mediated signaling of glucose uptake and utilization. LC-MS data and documented reports suggest that flavonoids, such as epicatechin, cinnamtannin B2, procyanidin B5, and proanthocyanidin A2, are the possible influencing compounds. The ethyl acetate extract of litchi peel could be a source of bioactive flavonoids that can potentiate glycemic control in diabetes and mitigate oxidative stress-related pathologies.

Salinity-responsive hyperaccumulation of flavonoids in Spirodela polyrrhiza, resultant maneuvering in the structure and antimicrobial as well as azo dye decontamination profile of biofabricated zinc oxide nanoentities.

Duckweeds (Spirodela polyrrhiza) are free-floating macrophytes that grow profusely in nutrient-rich waters. Under ideal conditions, they exhibit a rapid growth rate and can absorb a substantial amount of nutrients, macromolecules, and pollutants from bodies of water. Zinc oxide nanoparticles (ZnO NPs) synthesized from plant extracts, particularly under stress conditions, have opened new research avenues in the field of nanotechnology. Under salinity stress, the accumulation of flavonoids in duckweeds can affect the structure of ZnO NPs, helping researchers ascertain their antimicrobial role. In our study, we exposed mid-log phase duckweed monocultures to 75 mM NaCl in a full-strength Murashige and Skoog medium for 7 days, followed by a 15-day recovery period. We observed significant overexpression of superoxide and hydrogen peroxide as reactive oxygen species. As a result, chlorophyll and certain metabolites were produced in lesser amounts, while flavonoid and phenol content increased by 12% and 8%, respectively. This overproduction persisted up to 10 days into the recovery treatment period but dropped by 8% and 5%, respectively, by the 15th day. The flavonoid coating transformed the NPs into rosette clusters, which exhibited reduced antimicrobial activity against Aeromonas hydrophila, a Gram-negative, fish-pathogenic bacterium. Herein, we discuss potential mechanisms for the conformational transformation of ZnO NPs into finer dimensions in response to NaCl-induced oxidative stress in duckweed. In this study, the azo dye degradation capacity of salinity-treated plants increased as the flavonoid profile became enriched. Zinc oxide nanoparticles, both prior to and after salinity treatment, were found to be efficient in scavenging azo dye and mitigating its toxicity, as evidenced by improved germination, growth, and overall plant morphometry.

Quality control analyses of selected honey samples from Serbia based on their mineral and flavonoid profiles, and the invertase activity

Abstract Nowadays, climate changes induce deviations in the composition of honey varieties characteristic of a specific geographic region. Therefore, according to Codex Alimentarius for honey, the slight variations in values of determined parameters cannot be strictly regarded as a sign of its adulteration. Here, modified methods are presented for preparing honey samples for inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis and the high-performance liquid chromatography (HPLC) method to use them as fast and reliable methods in the food industry. ICP-OES analysis suggested that all analysed honey samples are natural, and HPLC-DAD (diode-arrray detection) analysis on the flavonoids showed that one sample is probably not natural. Invertase activity showed an overlap with this HPLC-DAD finding but suggested more samples as possibly adulterated, which can be neglected due to possible thermal treatment of those natural samples, causing a decrease in invertase activity. Therefore, results obtained from the analyses of investigated honey samples based on the mineral content, number, and quantity of flavonoids, together with the invertase activity, indicated that the combination of analyses could be a reliable tool for determining the quality of honey samples.

Targeted regulation of 5-aminolevulinic acid enhances flavonoids, anthocyanins and proanthocyanidins accumulation in Vitis davidii callus

BackgroundSpine grape (Vitis davidii) is a promising source of high-quality anthocyanins, with vast potential for application in food, pharmaceutical, and cosmetic industries. However, their availability is limited by resource constraints. Plant cell culture has emerged as a valuable approach for anthocyanin production and serves as an ideal model to investigate the regulation of anthocyanin biosynthesis. Elicitors are employed to achieve targeted enhancement of anthocyanin biosynthesis. The present study investigated the impact of 5-aminolevulinic acid (ALA) as an elicitor on the accumulation of anthocyanins and flavonoids during spine grape callus growth. Specifically, we examined the effects of ALA on anthocyanin and its component accumulation in callus, and biosynthetic anthocyanin gene expression.ResultsALA at 25 µg/L increased the biomass of spine grape callus. ALA induction enhanced the levels of flavonoids, anthocyanins and proanthocyanidins in callus, with maximum values reaching 911.11 mg/100 g DW, 604.60 mg/100 g DW, and 5357.00 mg/100 g DW, respectively, after callus culture for 45 days. Notably, those levels were 1.47-, 1.93- and 1.83-fold higher than controls. ALA induction modulated the flavonoid profile, and among 97 differential flavonoid metabolites differing from controls, 77 were upregulated and 20 were downregulated. Six kinds of anthocyanins, namely cyanidin (8), delphinidin (6), peonidin (5), malvidin (4), petunidin (3) and pelargonidin (3), were detected in callus, with peonidin most abundant. Compared with controls, anthocyanin components were increased in ALA-treated callus. The key genes PAL1, PAL2, PAL4, CHI, CHS3, F3’H, F3H, FLS, DFR, UFGT, MYBA1, LDOX, OMT3, GT1 and ACT involved in anthocyanin biosynthesis were upregulated following ALA treatment, resulting in anthocyanin accumulation.ConclusionThis study revealed a novel mode of ALA-mediated promotion of plant anthocyanin biosynthesis and accumulation at the cellular level, and a strategy for enhancing anthocyanin content in spine grape callus. The findings advance commercial-scale production of anthocyanins via spine grape callus culture. we also explored the accumulation patterns of flavonoids and anthocyanins under ALA treatment. Augmentation of anthocyanins coincided with elevated expression levels of most genes involved in anthocyanin biosynthesis within spine grape callus following ALA treatment.

Polyphenol composition and antioxidant activity of fermentation combined with enzymatic hydrolysis modified Astragalus membranaceus stems

Astragalus membranaceus (AM) roots are a well-known homologous medicine and food in China. AM stems, which are discarded and not used effectively, also contain many active compounds and exhibit beneficial effects. It has the potential to be explored as antibiotic alternative. Fermentation combined with enzymatic hydrolysis (FEH) is an effective strategy for extracting polyphenol and improving the usage of AM stems. Therefore, in this study, the conditions of FEH and extraction for polyphenol in AM stems were screened. The antioxidant activity of extract from AM stems without and with FEH (AMSE and FAMSE) was evaluated. The metabolite profiles of phenolic acids and flavonoids in AMSE and FAMSE were characterized by ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC–ESI-MS/MS). The results showed that the highest polyphenol content from AM stems was obtained with cellulase and pectinase (1:1, 2000 U/g), moisture content 43%, fermentation temperature 30 °C, and fermentation time 7 days. Selected extraction conditions of polyphenol were ethanol concentration 50%, ultrasonic power 500 W, extraction temperature 35 °C, and extraction time 40 min. On this condition, compared with AMSE, the polyphenol and flavonoid contents in FAMSE were significantly higher. FAMSE exhibited stronger DPPH, hydroxyl radical scavenging rate and reducing power than AMSE. The relative content of 3-(4-hydroxyphenyl)-propionic acid, dihydroferulic acid, isoferulic acid, 4-hydroxybenzoic acid, 4-hydroxyphenyllactic acid, ferulic acid, vanillic acid, syringic acid, gentisic acid, sinapic acid, apigenin, tricin, acacetin, daidzein, genistein, formononetin, prunetin, pratensein, rhamnocitrin and galangin were significantly upregulated in FAMSE.Graphical

Standardization of Ginger and Javanese Turmeric Crude Drugs and Total Flavonoid and Phenolic Content Profiles of Their Combination

A combination of ginger (Zingiber officinale Roscoe) and Javanese turmeric (Curcuma zanthorrhiza Roxb.) rhizomes is used by Baturraden, Central Java, people to treat an ailment called masuk angin. This study aimed to evaluate the quality profile of ginger and Javanese turmeric crude drugs and determine the total flavonoid content (TFC) and the total phenolic content (TPC) of combinations of both crude drugs in five different weight ratios. Standardization of crude drugs used parameters, methods, and standards of the compendial Indonesian Herbal Pharmacopeia (IHP). Ginger crude drugs met the standard in parameters of morphology, loss on drying, acid-insoluble ash, ethanol extractable, and water extractable, while morphology and values of loss on drying, acid-insoluble ash, ethanol extractable, water extractable, and volatile content of Javanese turmeric were within their respective specifications. The TFC of Javanese turmeric is lower than that of ginger, but the opposite trend was observed for TPC. The crude drug weight ratio significantly affected the TFC and TPC of the ginger and Javanese turmeric combination. The combination with the highest TFC and TPC was Formula IV (7.11±0.37 mg Quercetin equivalent (QE)/g) and Formula II (21.65±1.49 mg Gallic acid equivalent (GAE)/g), respectively. Our study suggested that ginger and Javanese turmeric crude drugs were not of good quality, and their mixture in weight ratio of 25-75 provided the highest TPC warrant for further bioactivity evaluations.

Bioefficacy, chromatographic profiling and drug-likeness analysis of flavonoids and terpenoids as potential inhibitors of H1N1 influenza viral proteins

Considering medicinal plants, natural products present in these plants are the best sources of medications for combating viral infection. The possible drug target against viral H1N1 influenza proteins lead to identification of selected secondary metabolites from potential plants Tinospora cordifolia, Ocimum sanctum, and Piper nigrum. On analysis of in vitro cell based antiviral activity of the selected plant extracts, an indication for a possible lead compound against neuraminidase activity was evident. Potent ligands were selected using drug docking and ADMET analysis, and the screened lead metabolites were ultimately identified as terpenoid (Columbin) and, flavonoid (Cubebin, and Apigenin). Among the selected ligands, the drug binding activity of Cubebin with all the 6 proteins of H1N1 influenza type A virus, HA (4r8w), NA (4qn7), M2 (3lbw), PA (4wsb), PB1 (2znl) and PB2 (3wil), was pronounced. In addition, physicochemical and pharmacokinetic parameters linked to absorption, distribution, metabolism, excretion and toxicity (ADMET) have been evaluated and corroborate with our in vitro results. Molecular dynamics modelling indicated Cubebin can be a potential phytochemical in a drug discovery pipeline for the development of neuraminidase inhibitors. Further studies can provide a possibility for an alternative therapy against Influenza viruses.

Comprehensive investigation of network pharmacology, computational modeling, and pharmacokinetic assessment to evaluate the efficacy of flavonoids in rheumatoid arthritis.

Rheumatoid arthritis is a chronic autoimmune disease characterized by inflammation and joint damage, imposing a significant burden on affected individuals worldwide. Flavonoids, a class of natural compounds abundant in various plant-based foods, have shown promising anti-inflammatory and immunomodulatory effects, suggesting their potential as therapeutic agents for RA. In this study, we conducted a comprehensive investigation of identified LCMS compounds utilizing network pharmacology, computational modeling, in silico approaches, and pharmacokinetic assessment to evaluate the efficacy of flavonoids in RA treatment. The study identified 5 flavonoid structures with common targets via LCMS and Integration of network pharmacology approaches enabled a comprehensive evaluation of the pharmacological profile of flavonoids in the context of RA treatment, guiding the selection of promising candidates for further experimental validation and clinical development. The top 10 targets were AKT1, PI3KR1, CDK2, EGFR, CDK6, NOS2, FLT3, ALOX5, CCNB1, and PTPRS via PPI network. The investigation emphasized several pathways, including the AGE-RAGE signaling pathway, resistance to EGFR tyrosine kinase inhibitors, the PI3K-AKT signaling network, and the Rap 1 signaling pathway. In silico studies estimated binding affinities that ranged from - 7.0 to - 10.0 kcal/mol. Schaftoside and Vitexin showed no toxicity in computational approach and found suitable for further investigations. Overall, our study underscores the potential of flavonoids as therapeutic agents for RA and highlights the utility of integrative approaches combining network pharmacology, computational modeling, in silico methods, and pharmacokinetic assessment in drug discovery and development processes.