Flavonoids Luteolin Research Articles

Integrating experimental model, LC-MS/MS chemical analysis, and systems biology approach to investigate the possible antidiabetic effect and mechanisms of Matricaria aurea (Golden Chamomile) in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a heterogeneous disease with numerous abnormal targets and pathways involved in insulin resistance, low-grade inflammation, oxidative stress, beta cell dysfunction, and epigenetic factors. Botanical drugs provide a large chemical space that can modify various targets simultaneously. Matricaria aurea (MA, golden chamomile) is a widely used herb in Middle Eastern communities for many ailments, including diabetes mellitus, without any scientific basis to support this tradition. For the first time, this study aimed to investigate the possible antidiabetic activity of MA in a type 2 diabetic rat model, identify chemical constituents by LC-MS/MS, and then elucidate the molecular mechanism(s) using enzyme activity assays, q-RTPCR gene expression analysis, network pharmacology analysis, and molecular docking simulation. Our results demonstrated that only the polar hydroethanolic extract of MA had remarkable antidiabetic activity. Furthermore, it improved dyslipidemia, insulin resistance status, ALT, and AST levels. LC-MS/MS analysis of MA hydroethanolic extract identified 62 compounds, including the popular chamomile flavonoids apigenin and luteolin, other flavonoids and their glycosides, coumarin derivatives, and phenolic acids. Based on pharmacokinetic screening and literature, 46 compounds were chosen for subsequent network analysis, which linked to 364 candidate T2DM targets from various databases and literature. The network analysis identified 123 hub proteins, including insulin signaling and metabolic proteins: IRS1, IRS2, PIK3R1, AKT1, AKT2, MAPK1, MAPK3, and PCK1, inflammatory proteins: TNF and IL1B, antioxidant enzymes: CAT and SOD, and others. Subsequent filtering identified 40 crucial core targets (major hubs) of MA in T2DM treatment. Functional enrichment analyses of the candidate targets revealed that MA targets were mainly involved in the inflammatory module, energy-sensing/endocrine/metabolic module, and oxidative stress module. q-RTPCR gene expression analysis showed that MA hydroethanolic extract was able to significantly upregulate PIK3R1 and downregulate IL1B, PCK1, and MIR29A. Moreover, the activity of the antioxidant hub enzymes was substantially increased. Molecular docking scores were also consistent with the networks’ predictions. Based on experimental and computational analysis, this study revealed for the first time that MA exerted antidiabetic action via simultaneous modulation of multiple targets and pathways, including inflammatory pathways, energy-sensing/endocrine/metabolic pathways, and oxidative stress pathways.

Target-based virtual screening and molecular interaction studies for lead identification of natural olive compounds against glioblastoma multiforme.

Glioblastoma multiforme, a rare traumatic brain disorder, is at the research climax for its uncontrolled growth leading to a catastrophic outcome. Throwing light on the target-based virtual screening of drugs using natural phytocompounds is a striking cornerstone in glioblastoma-based drug discovery, accelerating with leaps and bounds. This project aims to develop promising lead compounds against glioblastoma brain cancer using OliveNet™, an open-source database. In this pursuit, our rationale for selecting molecules was based on their capability to pass through the blood-brain barrier. Out of 51 derivative molecules from flavonoids and polyphenols, 17 molecules were screened out bearing the best ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, alongside fulfilling our rationale of lead selection. Two polyphenols, 3,4,5-trimethoxybenzoic acid and 4-ethyl guaiacol, have binding affinity for the antioxidant flavonoid luteolin of -5.1 and -4.3 kcal/mol, respectively. According to docking studies, the residues ASN1960, ASN1966, ASN1960, PHE1984, TYR1896, VAL1911, and LYS1966 make both polar and nonpolar interactions with 3,4,5-trimethoxybenzoic acid and 4-ethylguanidine, respectively. LD50 values of toxicity screening using TOX Pro brought to limelight the excellent safety profile of polyphenols and flavonoids. Furthermore, studies using in silico cytotoxicity prediction and molecular modelling have decisively shown that these polyphenols are likely to be effective brain cancer inhibitors and promising future lead candidates against glioblastoma multiforme.

Synaptic Effects of Palmitoylethanolamide in Neurodegenerative Disorders.

Increasing evidence strongly supports the key role of neuroinflammation in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Neuroinflammation may alter synaptic transmission contributing to the progression of neurodegeneration, as largely documented in animal models and in patients’ studies. In the last few years, palmitoylethanolamide (PEA), an endogenous lipid mediator, and its new composite, which is a formulation constituted of PEA and the well-recognized antioxidant flavonoid luteolin (Lut) subjected to an ultra-micronization process (co-ultraPEALut), has been identified as a potential therapeutic agent in different disorders by exerting potential beneficial effects on neurodegeneration and neuroinflammation by modulating synaptic transmission. In this review, we will show the potential therapeutic effects of PEA in animal models and in patients affected by neurodegenerative disorders.

PERILLA FRUTESCENS – A REVIEW ON PHARMACOLOGICAL ACTIVITIES, EXTRACTION PROCEDURE AND APPLICATIONS

Perilla frutescens, a member of the mint family Lamiaceae, is a medicinal, aromatic, edible, and beautiful plant. The source of perilla lies into East Asian countries (China, Japan, Korea, Taiwan, Vietnam, and India), in which it is been used as an important root of culinary and conventional medicinal uses. Perilla plant’s leaves, seeds, and stems are utilized in community medicine for a variety of ailments [1]. Recently, Perilla plant is gaining extra interest due to its medicinal advantages and phytochemical contents. The fundamental phytochemical compounds found in this species are phenolic compounds (Rosmarinic acid, caffeic acid, and ferulic acid), flavonoids (luteolin and apigenin), Phytosterols, Tocopherols, Policosanols, and Fatty acid. Perilla seed oil too is a wealthy supply of vital fatty acid which includes α-linolenic acid (54–64%) and linoleic acid (14%) [2]. Perilla has shown different biologicalactions for example, antioxidant, antimicrobial, anti-allergic, antidepressant, anti-inflammatory, anticancer, and neuroprotective actions. Perilla seed oil consists of omega-3-fatty acid, and alpha-linolenic acid (ALA). In comparison to other plant oils, perilla seed oil has one of the highest percentages of omega-3 (ALA) fatty acids, at 54–64%. The omega-6 (linoleic acid) is around 14% and omega-9 (Oleic acid) too is found in perilla oil. These polyunsaturated fatty acids are very useful to human wellbeing and in prevention of various illnesses such as cardiovascular disorders, cancer, inflammatory, and rheumatoid arthritis [3].

Effect of Date Palm (Phoenix dactylifera) Phytochemicals on Aβ1-40 Amyloid Formation: An in-silico Analysis.

Alzheimer's disease (AD) is a neurodegenerative disease and the most prevalent form of dementia. The generation of oxygen free radicals and oxidative damage is believed to be involved in the pathogenesis of AD. It has been suggested that date palm, a plant rich in phenolic compounds and flavonoids, can provide an alternative treatment to fight memory loss and cognitive dysfunction due to its potent antioxidant activity. Thus, we studied the effect of flavonoids present in date palm on Aβ1−40 amyloid formation using molecular docking and molecular dynamics simulation. AutoDock. Myricetin was used as a positive control drug. The flavonoids Diosmetin, Luteolin, and Rutin were found to be potent inhibitors of aggregation (docking energies ≤ −8.05 kcal mol−1) targeting Aβ1−40 fibrils (both 2LMO and 6TI5), simultaneously. Further screening by physicochemical properties and drug-likeness analysis suggested that all flavonoids except Rutin followed Lipinski's rule of five. Rutin was, thus, taken as a negative control (due to its violation of Lipinski's rule) to compare its dynamics with Diosmetin. Diosmetin exhibited the highest positive scores for drug likeness. Since Luteolin exhibited moderate drug-likeness and better absorption properties, it was also included in molecular dynamics simulation. Molecular dynamics of shortlisted compounds (Rutin, Diosmetin, and Luteolin) were performed for 200 ns, and the results were analyzed by monitoring root mean square deviations (RMSD), root mean square fluctuation (RMSF) analysis, the radius of gyration (Rg), and solvent accessible surface area (SASA). The results proved the formation of a stable protein-compound complex. Based on binding energies and non-bonded interactions, Rutin and Luteolin emerged as better lead molecules than Diosmetin. However, high MW (610.5), lowest absorption rate (16.04%), and more than one violation of Lipinski's rule make Rutin a less likely candidate as an anti-amyloidogenic agent. Moreover, among non-violators of Lipinski's rule, Diosmetin exhibited a greater absorption rate than Luteolin as well as the highest positive scores for drug-likeness. Thus, we can conclude that Diosmetin and Luteolin may serve as a scaffold for the design of better inhibitors with higher affinities toward the target proteins. However, these results warrant in-vitro and in-vivo validation before practical use.

The promoting effect of neutrophil-derived BAFF molecule on the proliferation and life span of CAL-27 oral squamous carcinoma cells

Tumor-associated neutrophils (TANs) are the major cellular component of the tumor microenvironment and have been shown to release of different bioactive molecules such as B-cell activating factor (BAFF). The data on the interactions between OSCC cells and neutrophils are limited and do not explain the actual role of the BAFF in the development of the OSCC. In the present study we examined the direct effect of neutrophils-derived BAFF on the OSCC cell line CAL-27 proliferation and apoptosis.PMNs of OSCC patients and healthy control were isolated from whole blood and separated by magnetic selection with monoclonal anti-human CD16 antibodies. CD-16 – positive neutrophils were incubated in the presence of TGF-β and/or LPS as well as flavonoids (luteolin and quercetin). CAL-27 cells were co-incubated with supernatants of neutrophils. BAFF expression in neutrophils, BAFF-R expression on CAL-27 cells and apoptosis of CAL-27 cells were assessed by flow cytometry. To determine the CAL-27 cells proliferation, the MTT test was used. Expression of select mitochondrial proteins in CAL-27 cells were measured by Western blot.Neutrophils from OSCC patients showed significantly higher expression of BAFF than those from the healthy controls. The results obtained revealed upregulation of the proliferation and downregulation of the apoptosis of the CAL-27 cells in the presence of the supernatants of TGF-β-treated neutrophils. Flavonoids reduced BAFF expression in neutrophils of patients with OSCC and control group. Lower intensity of apoptosis in CAL-27 cells was associated with the increased expression of anti-apoptotic Bcl-2, Mcl-1 and activated form of PI3K kinase (pPI3K) and simultaneously reduced expression of pro-apoptotic Bax protein in the presence of rhBAFF, as well as of supernatants of neutrophils derived from OSCC patients. In conclusion, the data presented confirm the previously suggested role of neutrophil-derived BAFF in OSCC development. The favorable effects of examined flavonoids on tumor-promoting BAFF expression in neutrophils suggest that they might be promising candidates as chemo-preventive agents in the therapy of patients with OSCC.

In vitro ovicidal activity of Brongniartia montalvoana against small ruminant gastrointestinal nematodes

Several plants of the Fabaceae family have been assessed regarding their high nutritional value and anthelmintic properties. The ovicidal effect of the hydroalcoholic extract (Bm-HAE) and subfractions from the aerial parts of Brongniartia montalvoana (Fabaceae) against a mixed strain of gastrointestinal nematodes (GIN) (Haemonchus spp., Trichostrongylus spp. and Oesophagostomum spp.) resistant to albendazole sulfoxide, ivermectin and levamisole was evaluated by the egg hatch test (EHT). The Bm-HAE was subjected to liquid-liquid chemical separation with ethyl acetate giving two fractions, an aqueous (Bm-Aq) and an organic (Bm-EtOAct). The purification of the bioactive fraction (Bm-EtOAct) through chromatographic separation resulted in four bioactive subfractions (BmR6, BmR7, BmR8 and BmR10). The treatments were designed as follows: Bm-HAE at 800, 1,500, 3,000 and 6,000 μg/mL, and Bm-Aq, Bm-EtOAct and subfractions (BmR6, BmR7, BmR8 and BmR10) at 100, 200, 400 and 800 μg/mL. Two properly negative controls (distilled water and 2% methanol) and thiabendazole (100 μg/mL) as a positive control were used for each bioassay. The chemical identification of the extract, fractions and subfractions was performed through chromatographic processes like open column chromatography, thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC-PDA). Additionally, the GIN eggs exposed to the bioactive compounds were observed through confocal laser scanning microscopy (CLSM). The Bm-HAE showed 99.5% egg hatching inhibition (EHI) at 6,000 μg/mL with a lethal concentration (LC50) of 1110 μg/mL. The Bm-EtOAc fraction displayed 99.1% EHI at 800 μg/mL with LC50 = 180 μg/mL. The ovicidal activity of the four subfractions was similar at 800 μg/mL: BmR6 (92% EHI); BmR7 (100% EHI); BmR8 (97.8%); and BmR10 (99.1%). The HPLC-PDA analysis of the bioactive subfractions allowed identification of p-coumaric acid, ferulic acid and coumarin derivatives as major compounds. The CLSM analysis allowed observation of morphological alterations in unhatched larvae caused by bioactive compounds present in the Bm-EtOAc and BmR10. In addition, the flavonoids eriodyctiol, luteolin and cynaroside were described for the first time for B. montalvoana.

Biosynthesis of a water solubility-enhanced succinyl glucoside derivative of luteolin and its neuroprotective effect.

SummaryThe natural flavonoids luteolin and luteoloside have anti‐bacterial, anti‐inflammatory, anti‐oxidant, anti‐tumour, hypolipidemic, cholesterol lowering and neuroprotective effects, but their poor water solubility limits their application in industrial production and the pharmaceutical industry. In this study, luteolin‐7‐O‐β‐(6″‐O‐succinyl)‐d‐glucoside, a new compound that was prepared by succinyl glycosylation of luteolin by the organic solvent tolerant bacterium Bacillus amyloliquefaciens FJ18 in an 8.0% DMSO (v/v) system, was obtained and identified. Its greater water solubility (2293 times that of luteolin and 12 232 times that of luteoloside) provides the solution to the application problems of luteolin and luteoloside. The conversion rate of luteolin (1.0 g l−1) was almost 100% at 24 h, while the yield of luteolin‐7‐O‐β‐(6″‐O‐succinyl)‐d‐glucoside reached 76.2%. In experiments involving the oxygen glucose deprivation/reoxygenation injury model of mouse hippocampal neuron cells, the cell viability was significantly improved with luteolin‐7‐O‐β‐(6″‐O‐succinyl)‐d‐glucoside dosing, and the expressions of the anti‐oxidant enzyme HO‐1 in the nucleus increased, providing a neuroprotective effect for ischemic cerebral cells. The availability of biosynthetic luteolin‐7‐O‐β‐(6″‐O‐succinyl)‐d‐glucoside, which is expected to replace luteolin and luteoloside, would effectively expand the clinical application value of luteolin derivatives.

Review on Lemon Balm Herb and its Evaluation

The development of drugs from medicinal herbs may be good to find novel therapeutic agents in the treatment of anxiety. Melissa officinalis L. (lemon balm) belongs to the Lamiaceae family and grows widely in the Mediterranean region, western Asia, southwestern Siberia, and northern Africa. Melissa officinalis L. has been used in traditional medicine to treat headaches, indigestion, colic, nervousness, cardiac failure and depression. In addition, it has been reported in several researches that lemon balm had many beneficial effects such as anti-inflammatory and ant nociceptive, Antioxidant. leaves contain several classes of constituents including polyphenolic compounds (rosmarinic acid, caffeic acid and protocatechuic acid), essential oils (geranial, neral, citronellal, geraniol, beta-pinene, alpha-pinene, beta-caryophyllene, germacrene D, and ocimene), monotherpenoid aldehydes, sesquiterpenes, flavonoids (luteolin) and tannins. The aims of this study were to evaluate the phytochemical screening of ethanolic extract of Melissa officinalis L. One study examined a chemically-validated essential oil derived from Melissa and found that Melissa inhibited binding of GABAA to receptor channel in the rat forebrain, but had no effect on or nicotinic acetylcholine receptors (Abuhamdah et al., 2008). They also found that Melissa elicited a significant dose-dependent reduction in both inhibitory and excitatory transmission.. The aromatic balm leaves are often used in beverages and as a seasoning in salads, dressings and sauces, as well as in cooked foods, e.g., in soups and stews. Some vernacular names are balm, common balm, blue balm, dropsy plant, honey plant, Herzkraut, citronelle, cytria, cedronella.

Biological Activities and Chemical Profile of Gentiana asclepiadea and Inula helenium Ethanolic Extracts.

This study aimed to investigate the antioxidant, antimicrobial, and cytotoxic potential of ethanolic extracts obtained from Gentiana asclepiadea L. and Inula helenium L. roots, in relation to their chemical composition. The total polyphenols, flavonoids, and phenolic acids were determined by spectrophotometric methods, while LC-MS analysis was used to evaluate the individual constituents. The antioxidant properties were tested using the FRAP and DPPH methods. The standard well diffusion and broth microdilution assays were carried out to establish in vitro antimicrobial efficacy and minimum inhibitory and bactericidal concentrations. The cytotoxicity was tested on rat intestinal epithelial cells using the MTT assay. The results pointed out important constituents such as secoiridoid glycoside (amarogentin), phenolic acids (caffeic acid, chlorogenic acid, trans-p-coumaric acid, salicylic acid), and flavonoids (apigenin, chrysin, luteolin, luteolin-7-O-glucoside, quercetin, rutoside, and naringenin) and promising antioxidant properties. The in vitro antimicrobial effect was noticed towards several pathogens (Bacillus cereus > Staphylococcus aureus > Enterococcus faecalis > Salmonella typhimurium and Salmonella enteritidis > Escherichia coli), with a pronounced bactericidal activity. Rat intestinal epithelial cell viability was not affected by the selected concentrations of these two extracts. These data support the ethnomedicinal recommendations of these species and highlight them as valuable sources of bioactive compounds.

Efficacy of Bio-fertilizer and Chemical Fertilization on Flavonoids Distribution in Different Plant Parts of Stevia rebaudiana (Bertoni.)

This study aims to investigate the effect of the biological and chemical fertilizers on the content of the flavonoid compounds distributed within the different plant parts (leaves, stems, branches, and roots) of Stevia rebaudiana (Bertoni.) grown in Iraq. The results showed that the treatments of the biological fertilizers, including Mycorrhiza (C2) achieved the highest content of the most flavonoids in different parts of the plant. The treatment C2 recorded a rise of the flavonoid compounds Naringin, Naringenin and Luteolin 7-glucose in the leaves, Naringin, Rutin, and Acacetin7-neorutinoside in the stems and branches, and Apiening6-rhamnose8- glucose, Apigenin7-o neohespiroside, Kampferol3-7dirmmoside, Quercetrin, Narengenin, Acacetin7-neorutinoside, Kampferol, and Luteolin 7-glucose in the roots. On the other hand, treatment C1 recorded the highest content of Quercetin in the leaves, Quercetrin3-O glucose in the stems and branches, and Quercetrin3-O glucose, Naringenin, and Acacetin7-neorutinoside in the leaves . Keywords. Flavonoid, Stevia, Mycorrhiza and chemical Fertilization

A review of biologically active flavonoids as inducers of autophagy and apoptosis in neoplastic cells and as cytoprotective agents in non‐neoplastic cells

Phytochemicals are a diverse group of compounds found in various fruits, vegetables, nuts, and legumes. Many phytochemicals have been observed to possess health benefits. Some have been found to be chemoprotective or can act as chemotherapeutics by inducing autophagy, apoptosis, or otherwise regulating the cell cycle. Many also act as potent antioxidants. Flavonoids are a subclass of bioactive phytochemicals consisting of two phenolic benzene rings, joined together by a heterocyclic pyran or pyrone. It has been observed in multiple studies that there is a correlation between diets rich in flavonoids and a reduction in cancer levels, heart disease, neurodegenerative diseases, and other pathologies. As foods containing flavonoids are widely consumed, and their mechanisms of action are still only partially understood, this review was compiled to compare the effects and mechanisms of action of some of the most widely characterized and publicized flavonoids. The flavonoids silibinin, quercetin, isorhamnetin, luteolin, curcumin genkwanin, and acacetin, together with flavonoid extracts from papaw and Tephroseris kirilowii (Turcz) Holub, a member of the Daisy family, were found to be potent regulators of the cell cycle. The decision to overview these specific flavonoids was based on their therapeutic effects, and/or their potential effects. The sparsity of data comparing these flavonoids was also a key consideration. These flavonoids all modulated to some extent the pathways of autophagy and/or apoptosis and regulated the cell cycle, inflammation, and free radical levels. This explains why they are protective of healthy or moderately damaged cells, but toxic to neoplastic or pre-cancerous cells.

Natural flavonoid luteolin promotes the differentiation of porcine myoblasts through activation of PI3K/Akt/mTOR signaling

A key step in the manufacturing of cultured meat is to produce myotubes by induced myogenic differentiation. The development of effective, low-cost, and food-safe components that promote the in vitro differentiation of myoblasts is essential for the industrialization of cultured meat. Flavonoids are a class of plant secondary metabolites with various biological activities, but their effects on the regulation of myoblast behaviors are a lack of study. In this study, we selected four representative flavonoids including luteolin, chrysin, apigenin, and genistein, and investigated their effects on porcine myoblasts in the aspects of proliferation, migration, and differentiation. The results showed that four flavonoids all had relatively low cell toxicity but weak ability to promote the proliferation of porcine myoblasts. A positive effect of luteolin was observed in the migration and differentiation of porcine myoblasts, as indicated by improved migration rate and fusion index, as well as upregulated expression of Myogenin and MyHC. Pharmacological inhibition of PI3K activity attenuated the efficacy of luteolin on porcine myoblasts, and further analysis showed that luteolin increased the phosphorylation of PI3K, Akt, and mTOR, indicating the activation of the PI3K/Akt/mTOR signaling pathway. In conclusion, these findings showed that luteolin promoted the migration and differentiation of porcine myoblast via the activation of PI3K/Akt/mTOR signaling, providing biological evidence for its application in cultured meat production.

Anti-inflammatory Activity and Isolation of Luteolin from Plagiochasma appendiculatum Methanol Extract

Plagiochasma appendiculatum, a flavonoid rich liverwort, is reported to be used in the treatment of cuts, burns, outside wounds, bacteriostatic, pulmonary tuberculosis, neurasthenia, fractures, convulsions, scalds, uropathy, and inflammation by tribal communities. In the present study, flavonoid luteolin, reported to possess anti-inflammatory potential, is isolated from P. appendiculatum methanol extract and extract is evaluated for anti-inflammatory effect. Anti-inflammatory potential was studied by protein denaturation assay and carrageenan-induced rat paw edema method. Plant flavonoid is isolated from methanol extract by column chromatography, using petroleum ether and ethyl acetate in various proportion, as mobile phase. Further identified by spectroscopic analysis. In vitro studies, at a concentration of 800 μg/ml, P. appendiculatum methanolic extract (PAME) exhibited 74% inhibition while indomethacin showed 79% inhibition at the same concentration. The extract exhibits a decrease in inflammation in rat hind paw when tested with carrageenan-induced paw edema. PAME at a dose of 150 mg/kg displayed the most potent anti-inflammatory activity compared to the other groups during the course of the observation period. The methanol extract yielded a yellow color crystalline compound which is characterized as 2-(3,4-Dihydroxyphenyl)-5,7-dihydroxy-4-chromenone, commonly known as luteolin. Isolation of luteolin from P. appendiculatum is first time reported, which supports the ethnobotanical claims and provides scientific explanation for anti-inflammatory use of mentioned liverwort.

Luteolin mediated synthesis of rod-shaped rutile titanium dioxide nanoparticles: Assay of their biocompatibility

Titanium dioxide nanoparticles (TiO2NPs) were produced using a crud flavonoid luteolin (LT) by the green process. Physicochemical characterizations of LT mediated synthesis of TiO2NPs (LT-TiO2NPs) were analyzed by different techniques. The biocompatibility of LT-TiO2NPs was evaluated by assessing their cytotoxicity, inhibition of protein denaturation, hemolysis effects, and membrane stabilization activity. The synthesized LT-TiO2NPs exhibited mostly rod-shaped morphology, rutile crystalline structure with length about 33.3–135 nm and width in 16.6–58 nm. Under LT-TiO2NPs treatments, the cell viability of cancer cells was decreased in a dose-dependent manner. According to the results, the IC50 values of LT-TiO2NPs were between 12.5–25 μg/mL for A375 and MCF-7 cancer cells, and its value was below 50 μg/mL for skin fibroblast. These NPs also induced intracellular reactive oxygen species (ROS) generation and caused mitochondrial disruption in cancer cells, leading to the induction of intrinsic apoptosis. These biosynthesized NPs did not show denaturation of bovine serum albumin (BSA) protein and hemolytic or heat-induced hemolytic effects, which confirmed their membrane stabilization activity without damaging red blood cells (RBCs) membrane integrity. Therefore, this research provides valuable results in the case of green synthesis of LT-TiO2NPs and their specific properties, biocompatibility, and their potential to be used in biomedical fields.

Capsicum Leaves under Stress: Using Multi-Omics Analysis to Detect Abiotic Stress Network of Secondary Metabolism in Two Species.

The plant kingdom contains an enormous diversity of bioactive compounds which regulate plant growth and defends against biotic and abiotic stress. Some of these compounds, like flavonoids, have properties which are health supporting and relevant for industrial use. Many of these valuable compounds are synthesized in various pepper (Capsicum sp.) tissues. Further, a huge amount of biomass residual remains from pepper production after harvest, which provides an important opportunity to extract these metabolites and optimize the utilization of crops. Moreover, abiotic stresses induce the synthesis of such metabolites as a defense mechanism. Two different Capsicum species were therefore exposed to chilling temperature (24/18 ℃ vs. 18/12 ℃), to salinity (200 mM NaCl), or a combination thereof for 1, 7 and 14 days to investigate the effect of these stresses on the metabolome and transcriptome profiles of their leaves. Both profiles in both species responded to all stresses with an increase over time. All stresses resulted in repression of photosynthesis genes. Stress involving chilling temperature induced secondary metabolism whereas stresses involving salt repressed cell wall modification and solute transport. The metabolome analysis annotated putatively many health stimulating flavonoids (apigetrin, rutin, kaempferol, luteolin and quercetin) in the Capsicum biomass residuals, which were induced in response to salinity, chilling temperature or a combination thereof, and supported by related structural genes of the secondary metabolism in the network analysis.

Inhibition of influenza virus replication by Apiaceae plants, with special reference to Peucedanum japonicum (Sacna) constituents

Ethnopharmacological relevanceApiaceae plants possess various pharmacological properties, such as antimicrobial, antioxidant, hypoglycemic, hypolipidemic, anxiolytic, analgesic, anti-inflammatory, anti-convulsant, and anti-cancer activities; however, data on their antiviral activity are limited. Peucedanum japonicum, also known as Sacna, is a plant used as food and as a traditional folk medicine for treating coughs. However, the active components in the leaves of this plant are yet unexplored. Aim of the studyTo assess Apiaceae plants, especially Peucedanum japonicum, with anti-viral activity, and the function and antiviral potential of Sacna constituents, considering the emergence of influenza virus strains resistant to the currently available drugs. Materials and methodsWe prepared grinds of the freeze-dried leaves and roots of the Apiaceae family and the hot water extracts. The antiviral activities of the extracts were determined by focus formation reduction assay. In the time-of-addition assay, the test medium containing Sacna extract at 2 mg/mL was added at −1 to 0 h (adsorption) or from 0 to 4, 4 to 8, or 0 to 8 h (replication). The Sacna extract was separated by reversed-phase flash column chromatography using an Isolera Spektra system. The antiviral activity of each fraction was then determined using the focus formation reduction assay. The active fraction was analyzed using an LC20ADXR high performance liquid chromatography system equipped with a microTOF-QII quadrupole time-of-flight tandem mass spectrometer. ResultsAll examined extracts of Apiaceae plants showed anti-influenza activity. Sacna extract most strongly inhibited the replication of influenza viruses. Individual components of Sacna possess antiviral activities against the influenza A/PR/8/34 virus. Sacna was found to inhibit the multiplication of A (H1N1 and H3N2) types and B types of influenza viruses, including amantadine-resistant and oseltamivir-resistant viruses. Sacna also inhibited influenza infection during viral replication. However, Sacna did not inhibit influenza infection during cell adsorption and did not suppress hemagglutination inhibition or cell fusion. Further, our findings suggest that the antiviral compounds in Sacna include flavonoids (quercetin and luteolin) and other polyphenols (caffeic acid, hymecromone, and umbelliferone). Although several effective compounds in Sacna inhibit multiple steps of viral replication, caffeic acid, which was increased by heat treatment at the time of extraction, significantly inhibited only the late period of viral growth, similar to the Sacna extract, indicating that it is the major component responsible for the antiviral activity of Sacna. ConclusionsApiaceae plants possess antiviral activity. Caffeic acid is the major component responsible for the antiviral activity of Sacna. To our knowledge, this is the first report regarding the anti-influenza virus activity of Sacna. Overall, these results indicate that Sacna has potential as a novel treatment against influenza A and B viruses.

Production of Flavonoid 7-O-glucosides by Bioconversion Using Escherichia coli Expressing a 7-O-glucosyltransferase from Tobacco (Nicotiana tabacum).

Flavonoid 7-O-glucosides exhibit various biological activities; however, some are not abundant in nature. Therefore, a method to produce flavonoid 7-O-glucosides was investigated. Escherichia coli expressing tobacco-derived glucosyltransferase (Ec-NtGT2) converted several flavonoids (apigenin, luteolin, quercetin, kaempferol, and naringenin) to their 7-O-glucosides with conversion rates of 67-98%. In scaled-up production, Ec-NtGT2 yielded 24mg/L of apigenin 7-O-glucoside, 41mg/L of luteolin 7-O-glucoside, 118mg/L of quercetin 7-O-glucoside, 40mg/L of kaempferol 7-O-glucoside, and 75mg/L of naringenin 7-O-glucoside through sequential administration of substrates in 4-9h. The conversion rates of apigenin, luteolin, quercetin, kaempferol, and naringenin were 97%, 72%, 77%, 98%, and 96%, respectively. These results indicated that Ec-NtGT2 is a simple and efficient bioconversion system for the production of flavonoid 7-O-glucosides.

Melissa officinalis: Composition, Pharmacological Effects and Derived Release Systems-A Review.

Melissa officinalis is a medicinal plant rich in biologically active compounds which is used worldwide for its therapeutic effects. Chemical studies on its composition have shown that it contains mainly flavonoids, terpenoids, phenolic acids, tannins, and essential oil. The main active constituents of Melissa officinalis are volatile compounds (geranial, neral, citronellal and geraniol), triterpenes (ursolic acid and oleanolic acid), phenolic acids (rosmarinic acid, caffeic acid and chlorogenic acid), and flavonoids (quercetin, rhamnocitrin, and luteolin). According to the biological studies, the essential oil and extracts of Melissa officinalis have active compounds that determine many pharmacological effects with potential medical uses. A new field of research has led to the development of controlled release systems with active substances from plants. Therefore, the essential oil or extract of Melissa officinalis has become a major target to be incorporated into various controlled release systems which allow a sustained delivery.

Pharmacological, biological and phytochemical aspects of Thymus munbyanus Boiss. & Reut.: A review

Thymus munbyanus Boiss. & Reut., is a small shrub endemic to Morocco and Algeria, and it is commonly used to treat several diseases, including digestive, circulatory, genital, skin, urinary, nervous and respiratory diseases. The extracts of this thyme are rich in a wide variety of phenolic compounds such as polyphenols and volatile phenols and exhibit numerous biological activities. The present review summarizes the literature investigations reported on Thymus munbyanus concerning various pharmacological and biological properties as well as phytochemical aspects. This species revealed a richness in phenolic compounds in its volatile oils, including thymol and carvacrol, as well as in its non-volatile extracts including phenolic acids phenolic acids (rosmarinic acid, caffeic acid, salvianolic acid, ferulic acid, etc.), flavonoids (luteolin, gallocatechin, quercetin, isorhamnetin, etc.). Moreover, powerful antioxidant and antimicrobial properties were reported for this Thymus species, which are attributed to its richness in bioactive antioxidants. Furthermore, this thyme was found to possess important nephroprotective, hepatoprotective, and tumor cytotoxic properties. In conclusion, Thymus munbyanus is an important natural source of bioactive phenolic compounds that can be used for developing alternative natural drugs for the treatment and prevention of several pathologies.