Potential application of green extracts rich in phenolics for innovative functional foods: natural deep eutectic solvents as media for isolation of biocompounds from berries.

The health-promoting effects of berries have attracted attention due to the possible application of their extracts as functional ingredients in food products. Natural deep eutectic solvents (NADESs) are a new generation of environmentally friendly solvents for the extraction of natural products, and they are green alternatives to organic solvents, and they can improve the solubility, stability, and bioavailability of isolated biocompounds. In this study, an efficient eco-friendly method was used for the extraction of phenolic compounds from different berries: chokeberries, blueberries, and black goji berries with a range of eutectic solvents consisting of hydrogen bond acceptors (HBAs) such as choline chloride, L-proline, L-glycine, and L-lysine and hydrogen bond donors (HBDs) such as malic, citric, tartaric, lactic and succinic acids, glucose and glycerol. The obtained results indicated the ability of NADESs towards selective extraction of phenolics; the eutectic system choline chloride : malic acid showed selective extraction of anthocyanins, while choline chloride : glycerol and choline chloride : urea showed selectivity towards flavonoids and phenolic acids. The methodology for screening of the NADES extraction performance, which included chromatographic profiling via high-performance thin layer chromatography combined with chemometrics and spectrophotometric essays, allowed effective assessment of optimal eutectic solvents for isolation of different groups of phenolics. Great antioxidant and antimicrobial activities of extracts, along with the green nature of eutectic solvents, enable NADES berry extracts to be used as "green-labelled" functional foods or ingredients.

Phytoalexins of the crucifer Barbarea vulgaris: Structural profile and correlation with glucosinolate turnover.

Phytoalexins are antimicrobial plant metabolites elicited by microbial attack or abiotic stress. We investigated phytoalexin profiles after foliar abiotic elicitation in the crucifer Barbarea vulgaris and interactions with the glucosinolate-myrosinase system. The treatment for abiotic elicitation was a foliar spray with CuCl2 solution, a usual eliciting agent, and three independent experiments were carried out. Two genotypes of B. vulgaris (G-type and P-type) accumulated the same three major phytoalexins in rosette leaves after treatment: phenyl-containing nasturlexin D and indole-containing cyclonasturlexin and cyclobrassinin. Phytoalexin levels were investigated daily by UHPLC-QToF MS and tended to differ among plant types and individual phytoalexins. In roots, phytoalexins were low or not detected. In treated leaves, typical total phytoalexin levels were in the range 1-10 nmol/g fresh wt. during three days after treatment while typical total glucosinolate (GSL) levels were three orders of magnitude higher. Levels of some minor GSLs responded to the treatment: phenethylGSL (PE) and 4-substituted indole GSLs. Levels of PE, a suggested nasturlexin D precursor, were lower in treated plants than controls. Another suggested precursor GSL, 3-hydroxyPE, was not detected, suggesting PE hydrolysis to be a key biosynthetic step. Levels of 4-substituted indole GSLs differed markedly between treated and control plants in most experiments, but not in a consistent way. The dominant GSLs, glucobarbarins, are not believed to be phytoalexin precursors. We observed statistically significant linear correlations between total major phytoalexins and the glucobarbarin products barbarin and resedine, suggesting that GSL turnover for phytoalexin biosynthesis was unspecific. In contrast, we did not find correlations between total major phytoalexins and raphanusamic acid or total glucobarbarins and barbarin. In conclusion, two groups of phytoalexins were detected in B. vulgaris, apparently derived from the GSLs PE and indol-3-ylmethylGSL. Phytoalexin biosynthesis was accompanied by depletion of the precursor PE and by turnover of major non-precursor GSLs to resedine. This work paves the way for identifying and characterizing genes and enzymes in the biosyntheses of phytoalexins and resedine.

Jusanin, a New Flavonoid from Artemisia commutata with an In Silico Inhibitory Potential against the SARS-CoV-2 Main Protease.

A new flavonoid, Jusanin, (1) has been isolated from the aerial parts of Artemisia commutata. The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone. Being new in nature, the inhibition potential of 1 has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of eight different SARS-CoV-2 essential proteins. The studies indicated the similarity between 1 and X77, the co-crystallized ligand SARS-CoV-2 main protease (PDB ID: 6W63). To confirm the obtained results, a DFT study was carried out and indicated the similarity of (total energy, HOMO, LUMO, gap energy, and dipole moment) between 1 and X77. Accordingly, molecular docking studies of 1 against the target enzyme have been achieved and showed that 1 bonded correctly in the protein's active site with a binding energy of -19.54 Kcal/mol. Additionally, in silico ADMET in addition to the toxicity evaluation of Jusanin against seven models have been preceded and indicated the general safety and the likeness of Jusanin to be a drug. Finally, molecular dynamics simulation studies were applied to investigate the dynamic behavior of the Mpro-Jusanin complex and confirmed the correct binding at 100 ns. In addition to 1, three other metabolites have been isolated and identified to be сapillartemisin A (2), methyl-3-[S-hydroxyprenyl]-cumarate (3), and ß-sitosterol (4).

Potential active constituents responsible for treating acute pharyngitis in the flowers of Hosta plantaginea (Lam.) Aschers and their pharmacokinetics.

In Asia, the flower of Hosta plantaginea (Lam.) Aschers (hosta flower) is both an edible food and medicine. The hosta flower is often used as a material for cooking porridge and scented tea and in combination with other plants for alleviating pharyngitis. To clarify the anti-pharyngitis effect of the hosta flower and evaluate its potential active ingredients, an ethanol extract of the hosta flower was prepared and partially purified via chromatography on a column packed with D101 macroporous resin, which was eluted with different concentrations of ethanol. The anti-pharyngitis effect of the crude extract and the various partially purified fractions was examined in an ammonia-induced acute pharyngitis rat model. The 30% ethanol-eluted fraction significantly alleviated the severity of pharyngitis in the rat, as evaluated by changes in the levels of cytokines (IL-1ß, IL-6, and TNF-α) and histological changes in the pharynx tissues. Subsequent HPLC-QTOF/MS (high-performance liquid chromatography coupled with quadrupole-time of flight tandem mass spectrometry) analysis of this fraction revealed kaempferol and its glycosides as the main components. Three of the main components were isolated and identified by 1D NMR. Their pharmacokinetics were studied for the first time by UHPLC-QQQ/MS (ultrahigh-performance liquid chromatography coupled with mass spectrometry). The findings suggested that the 30% ethanol-eluted fraction of the hosta flower extract may be a potential functional food for treating pharyngitis.

Heartwood of Dalbergia cochinchinensis: 4,7,2'-Trihydroxy-4'-methoxyisoflavanol and 6,4'-Dihydroxy-7-methoxyflavane Reduce Cytokine and Chemokine Expression In Vitro.

Dalbergia cochinchinensis has been widely used in traditional medicine because of its flavonoids; however, the impact of the flavonoids to modulate the inflammatory response to oral cells remains to be described. For this aim, we isolated 4,7,2'-trihydroxy-4'-methoxyisoflavanol (472T4MIF) and 6,4'-dihydroxy-7-methoxyflavane (64D7MF) from the heartwood of D. cochinchinensis and confirmed the chemical structure by nuclear magnetic resonance. We show here that both flavonoids are inhibitors of an inflammatory response of murine RAW 264.7 inflammatory macrophages stimulated by LPS. This is indicated by interleukin (IL)1, IL6, and chemokine CCL2 production besides the phosphorylation of p65. Consistently, in primary murine macrophages, both flavonoids decreased the inflammatory response by lowering LPS-induced IL1 and IL6 expression. To introduce oral cells, we have used human gingival fibroblasts and provoked the inflammatory response by exposing them to IL1ß and TNFα. Under these conditions, 472T4MIF, but not 64D7MF, reduced the expression of chemokines CXCL1 and CXCL2. Taken together, we identified two flavonoids that can reduce the expression of cytokines and chemokines in macrophages and fibroblastic cells.

Isolation, Characterization and In Silico Studies of Secondary Metabolites from the Whole Plant of Polygala inexpectata Pesmen & Erik.

Polygala species are frequently used worldwide in the treatment of various diseases, such as inflammatory and autoimmune disorders as well as metabolic and neurodegenerative diseases, due to the large number of secondary metabolites they contain. The present study was performed on Polygala inexpectata, which is a narrow endemic species for the flora of Turkey, and resulted in the isolation of nine known compounds, 6,3'-disinapoyl-sucrose (1), 6-O-sinapoyl,3'-O-trimethoxy-cinnamoyl-sucrose (tenuifoliside C) (2), 3'-O-(O-methyl-feruloyl)-sucrose (3), 3'-O-(sinapoyl)-sucrose (4), 3'-O-trimethoxy-cinnamoyl-sucrose (glomeratose) (5), 3'-O-feruloyl-sucrose (sibiricose A5) (6), sinapyl alcohol 4-O-glucoside (syringin or eleutheroside B) (7), liriodendrin (8), and 7,4'-di-O-methylquercetin-3-O-ß-rutinoside (ombuin 3-O-rutinoside or ombuoside) (9). The structures of the compounds were determined by the spectroscopic methods including 1D-NMR (1H NMR, 13C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC), and HRMS. The isolated compounds were shown in an in silico setting to be accommodated well within the inhibitor-binding pockets of myeloperoxidase and inducible nitric oxide synthase and anchored mainly through hydrogen-bonding interactions and π-effects. It is therefore plausible to suggest that the previously established anti-inflammatory properties of some Polygala-derived phytochemicals may be due, in part, to the modulation of pro-inflammatory enzyme activities.

Extraction and Study of Hypoglycemic Constituents from Myrica rubra Pomace.

Myrica rubra pomace accounts for 20% of the fruit's weight that is not utilized when it is juiced. The pomace contains bioactive phenolic substances such as anthocyanins and flavonoids. To improve the utilization value of Myrica rubra pomace, an optimized extraction method for the residual polyphenols was developed using response surface methodology (RSM). The resulting extract was analyzed by high performance liquid chromatography (HPLC), and the in vitro hypoglycemic activity and antioxidant activity of the polyphenolic compounds obtained were also investigated. The optimum extraction conditions (yielding 24.37 mg·g-1 total polyphenols content) were: extraction temperature 60 °C, ultrasonic power 270 W, ethanol concentration 53%, extraction time 57 min, and solid to liquid ratio 1:34. Four polyphenolic compounds were identified in the pomace extract by HPLC: myricitrin, cyanidin-O-glucoside, hyperoside, and quercitrin. DPPH and hydroxyl radical scavenging tests showed that the Myrica rubra polyphenols extract had strong antioxidant abilities. It is evident that the residual polyphenols present in Myrica rubra pomace have strong hypoglycemic activity and the juiced fruits can be further exploited for medicinal purposes.

A Green Method of Extracting and Recovering Flavonoids from Acanthopanax senticosus Using Deep Eutectic Solvents.

In recent years, green extraction of bioactive compounds from herbal medicines has generated widespread interest. Deep eutectic solvents (DES) have widely replaced traditional organic solvents in the extraction process. In this study, the efficiencies of eight DESs in extracting flavonoids from Acanthopanax senticosus (AS) were compared. Response surface methodology (RSM) was employed to optimize the independent variable including ultrasonic power, water content, solid-liquid ratio, extraction temperature, and extraction time. DES composed of glycerol and levulinic acid (1:1) was chosen as the most suitable extraction medium. Optimal conditions were ultrasonic power of 500 W, water content of 28%, solid-liquid ratio of 1:18 g·mL-1, extraction temperature of 55 °C, and extraction time of 73 min. The extraction yield of total flavonoids reached 23.928 ± 0.071 mg·g-1, which was 40.7% higher compared with ultrasonic-assisted ethanol extraction. Macroporous resin (D-101, HPD-600, S-8 and AB-8) was used to recover flavonoids from extracts. The AB-8 resin showed higher adsorption/desorption performance, with a recovery rate of total flavonoids of up to 71.56 ± 0.256%. In addition, DES solvent could efficiently be reused twice. In summary, ultrasonic-assisted DES combined with the macroporous resin enrichment method is exceptionally effective in recovering flavonoids from AS, and provides a promising environmentally friendly and recyclable strategy for flavonoid extraction from natural plant sources.

Validation of a High-Performance Liquid Chromatography with Photodiode Array Detection Method for the Separation and Quantification of Antioxidant and Skin Anti-Aging Flavonoids from Nelumbo nucifera Gaertn. Stamen Extract.

Nelumbo nucifera Gaertn., or the so-called sacred lotus, is a useful aquatic plant in the Nelumbonaceae family that has long been used to prepare teas, traditional medicines as well as foods. Many studies reported on the phytochemicals and biological activities of its leaves and seeds. However, to date, only few studies were conducted on its stamen, which is the most important ingredient for herbal medicines, teas and other phytopharmaceutical products. Thus, this present study focuses on the following: (1) the application of high-performance liquid chromatography with photodiode array detection for a validated separation and quantification of flavonoids from stamen; (2) the Nelumbo nucifera stamen's in vitro and in cellulo antioxidant activities; as well as (3) its potential regarding the inhibition of skin aging enzymes for cosmetic applications. The optimal separation of the main flavonoids from the stamen ethanolic extract was effectively achieved using a core-shell column. The results indicated that stamen ethanolic extract has higher concentration of in vitro and in cellulo antioxidant flavonoids than other floral components. Stamen ethanolic extract showed the highest protective effect against reactive oxygen/nitrogen species formation, as confirmed by cellular antioxidant assay using a yeast model. The evaluation of potential skin anti-aging action showed that the stamen extract has higher potential to inhibit tyrosinase and collagenase compared with its whole flower. These current findings are the first report to suggest the possibility to employ N. nucifera stamen ethanolic extract as a tyrosinase and collagenase inhibitor in cosmetic applications, as well as the utility of the current separation method.

Identification of galangin as the bioactive compound from Alpinia calcarata (Haw.) Roscoe rhizomes to inhibit IRAK-1/ MAPK/ NF-κB p65 and JAK-1 signaling in LPS stimulated RAW 264.7 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia calcarata (Haw.) Roscoe rhizomes are used to treat diabetes, rheumatism, gastrointestinal problems, inflammatory diseases, cough and respiratory problems in traditional practices. The primary objective of the study is to identify and isolate anti-inflammatory bioactive compounds from A.calcarata rhizomes and to assess its molecular mechanism. MATERIALS AND METHODS: The bioassay-guided fractionation of methanolic extract of A. calcarata rhizomes yielded chloroform fraction as the effective fraction and galangin as the bioactive compound identified by NMR studies. The anti-inflammatory action of galangin was evaluated by determining NO and cytokine production in LPS stimulated RAW264.7 cells. Further, its mechanism was studied on the expression levels of mRNA and protein targets by qPCR and Western blot analysis. RESULTS: Based on the MTT assay, the concentration of 3.1-25 µM of galangin was selected for further studies. Galangin reduced the levels of NO and proinflammatory cytokines (TNF-α, IL-1ß and IL-6) production in LPS induced RAW 264.7 cells in a dose-dependent manner. In addition, the qPCR analysis revealed a reduction in the mRNA expression levels of COX-2, IRAK 1 and JAK 1 in galangin treated LPS stimulated RAW 264.7 cells in a dose-dependent manner. Western blot analysis implicated that galangin has markedly reduced the protein expression levels of cell signaling regulators (JAK-1, IRAK-1, MyD88, MAPK (p38 and ERK) and NF-κB p65). CONCLUSION: From the results, it is evident that the inhibition of these cell signaling regulators has contributed to the anti-inflammatory effects of galangin. To our knowledge, we are the first to report IRAK-1 and JAK-1 as therapeutic targets of galangin for its anti-inflammatory effect.

In vitro and in vivo antidiabetic activity, isolation of flavonoids, and in silico molecular docking of stem extract of Merremia tridentata (L.).

The antidiabetic activity of stem-ethanol extract (SE) and the flavonoid-rich fraction (FF) of Merremia tridentata (L.) were investigated on alloxan-induced diabetic mice. Apigenin, cosmosiin, and quercitrin are flavonoids isolated for the first time from stem extracts. In addition, cynaroside was found to be at the highest level in SE and FF with a percentage of 4.375% and 58.430%, respectively. The administration of SE (100 mg/kg) and FF (50, 75 mg/kg) daily for 20 days resulted in a better hypoglycemic effect than the reference drugs, glibenclamide (5 mg/kg), and metformin (10 mg/kg). Furthermore, SE and FF were shown to significantly improve the plasma lipid profiles at the end of the study. Docking's study suggests that cynaroside, cosmosiin, and quercitrin are the most desirable compounds for hypoglycemic effects in many antidiabetic targets. Especially, SE and FF showed strongly α-amylase and α-glucosidase inhibitory activities (IC50 = 1.61-1.72 mg/mL on α-amylase and IC50 = 0.24-0.44 mg/mL on α-glucosidase). Therefore, SE and FF of Merremia tridentata is a potential drug with antidiabetic and hypoglycemic action as indicated by in vivo, in silico, and in vitro studies.

The chemical composition of different leaf extracts of Lantana fucata Lindl. influences its cytotoxic potential: A study using the Allium cepa model.

ETHNOPHARMACOLOGICAL RELEVANCE: One of the most popular plants used to treat diseases in Brazil is Lantana fucata. Like most herbal medicines, its consumption is based on popular knowledge, which, despite being considered effective, may cause side effects. AIM OF THE STUDY: Since the scientific data on the pharmacological properties of L. fucata are still incipient, this research aimed to evaluate the cytotoxic and genotoxic potential of different types of extracts (infusion, aqueous and hydroalcoholic), characterizing them chemically. MATERIALS AND METHODS: The cytotoxicity assay was performed by the A. cepa model. The cytotoxicity parameters studied were number of dividing cells and percentage mitotic index (%MI). RESULTS: The result of the A. cepa assay showed that there was a decrease in the number of dividing cells and the percentage mitotic index as concentrations increased, for all extracts, indicating cytotoxicity. However, the hydroalcoholic extract was the most cytotoxic. Chromatography analysis allowed the characterization of secondary metabolites in the extracts, which were very similar. However, a greater abundance of flavonoids and triterpenoids was observed in the hydroalcoholic extract, suggesting that these compounds are responsible for its greater toxicity. CONCLUSIONS: Since the highest doses of extracts showed to have a cytotoxic effect, it is suggested that the ingestion of this species occurs in a moderate way.

Saponins and flavonoids from Bacopa floribunda plant extract exhibit antioxidant and anti-inflammatory effects on amyloid beta 1-42-induced Alzheimer's disease in BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa floribunda (BF), a locally available plant has been employed traditionally as memory enhancer in Southwestern, Nigeria. It has been utilized in traditional and Ayurvedic medicine as brain tonic for enhancing memory, anti-aging and forestalling series of psychological disorders. However, there is a dearth of scientific information on the mechanism(s) of action of important phytochemicals from BF extract on dementia. AIM OF THE STUDY: Alzheimer's disease, the commonest form of dementia has been postulated to triple by 2050 as a result of increase in life expectancy. This study therefore assessed and compared the possible mechanism(s) of action of flavonoids and saponins from BF on Amyloid beta (Aß1-42)-induced dementia in male BALB/c mice. MATERIALS AND METHODS: Eighty (80) healthy BALB/c mice divided into 10 groups (n = 8) were given a single bilateral ICV injection of Aß1-42 or normal saline. Graded doses of Saponins and flavonoids (50, 100 and 200 mg/kg) were used as treatment for 21 days. Hippocampal homogenates were assayed for the levels of antioxidants, oxidative stress and neuroinflammatory markers. In vitro antioxidant activity of flavonoids and saponins were equally assessed using standard procedures. The extent of microglial activation was quantified through immunohistochemistry procedure. RESULTS: Aß1-42 successfully caused a spike in hippocampal levels of MDA, IL1ß, TNF-α including MPO levels and invariably decreased antioxidant activities. Likewise an increase in reactive microglia (microgliosis) was observed. However, crude saponins and flavonoids from BF were able to suppress microgliosis, oxidative stress and neuroinflammation induced by Aß1- 42 and were observed to be more effective at higher doses of saponins (100 mg/kg and 200 mg/kg) and flavonoid (100 mg/kg). CONCLUSIONS: Phytochemicals from BF efficiently exhibited dose dependent alleviation of some symptoms associated with Alzheimer's disease.

Total extract of Anemarrhenae Rhizoma attenuates bleomycin-induced pulmonary fibrosis in rats.

Pulmonary fibrosis is a progressive interstitial lung disease with poor prognosis. Anemarrhenae Rhizoma is a traditional Chinese herbal medicine and has been applied in clinical practice for a long history. Recently, components of Anemarrhenae Rhizoma were reported to possess anti-inflammatory and immunomodulatory features; however, the effect of them on pulmonary fibrosis remains unknown. In this study, we explored the therapeutic effect of total extract of Anemarrhenae Rhizoma (TEAR) on bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis rat model was established by a single intratracheal instillation of bleomycin, three doses of TEAR were intragastrically administered for consecutive 28 days. Subsequent to sacrificing of rats, pulmonary fibrosis was observed in rats treated with bleomycin, but administration of TEAR attenuated lung fibrosis, as evidenced by the improved lung histopathological damage and decreased weight loss and lung index. Moreover, TEAR treatment inhibited the inflammatory response in lung fibrosis, which was shown by the reduced nitrogen oxide level and myeloperoxidase activity. Furthermore, TEAR modulated the redox balance in lung tissue by alleviated lipid peroxidation and enhanced enzymatic antioxidants activity. Meanwhile, TEAR protected the rats from fibrosis in a dose-dependent manner, and the anti-fibrotic activity of TEAR may be related to the modulation of TGF-ß1/Smad signaling pathway. Collectively, TEAR alleviates bleomycin-induced pulmonary fibrosis, indicating perspectives for development of a potential agent for lung fibrosis therapy.

Extraction, purification, structural character and biological properties of propolis flavonoids: A review.

Propolis is an aromatic substance which is collected by bees and mixed with bee saliva. The plant sources of propolis are mainly consisted with plant exudates from bark, buds and etc. Flavonoids are secondary metabolites widely found in natural plants, which have a variety of health care functions and are the main active ingredients of propolis. This article summarized the types, active ingredients, pharmacological effects, extraction methods and applications of propolis flavonoids, the aim was to provide the theoretical basis for further research and development of propolis flavonoids.

Hypoglycemic and hypolipidemic dual activities of extracts and flavonoids from Desmodium caudatum and an efficient synthesis of the most potent 8-prenylquercetin.

Since glucolipid metabolism disorders is often the mono-target therapy fails in managing blood glucose and lipid levels and the other complications, it is urgent and necessary to seek for the new potential drugs or functional food acting on multi-targets. The hypoglycemic and hypolipidemic dual activities of the root, stems and leaves of Desmodium caudatum, which is used for traditional Chinese medicine, was evaluated. Twelve extracts with different extraction conditions were prepared and extract 9 was find to exhibit potential inhibitory activities of fructose-1, 6-bisphosphatase (FBPase), α-glucosidase, and pancrelipase, as well as promote cellular glucose consumption and reduce cellular content of lipid. Five flavonoids were isolated and identified from extract 9, among which 8-prenylquercetin exhibited potent α-glucosidase (IC50 = 4.38 µM) and FBPase (IC50 = 3.62 µM) dual inhibitory activity, which were 75-fold higher than acarbose (IC50 = 330.10 µM) and comparable with AMP (IC50 = 2.92 µM). In addition, 8-prenylquercetin was able to promote glucose consumption and reduce lipid content. Besides, an efficient synthesis of the most potent 8-prenylquercetin was developed from inexpensive and commercially available rutin in 21% overall yield by 6 steps, which lay the foundation of preparation sufficient amount for follow-up study.

Optimization of extraction and bioactivity detection of celery leaf flavonoids using BP neural network combined with genetic algorithm and response.

In the present study, ultrasound-assisted extraction was employed to extract the general flavone from celery leaves using response surface methodology and BP neural network model with a genetic algorithm (GA). The effects of temperature, time, solid-liquid ratio, and ethanol concentration on the extraction results were assessed by Box-Behnken design. Further optimization of the process was performed by GA-BP. Our results showed that the optimal conditions were an ethanol concentration of 70.31%, a temperature of 67.2 °C and an extraction time of 26.6 min. In addition, significant antioxidant activity and in vitro bacteriostasis were observed. We found that the total flavonoids of the celery leaves exerted a strong inhibitory effect on Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. Additionally, considerable DPPH· and ·OH scavenging effects were exerted by flavonoids. Therefore, flavonoids from celery leaves can be considered natural antioxidants and bacterial inhibitors.

Disclosing targets and pharmacological mechanisms of total bioflavonoids extracted from Selaginella doederleinii against non-small cell lung cancer by combination of network pharmacology and proteomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Previously, the total bioflavonoids extract from Selaginella doederleinii (SDTBE) presented favorable in vitro and in vivo activities against non-small cell lung cancer (NSCLC), hinting at its medicinal potential. However, up to nowadays, targets and integrative action mechanisms of SDTBE are still not very clear, which presents an obstacle to the development of herbal medicine. AIM OF THE STUDY: The present study aimed to disclose the potential targets and integrative action mechanism of SDTBE against NSCLC. MATERIALS AND METHODS: A system pharmacology-based strategy including target fishing, network pharmacology analysis and molecular docking were applied to predict the potential targets and pathways for the seven main active ingredients in SDTBE. A proteomics study was subsequently performed for validating the affected pathways and possible targets. Western blot assay, mouse xenograft tumor model and immunofluorescence assays were used to further confirm the key targets and integrative action mechanisms of SDTBE against NSCLC. RESULTS: By system pharmacology, it was inferred that SDTBE could mainly act on mitogen-activated protein kinase (MAPK) and PI3K-AKT signaling pathways by targeting epidermal growth factor receptor (EGFR), protein kinase B (AKT) and mitogen-activated or extracellular signal-regulated protein kinase (MEK), which was validated by proteomics results, and further confirmed in vitro and in vivo by Western blot and immunofluorescence assays. CONCLUSION: SDTBE targeting multi-targets including EGFR, AKT and MEK could exert its anti-NSCLC effect mainly via MAPK and PI3K-AKT signaling pathways.

Anti-α-glucosidase and anti-oxidative isoflavonoids from the immature fruits of Maclura tricuspidata.

The composition of a plant, together with its efficacy, vary depending on its maturity and plant parts. In this study, the chemical constituents of immature fruits of Maclura tricuspidata (Moraceae) were investigated together with their anti-diabetic and antioxidant effects. A total of 34 compounds were isolated from the immature fruits of M. tricuspidata using various chromatographic methods. Structure elucidation using extensive spectroscopic analysis led to the characterization of isolated compounds as isoflavonoids with prenyl substituents. Among them, macluraisoflavones A-O were first isolated from nature. The anti-diabetic and antioxidant activity of the isolated compounds were also suggested by α-glucosidase inhibitory activity and DPPH radical scavenging activity, respectively. In particular, macluraisoflavone I, an isoflavonoid with 2,2-dimethylpyran and 2-hydroperoxy-3-methylbut-3-enyl moieties, showed potent α-glucosidase inhibitory activity and DPPH radical scavenging activity. Further molecular docking analysis suggested hydrogen bond and alkyl interactions between α-glucosidase and macluraisoflavone I. Therefore, the immature fruits of M. tricuspidata can be used as an important natural product with antioxidant and anti-diabetic properties.

Natural products isolation studies of the paleoendemic plant species Nothofagus gunnii and Nothofagus cunninghamii.

The first natural product isolation studies of Nothofagus gunnii (Hook.f.) Oerst and Nothofagus cunninghamii (Hook.f.) Oerst have been undertaken. A previously unreported stilbene derivative, pinosylvin monoacetate, was isolated from the leaves of N. gunnii, in addition to 14 known compounds; including the flavonoids galangin, pinobanksin, catechin and quercetin; sesquiterpenoids such as, ilicol and (+)-ß-costol acetate; 2,4-dihydroxy-6-methoxychalcone and pinosylvin. Four known flavonoid natural products, catechin, quercetin, ayanin, and avicularin were isolated from the leaves of N. cunninghamii. This study reveals that N. gunnii is a rich source of flavonoid, chalcone and stilbene compounds, while primarily hydroxyflavonoid compounds are found in N. cunninghamii. The isolated phytochemicals are consistent with the evolutionary relationships suggested to exist among Nothofagus species.