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Ethanolic extracts of samples of temperate zone propolis, four from the UK and one from Poland, were tested against three Trypanosoma brucei strains and displayed EC50 values &lt, 20 µg/mL. The extracts were fractionated, from which 12 compounds and one two-component mixture were isolated, and characterized by NMR and high-resolution mass spectrometry, as 3-acetoxypinobanksin, tectochrysin, kaempferol, pinocembrin, 4′-methoxykaempferol, galangin, chrysin, apigenin, pinostrobin, cinnamic acid, coumaric acid, cinnamyl ester/coumaric acid benzyl ester (mixture), 4′,7-dimethoxykaempferol, and naringenin 4′,7-dimethyl ether. The isolated compounds were tested against drug-sensitive and drug-resistant strains of T. brucei and Leishmania mexicana, with the highest activities ≤ 15 µM. The most active compounds against T. brucei were naringenin 4′,7 dimethyl ether and 4′methoxy kaempferol with activity of 15–20 µM against the three T. brucei strains. The most active compounds against L. mexicana were 4′,7-dimethoxykaempferol and the coumaric acid ester mixture, with EC50 values of 12.9 ± 3.7 µM and 13.1 ± 1.0 µM. No loss of activity was found with the diamidine- and arsenical-resistant or phenanthridine-resistant T. brucei strains, or the miltefosine-resistant L. mexicana strain, no clear structure activity relationship was observed for the isolated compounds. Temperate propolis yields multiple compounds with anti-kinetoplastid activity.

Natural deep eutectic solvent (NADES) has received increasing interest as a green alternative to traditional organic solvents for efficient extraction of bioactive compounds from natural sources. In this study, phytochemicals in Carya cathayensis Sarg. peels extracted with Choline chloride-Malic acid (ChCl-MA) were identified using UPLC-Triple-TOF/MS. Effect of NADES on phenolic composition, antioxidant properties and inhibition of α-glucosidase and α-amylase were evaluated. Furthermore, extraction mechanism caused by different solvents were investigated by quantum chemical calculation combined with molecular dynamic simulation. A total of 29 phytochemicals were identified, and catechin, procyanidin B1, 2,3-dihydroxybenzoic acid, pinocembrin, procyanidin B3, myricetrin were the most abundant compounds. The extract using ChCl-MA exhibited the highest phenolic compounds content, antioxidant capacity, and α-glucosidase and α-amylase inhibition activities. Larger solvent accessible surface area, more hydrogen bonds between ChCl-MA and extract, longer lifetime of the hydrogen bonds, and lower intermolecular interaction energy account for higher extraction efficiency of ChCl-MA.

Background Oxidative stress is an important factor involved in the progress of heart failure. The current study was performed to investigate whether pinocembrin was able to ameliorate post-infarct heart failure (PIHF) and the underlying mechanisms. Methods Rats were carried out left anterior descending artery ligation to induce myocardial infarction and subsequently raised for 6 weeks to produce chronic heart failure. Then pinocembrin was administrated every other day for 2 weeks. The effects were evaluated by echocardiography, western blot, Masson’s staining, biochemical examinations, immunohistochemistry, and fluorescence. In vitro we also cultured H9c2 cardiomyocytes and cardiac myofibroblasts to further testify the mechanisms. Results We found that PIHF-induced deteriorations of cardiac functions were significantly ameliorated by administrating pinocembrin. In addition, the pinocembrin treatment also attenuated collagen deposition and augmented vascular endothelial growth factor receptor 2 in infarct border zone along with an attenuated apoptosis, which were related to an amelioration of oxidative stress evidenced by reduction of reactive oxygen species (ROS) in heart tissue and malondialdehyde (MDA) in serum, and increase of superoxide dismutase (SOD). This were accompanied by upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway. In vitro experiments we found that specific Nrf2 inhibitor significantly reversed the effects resulted from pinocembrin including antioxidant, anti-apoptosis, anti-fibrosis and neovascularization, which further indicated the amelioration of PIHF by pinocembrin was in a Nrf2/HO-1 pathway-dependent manner. Conclusion Pinocembrin ameliorated cardiac functions and remodeling resulted from PIHF by ROS scavenging and Nrf2/HO-1 pathway activation which further attenuated collagen fibers deposition and apoptosis, and facilitated angiogenesis.

The use of sunscreens in our daily lives to reduce UV exposure on our skin is a good measure against photoaging. However, the current active ingredients in the market are not able to cover the entire spectrum range of UVA and UVB. Therefore, broader spectrum compounds are constantly being searched by cosmetic companies to replace the commercially available UV filters. In this study, an experimental model utilizing the MATLAB software was developed to measure a compound’s critical wavelength (λc). The purpose of this research was to ease the cost and speed up the screening of bioactive compounds for photoprotective properties while maintaining accuracy in the process. In this paper, the measurement of caffeic acid, gallic acid, and pinocembrin’s critical wavelength in the MATLAB software was explained in a step-by-step guide. This was done to create an understandable and executable procedure for future researchers to utilize. Subsequently, from the results, the critical wavelength of caffeic acid, gallic acid, and pinocembrin was 378.2nm, 324.6nm, and 364.8nm, respectively. This shows that caffeic acid has the broadest absorbance spectrum, followed by pinocembrin, and finally gallic acid. Thus, it may be possible that caffeic acid might have stronger photoprotective abilities as compared to pinocembrin and gallic acid, based on its critical wavelength.

Chlorpyrifos (CPF), an insecticide, induces pro-oxidant, pro-inflammatory, and pro-apoptotic effects in animal cells. Contamination with CPF occurs not only in farms, since CPF is found in the food consumed in homes. Recently, it was demonstrated that CPF affects the mitochondria, inhibiting components of the electron transfer chain (ETC), causing loss of mitochondrial membrane potential (MMP), and reducing the synthesis of adenosine triphosphate (ATP) by the Complex V. Pinocembrin (PB) is found in propolis and exhibits antioxidant, anti-inflammatory, and anti-apoptotic effects in mammalian cells. PB is a potent inducer of the nuclear factor erythroid 2-related factor 2 (Nrf2), which is a major transcription factor controlling the expression of heme oxygease-1 (HO-1), among others. In the present work, we investigated whether PB would be able to prevent the mitochondrial and immune dysfunctions in the human neuroblastoma SH-SY5Y cells exposed to CPF. PB was tested at 1–25 µM for 4 h before the administration of CPF at 100 µM for additional 24 h. We found that PB prevented the CPF-induced inhibition of ETC, loss of MMP, and decline in the ATP synthesis. PB also promoted anti-inflammatory actions in this experimental model. Silencing of Nrf2 or inhibition of HO-1 suppressed the PB-induced effects in the CPF-challenged cells. Thus, PB promoted beneficial effects by a mechanism dependent on the Nrf2/HO-1/CO + BR axis in the CPF-treated cells.

Ischemic stroke is a challenging disease with high mortality and disability rates, causing a great economic and social burden worldwide. During ischemic stroke, ionic imbalance and excitotoxicity, oxidative stress, and inflammation are developed in a relatively certain order, which then activate the cell death pathways directly or indirectly via the promotion of organelle dysfunction. Neuroprotection, a therapy that is aimed at inhibiting this damaging cascade, is therefore an important therapeutic strategy for ischemic stroke. Notably, phytochemicals showed great neuroprotective potential in preclinical research via various strategies including modulation of calcium levels and antiexcitotoxicity, antioxidation, anti-inflammation and BBB protection, mitochondrial protection and antiapoptosis, autophagy/mitophagy regulation, and regulation of neurotrophin release. In this review, we summarize the research works that report the neuroprotective activity of phytochemicals in the past 10 years and discuss the neuroprotective mechanisms and potential clinical applications of 148 phytochemicals that belong to the categories of flavonoids, stilbenoids, other phenols, terpenoids, and alkaloids. Among them, scutellarin, pinocembrin, puerarin, hydroxysafflor yellow A, salvianolic acids, rosmarinic acid, borneol, bilobalide, ginkgolides, ginsenoside Rd, and vinpocetine show great potential in clinical ischemic stroke treatment. This review will serve as a powerful reference for the screening of phytochemicals with potential clinical applications in ischemic stroke or the synthesis of new neuroprotective agents that take phytochemicals as leading compounds.

Propolis shows a great variation in its chemical content depending on the vegetation around the beehive. Determination of its botanical origin and the chemical characterization are the most important issues for the standardization and the quality evaluation for propolis samples that are intended to be used in the pharmaceutical industry. This study has focused on the identification of the botanical origin of 47 propolis samples collected from different locations in the Black Sea Region of Turkey. Firstly, palynolog-ical and chromatographic analyses were carried out. Then, the major distinguishing components were identified by high-performance thin-layer chromatography (HPTLC), or by nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS) after isolation of the components. Based on the results, the samples were categorized into three main groups as black poplar-type, Euroasian aspen-type, and non-phenolic-type. Key markers of black poplar-type were assigned as phenolic acids and flavonoids, whereas lasiocarpin B and C (phenolic glycerides) were determined as markers for Euroasian aspen-type propolis. The total phenolics and flavonoid contents (TPC and TFC) and antioxidant capacities of the sam-ples were comparatively assessed by free radical-scavenging activity (DPPH) and metal-reducing activity (CUPRAC and FRAP) methods. Additionally, HPTLC-direct bioautography was applied to determine the contribution of components to antioxidant activity. Hierarchical clustering analysis revealed similarities in TFC, TPC values, and antioxidant activity related to the sample origins' geographic proximity. The anti-inflammatory activities of the black poplar sub-type and Euroasian aspen-type propolis samples were comparatively investigated on RAW 264.7 macrophage cells. The black poplar-type propolis extract dom-inated by caffeic acid, caffeic acid phenethyl ester, apigenin, quercetin, kaempferol, pinocembrin, and galangin exhibited the highest anti-inflammatory and antioxidant activities. Therefore, chemically char-acterized black poplar-type propolis may be suggested as a good candidate to develop pharmaceutical products. (c) 2021 Elsevier B.V. All rights reserved.

Several extracts of Syzygium species have been shown to inhibit the growth of some fungal microorganisms implicated in skin diseases, such as Candida albicans included S. samarangense. However, an antifungal test of C. Albicans on this plant's stem bark had not been reported. This study aimed to identify chemical constituents of the selected fraction from dichloromethane extracts of the stem bark of S. samarangense and determine the antifungal activity of the selected fraction at various concentrations on C. Albicans. The identification of the chemical constituent of the selected fraction has been performed by the LC-ESI-MS technique. An antifungal test of the selected fraction was carried out using the disk diffusion method. The samples used included the selected fraction with 5 variations of concentration (2.5; 2.0; 1.5; 1.0; and 0.5%), positive control (ketoconazole 1%), and negative control (DMSO). The results showed that the selected fraction has antifungal activity on C. Albicans. The results showed that the selected fraction contains four flavonoids: pinocembrin, uvangoletin, stercurensin, and aurentiacin. Due to antifungal activity on C. Albicans, it has moderate activity at a concentration of 2.5%, while concentrations of 2.0, 1.5, 1.0, and 0.5% have weak activity.

Propolis is a multi-functional bee product with a rich in polyphenols. In this study, the inhibition effect of Anatolian propolis against SARS coronavirus-2 (SARS CoV-2) was investigated asin vitroandin silico. Raw and commercial of propolis samples were used in the study and it was found that both of were rich in caffeic acid, p-coumaric acid, ferulic acid, t-cinnamic acid, hesperetin, chrysin, pinocembrin and caffeic acid phenethyl ester (CAPE) by HPLC-UV analysis. The ethanolic propolis extracts (EPE) were used in the screening ELISA test against the spike S1 protein (SARS Cov-2): ACE-2 inhibition KIT forin vitrostudy. Binding energy constants of these polyphenols to the CoV-2 Spike S1 RBD and ACE-2proteinwere calculated separately as molecular docking study using AutoDock 4.2 molecular docking software. In addition, pharmacokinetics and drug-likeness properties of these eight polyphenols were calculated according to the SwissADME tool. Binding energy constant of pinocembrin was the highest for both of the receptors, followed by chrysin, CAPE and hesperetin.In silicoADME behavior of the eight polyphenols were found potential ability to work effectively as novel drugs. The findings of both studies showed that propolis has a high inhibitory potential against Covid-19 virus. However, further studies are needed.

Propolis is a bee product with known medical properties, including antioxidant activity. The scope of the study is profiling 19 different Eurasian propolis samples (mostly from Russia and Kazakhstan, Kyrgyzstan, Poland, Ukraine, and Slovakia). Profiles of propolises were investigated by ultra-high-performance liquid chromatography&ndash, diode array detector&ndash, mass spectrometry (UPLC-DAD-MS). Classical antioxidant properties, which are based on electron donation mechanism, were assessed by DPPH, ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) assays. Total phenolic and flavonoid contents were also evaluated by colorimetric tests. Most of the samples exhibited significant content of polyphenols (from 30.28 to 145.24 mg GAE/g of propolis) and flavonoids (from 10.45 to 82.71 mg GAE/g of propolis). Most of the propolis samples exhibited potent antiradical (DPPH test&mdash, from 8.83 to 64.47mg GAE/g of propolis) and reducing activity (FRAP test&mdash, from 0.08 to 1.17 mmol Fe2+/g of propolis). Based on the occurrence of marker compounds, propolis samples were classified as poplar, aspen&ndash, birch, aspen&ndash, poplar, and aspen&ndash, birch&ndash, poplar type. Main markers present in propolis of poplar (e.g., chrysin, pinocembrin, galangin, and 3-O-acetyl-pinobanksin), birch (ermanin and acacetin) and aspen (2-acetyl-1,3-di-p-coumaroylglycerol) origin were used. DPPH, FRAP, and ORAC tests results were correlated with flavonoids, total polyphenols, or the polyphenols other than flavonoids content. In term of activity, poplar propolis type was variable, while aspen&ndash, poplar type usually exhibited high DPPH and FRAP activity.

This study aimed to determine the standard amount of antioxidant content and compounds of the propolis for the standardization of propolis. For this purpose, the total flavonoids, total phenolic, CUPRAC antioxidant capacity content and the diversity of phenolic and flavonoid components of these propolis samples were found by HPLC determined at the 23 propolis samples which were collected different regions of Turkey. Beside that, the similarities and differences of these 23 provinces to each other according to their antioxidant capacities were investigated by multidimensional scaling analysis. The total flavonoid content in the propolis samples were determined between 21.28 and 152.56 mg CE/g. The total phenolic content in the propolis samples was found between 34.53 mg and 259.4 mg GAE/g. CUPRAC antioxidant capacity of the propolis samples and antioxidant range was found from 95.35 to 710.43 mg TE/g. Also, 4 flavonoid [Quercetin (min.1.12–max.4.14 mg/g), Galangin (min.0.72–max.40.79 mg/g), Apigenin (min.1.07–max.17.35 mg/g), Pinocembrin (min.1.32–max.39.92 mg/g] and 6 phenolic acid [Caffeic acid (min.1.20–max.7.6 mg/g), p-Coumaric acid (min.1.26–max.4.47 mg/g), trans-Ferulic acid (min.1.28–max.4.92 mg/g), Protocatechuic acid (1.78 mg/g), trans-Cinnamic acid (min.1.05–max.3.83 mg/g), Caffeic Acid Phenethyl Ester (CAPE) (min.1.41–max.30.15 mg/g)] components were detected as mg/g, in different ratios in propolis samples collected from different regions. The feature of this study, so far, is to have the maximum number of samples representing the Turkish propolis, and so is thought to help to national and international propolis standard workings. © 2021, The Author(s)., Saudi Biological Society, SBS, This work was supported by SBS Bilimsel Bio Çözümler Inc. Bee&You Propolis R&D Center., This work was supported by SBS Bilimsel Bio ??z?mler Inc. Bee&You Propolis R&D Center.

Flavonoidi su spojevi koji se u većim količinama nalaze u biljkama. Čovjek prehranom svakodnevno konzumira flavonoide. Enzimi citokrom P450 su najvažniji enzimi koji sudjeluju u metabolizmu lijekova i lipofilnih ksenobiotika. Najveći broj lijekova na tržištu metabolizira se putem CYP3A4 enzima. Poznato je da flavonoidi mogu stupati u reakcije s CYP3A4 enzimom, pri čemu ga mogu inhibirati. Važno je razjasniti dosad nepoznat mehanizam inhibicijskog učinka flavonoida na CYP3A4 enzim. Ispitana je vrsta inhibicije kojom akacetin, apigenin, krizin i pinocembrin inhibiraju aktivnost CYP3A4 enzima. Inaktivacijska kinetika flavonoida određena je uz testosteron i nifedipin kao marker supstrate. Određeni su osnovni parametri enzimske inaktivacije (konstanta inhibicije, konstanta brzine inaktivacije, učinkovitost inaktivacije i polovica maksimalne inhibitorne koncentracije). Ispitana je pseudoireverzibilna inhibicija enzima uz pomoć hemokrom-piridin testa. Primjenom glutationa, hvatača slobodnih radikala, nastojala se utvrditi struktura reaktivnih intermedijera odgovornih za inaktivaciju enzima. Apigenin je uzrokovao o metabolizmu ovisnu inhibiciju CYP3A4 enzima (ostatna aktivnost enzima 10, 6 ± 1, 3%). Za krizin je utvrđena IC50 vrijednost od 0, 6 ± 0, 5 µM, konstanta inhibicije Ki = 0, 6 ± 0, 3 µM te učinkovitost inhibicije 0, 108 min-1 µM-1. Za apigenin je utvrđena konstanta brzine inaktivacije, kinact = 0, 11 ± 0, 01 µM-1. Svi flavonoidi su smanjili koncentraciju hema, a krizin najviše (ostatna koncentracija hema 5, 5%, odnosno 2, 9%). Nije uočena statistički značajna razlika između ostatne aktivnosti enzima nakon dijalize s i bez dodatka kalijevog heksacijanoferata. Reaktivni međuprodukti flavonoida nisu uočeni na spektrometru masa. Svi flavonoidi pokazuju o metabolizmu ovisnu inhibiciju CYP3A4 enzima, pri čemu se krizin pokazao kao najsnažniji inhibitor. Flavonoidi se kovalentno vežu za hem te na taj način dovode do inaktivacije enzima. Niti jedan flavonoid nije pokazao inhibiciju pseudoireverzibilnog karaktera na CYP3A4 enzim. Reaktivni međuprodukti flavonoida nisu uočeni zbog niskih koncentracija ili nestabilnosti produkata.

Kako i na koji način flavonoidi ostvaruju inhibiciju CYP3A4 enzima? Akacetin, apigenin, krizin i pinocembrin inhibiraju CYP3A4 enzim. Uočene su različite vrste inhibicija te različite jačine inhibicije.

Thai Bulletin of Pharmaceutical Sciences, 16, 2(July-December)2021, 1-9

Calabrian licorice (roots of G. glabra var. typica), PDO certified, is one of the most valuable commercial within Glycyrrhiza species. Specialized metabolites profiling of below and aboveground parts of PDO Calabrian G. glabra was established by untargeted UHPLC-HRMS either to elucidate their distinctive accumulation among tissues and to gain insight about the chemical composition of leaves and exudate, also to provide fingerprints for PDO products authentication. Roots showed the typical profile of G. glabra, namely glabridin and prenylated phenolic compounds (erybacin B, kanzonol Y, mulberrofuran K isomers, 3-hydroxyglabrol and glabrol) were confirmed as useful species-specific markers for authenticity and traceability of Calabrian licorice. Aerial tissues contained exclusively phenolics compounds, with pinocembrin, prenylated flavanones (licoflavanone and glabranin) and dihydrostilbenes as distinctive metabolites accumulated in the leaf-exudates, and glycosylated flavonoids (isoquercitrin, astragalin and their malonyl derivatives) distributed solely in the inner leaf tissues and flowers. This comparative study provides insights on tissue-distribution of G. glabra specialized metabolites and paves the way for sustainable valorization of untapped resources and improves the economic value of supply licorice-chain.

Flavonoids are natural compounds with antioxidant properties that have positive effects on human health, which reduce toxic effects of reactive oxygen species (ROS) and partially oxidative damage. In the work, the density functional theory (DFT/BMK) calculations were performed for antioxidant activity evaluation of pinocembrin (P), isosakuranetin (I) and eriodictyol (E). Four main mechanisms were examined: hydrogen atom transfer (HAT), radical adduct formation (RAF), single electron transfer-proton transfer (SET-PT) and Sequential proton loss electron transfer (SPLET). HAT and SPLET are thermodynamically the most probable process in gas phase and water. The three flavonoids examined + •OH HAT and RAF mechanisms for each possible location were investigated theoretically for the first time. The results were discussed by considering thermodynamic, kinetic and structural data of various reaction paths using IRC approach.Communicated by Ramaswamy H. Sarma.

Acacetin, apigenin, chrysin, and pinocembrin are flavonoid aglycones found in foods such as parsley, honey, celery, and chamomile tea. Flavonoids can act as substrates and inhibitors of the CYP3A4 enzyme, a heme containing enzyme responsible for the metabolism of one third of drugs on the market. The aim of this study was to investigate the inhibitory effect of selected flavonoids on the CYP3A4 enzyme, the kinetics of inhibition, the possible covalent binding of the inhibitor to the enzyme, and whether flavonoids can act as pseudo-irreversible inhibitors. For the determination of inhibition kinetics, nifedipine oxidation was used as a marker reaction. A hemochromopyridine test was used to assess the possible covalent binding to the heme, and incubation with dialysis was used in order to assess the reversibility of the inhibition. All the tested flavonoids inhibited the CYP3A4 enzyme activity. Chrysin was the most potent inhibitor: IC50 = 2.5 ± 0.6 µM, Ki = 2.4 ± 1.0 µM, kinact = 0.07 ± 0.01 min−1, kinact/Ki = 0.03 min−1 µM−1. Chrysin caused the highest reduction of heme (94.5 ± 0.5% residual concentration). None of the tested flavonoids showed pseudo-irreversible inhibition. Although the inactivation of the CYP3A4 enzyme is caused by interaction with heme, inhibitor-heme adducts could not be trapped. These results indicate that flavonoids have the potential to inhibit the CYP3A4 enzyme and interact with other drugs and medications. However, possible food–drug interactions have to be assessed clinically.

Peptic ulcer including gastric and duodenal ulcers is a common gastro-intestinal disorder worldwide, associated with a significant mortality due to bleeding and perforation. Numerous efforts are being exerted to look for natural drugs that lack the potential side effects but still keep beneficial effects for treatment and/or prevention of gastric ulcer. Pinocembrin (PINO) is a natural flavonoid retaining anti-microbial, anti-oxidant, and anti-inflammatory activities. The present study was conducted to investigate the protective and therapeutic effects of PINO against indomethacin (INDO)-induced gastric ulcer in rats and the possible underlying mechanisms. PINO (25 and 50 mg/kg) promoted mucus secretion, decreased ulcer index, and inhibited histopathological changes induced by INDO. Further investigation of possible mechanisms showed that PINO significantly attenuated INDO-induced oxidative and inflammatory responses in both doses when administrated before or after ulcer induction. PINO downregulated mRNA expression level of p38-mitogen-activated protein kinase (p38-MAPK) which subsequently inhibited NF-κB activation and inflammatory cytokine release including tumor necrosis factor-α (TNF-α) and interleukin-1beta (IL-1β). Additionally, PINO inhibited apoptotic activity which was confirmed by downregulation of caspase-3 transcription. The current results demonstrated the promising therapeutic activity of PINO against INDO-induced gastric ulcer due to-at least partly-its anti-oxidant, anti-inflammatory, and anti-apoptotic effects.

Doxorubicin (DOX) is a potent chemotherapeutic drug but the clinical use was limited by its dose-dependent cardiotoxicity. Pinocembrin (PCB), a flavonoid originally isolated from honeybee propolis and rhizomes of Boesenbergia pandurate displays diverse biological activities. However, the role of PCB in DOX-induced cardiac injury and its underlying molecular mechanism are not fully elucidated. The present study was designed to evaluate the protective role of PCB in a DOX-induced cardiotoxicity in vivo and in vitro. Our results revealed that PCB administration greatly improved cardiac function and reduced cardiac fibrosis manifested by LVEF, LVFS, LVIDd, LVIDs, and myocardial fibrotic area which were impaired by DOX treatment. The cardiac injury evidenced by LDH and CK-MB activities were reduced while the levels of IL-1β and IL-18 were decreased following PCB treatment compared to DOX-treated mice. Mechanically, our present results showed that PCB significantly inhibited DOX-induced cardiomyocyte pyroptosis via activating Nrf2/Sirt3 signal pathway. Furthermore, the inhibition of Nrf2 in H9c2 cells abolished the protective role of PCB against DOX-induced cell toxicity, which was at least partly via upregulation of NLRP3-mediated pyroptosis. In conclusion, our study clearly demonstrated that PCB reduced cardiomyocyte pyroptosis to protect hearts from DOX-induced cardiotoxicity through activation of Nrf2/Sirt3 signal pathway.

Three new β-triketone flavanone hybrids, cajuputones A-C were obtained from Melaleuca cajuputi (the Australian 'tea tree'). The structures of cajuputones A-C were elucidated by 1D/2D NMR spectroscopy and HR-ESI-MS analyses; and their absolute configurations were established by electric circular dichroism (ECD) calculations using TDDFT method. Structurally, cajuputones A-C feature a rare 6/6/6/6 oxatetracyclic ring system fused between an acylphloroglucinol-derived β-triketone and a pinocembrin or strobopinin moiety via an angle-type pyran-like motif. DFT-based conformational optimization in chloroform explained the similarity of the 1D NMR data of cajuputones B and C (C-2 epimers).

Benzo(a)pyrene [B(a)P], which is a carcinogen, is a substance most typically known in cigarette smoke and considered as an important intermediary of lung cancer. The enzyme CYP1A1 is crucial for the metabolic conversion of B(a)P into the intermediates that induce carcinogenesis. Stimulation of the aryl hydrocarbon receptor, which is regulated by B(a)P, is thought to induce numerous signaling cascades. Interruption in the mitogen-activated protein kinase (MAPK) pathway causes changes in cellular processes and may alter the AhR pathway. The aim of this investigation is to examine the potential ability of a flavonoid pinocembrin (PCB) to alleviate B(a)P toxicity and analyze the underlying molecular mechanisms. We found that PCB inhibited DNA adduct formation by attenuating CYP1A1 expression through the suppression of the AhR/Src/ERK pathways. PCB mitigated the B(a)P-stimulated DNA damage, inhibited Src and ERK1/2 expression, decreased CYP1A1 expression, and reduced the B(a)P-induced stimulation of NF-κB and MAPK signaling in lung epithelial cells. Finally, the activity of CYP1A1 and Src in lung tissues from mice supplemented with PCB was noticeably decreased and lower than that in lung tissues from mice supplemented with B(a)P alone. Collectively, these data suggest that PCB may alleviate the toxic effects of PAHs, which are important environmental pollutants.

This study aimed to investigate the protective effects of three propolis-abundant flavonoids, pinocembrin (PI), galangin (GA), and chrysin (CH) against ethanol-induced injuries in HepG2 cells. Results showed that the pre-treatment of flavonoids could significantly reverse cellular injuries caused by ethanol, which was evidenced by the decreased production of reactive oxygen species and malondialdehyde, less DNA damages, and the increased antioxidant status. Results from RNA-Seq revealed that differentially expressed genes in response to the pre-treatment of PI, GA, and CH were significantly enriched in different biological processes. Three flavonoids could significantly suppress ERK1/2 phosphorylation, AHR nuclear translocation, and CYP1A1 expression. In summary, three flavonoids had significant protective effects on ethanol-induced injuries through the inhibition of the ERK1/2-AHR-CYP1A1 signaling pathway. Our results provided theoretical bases for the promising use of PI, GA and CH in the prevention and treatment of ethanol-induced fatty liver diseases.

Populus nigra L. (Salicaceae family) is one of the most popular trees that can be found in deciduous forests. Some particularities that characterize the Populus genus refer to the fact that it includes more than 40 species, being widespread especially in Europe and Asia. Many residues, parts of this tree can be used as a bioresource for different extracts as active ingredients in pharmaceuticals next to multiple benefits in many areas of medicine. The present review discusses the latest findings regarding the phytochemical composition and the therapeutic properties of Populus nigra L. buds. The vegetal product has been described mainly to contain phenolic compounds (phenols, phenolic acids and phenylpropanoids), terpenoids (mono and sesquiterpenoids), flavones (e.g., apigenol and crysin), flavanones (e.g., pinocembrin and pinostrombin), caffeic/ferulic acids and their derivates, and more than 48 phytocompounds in the essential oils. The resinous exudates present on the buds have been the major plant source used by bees to form propolis. Several studies depicted its antioxidant, anti-inflammatory, antibacterial, antifungal, antidiabetic, antitumor, hepatoprotective, hypouricemic properties and its effects on melanin production. All these lead to the conclusion that black poplar buds are a valuable and important source of bioactive compounds responsible for a wide range of therapeutic uses, being a promising candidate as a complementary and/or alternative source for a large number of health problems. The aim of the review is to gather the existing information and to bring an up to date regarding the phytochemical and therapeutic uses of Populus nigra L. buds.

Tessaria dodoneifolia [Asteraceae] is traditionally employed in Northwestern Argentina for fungal infections treatment. We report the antifungal activity guided isolation and identification of substances from aerial parts of this species, both individually and in combination with fluconazole (FLU), against Candida albicans strains. Two antifungal flavanones were identified as naringenin (NAR) and pinocembrin (PIN). These compounds could individually inhibit the growth of C. albicans strains. Combinations of NAR and PIN with FLU were synergistic against the FLU resistant and sensitive C. albicans strains. Genotoxic and cytotoxic evaluations were also performed. NAR, PIN and their combinations with FLU did not have a genotoxic effect on Bacillus subtilis rec strains. Finally, these compounds did not show cytotoxicity at concentrations below 80 μg/mL., Plant biology; Toxicology; Bioactive plant product; Mycology; Secondary metabolite; Flavonoid; Chromatography; Spectroscopy; Tessaria dodoneifolia; Antifungal activity; Candida albicans; Synergistic effect; Toxicity assays.

We identified and quantified by LC-MS/MS 11 (quercetin, galangin, pinocembrin, kaempferol, vanillin, chrysin, gallic acid, p-coumaric acid, trans-ferulic acid, caffeic acid, and caffeic acid phenethyl ester) out of the 21 polyphenolic compounds we looked for in ethanolic (25% and 50%) and aqueous propolis extracts by comparison with standards and literature data.

Propolis is a natural bee product with various beneficial biological effects. The health-promoting properties of propolis depend on its chemical composition, particularly the presence of phenolic compounds. The aim of this study was to evaluate the relationship between extraction solvent (acetone 100%, ethanol 70% and 96%) and the antifungal, antioxidant, and cytoprotective activity of the extracts obtained from propolis. Concentrations of flavonoids and phenolic acids in the propolis extracts were determined using ultrahigh-performance liquid chromatography. The antioxidant potential of different extracts was assessed on the basis of 2,2-diphenyl-1-picrylhydrazyl (DPPH&middot, ) free-radical-scavenging activity, Fe3+-reducing power, and ferrous ion (Fe2+)-chelating activity assays. The ability of the extracts to protect human red blood cell membranes against free-radical-induced damage and their antifungal activity was also determined. The results showed that the concentration of flavonoids in the propolis extracts was dependent on the solvent used in the extraction process and pinocembrin, chrysin, galangin, and coumaric acid were the most abundant phenols. All extracts exhibited high antioxidant potential and significantly protected human erythrocytes against oxidative damage. On the other hand, the antifungal activity of the propolis extracts depended on the solvent used in extraction and the fungal strains tested. It needs to be stressed that, to the best of our knowledge, there is no study relating the effect of solvent used for extraction of Polish propolis to its phenolic profile, and its antifungal, antioxidant, and cytoprotective activity.

Background: The chemotherapeutic use of Doxorubicin (Dox) has drastically decreased because of its dose-dependent cardiotoxic side effect. Numerous mechanisms, amongst them oxidative stress, mitochondrial depolarization and apoptosis have been identified to be at the forefront of Dox-induced cardiotoxicity. Flavonoids, such as pinocembrin, have been proposed to have therapeutic properties that could target some of these toxic effects. As such, we investigated the ability of pinocembrin (Pin) to attenuate Dox-induced cardiotoxicity in an in vitro H9c2 cardiomyoblast model. Methodology: To induce chronic cardiotoxicity, H9c2 cardiomyoblasts were treated with Dox (2μM) every second day for six days. The cells were also co-treated with pinocembrin (1μM) in order to assess the flavonoid’s cardioprotective potential as well as Dexrazoxane (20μM), which served as a positive control. Untreated cells served as a normal control. On day seven, we conducted biochemical analysis (ATP levels, oxidative stress, lipid peroxidation, antioxidant activity, mitochondrial potential and apoptosis) to assess the efficacy of pinocembrin. Results: Pinocembrin significantly attenuated Dox-induced oxidative stress and lipid peroxidation by increasing the activity of endogenous antioxidants such as superoxide dismutase and total glutathione content. Moreover, pinocembrin prevented Dox-induced loss in mitochondrial membrane potential (MMP), which led to an increase in cellular metabolic activity. Subsequently, pinocembrin was able to mitigate Dox-induced apoptosis by increasing the amount of viable cells as indicated by a significant reduction in apoptotic and necrotic cells. Conclusion: These findings demonstrate that pinocembrin attenuates the chronic cardiotoxicity inferred by Dox administration on the H9c2 cardiomyoblasts through its antioxidant and anti-apoptotic properties. We therefore, suggest that pinocembrin should be further investigated as a suitable candidate in the prevention of Doxorubicin-induced cardiomyopathy.

The purpose of this study was to determine the changes in the contents of flavonoids that were the most prevalent in acacia and multifloral honey during one year of storage. Samples were stored in transparent glass containers, at room temperature, on open shelves exposed to light during daytime. Eight individual flavonoids identified and quantified using HPLC-Diode Array Detector (DAD) belongs to three subgroups: flavonols (quercetin, luteolin, kaempferol and galangin), total flavanons (hesperetin and pinocembrin) and total flavones (apigenin and chrysin). Obtained results revealed that multifloral honey had more total flavonoids than acacia samples did. On average from all of the samples, multifloral honey had more of quercetin, hesperetin, luteolin, kaempferol and apigenin than acacia honey did. Content of flavonoids increased in samples between the 1st and 6th month of storage and then started to decrease until the 9th month, when they remained relatively constant all the way until the 12th month of storage. In conclusion, acacia and multifloral honey after one-year of storage still can be a valuable source of flavonoids.

49 samples of propolis from different regions in China were collected and analyzed for their chemical compositions, contents of total flavonoids (TFC), total phenolic acid (TPC) and antioxidant activity. High-performance liquid chromatography (HPLC) analysis identified 15 common components, including key marker compounds pinocembrin, 3-O-acetylpinobanksin, galangin, chrysin, benzyl p-coumarate, pinobanksin and caffeic acid phenethyl ester (CAPE). Cluster analysis (CA) and correlation coefficients (CC) analysis showed that these propolis could be divided into three distinct groups. Principal component analysis (PCA) and multiple linear regression analysis (MLRA) revealed that the contents of isoferulic acid, caffeic acid, CAPE, 3,4-dimethoxycinnamic acid, chrysin and apigenin are closely related to the antioxidant properties of propolis. In addition, eight peak areas decreased after reacting with 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals, indicating that these compounds have antioxidant activity. The results indicate that the grouping and spectrum&ndash, effect relationship of Chinese propolis are related to their chemical compositions, and several compounds may serve as a better marker for the antioxidant activity of Chinese propolis than TFC and TPC. The findings may help to develop better methods to evaluate the quality of propolis from different geographic origins.

Pinocembrin, a plant-derived flavonoid, has a variety of pharmacological activities, including anti-infection, anti-cancer, anti-inflammation, cardiovascular protection, etc. However, the mechanism of pinocembrin on the anti-colitis efficacy remains elusive and needs further investigation. Here, we reported that pinocembrin eased the severity of dextran sulfate sodium (DSS)-induced colitis in mice by suppressing the abnormal activation of toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signal pathway in vivo. In addition, the gut microbiota was disordered in DSS colitis mice, which was associated with a significant decrease in microbiota diversity and a great shift in bacteria profiles; however, pinocembrin treatment improved the imbalance of gut microbiota and made it similar to that in normal mice. On the other hand, in vitro, pinocembrin down-regulated the TLR4/NF-κB signaling cascades in lipopolysaccharide (LPS)-stimulated macrophages. At the upstream level, pinocembrin competitively inhibited the binding of LPS to myeloid differentiation protein 2 (MD2), thereby blocking the formation of receptor multimer TLR4/MD2·LPS. Furthermore, pinocembrin dose-dependently promoted the expression of tight junction proteins (ZO-1, Claudin-1, Occludin and JAM-A) in Caco-2 cells. In conclusion, our work presented evidence that pinocembrin attenuated DSS-induced colitis in mouse, at least in part, via regulating intestinal microbiota, inhibiting the over-activation of TLR4/MD2/NF-κB signaling pathway, and improving the barriers of intestine.

Background: Honey, pollen, and propolis are among the products that bees process and derive from plants and flowers. Propolis is a resinous material that bees gather from the buds and bark of some trees and small plants. Propolis from temperate climates mainly contains phenolic compounds, in contrast with propolis from tropical climates, which mainly contains terpenes. This study aimed to determine, characterise, and quantify the phenolic content of raw propolis from Burundi. Methods: In this study, a total of 6 samples were collected from the provinces of Rumonge, Cibitoke, and Ruyigi in Burundi. Fifteen phenolic compounds (caffeic acid, ferulic acid, epigallocatechin gallate, isoferulic acid, cinnamic acid, caffeic acid phenethyl ester, gallic acid, apigenin, chrysin, galangin, quercetin, kaempherol, rutin trihydrate, naringenin, and pinocembrin) were used as high-performance liquid chromatography (HPLC) standards for qualitative and quantitative analyses of the propolis samples. Results: Among the 15 phenolic compounds checked, only 1 – gallic acid – was detected at a measurable level using an HPLC-diode array detector system. Conclusion: In addition to terpenes, propolis found in sub-Saharan Africa may contain phenolic compounds. Further advanced investigation of sub-Saharan African propolis is required for more detailed characterisation.

Background:Propolis is a resinous substance produced by bees and known to possess antioxidant, antimicrobial, antiproliferative and anti-inflammatory activities.Objective:This study is aimed at evaluating the in vivo and in vitro anti-inflammatory potential of the Crude Ethanolic Extract (CE) of Lebanese propolis and its Ethyl Acetate Fraction (EAF).Method:Chemical content of propolis was characterized using high-performance liquid chromatography and LC-MS/MS. COX-2 and iNOS protein expression, nitric oxide (NO) and prostaglandin (PGE2) release in LPS-activated RAW monocytes were achieved respectively by western blot and spectrophotometry. Antioxidant activity was evaluated by DPPH free radical scavenging assay. Measurement of paw thickness in carrageenan-induced paw edema in mice and pathologic assessment of inflammation in paw sections were used to judge the anti-inflammatory properties of propolis.Results:Pathology analysis revealed in the treated group significant reduction of immune cell infiltration and edema. Both extract and ethyl acetate fraction showed significant anti-inflammatory and antioxidant effects in LPS-treated RAW cells characterized by the inhibition of COX-2 and iNOS protein expression, as well as PGE2 and NO release. Chemical analysis of the crude extract and its ethyl acetate fraction identified 28 different compounds of which two phenolic acids and nine other flavonoids were also quantified. Ferulic acid, caffeic acid, chrysin, galangin, quercetin, and pinocembrin were among the most representative compounds.Conclusion:Lebanese propolis is rich in a various amount of flavonoids which showed promising antiinflammatory and antioxidant properties. Additionally, chemical analysis showed unique chemical compositions with the potential of identifying ingredients with interesting anti-inflammatory activities.