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12 pages, 1507 KiB

Open AccessArticle

Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

by Sanaa Almowallad, Etimad Huwait, Rehab Al-Massabi, Salma Saddeek, Kalamegam Gauthaman and Alexandre Prola

Pharmaceuticals 2020, 13(11), 372; https://doi.org/10.3390/ph13110372 - 08 Nov 2020

Cited by 9 | Viewed by 3297

Abstract

Atherosclerosis may lead to cardiovascular diseases (CVD), which are the primary cause of death globally. In addition to conventional therapeutics for CVD, use of nutraceuticals that prevents cholesterol deposition, reduce existing plaques and hence anti-atherosclerotic effects of nutraceuticals appeared to be promising. As [...] Read more.

Atherosclerosis may lead to cardiovascular diseases (CVD), which are the primary cause of death globally. In addition to conventional therapeutics for CVD, use of nutraceuticals that prevents cholesterol deposition, reduce existing plaques and hence anti-atherosclerotic effects of nutraceuticals appeared to be promising. As such, in the present study we evaluated the beneficial effects of punicalagin, a phytochemical against an atherosclerotic cell model in vitro. Cytotoxicity assays were examined for 10 µM concentration of punicalagin on THP-1 macrophages. Real-time-polymerase chain reaction (RT-PCR) was used to analyze monocyte chemoattractant protein-1 (MCP-1) and Intercellular adhesion molecule (ICAM-1) expressions. Monocyte migration and cholesterol efflux assays were performed to investigate punicalagin’s further impact on the key steps of atherosclerosis. Cytotoxicity assays demonstrated no significant toxicity for punicalagin (10 µM) on THP-1 macrophages. Punicalagin inhibited the IFN-γ-induced overexpression of MCP-1 and ICAM-1 in macrophages by 10 fold and 3.49 fold, respectively, compared to the control. Punicalagin also reduced the MCP-1- mediated migration of monocytes by 28% compared to the control. Percentages of cellular cholesterol efflux were enhanced in presence or absence of IFN-γ by 88% and 84% compared to control with 58% and 62%, respectively. Punicalagin possesses anti-inflammatory and anti-atherosclerotic effects. Punicalagin also did not exhibit any cytotoxicity and therefore can be considered a safe and potential candidate for the treatment and prevention of atherosclerosis. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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33 pages, 5400 KiB

Open AccessArticle

Phenolic Compounds Reduce the Fat Content in Caenorhabditis elegans by Affecting Lipogenesis, Lipolysis, and Different Stress Responses

by Paula Aranaz, David Navarro-Herrera, María Zabala, Ana Romo-Hualde, Miguel López-Yoldi, José Luis Vizmanos, Fermín I. Milagro and Carlos J. González-Navarro

Pharmaceuticals 2020, 13(11), 355; https://doi.org/10.3390/ph13110355 - 30 Oct 2020

Cited by 27 | Viewed by 3581

Abstract

Supplementation with bioactive compounds capable of regulating energy homeostasis is a promising strategy to manage obesity. Here, we have screened the ability of different phenolic compounds (myricetin, kaempferol, naringin, hesperidin, apigenin, luteolin, resveratrol, curcumin, and epicatechin) and phenolic acids (p-coumaric, ellagic, [...] Read more.

Supplementation with bioactive compounds capable of regulating energy homeostasis is a promising strategy to manage obesity. Here, we have screened the ability of different phenolic compounds (myricetin, kaempferol, naringin, hesperidin, apigenin, luteolin, resveratrol, curcumin, and epicatechin) and phenolic acids (p-coumaric, ellagic, ferulic, gallic, and vanillic acids) regulating C. elegans fat accumulation. Resveratrol exhibited the strongest lipid-reducing activity, which was accompanied by the improvement of lifespan, oxidative stress, and aging, without affecting worm development. Whole-genome expression microarrays demonstrated that resveratrol affected fat mobilization, fatty acid metabolism, and unfolded protein response of the endoplasmic reticulum (UPR^ER), mimicking the response to calorie restriction. Apigenin induced the oxidative stress response and lipid mobilization, while vanillic acid affected the unfolded-protein response in ER. In summary, our data demonstrates that phenolic compounds exert a lipid-reducing activity in C. elegans through different biological processes and signaling pathways, including those related with lipid mobilization and fatty acid metabolism, oxidative stress, aging, and UPR-ER response. These findings open the door to the possibility of combining them in order to achieve complementary activity against obesity-related disorders. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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17 pages, 4083 KiB

Open AccessArticle

Chemical Investigation and Screening of Anti-Proliferative Activity on Human Cell Lines of Pure and Nano-Formulated Lavandin Essential Oil

by Elisa Ovidi, Valentina Laghezza Masci, Anna Rita Taddei, Patrizia Paolicelli, Stefania Petralito, Jordan Trilli, Fabio Mastrogiovanni, Antonio Tiezzi, Maria Antonietta Casadei, Pierluigi Giacomello and Stefania Garzoli

Pharmaceuticals 2020, 13(11), 352; https://doi.org/10.3390/ph13110352 - 29 Oct 2020

Cited by 15 | Viewed by 2849

Abstract

Lavandin essential oil (LEO), a natural sterile hybrid obtained by crossbreeding L. angustifolia × L. latifolia, is mainly composed by active components belonging to the family of terpenes endowed with relevant anti-proliferative activity, which can be enhanced by proper application of nanotechnology. In [...] Read more.

Lavandin essential oil (LEO), a natural sterile hybrid obtained by crossbreeding L. angustifolia × L. latifolia, is mainly composed by active components belonging to the family of terpenes endowed with relevant anti-proliferative activity, which can be enhanced by proper application of nanotechnology. In particular, this study reports the chemical characterization and the screening of the anti-proliferative activity on different human cell lines of pure and nano-formulated lavandin essential oil (EO). LEO and its formulation (NanoLEO) were analyzed by HS/GC-MS (Headspace/Gas Chromatography-Mass Spectrometry) to describe and compare their chemical volatile composition. The most abundant compounds were linalool and 1,8-cineole (LEO: 28.6%; 27.4%) (NanoLEO: 60.4%; 12.6%) followed by α-pinene (LEO: 9.6%; NanoLEO: 4.5%), camphor (LEO: 6.5%; NanoLEO: 7.0%) and linalyl acetate (LEO: 6.5%; NanoLEO: 3.6%). The cytotoxic effects of LEO and NanoLEO were investigated on human neuroblastoma cells (SHSY5Y), human breast adenocarcinoma cells (MCF-7), human lymphoblastic leukemia cells (CCRF CEM), human colorectal adenocarcinoma cells (Caco-2) and one normal breast epithelial cell (MCF10A) by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide)-assay. Caco-2, MCF7 and MCF10A normal cells resulted more resistant to the treatment with LEO, while CCRF-CEM and SHSY5Y cells were more sensitive. The antiproliferative effect of LEO resulted amplified when the essential oil was supplied as nanoformulation, mainly in Caco-2 cells. Scanning and transmission electron microscopy investigations were carried out on Caco-2 cells to outline at ultrastructural level possible affections induced by LEO and NanoLEO treatments. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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13 pages, 1914 KiB

Open AccessFeature PaperArticle

Regioselective Hydroxylation of Phloretin, a Bioactive Compound from Apples, by Human Cytochrome P450 Enzymes

by Ngoc Anh Nguyen, Ngoc Tan Cao, Thi Huong Ha Nguyen, Thien-Kim Le, Gun Su Cha, Soo-Keun Choi, Jae-Gu Pan, Soo-Jin Yeom, Hyung-Sik Kang and Chul-Ho Yun

Pharmaceuticals 2020, 13(11), 330; https://doi.org/10.3390/ph13110330 - 22 Oct 2020

Cited by 11 | Viewed by 2885

Abstract

Phloretin, the major polyphenol compound in apples and apple products, is interesting because it shows beneficial effects on human health. It is mainly found as a form of glucoside, phlorizin. However, the metabolic pathway of phloretin in humans has not been reported. Therefore, [...] Read more.

Phloretin, the major polyphenol compound in apples and apple products, is interesting because it shows beneficial effects on human health. It is mainly found as a form of glucoside, phlorizin. However, the metabolic pathway of phloretin in humans has not been reported. Therefore, identifying phloretin metabolites made in human liver microsomes and the human cytochrome P450 (P450) enzymes to make them is interesting. In this study, the roles of human liver P450s for phloretin oxidation were examined using human liver microsomes and recombinant human liver P450s. One major metabolite of phloretin in human liver microsomes was 3-OH phloretin, which is the same product of a bacterial CYP102A1-catalyzed reaction of phloretin. CYP3A4 and CYP2C19 showed k_cat values of 3.1 and 5.8 min⁻¹, respectively. However, CYP3A4 has a 3.3-fold lower K_m value than CYP2C19. The catalytic efficiency of a CYP3A4-catalyzed reaction is 1.8-fold higher than a reaction catalyzed by CYP2C19. Whole-cell biotransformation with CYP3A4 was achieved 0.16 mM h⁻¹ productivity for 3-OH phlorein from 8 mM phloretin at optimal condition. Phloretin was a potent inhibitor of CYP3A4-catalyzed testosterone 6β-hydroxylation activity. Antibodies against CYP3A4 inhibited up to 90% of the microsomal activity of phloretin 3-hydroxylation. The immunoinhibition effect of anti-2C19 is much lower than that of anti-CYP3A4. Thus, CYP3A4 majorly contributes to the human liver microsomal phloretin 3-hydroxylation, and CYP2C19 has a minor role. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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16 pages, 2730 KiB

Open AccessArticle

Attenuation of Oxidative Stress by Cannabinoids and Cannabis Extracts in Differentiated Neuronal Cells

by Aruna Raja, Soha Ahmadi, Fernanda de Costa, Nan Li and Kagan Kerman

Pharmaceuticals 2020, 13(11), 328; https://doi.org/10.3390/ph13110328 - 22 Oct 2020

Cited by 20 | Viewed by 5424

Abstract

In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were investigated using an in vitro system of differentiated human neuronal SY-SH5Y cells. The oxidative stress was induced by hydrogen peroxide, as reactive oxygen species (ROS). Alzheimer’s [...] Read more.

In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were investigated using an in vitro system of differentiated human neuronal SY-SH5Y cells. The oxidative stress was induced by hydrogen peroxide, as reactive oxygen species (ROS). Alzheimer’s disease (AD)-like pathological conditions were mimicked in vitro by treating the differentiated neuronal cells with amyloid-β_1–42 (Aβ_1–42) in the presence of Cu(II). We showed that THC had a high potency to combat oxidative stress in both in vitro models, while CBD did not show a remarkable antioxidant activity. The cannabis extracts also exhibited a significant antioxidant activity, which depended on the ratio of the THC and CBD. However, our results did not suggest any antagonist effect of the CBD on the antioxidant activity of THC. The effect of cannabis extracts on the cell viability of differentiated human neuronal SY-SH5Y cells was also investigated, which emphasized the differences between the bioactivity of cannabis extracts due to their composition. Our preliminary results demonstrated that cannabis extracts and phytocannabinoids have a promising potential as antioxidants, which can be further investigated to develop novel pharmaceuticals targeting oxidative stress therapy. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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14 pages, 1494 KiB

Open AccessArticle

Rosmarinic Acid Methyl Ester Regulates Ovarian Cancer Cell Migration and Reverses Cisplatin Resistance by Inhibiting the Expression of Forkhead Box M1

by Soo Hyun Lim, Ki Hong Nam, Kyungtae Kim, Sang Ah Yi, Jaecheol Lee and Jeung-Whan Han

Pharmaceuticals 2020, 13(10), 302; https://doi.org/10.3390/ph13100302 - 12 Oct 2020

Cited by 12 | Viewed by 3064

Abstract

Rosmarinic acid methyl ester (RAME), a derivative of rosmarinic acid (RA), is reported to have several therapeutic effects, including anti-tumor effects against cervical cancer. However, its anti-tumor effects in ovarian cancer is unclear. In this study, we studied the molecular pathways associated with [...] Read more.

Rosmarinic acid methyl ester (RAME), a derivative of rosmarinic acid (RA), is reported to have several therapeutic effects, including anti-tumor effects against cervical cancer. However, its anti-tumor effects in ovarian cancer is unclear. In this study, we studied the molecular pathways associated with the anti-tumor effects of RAME in ovarian cancer. To identify the effects of RAME in ovarian cancer, RNA sequencing was performed in RAME-treated ovarian cancer cells; we found that RAME treatment downregulated the genes closely involved with the target genes of the transcription factor Forkhead box M1 (FOXM1). It was reported that FOXM1 is overexpressed in a variety of cancer cells and is associated with cell proliferation and tumorigenesis. Therefore, we hypothesized that FOXM1 is a key target of RAME; this could result in its anti-tumor effects. Treatment of ovarian cancer cells with RAME-inhibited cell migration and invasion, as shown by wound healing and transwell migration assays. To examine whether RAME represses the action of FOXM1, we performed quantitative RT-PCR and ChIP-qPCR. Treatment of ovarian cancer cells with RAME decreased the mRNA expression of FOXM1 target genes and the binding of FOXM1 to its target genes. Moreover, FOXM1 expression was increased in cisplatin-resistant ovarian cancer cells, and combination treatment with RAME and cisplatin sensitized the cisplatin-resistant ovarian cancer cells, which was likely due to FOXM1 inhibition. Our research suggests that RAME is a promising option in treating ovarian cancer patients, as it revealed a novel molecular pathway underlying its anti-tumor effects. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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18 pages, 3336 KiB

Open AccessArticle

A Novel Integrated Active Herbal Formulation Ameliorates Dry Eye Syndrome by Inhibiting Inflammation and Oxidative Stress and Enhancing Glycosylated Phosphoproteins in Rats

by Omer Ersin Muz, Cemal Orhan, Fusun Erten, Mehmet Tuzcu, Ibrahim Hanifi Ozercan, Prafull Singh, Abhijeet Morde, Muralidhara Padigaru, Deshanie Rai and Kazim Sahin

Pharmaceuticals 2020, 13(10), 295; https://doi.org/10.3390/ph13100295 - 07 Oct 2020

Cited by 12 | Viewed by 4575

Abstract

Dry eye syndrome (DES) is a chronic condition of the eye with insufficient production of tears leading to inadequate lubrication of eyes. Symptoms of DES are associated with discomfort and redness of the eye, blurred vision, and tear film instability which leads to [...] Read more.

Dry eye syndrome (DES) is a chronic condition of the eye with insufficient production of tears leading to inadequate lubrication of eyes. Symptoms of DES are associated with discomfort and redness of the eye, blurred vision, and tear film instability which leads to the damaged ocular surface. Inflammation and oxidative stress play a significant role in the pathogenesis of the disease. In this study, the protective effect of different doses (100 or 200 mg/kg) of a novel multi-component oral formulation of lutein/zeaxanthin, curcumin, and vitamin D3 (LCD) was evaluated using a rat model with benzalkonium chloride (BAC)-induced dry eye syndrome. The formulation was administered orally to rats for 4 weeks. We observed a significant improvement in tear volume, tear breakup time, tear film integrity, and reduction in overall inflammation in rats fed with the LCD at dose 200 mg/kg performing better than 100 mg/kg. Furthermore, the formulation helped in lowering oxidative stress by increasing antioxidant levels and restored protective tear protein levels including MUC1, MUC4, and MUC5AC with 200 mg of LCD having the most significant effect. The results strongly suggest that the combination of lutein/zeaxanthin, curcumin, and vitamin-D3 is effective in alleviating the symptoms of dry eye condition with a multi-modal mechanism of action. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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16 pages, 3448 KiB

Open AccessArticle

Enhancement of α-Mangostin Wound Healing Ability by Complexation with 2-Hydroxypropyl-β-Cyclodextrin in Hydrogel Formulation

by Nasrul Wathoni, Diah Permata Sari, Ine Suharyani, Keiichi Motoyama, Ahmed Fouad Abdelwahab Mohammed, Arief Cahyanto, Marline Abdassah and Muchtaridi Muchtaridi

Pharmaceuticals 2020, 13(10), 290; https://doi.org/10.3390/ph13100290 - 02 Oct 2020

Cited by 17 | Viewed by 3237

Abstract

α-Mangostin (α-M), one of the active compounds in Garcinia mangostana peel, has been effectively used in wound healing. However, its poor solubility in aqueous solution causes low bioavailability for skin ulcers, hindering its application in wound healing. The aim of this study was [...] Read more.

α-Mangostin (α-M), one of the active compounds in Garcinia mangostana peel, has been effectively used in wound healing. However, its poor solubility in aqueous solution causes low bioavailability for skin ulcers, hindering its application in wound healing. The aim of this study was to improve the solubility of α-M through complex formation with 2-hydroxypropyl-β-cyclodextrin (α-M/HP-β-CD CX) and to evaluate the healing activity of the complex. The α-M/HP-β-CD CX was incorporated in a sodium carboxymethylcellulose hydrogel (α-M/HP-β-CD CX HG), and the in vivo healing activity was examined in mice. Evaluation of α-M/HP-β-CD CX HG, including organoleptic evaluation, homogeneity, pH, spreadability, swelling ratio, consistency, scanning electron microscopy (SEM), and in vitro drug release, was carried out. The complex formation of α-M/HP-β-CD CX was confirmed by FTIR and PXRD analysis. The solubility of the α-M/HP-β-CD CX in water linearly increased about 11.7-fold compared to α-M alone, and by 3.5-fold compared to the α-M/HP-β-CD physical mixture (α-M/HP-β-CD CX PM). The α-M/HP-β-CD CX HG was homogenous, the pH was found to be in the neutral range, the spread area was 5 cm, and the consistency was stable until 14 days. SEM analysis showed that α-M/HP-β-CD CX HG surged due to the porous structure of the HG. In addition, in vitro release of α-M from α-M/HP-β-CD CX HG was considerably increased compared to α-M/HP-β-CD PM HG and α-M HG. Notably, in vivo evaluation in mice showed that α-M/HP-β-CD CX HG significantly accelerated the wound healing ability compared to other HGs. Thus, α-M/HP-β-CD CX HG has potential as a new formulation of α-M for wound healing therapy. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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17 pages, 4240 KiB

Open AccessArticle

Resveratrol Metabolites Are Able to Reduce Steatosis in Cultured Hepatocytes

by Jenifer Trepiana, Stéphanie Krisa, Elodie Renouf and María Puy Portillo

Pharmaceuticals 2020, 13(10), 285; https://doi.org/10.3390/ph13100285 - 30 Sep 2020

Cited by 16 | Viewed by 4019

Abstract

Steatosis is characterized primarily by excessive lipid accumulation in the form of triglycerides in the liver. Although resveratrol shows a low bioavailability, it has significant positive effects on steatosis. The aim of this study was to analyze whether some phase II and microbial [...] Read more.

Steatosis is characterized primarily by excessive lipid accumulation in the form of triglycerides in the liver. Although resveratrol shows a low bioavailability, it has significant positive effects on steatosis. The aim of this study was to analyze whether some phase II and microbial resveratrol metabolites (trans-resveratrol-4′-O-glucuronide (R-4G); trans-resveratrol-3-O-glucuronide (R-3G); trans-resveratrol-3-O-sulfate (R-S) and dihydro-resveratrol (DH-R) were effective in reducing hepatocyte fat accumulation. An in vitro model mimicking the hepatocyte situation in fatty liver was developed by incubating mouse AML12 hepatocytes with palmitic acid (PA). For cell treatments, hepatocytes were incubated with 1, 10, or 25 µM resveratrol or its metabolites. Triglycerides and cell viability were assessed using commercial kits. Protein expression of enzymes and transporters involved in triglyceride metabolism were analyzed by western blot. We show for the first time that resveratrol and all the tested metabolites, at 1 µM, partially prevented lipid accumulation induced by the saturated fatty acid PA in AML12 hepatocytes. This effect was mainly due to the inhibition of de novo lipogenesis. This demonstrates that the low bioavailability of resveratrol is not as big a problem as it was thought to be, because resveratrol metabolites contribute to the delipidating effects of the parent compound. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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17 pages, 1347 KiB

Open AccessArticle

Incubation with a Complex Orange Essential Oil Leads to Evolved Mutants with Increased Resistance and Tolerance

by Daniel Berdejo, Elisa Pagán, Natalia Merino, Rafael Pagán and Diego García-Gonzalo

Pharmaceuticals 2020, 13(9), 239; https://doi.org/10.3390/ph13090239 - 09 Sep 2020

Cited by 7 | Viewed by 2544

Abstract

Emergence of strains with increased resistance/tolerance to natural antimicrobials was evidenced after cyclic exposure to carvacrol, citral, and (+)-limonene oxide. However, no previous studies have reported the development of resistance and tolerance to complex essential oils (EOs). This study seeks to evaluate the [...] Read more.

Emergence of strains with increased resistance/tolerance to natural antimicrobials was evidenced after cyclic exposure to carvacrol, citral, and (+)-limonene oxide. However, no previous studies have reported the development of resistance and tolerance to complex essential oils (EOs). This study seeks to evaluate the occurrence of Staphylococcus aureus strains resistant and tolerant to a complex orange essential oil (OEO) after prolonged cyclic treatments at low concentrations. Phenotypic characterization of evolved strains revealed an increase of minimum inhibitory and bactericidal concentration for OEO, a better growth fitness in presence of OEO, and an enhanced survival to lethal treatments, compared to wild-type strain. However, no significant differences (p > 0.05) in cross-resistance to antibiotics were observed. Mutations in hepT and accA in evolved strains highlight the important role of oxidative stress in the cell response to OEO, as well as the relevance of the cell membrane in the cell response to these natural antimicrobials. This study demonstrates the emergence of S. aureus strains that are resistant and tolerant to EO (Citrus sinensis). This phenomenon should be taken into account to assure the efficacy of natural antimicrobials in the design of food preservation strategies, in cleaning and disinfection protocols, and in clinical applications against resistant bacteria. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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13 pages, 3180 KiB

Open AccessArticle

Characterization of Resveratrol, Oxyresveratrol, Piceatannol and Roflumilast as Modulators of Phosphodiesterase Activity. Study of Yeast Lifespan

by Adrián Matencio, Francisco García-Carmona and José Manuel López-Nicolás

Pharmaceuticals 2020, 13(9), 225; https://doi.org/10.3390/ph13090225 - 30 Aug 2020

Cited by 6 | Viewed by 2991

Abstract

Our desire to live longer has led to an ever-increasing number of novel antiaging products. However, few molecules have any real effect and new ones need to be studied before they can be used commercially. In this contribution, activation of the caloric restriction [...] Read more.

Our desire to live longer has led to an ever-increasing number of novel antiaging products. However, few molecules have any real effect and new ones need to be studied before they can be used commercially. In this contribution, activation of the caloric restriction (CR) pathway was studied using different three (resveratrol, oxyresveratrol and piceatannol)—a family with demonstrated bioactivity on phosphodiesterase activity. The high-affinity phosphodiesterase type 2 (PDE2) of Saccharomyces cerevisiae was expressed in Escherichia coli, purified and characterized. The activity and the inhibitory activity of each stilbene was studied, and the findings were compared in vitro and in silico with those obtained with roflumilast—a human PDE4 inhibitor widely used in chronic obstructive pulmonary diseases. Finally, an in vivo chronological lifespan assay using WT S. cerevisiae and ΔPDE2 S. cerevisiae strains was carried out. It was demonstrated that stilbenes can modulate yPDE2 activity, increasing the lifespan of the yeast by 18% over a control (in combination with other pathways). In addition, roflumilast increased the lifespan in the WT strain. The findings as a whole would increase the range of lifespan products available and suggest novel uses for approved drugs. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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16 pages, 2708 KiB

Open AccessArticle

Ganoderma lucidum Ethanol Extracts Enhance Re-Epithelialization and Prevent Keratinocytes from Free-Radical Injury

by Mario Abate, Giacomo Pepe, Rosario Randino, Simona Pisanti, Manuela Giovanna Basilicata, Verdiana Covelli, Maurizio Bifulco, Walter Cabri, Anna Maria D’Ursi, Pietro Campiglia and Manuela Rodriquez

Pharmaceuticals 2020, 13(9), 224; https://doi.org/10.3390/ph13090224 - 29 Aug 2020

Cited by 17 | Viewed by 5543

Abstract

Ganoderma lucidum or Reishi is recognized as the most potent adaptogen present in nature, and its anti-inflammatory, antioxidant, immunomodulatory and anticancer activities are well known. Moreover, lately, there has been an increasing interest from pharmaceutical companies in antiaging G. lucidum-extract-based formulations. Nevertheless, [...] Read more.

Ganoderma lucidum or Reishi is recognized as the most potent adaptogen present in nature, and its anti-inflammatory, antioxidant, immunomodulatory and anticancer activities are well known. Moreover, lately, there has been an increasing interest from pharmaceutical companies in antiaging G. lucidum-extract-based formulations. Nevertheless, the pharmacological mechanisms of such adaptogenic and regenerative actions remain unclear. The present investigation aimed to explore its molecular and cellular effects in vitro in epidermal keratinocyte cultures by applying liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LCMS-IT-TOF) for analysis of ethanol extracts using ganoderic acid-A as a reference compound. The G. lucidum extract showed a keratinocyte proliferation induction accompanied by an increase of cyclic kinase protein expressions, such as CDK2 and CDK6. Furthermore, a noteworthy migration rate increase and activation of tissue remodelling factors, such as matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), were observed. Finally, the extract showed an antioxidant effect, protecting from H₂O₂-induced cytotoxicity; preventing activation of AKT (protein kinase B), ERK (extracellular signal-regulated kinase), p53 and p21; and reducing the number of apoptotic cells. Our study paves the path for elucidating pharmacological properties of G. lucidum and its potential development as cosmeceutical skin products, providing the first evidence of its capability to accelerate the healing processes enhancing re-epithelialization and to protect cells from free-radical action. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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13 pages, 3334 KiB

Open AccessArticle

The Possible Contribution of P-Glycoprotein in the Protective Effect of Paeonol against Methotrexate-Induced Testicular Injury in Rats

by Mohamed A. Morsy, Asmaa M. Abdel-Aziz, Sara M. N. Abdel-Hafez, Katharigatta N. Venugopala, Anroop B. Nair and Seham A. Abdel-Gaber

Pharmaceuticals 2020, 13(9), 223; https://doi.org/10.3390/ph13090223 - 29 Aug 2020

Cited by 29 | Viewed by 3090

Abstract

Paeonol, a phenolic ingredient in the genus Paeonia, possesses antioxidant and anti-inflammatory effects. Methotrexate (MTX) is a commonly used chemotherapeutic agent; however, its germ cell damage is a critical problem. P-glycoprotein (P-gp), an efflux transporter, is a member of the blood–testis barrier. [...] Read more.

Paeonol, a phenolic ingredient in the genus Paeonia, possesses antioxidant and anti-inflammatory effects. Methotrexate (MTX) is a commonly used chemotherapeutic agent; however, its germ cell damage is a critical problem. P-glycoprotein (P-gp), an efflux transporter, is a member of the blood–testis barrier. The present study evaluated the protective effect of paeonol on MTX-induced testicular injury in rats with the exploration of its mechanism and the possible contribution of P-gp in such protection. Testicular weight, serum testosterone, and testicular P-gp levels were measured. Testicular oxidant/antioxidant status was evaluated via determining the levels of malondialdehyde, total nitrite, reduced glutathione, and superoxide dismutase activity. The inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and the apoptotic marker caspase 3 were estimated immunohistochemically. Testicular histopathology and spermatogenesis scores were also examined. MTX caused histopathologically evident testicular damage with decreased testicular weight, testosterone level, and spermatogenesis score, as well as significant increases in oxidative, inflammatory, and apoptotic responses. Paeonol significantly restored testicular weight, testosterone level, spermatogenesis score, and oxidant/antioxidant balance. Moreover, paeonol increased the testicular P-gp level and significantly decreased TNF-α and caspase 3 immunostaining. In conclusion, paeonol offered a protective effect against MTX-induced testicular injury through its antioxidant, anti-inflammatory, and antiapoptotic effects, as well as by increasing testicular P-gp level. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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14 pages, 4396 KiB

Open AccessArticle

Entrapment of Citrus limon var. pompia Essential Oil or Pure Citral in Liposomes Tailored as Mouthwash for the Treatment of Oral Cavity Diseases

by Lucia Palmas, Matteo Aroffu, Giacomo L. Petretto, Elvira Escribano-Ferrer, Octavio Díez-Sales, Iris Usach, José-Esteban Peris, Francesca Marongiu, Mansureh Ghavam, Sara Fais, Germano Orrù, Rita Abi Rached, Maria Letizia Manca and Maria Manconi

Pharmaceuticals 2020, 13(9), 216; https://doi.org/10.3390/ph13090216 - 28 Aug 2020

Cited by 18 | Viewed by 3371

Abstract

This work aimed at developing a mouthwash based on liposomes loading Citrus limon var. pompia essential oil or citral to treat oropharyngeal diseases. Vesicles were prepared by dispersing phosphatidylcholine and pompia essential oil or citral at increasing amounts (12, 25 and 50 mg/mL) [...] Read more.

This work aimed at developing a mouthwash based on liposomes loading Citrus limon var. pompia essential oil or citral to treat oropharyngeal diseases. Vesicles were prepared by dispersing phosphatidylcholine and pompia essential oil or citral at increasing amounts (12, 25 and 50 mg/mL) in water. Transparent vesicle dispersions were obtained by direct sonication avoiding the use of organic solvents. Cryogenic transmission electron microscopy (cryo-TEM) confirmed the formation of unilamellar, spherical and regularly shaped vesicles. Essential oil and citral loaded liposomes were small in size (~110 and ~100 nm, respectively) and negatively charged. Liposomes, especially those loading citral, were highly stable as their physico-chemical properties did not change during storage. The formulations were highly biocompatible against keratinocytes, were able to counteract the damages induced in cells by using hydrogen peroxide, and able to increase the rate of skin repair. In addition, liposomes loading citral at higher concentrations inhibited the proliferation of cariogenic bacterium. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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21 pages, 3888 KiB

Open AccessArticle

Formulation Design, Statistical Optimization, and In Vitro Evaluation of a Naringenin Nanoemulsion to Enhance Apoptotic Activity in A549 Lung Cancer Cells

by Shadab Md, Nabil A. Alhakamy, Hibah M. Aldawsari, Mohammad Husain, Sabna Kotta, Samaa T. Abdullah, Usama A. Fahmy, Mohamed A. Alfaleh and Hani Z. Asfour

Pharmaceuticals 2020, 13(7), 152; https://doi.org/10.3390/ph13070152 - 15 Jul 2020

Cited by 69 | Viewed by 4810

Abstract

Naringenin (NAR), a flavonoid mainly found in citrus and grapefruits, has proven anti-cancer activities. However, the poor water solubility and low bioavailability of NAR limits its use as a therapeutic agent. The aim of this study was to develop and optimize stable naringenin [...] Read more.

Naringenin (NAR), a flavonoid mainly found in citrus and grapefruits, has proven anti-cancer activities. However, the poor water solubility and low bioavailability of NAR limits its use as a therapeutic agent. The aim of this study was to develop and optimize stable naringenin nanoemulsions (NAR-NE) using a Box–Behnken experimental design to obtain a formulation with a higher efficiency. Anticancer activity of optimized NAR-NE was evaluated in A549 lung cancer cells using cell viability, flow-cytometric assays, and enzyme-linked immunosorbent assay. The stabilized nanoemulsion, which showed a spherical surface morphology, had a globule size of 85.6 ± 2.1 nm, a polydispersity index of 0.263 ± 0.02, a zeta potential of −9.6 ± 1.2 mV, and a drug content of 97.34 ± 1.3%. The NAR release from the nanoemulsion showed an initial burst release followed by a stable and controlled release for a longer period of 24 h. The nanoemulsion exhibited excellent thermodynamic and physical stability against phase separation and storage. The NAR-NE showed concentration-dependent cytotoxicity in A549 lung cancer cells, which was greater than that of free NAR. The percentage of apoptotic cells and cell cycle arrest at the G2/M and pre-G1 phases induced by NAR-NE were significantly higher than those produced by free NAR (p < 0.05). NAR-NEs were more effective than the NAR solution in reducing Bcl2 expression, while increasing pro-apoptotic Bax and caspase-3 activity. Therefore, stabilized NAR-NE could be a suitable drug delivery system to enhance the effects of NAR in the treatment of lung cancer. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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15 pages, 677 KiB

Open AccessArticle

A Pilot Study of a Natural Food Supplement as New Possible Therapeutic Approach in Chronic Kidney Disease Patients

by Annalisa Noce, Alessio Bocedi, Margherita Campo, Giulia Marrone, Manuela Di Lauro, Giada Cattani, Nicola Di Daniele and Annalisa Romani

Pharmaceuticals 2020, 13(7), 148; https://doi.org/10.3390/ph13070148 - 10 Jul 2020

Cited by 24 | Viewed by 4464

Abstract

The identification of natural bioactive compounds, able to counteract the abnormal increase of oxidative stress and inflammatory status in chronic degenerative non-communicable diseases is useful for the clinical management of these conditions. We tested an oral food supplement (OFS), chemically characterized and evaluated [...] Read more.

The identification of natural bioactive compounds, able to counteract the abnormal increase of oxidative stress and inflammatory status in chronic degenerative non-communicable diseases is useful for the clinical management of these conditions. We tested an oral food supplement (OFS), chemically characterized and evaluated for in vitro and in vivo activity. Vitamin C, analyzed by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD), was 0.19 mg/g in rosehip dry extract and 15.74 mg/capsule in the OFS. The identification of polyphenols was performed by HPLC-DAD; the total antioxidant capacity was assessed by Folin–Ciocalteu test. Total polyphenols were 14.73 mg/g gallic acid equivalents (GAE) for rosehip extract and 1.93 mg/g GAE for OFS. A total of 21 chronic kidney disease (CKD) patients and 10 healthy volunteers were recruited. The evaluation of routine laboratory and inflammatory parameters, erythrocyte glutathione transferase (e-GST), human oxidized serum albumin (HSAox), and assessment of body composition were performed at two different times, at baseline and after 5 weeks of OFS assumption. In the study, we highlighted a significant decrease of traditional inflammatory biomarkers (such as C-reactive protein, erythrocyte sedimentation rate, platelet to lymphocyte ratio) and other laboratory parameters like e-GST, azotaemia, and albuminuria after OFS treatment in CKD patients. Moreover, we demonstrated a lipid profile improvement in CKD patients after OFS supplementation. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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17 pages, 1406 KiB

Open AccessArticle

Phytochemicals and Enzyme Inhibitory Capacities of the Methanolic Extracts from the Italian Apple Cultivar Mela Rosa dei Monti Sibillini

by Víctor López, Francisco Les, Serena Mevi, Joice Guileine Nkuimi Wandjou, Guillermo Cásedas, Giovanni Caprioli and Filippo Maggi

Pharmaceuticals 2020, 13(6), 127; https://doi.org/10.3390/ph13060127 - 22 Jun 2020

Cited by 8 | Viewed by 2900

Abstract

The phytochemical profile of the methanolic extracts (pulp and peel) obtained from two dehydration methods (drying and freeze-lyophilization) of the traditional Italian apple Mela Rosa dei Monti Sibillini, as well as their inhibitory properties against some biological enzymes (α-glucosidase, lipase, monoamine oxidase A, [...] Read more.

The phytochemical profile of the methanolic extracts (pulp and peel) obtained from two dehydration methods (drying and freeze-lyophilization) of the traditional Italian apple Mela Rosa dei Monti Sibillini, as well as their inhibitory properties against some biological enzymes (α-glucosidase, lipase, monoamine oxidase A, tyrosinase and acetylcholinesterase) were assessed in this study. HPLC-DAD-MS technique was used for the determination of polyphenolic and triterpenic compounds. The determination of the enzymes inhibitory effect was made through spectrophotometric techniques. The peel extracts were richer in bioactive compounds than the pulp. In this regard, the extracts from freeze-lyophilization displayed higher levels of flavan-3-ols, flavonol glycosides and dihydrochalcones. However, the extracts obtained from dried material displayed a stronger enzyme inhibition. Notably, the peel extracts showed a higher activity than the pulp ones, especially in terms of α-glucosidase whereby some samples exerted a similar enzymatic inhibition than acarbose (100% inhibition) at high concentrations (1 mg/mL). These results encourage thus further studies on this traditional Italian apple as a potential source of nutraceuticals helpful to prevent the insurgence of some pathologies. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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16 pages, 4726 KiB

Open AccessArticle

Diterpenoids from Plectranthus spp. as Potential Chemotherapeutic Agents via Apoptosis

by Tomasz Śliwiński, Przemysław Sitarek, Ewa Skała, Vera M. S. Isca, Ewelina Synowiec, Tomasz Kowalczyk, Michał Bijak and Patrícia Rijo

Pharmaceuticals 2020, 13(6), 123; https://doi.org/10.3390/ph13060123 - 16 Jun 2020

Cited by 14 | Viewed by 2980

Abstract

Plectranthus spp. is widely known for its medicinal properties and bioactive metabolites. The cytotoxic and genotoxic properties of the four known abietane diterpenoids: 7α-Acetoxy-6β-hydroxyroyleanone (Roy), 6,7-dehydroroyleanone (Deroy), 7β,6β-dihydroxyroyleanone6 (Diroy), and Parvifloron D (Parv), isolated from P. madagascariensis (Roy, DeRoy, and Diroy) and P. [...] Read more.

Plectranthus spp. is widely known for its medicinal properties and bioactive metabolites. The cytotoxic and genotoxic properties of the four known abietane diterpenoids: 7α-Acetoxy-6β-hydroxyroyleanone (Roy), 6,7-dehydroroyleanone (Deroy), 7β,6β-dihydroxyroyleanone6 (Diroy), and Parvifloron D (Parv), isolated from P. madagascariensis (Roy, DeRoy, and Diroy) and P. ecklonii (Parv) were evaluated. The tested compounds showed cytotoxic effects against the human leukemia cell line CCRF-CEM and the lung adenocarcinoma cell line A549. All tested compounds induced apoptosis by altering the level of pro- and anti-apoptotic genes. The results show that from the tested diterpenoids, Roy and Parv demonstrated the strongest activity in both human cancer cell lines, changing the permeability mitochondrial membrane potential and reactive oxygen species (ROS) levels, and possibly inducing mtDNA or nDNA damage. In conclusion, the abietane diterpenoids tested may be used in the future as potential natural chemotherapeutic agents Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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18 pages, 2969 KiB

Open AccessArticle

Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing

by Najeeb Ur Rehman, Sobia Ahsan Halim, Majid Khan, Hidayat Hussain, Husain Yar Khan, Ajmal Khan, Ghulam Abbas, Kashif Rafiq and Ahmed Al-Harrasi

Pharmaceuticals 2020, 13(5), 94; https://doi.org/10.3390/ph13050094 - 13 May 2020

Cited by 21 | Viewed by 4256

Abstract

Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the [...] Read more.

Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., 1–9 from L. shawii and 10–20 from A. vera. Their structures were confirmed by combined spectroscopic techniques including 1D (¹H and ¹³C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound 5 exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds 1–3, 7, and 12, which depicted IC₅₀ values in the range of 35–60 μM, while 8, 6, and 9 also demonstrated IC₅₀ values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds 5 (IC₅₀ = 14.4 µM), 12 (IC₅₀ = 23.3), and 2 (IC₅₀ = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, 4 possesses the highest antioxidant (55 μM) activity followed by 14 (241 μM). The results indicated that compound 4 can be a promising candidate for antioxidant drugs, while compound 5 is a potential candidate for anticancer drugs. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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14 pages, 1797 KiB

Open AccessArticle

Vasorelaxant Effects Induced by Red Wine and Pomace Extracts of Magliocco Dolce cv.

by Gabriele Carullo, Amer Ahmed, Fabio Fusi, Fabio Sciubba, Maria Enrica Di Cocco, Donatella Restuccia, Umile Gianfranco Spizzirri, Simona Saponara and Francesca Aiello

Pharmaceuticals 2020, 13(5), 87; https://doi.org/10.3390/ph13050087 - 03 May 2020

Cited by 13 | Viewed by 3502

Abstract

Several epidemiological studies demonstrate that moderate (red) wine consumption may afford protection against cardiovascular diseases. Protection is ascribed to the biological activity of wine components, many of which, however, are discarded during winemaking. In vitro rat thoracic aorta rings contracted with phenylephrine or [...] Read more.

Several epidemiological studies demonstrate that moderate (red) wine consumption may afford protection against cardiovascular diseases. Protection is ascribed to the biological activity of wine components, many of which, however, are discarded during winemaking. In vitro rat thoracic aorta rings contracted with phenylephrine or KCl were used to assess the vasorelaxant activity of extracts from wine pomaces (seeds and skins) of the Calabrian autochthonous grape variety Magliocco dolce (Arvino). NMR spectroscopy was used to ascertain their chemical composition. Data demonstrate that seed and skin, but not must, extracts are capable of relaxing vascular preparations in an endothelium-dependent manner, similarly to the red wine extract, due to the presence of comparable amounts of bioactive constituents. In rings pre-contracted with 20–30 mM KCl, only seed extracts showed a moderate relaxation. The most efficacious vasodilating extract (wine) showed a good antioxidant profile in both [(2,2-diphenyl-1-picrylhydrazyl)acid] radical (DPPH) and [2,2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)] radical (ABTS) assays. In conclusion, winemaking from Magliocco dolce grape can provide potentially health-promoting by-products useful in cardiovascular disease management. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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14 pages, 1082 KiB

Open AccessArticle

Polyphenolic Profile and Varied Bioactivities of Processed Taiwanese Grown Broccoli: A Comparative Study of Edible and Non-Edible Parts

by Thanh Ninh Le, Napat Sakulsataporn, Chiu-Hsia Chiu and Pao-Chuan Hsieh

Pharmaceuticals 2020, 13(5), 82; https://doi.org/10.3390/ph13050082 - 28 Apr 2020

Cited by 13 | Viewed by 3540

Abstract

Broccoli contains a substantial amount of bioactive compounds such as glucosinolates, phenolics, and essential nutrients, which are positively linked to health-promoting effects. This work aimed to evaluate whether both edible and non-edible parts of broccoli could be effective by examining in vitro antioxidant, [...] Read more.

Broccoli contains a substantial amount of bioactive compounds such as glucosinolates, phenolics, and essential nutrients, which are positively linked to health-promoting effects. This work aimed to evaluate whether both edible and non-edible parts of broccoli could be effective by examining in vitro antioxidant, cytotoxic, apoptotic, and antibacterial properties of its floret, leaf, and seed extracts (FE, LE, and SE, correspondingly). High-performance liquid chromatography (HPLC) and various assays exhibited strong antioxidant activities of all samples. LE obtained the highest capacity, correlated to its polyphenolic contents. SE exerted significant cytotoxicity against A549, Caco-2, and HepG2 cancer cell lines at low inhibitory concentration (IC)₅₀ values (0.134, 0.209, and 0.238 mg/mL, respectively), as tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry confirmed apoptosis induction of extracts in Caco-2 cells by revealing an increased subG1 population and a decreased mitochondrial membrane potential. The considerable antibacterial efficacy was observed in either LE and SE against Bacillus subtilis and Salmonella typhimurium (0.39–0.78 mg/mL) using well-agar diffusion and minimum inhibitory concentration (MIC) techniques, along with the weak activity against Staphylococcus aureus and Escherichia coli (1.56–3.13 mg/mL). The findings suggest that broccoli and its byproducts might serve as a promising source for further development of food or pharmaceutical products. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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13 pages, 1356 KiB

Open AccessFeature PaperArticle

Methanolic Extract of the Herb Ononis spinosa L. Is an Antifungal Agent with no Cytotoxicity to Primary Human Cells

by Dejan Stojković, Maria Inês Dias, Danijela Drakulić, Lillian Barros, Milena Stevanović, Isabel C. F. R. Ferreira and Marina D. Soković

Pharmaceuticals 2020, 13(4), 78; https://doi.org/10.3390/ph13040078 - 24 Apr 2020

Cited by 23 | Viewed by 4219

Abstract

Ononis spinosa L. is a plant traditionally used as folk remedy. There are numerous studies regarding chemical constituents and health beneficial properties of Ononidis Radix. The following study was designed to investigate chemical composition and antifungal potential of the methanolic extract obtained from [...] Read more.

Ononis spinosa L. is a plant traditionally used as folk remedy. There are numerous studies regarding chemical constituents and health beneficial properties of Ononidis Radix. The following study was designed to investigate chemical composition and antifungal potential of the methanolic extract obtained from the O. spinosa L. herb. Chemical analyses regarding phenolic compounds of O. spinosa were performed by liquid chromatography with mass spectrometry (LC-DAD-ESI/MSn). Antifungal activity, antibiofilm properties and antifungal mode of action of the extract were evaluated, as well as cytotoxicity. Chemical analyses revealed the presence of flavonoids, isoflavonoids and phenolic acids in O. spinosa, with kaempherol-O-hexoside-pentoside being the most abundant compound (5.1 mg/g extract). Methanolic extract was active against all of the tested microfungi with Penicillium aurantiogriseum being the most sensitive to the extract inhibitory effect at 0.02 mg/mL; and effectively inhibited biofilms formed by Candida strains. Minimum fungicidal concentrations of extract rose in the presence of ergosterol and leakage of cellular components was detected. The extract showed no cytotoxicity to human gingival fibroblast (HGF-1) cells. This study significantly contributes to overall knowledge about medicinal potential of O. spinosa herbal extract and enlightens previously unrevealed properties. O. spinosa aerial parts seem to be an interesting candidate for the development of antifungal preparations, non-toxic to human cells. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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14 pages, 1661 KiB

Open AccessArticle

In Vitro Antibacterial and Antiproliferative Potential of Echinops lanceolatus Mattf. (Asteraceae) and Identification of Potential Bioactive Compounds

by Armel Jackson Seukep, Yong-Li Zhang, Yong-Bing Xu and Ming-Quan Guo

Pharmaceuticals 2020, 13(4), 59; https://doi.org/10.3390/ph13040059 - 30 Mar 2020

Cited by 26 | Viewed by 3863

Abstract

Many species belonging to the genus Echinops are widely used in traditional medicine to treat infectious diseases and cancers. The present study aimed to evaluate the antibacterial and antiproliferative properties of Echinops lanceolatus Mattf. (Asteraceae). The activity of the methanolic extract and subsequent [...] Read more.

Many species belonging to the genus Echinops are widely used in traditional medicine to treat infectious diseases and cancers. The present study aimed to evaluate the antibacterial and antiproliferative properties of Echinops lanceolatus Mattf. (Asteraceae). The activity of the methanolic extract and subsequent partition fractions was investigated against drug-resistant bacteria (Gram-negative and Gram-positive) and human tumor cell lines using broth microdilution and sulforhodamine B (SRB) assay, respectively. Our findings revealed weak to moderate antibacterial activities of tested extracts, with the recorded minimal inhibitory concentrations ranging from 256 to 1024 µg/mL. The ethyl acetate fraction (EL-EA) was found to be the most effective. Likewise, that fraction displayed strong antiproliferative potential with recorded IC₅₀ of 8.27 µg/mL and 28.27 µg/mL on A549 and HeLa cells, respectively. An analysis based on the ultra-performance liquid chromatography–electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS) of the EL-EA fraction allowed the identification of 32 compounds, of which quinic acid and derivatives, cinnamic acid derivatives, dihydrokaempferol, naringenin-7-O-glucoside, apigenin-7-O-d-glucoside, naringin, apigenin, rhoifolin, coniferyl aldehyde, and secoisolariciresinol are well-known compounds of biological importance. This study is first to report on the biological activity and phytochemical profile of E. lanceolatus. We provide a baseline to consider E. lanceolatus as a valuable source of anti-infective and antiproliferative agents. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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Review

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23 pages, 3051 KiB

Open AccessFeature PaperReview

Mānuka Oil—A Review of Antimicrobial and Other Medicinal Properties

by Cynthia Mathew, Wubshet Tesfaye, Phil Rasmussen, Gregory M Peterson, Andrew Bartholomaeus, Manab Sharma and Jackson Thomas

Pharmaceuticals 2020, 13(11), 343; https://doi.org/10.3390/ph13110343 - 26 Oct 2020

Cited by 19 | Viewed by 7447

Abstract

Mānuka oil is an essential oil derived from Leptospermum scoparium, a plant that has been used by the indigenous populations of New Zealand and Australia for centuries. Both the extracted oil and its individual components have been associated with various medicinal properties. [...] Read more.

Mānuka oil is an essential oil derived from Leptospermum scoparium, a plant that has been used by the indigenous populations of New Zealand and Australia for centuries. Both the extracted oil and its individual components have been associated with various medicinal properties. Given the rise in resistance to conventional antibiotics, natural products have been targeted for the development of antimicrobials with novel mechanism of action. This review aimed to collate available evidence on the antimicrobial, anti-parasitic and anti-inflammatory activities of mānuka oil and its components. A comprehensive literature search of was conducted using PubMed and Embase (via Scopus) targeting articles from database inception until June 2020. Chemical structures and IUPAC names were sourced from PubChem. Unpublished information from grey literature databases, Google search, targeted websites and Google Patents were also included. The present review found extensive in vitro data supporting the antimicrobial effects of mānuka oil warrants further clinical studies to establish its therapeutic potential. Clinical evidence on its efficacy, safety and dosing guidelines are necessary for its implementation for medical purposes. Further work on regulation, standardization and characterization of the medicinal properties of mānuka oil is required for establishing consistent efficacy of the product. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

26 pages, 1236 KiB

Open AccessFeature PaperReview

Role of Flavonoids in the Interactions among Obesity, Inflammation, and Autophagy

by María José García-Barrado, María Carmen Iglesias-Osma, Elena Pérez-García, Sixto Carrero, Enrique J. Blanco, Marta Carretero-Hernández and José Carretero

Pharmaceuticals 2020, 13(11), 342; https://doi.org/10.3390/ph13110342 - 26 Oct 2020

Cited by 31 | Viewed by 4224

Abstract

Nowadays, obesity is considered as one of the main concerns for public health worldwide, since it encompasses up to 39% of overweight and 13% obese (WHO) adults. It develops because of the imbalance in the energy intake/expenditure ratio, which leads to excess nutrients [...] Read more.

Nowadays, obesity is considered as one of the main concerns for public health worldwide, since it encompasses up to 39% of overweight and 13% obese (WHO) adults. It develops because of the imbalance in the energy intake/expenditure ratio, which leads to excess nutrients and results in dysfunction of adipose tissue. The hypertrophy of adipocytes and the nutrients excess trigger the induction of inflammatory signaling through various pathways, among others, an increase in the expression of pro-inflammatory adipocytokines, and stress of the endoplasmic reticulum (ER). A better understanding of obesity and preventing its complications are beneficial for obese patients on two facets: treating obesity, and treating and preventing the pathologies associated with it. Hitherto, therapeutic itineraries in most cases are based on lifestyle modifications, bariatric surgery, and pharmacotherapy despite none of them have achieved optimal results. Therefore, diet can play an important role in the prevention of adiposity, as well as the associated disorders. Recent results have shown that flavonoids intake have an essential role in protecting against oxidative damage phenomena, and presents biochemical and pharmacological functions beneficial to human health. This review summarizes the current knowledge of the anti-inflammatory actions and autophagic flux of natural flavonoids, and their molecular mechanisms for preventing and/or treating obesity. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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15 pages, 982 KiB

Open AccessReview

The Phytochemical Constituents and Pharmacological Activities of Annona atemoya: A Systematic Review

by Bassam S. M. Al Kazman, Joanna E. Harnett and Jane R. Hanrahan

Pharmaceuticals 2020, 13(10), 269; https://doi.org/10.3390/ph13100269 - 24 Sep 2020

Cited by 10 | Viewed by 5084

Abstract

Annona atemoya also known as the custard apple is a hybrid between two Annonaceae species: Cherimoya (Annona cherimola) and the sugar apple (Annona squamosa). It is widely cultivated in tropical and subtropical continents including north and south America, Asia, [...] Read more.

Annona atemoya also known as the custard apple is a hybrid between two Annonaceae species: Cherimoya (Annona cherimola) and the sugar apple (Annona squamosa). It is widely cultivated in tropical and subtropical continents including north and south America, Asia, Africa and Australia. Despite becoming an increasingly important commercial fruit plant due to its’ creamy succulent flesh, compared to other Annonaceae species relatively few studies have investigated the phytochemistry and bioactivities of A. atemoya. Studies that evaluated A. atemoya extracts and its constituents were searched through the databases Scopus, Pubmed and Embase from inception to June 2020. Constituents of A. atemoya include alkaloids, flavonoids, terpenes and acetogenins. The results indicate that the constituents of A. atemoya possess cytotoxic, anti-angiogenic, hypolipidemic, antioxidant, anti-inflammatory and neuroprotective activities. However, many of these studies are currently limited in quality and further phytochemical and pharmacological studies are required. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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14 pages, 298 KiB

Open AccessReview

Future of Chondroprotectors in the Treatment of Degenerative Processes of Connective Tissue

by Stanislav Sukhikh, Olga Babich, Alexander Prosekov, Nikolai Patyukov and Svetlana Ivanova

Pharmaceuticals 2020, 13(9), 220; https://doi.org/10.3390/ph13090220 - 28 Aug 2020

Cited by 19 | Viewed by 4837

Abstract

Osteoarthritis is one of the most common diseases of the connective tissue of the elderly. It was found that most epidemiological studies used the Kellgren and Lawrence system for classification of osteoarthritis, which indicates one of the 5 degrees (0–4) of osteoarthritis in [...] Read more.

Osteoarthritis is one of the most common diseases of the connective tissue of the elderly. It was found that most epidemiological studies used the Kellgren and Lawrence system for classification of osteoarthritis, which indicates one of the 5 degrees (0–4) of osteoarthritis in various joints according to the radiographic atlas. It has been proven that chondroprotectors are represented by the following active substances: chondroitin sulfate, glucosamine sulfate or hydrochloride, hyaluronic acid, glycosaminoglycans, extraction preparations from animal or plant raw materials. The sources of raw materials for the manufacture of combined chondroprotectors are known, methods for their preparation and use are described. The main drugs on the chondroprotective market are presented. The effectiveness of their use for the treatment of osteoarthritis has been proven. It was found that preparations containing chondroitin sulfate have anti-inflammatory activity, affecting mainly the cellular component of inflammation, stimulate the synthesis of hyaluronic acid and proteoglycans. Methods of treating osteoarthritis using cell therapy (the use of readily available, highly proliferative, and multipotent mesenchymal stromal cells) are presented. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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30 pages, 1166 KiB

Open AccessReview

Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies

by Malgorzata Sztiller-Sikorska and Malgorzata Czyz

Pharmaceuticals 2020, 13(8), 194; https://doi.org/10.3390/ph13080194 - 14 Aug 2020

Cited by 62 | Viewed by 5241

Abstract

Primary and acquired resistance of cancer to therapy is often associated with activation of nuclear factor kappa B (NF-κB). Parthenolide (PN) has been shown to inhibit NF-κB signaling and other pro-survival signaling pathways, induce apoptosis and reduce a subpopulation of cancer stem-like cells [...] Read more.

Primary and acquired resistance of cancer to therapy is often associated with activation of nuclear factor kappa B (NF-κB). Parthenolide (PN) has been shown to inhibit NF-κB signaling and other pro-survival signaling pathways, induce apoptosis and reduce a subpopulation of cancer stem-like cells in several cancers. Multimodal therapies that include PN or its derivatives seem to be promising approaches enhancing sensitivity of cancer cells to therapy and diminishing development of resistance. A number of studies have demonstrated that several drugs with various targets and mechanisms of action can cooperate with PN to eliminate cancer cells or inhibit their proliferation. This review summarizes the current state of knowledge on PN activity and its potential utility as complementary therapy against different cancers. Full article

(This article belongs to the Special Issue Bioactive Compounds from Plants and Foods with Pharmaceutical Interest)

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