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14 pages, 3664 KiB

Open AccessArticle

Chrysin Is Immunomodulatory and Anti-Inflammatory against Complete Freund’s Adjuvant-Induced Arthritis in a Pre-Clinical Rodent Model

by Muhammad Asif Faheem, Tasleem Akhtar, Nadia Naseem, Usman Aftab, Muhammad Shoaib Zafar, Safdar Hussain, Muhammad Shahzad and Glenda Carolyn Gobe

Pharmaceutics 2023, 15(4), 1225; https://doi.org/10.3390/pharmaceutics15041225 - 12 Apr 2023

Cited by 1 | Viewed by 1686

Abstract

Chrysin (5,7-dihydroxyflavone) has many pharmacological properties including anti-inflammatory actions. The objective of this study was to evaluate the anti-arthritic activity of chrysin and to compare its effect with the non-steroidal anti-inflammatory agent, piroxicam, against complete Freund’s adjuvant (CFA)-induced arthritis in a pre-clinical model [...] Read more.

Chrysin (5,7-dihydroxyflavone) has many pharmacological properties including anti-inflammatory actions. The objective of this study was to evaluate the anti-arthritic activity of chrysin and to compare its effect with the non-steroidal anti-inflammatory agent, piroxicam, against complete Freund’s adjuvant (CFA)-induced arthritis in a pre-clinical model in rats. Rheumatoid arthritis was induced by injecting CFA intra-dermally in the sub-plantar region of the left hind paw of rats. Chrysin (50 and 100 mg/kg) and piroxicam (10 mg/kg) were given to rats with established arthritis. The model of arthritis was characterized using an index of arthritis, with hematological, biological, molecular, and histopathological parameters. Treatment with chrysin significantly reduced the arthritis score, inflammatory cells, erythrocyte sedimentation rate, and rheumatoid factor. Chrysin also reduced the mRNA levels of tumor necrosis factor, nuclear factor kappa-B, and toll-like recepter-2 and increased anti-inflammatory cytokines interleukin-4 and -10, as well as the hemoglobin levels. Using histopathology and microscopy, chrysin reduced the severity of arthritis in joints, infiltration of inflammatory cells, subcutaneous inflammation, cartilage erosion, bone erosion, and pannus formation. Chrysin showed comparable effects to piroxicam, which is used for the treatment of rheumatoid arthritis. The results showed that chrysin possesses anti-inflammatory and immunomodulatory effects that make it a potential drug for the treatment of arthritis. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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17 pages, 2170 KiB

Open AccessArticle

The Importance of Epigallocatechin as a Scaffold for Drug Development against Flaviviruses

by Mônika A. Coronado, Ian Gering, Marc Sevenich, Danilo S. Olivier, Mohammadamin Mastalipour, Marcos S. Amaral, Dieter Willbold and Raphael J. Eberle

Pharmaceutics 2023, 15(3), 803; https://doi.org/10.3390/pharmaceutics15030803 - 01 Mar 2023

Cited by 1 | Viewed by 1906

Abstract

Arboviruses such as Dengue, yellow fever, West Nile, and Zika are flaviviruses vector-borne RNA viruses transmitted biologically among vertebrate hosts by blood-taking vectors. Many flaviviruses are associated with neurological, viscerotropic, and hemorrhagic diseases, posing significant health and socioeconomic concerns as they adapt to [...] Read more.

Arboviruses such as Dengue, yellow fever, West Nile, and Zika are flaviviruses vector-borne RNA viruses transmitted biologically among vertebrate hosts by blood-taking vectors. Many flaviviruses are associated with neurological, viscerotropic, and hemorrhagic diseases, posing significant health and socioeconomic concerns as they adapt to new environments. Licensed drugs against them are currently unavailable, so searching for effective antiviral molecules is still necessary. Epigallocatechin molecules, a green tea polyphenol, have shown great virucidal potential against flaviviruses, including DENV, WNV, and ZIKV. The interaction of EGCG with the viral envelope protein and viral protease, mainly identified by computational studies, describes the interaction of these molecules with viral proteins; however, how the viral NS2B/NS3 protease interacts with epigallocatechin molecules is not yet fully deciphered. Consequently, we tested the antiviral potential of two epigallocatechin molecules (EGC and EGCG) and their derivative (AcEGCG) against DENV, YFV, WNV, and ZIKV NS2B/NS3 protease. Thus, we assayed the effect of the molecules and found that a mixture of the molecules EGC (competitive) and EGCG (noncompetitive) inhibited the virus protease of YFV, WNV, and ZIKV more effectively with IC₅₀ values of 1.17 ± 0.2 µM, 0.58 ± 0.07 µM, and 0.57 ± 0.05 µM, respectively. As these molecules fundamentally differ in their inhibitory mode and chemical structure, our finding may open a new line for developing more effective allosteric/active site inhibitors to combat flaviviruses infection. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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13 pages, 2008 KiB

Open AccessArticle

A Multifunctional Trypsin Protease Inhibitor from Yellow Bell Pepper Seeds: Uncovering Its Dual Antifungal and Hypoglycemic Properties

by Juliana Cotabarren, Brenda Ozón, Santiago Claver, Florencia Geier, Martina Rossotti, Javier Garcia-Pardo and Walter David Obregón

Pharmaceutics 2023, 15(3), 781; https://doi.org/10.3390/pharmaceutics15030781 - 27 Feb 2023

Cited by 1 | Viewed by 1753

Abstract

Fungal infections are a growing public health concern worldwide and the emergence of antifungal resistance has limited the number of therapeutic options. Therefore, developing novel strategies for identifying and developing new antifungal compounds is an active area of research in the pharmaceutical industry. [...] Read more.

Fungal infections are a growing public health concern worldwide and the emergence of antifungal resistance has limited the number of therapeutic options. Therefore, developing novel strategies for identifying and developing new antifungal compounds is an active area of research in the pharmaceutical industry. In this study, we purified and characterized a trypsin protease inhibitor obtained from Yellow Bell Pepper (Capsicum annuum L.) seeds. The inhibitor not only showed potent and specific activity against the pathogenic fungus Candida albicans, but was also found to be non-toxic against human cells. Furthermore, this inhibitor is unique in that it also inhibits α-1,4-glucosidase, positioning it as one of the first plant-derived protease inhibitors with dual biological activity. This exciting discovery opens new avenues for the development of this inhibitor as a promising antifungal agent and highlights the potential of plant-derived protease inhibitors as a rich source for the discovery of novel multifunctional bioactive molecules. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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14 pages, 3368 KiB

Open AccessArticle

In Vitro Study of Biological Activity of Tanacetum vulgare Extracts

by Olga Babich, Viktoria Larina, Olesia Krol, Elena Ulrikh, Stanislav Sukhikh, Maxim A. Gureev, Alexander Prosekov and Svetlana Ivanova

Pharmaceutics 2023, 15(2), 616; https://doi.org/10.3390/pharmaceutics15020616 - 12 Feb 2023

Cited by 10 | Viewed by 4921

Abstract

Tanacetum vulgare is an herbaceous plant widely used in folk medicine. It is rich in phenolic acids and flavonoids, which have pharmacological and medicinal properties, such as anthelmintic, antispasmodic, tonic, antidiabetic, diuretic, and antihypertensive. This study aimed to confirm the presence of biologically [...] Read more.

Tanacetum vulgare is an herbaceous plant widely used in folk medicine. It is rich in phenolic acids and flavonoids, which have pharmacological and medicinal properties, such as anthelmintic, antispasmodic, tonic, antidiabetic, diuretic, and antihypertensive. This study aimed to confirm the presence of biologically active substances in Tanacetum vulgare and to determine the pharmacological spectrum of biological activity of Tanacetum vulgare extract components. When preparing Tanacetum vulgare extracts, the highest yield was observed when using the maceration method with a mixture of solvents methanol + trifluoroacetic acid (22.65 ± 0.68%). The biologically active substances in Tanacetum vulgare extract samples were determined using high-performance liquid chromatography. Biologically active substances such as luteolin-7-glucoside (550.80 mg/kg), chlorogenic acid (5945.40 mg/kg), and rosmarinic acid (661.31 mg/kg) were identified. Their structures were determined. The experiments have confirmed the antioxidant and antibacterial activities. Secondary metabolites of Tanacetum vulgare extracts have been found to have previously unknown biological activity types; experimental confirmation of their existence will advance phytochemical research and lead to the development of new drugs. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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28 pages, 2813 KiB

Open AccessArticle

Anti-Candida Activity of Extracts Containing Ellagitannins, Triterpenes and Flavonoids of Terminalia brownii, a Medicinal Plant Growing in Semi-Arid and Savannah Woodland in Sudan

by Enass Y. A. Salih, Riitta Julkunen-Tiitto, Olavi Luukkanen and Pia Fyhrqvist

Pharmaceutics 2022, 14(11), 2469; https://doi.org/10.3390/pharmaceutics14112469 - 15 Nov 2022

Cited by 3 | Viewed by 1678

Abstract

Various parts of Terminalia brownii (Fresen) are used in Sudanese traditional medicine against fungal infections. The present study aimed to verify these uses by investigating the anti-Candida activity and phytochemistry of T. brownii extracts. Established agar diffusion and microplate dilution methods were used [...] Read more.

Various parts of Terminalia brownii (Fresen) are used in Sudanese traditional medicine against fungal infections. The present study aimed to verify these uses by investigating the anti-Candida activity and phytochemistry of T. brownii extracts. Established agar diffusion and microplate dilution methods were used for the antifungal screenings. HPLC-DAD and UHPLC/QTOF-MS were used for the chemical fingerprinting of extracts and for determination of molecular masses. Large inhibition zones and MIC values of 312 µg/mL were obtained with acetone, ethyl acetate and methanol extracts of the leaves and acetone and methanol extracts of the roots. In addition, decoctions and macerations of the leaves and stem bark showed good activity. Sixty compounds were identified from a leaf ethyl acetate extract, showing good antifungal activity. Di-, tri- and tetra-gallotannins, chebulinic acid (eutannin) and ellagitannins, including an isomer of methyl-(S)-flavogallonate, terflavin B and corilagin, were detected in T. brownii leaves for the first time. In addition, genipin, luteolin-7-O-glucoside, apigenin, kaempferol-4’-sulfate, myricetin-3-rhamnoside and sericic acid were also characterized. Amongst the pure compounds present in T. brownii leaves, apigenin and β-sitosterol gave the strongest growth inhibitory effects. From this study, it was evident that the leaf extracts of T. brownii have considerable anti-Candida activity with MIC values ranging from 312 to 2500 µg/mL. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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18 pages, 2838 KiB

Open AccessArticle

Bactericidal Activity of Carvacrol against Streptococcus pyogenes Involves Alteration of Membrane Fluidity and Integrity through Interaction with Membrane Phospholipids

by Niluni M. Wijesundara, Song F. Lee, Zhenyu Cheng, Ross Davidson, David N. Langelaan and H. P. Vasantha Rupasinghe

Pharmaceutics 2022, 14(10), 1992; https://doi.org/10.3390/pharmaceutics14101992 - 21 Sep 2022

Cited by 3 | Viewed by 1654

Abstract

Background: Carvacrol, a mono-terpenoid phenol found in herbs, such as oregano and thyme, has excellent antibacterial properties against Streptococcus pyogenes. However, its mechanism of bactericidal activity on S. pyogenes has not been elucidated. Objectives: This study investigated the bactericidal mechanism of carvacrol [...] Read more.

Background: Carvacrol, a mono-terpenoid phenol found in herbs, such as oregano and thyme, has excellent antibacterial properties against Streptococcus pyogenes. However, its mechanism of bactericidal activity on S. pyogenes has not been elucidated. Objectives: This study investigated the bactericidal mechanism of carvacrol using three strains of S. pyogenes. Methods: Flow cytometry (FCM) experiments were conducted to determine carvacrol’s membrane permeabilization and cytoplasmic membrane depolarization activities. Protoplasts of S. pyogenes were used to investigate carvacrol’s effects on the membrane, followed by gel electrophoresis. The carvacrol-treated protoplasts were examined by transmission electron microscopy (TEM) to observe ultrastructural morphological changes. The fluidity of the cell membrane was measured by steady-state fluorescence anisotropy. Thin-layer chromatographic (TLC) profiling was conducted to study the affinity of carvacrol for membrane phospholipids. Results: Increased membrane permeability and decreased membrane potential from FCM and electron microscopy observations revealed that carvacrol killed the bacteria primarily by disrupting membrane integrity, leading to whole-cell lysis. Ultra-structural morphological changes in the membrane induced by carvacrol over a short period were confirmed using the S. pyogenes protoplast and membrane isolate models in vitro. In addition, changes in the other biophysical properties of the bacterial membrane, including concentration- and time-dependent increased fluidity, were observed. TLC experiments showed that carvacrol preferentially interacts with membrane phosphatidylglycerol (P.G.), phosphatidylethanolamine (P.E.), and cardiolipins (CL). Conclusions: Carvacrol exhibited rapid bactericidal action against S. pyogenes by disrupting the bacterial membrane and increasing permeability, possibly due to affinity with specific membrane phospholipids, such as P.E., P.G., and CL. Therefore, the bactericidal concentration of carvacrol (250 µg/mL) could be used to develop safe and efficacious natural health products for managing streptococcal pharyngitis or therapeutic applications. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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16 pages, 2579 KiB

Open AccessArticle

Antibacterial Activity from Momordica charantia L. Leaves and Flavones Enriched Phase

by Abraão de Jesus B. Muribeca, Paulo Wender P. Gomes, Steven Souza Paes, Ana Paula Alves da Costa, Paulo Weslem Portal Gomes, Jéssica de Souza Viana, José Diogo E. Reis, Sônia das Graças Santa R. Pamplona, Consuelo Silva, Anelize Bauermeister, Lourivaldo da Silva Santos and Milton Nascimento da Silva

Pharmaceutics 2022, 14(9), 1796; https://doi.org/10.3390/pharmaceutics14091796 - 26 Aug 2022

Cited by 5 | Viewed by 2495

Abstract

Momordica charantia L. (Cucurbitaceae) is a plant known in Brazil as “melão de São Caetano”, which has been related to many therapeutic applications in folk medicine. Herein, we describe antibacterial activities and related metabolites for an extract and fractions obtained from the leaves [...] Read more.

Momordica charantia L. (Cucurbitaceae) is a plant known in Brazil as “melão de São Caetano”, which has been related to many therapeutic applications in folk medicine. Herein, we describe antibacterial activities and related metabolites for an extract and fractions obtained from the leaves of that species. An ethanolic extract and its three fractions were used to perform in vitro antibacterial assays. In addition, liquid chromatography coupled to mass spectrometry and the molecular networking approach were used for the metabolite annotation process. Overall, 25 compounds were annotated in the ethanolic extract from M. charantia leaves, including flavones, terpenes, organic acids, and inositol pyrophosphate derivatives. The ethanolic extract exhibited low activity against Proteus mirabilis (MIC 312.5 µg·mL⁻¹) and Klebsiella pneumoniae (MIC 625 µg·mL⁻¹). The ethyl acetate phase showed interesting antibacterial activity (MIC 156.2 µg·mL⁻¹) against Klebsiella pneumoniae, and it was well justified by the high content of glycosylated flavones. Therefore, based on the ethyl acetate phase antibacterial result, we suggest that M. charantia leaves could be considered as an alternative antibacterial source against K. pneumoniae and can serve as a pillar for future studies as well as pharmacological application against the bacteria. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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15 pages, 1558 KiB

Open AccessArticle

The Effect on Hemostasis of Gelatin-Graphene Oxide Aerogels Loaded with Grape Skin Proanthocyanidins: In Vitro and In Vivo Evaluation

by Jessica Borges-Vilches, Claudio Aguayo and Katherina Fernández

Pharmaceutics 2022, 14(9), 1772; https://doi.org/10.3390/pharmaceutics14091772 - 25 Aug 2022

Cited by 3 | Viewed by 1205

Abstract

Using in vitro and in vivo models, this study investigated the hemostatic potential to control bleeding of both unloaded gelatin-graphene oxide aerogels and the same loaded with proanthocyanidins (PAs) from Vitis vinifera grape skin extract. Our results showed that the physicochemical and mechanical [...] Read more.

Using in vitro and in vivo models, this study investigated the hemostatic potential to control bleeding of both unloaded gelatin-graphene oxide aerogels and the same loaded with proanthocyanidins (PAs) from Vitis vinifera grape skin extract. Our results showed that the physicochemical and mechanical properties of the aerogels were not affected by PA inclusion. In vitro studies showed that PA-loaded aerogels increased the surface charge, blood absorption capacity and cell viability compared to unloaded ones. These results are relevant for hemostasis, since a greater accumulation of blood cells on the aerogel surface favors aerogel–blood cell interactions. Although PAs alone were not able to promote hemostasis through extrinsic and intrinsic pathways, their incorporation into aerogels did not affect the in vitro hemostatic activity of these composites. In vivo studies demonstrated that both aerogels had significantly increased hemostatic performance compared to Spongostan^TM and gauze sponge, and no noticeable effects of PA alone on the in vivo hemostatic performance of aerogels were observed; this may have been related to its poor diffusion from the aerogel matrix. Thus, PAs have a positive effect on hemostasis when incorporated into aerogels, although further studies should be conducted to elucidate the role of this extract in the different stages of hemostasis. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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14 pages, 4621 KiB

Open AccessArticle

Cordycepin Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats via Modulation of AMPK and AKT Activation

by Abdulmohsin J. Alamoudi, Sami A. Alessi, Waleed Y. Rizg, Abdulmajeed M. Jali, Awaji Y. Safhi, Fahad Y. Sabei, Sameer Alshehri, Khaled M. Hosny and Ashraf B. Abdel-Naim

Pharmaceutics 2022, 14(8), 1652; https://doi.org/10.3390/pharmaceutics14081652 - 08 Aug 2022

Cited by 2 | Viewed by 2127

Abstract

Benign prostatic hyperplasia (BPH) is a disease that commonly affects elderly men. Cordycepin is an adenosine analog with a wide range of pharmacological activities including antiproliferative and prostatic smooth muscle relaxant effects. This study was designed to assess the actions of cordycepin in [...] Read more.

Benign prostatic hyperplasia (BPH) is a disease that commonly affects elderly men. Cordycepin is an adenosine analog with a wide range of pharmacological activities including antiproliferative and prostatic smooth muscle relaxant effects. This study was designed to assess the actions of cordycepin in testosterone-induced BPH in rats. Animals were divided into six treatment groups: control, cordycepin-alone (10 mg/kg), testosterone-alone (3 mg/kg), cordycepin (5 mg/kg) + testosterone, cordycepin (10 mg/kg) + testosterone, and finasteride (0.5 mg/kg) + testosterone. Treatments were continued daily, 5 days a week, for 4 weeks. Cordycepin significantly prevented the increase in prostate weight and prostate index induced by testosterone. This was confirmed by histopathological examinations. Cordycepin antiproliferative activity was further defined by its ability to inhibit cyclin-D1 and proliferating cell nuclear antigen (PCNA) expression. In addition, cordycepin exhibited significant antioxidant properties as proven by the prevention of lipid peroxidation, reduced glutathione diminution, and superoxide dismutase exhaustion. This was paralleled by anti-inflammatory activity as shown by the inhibition of interleukin-6, tumor necrosis factor-α, and nuclear factor-κB expression in prostatic tissues. It also enhanced apoptosis as demonstrated by its ability to enhance and inhibit mRNA expression of Bax and Bcl2, respectively. Western blot analysis indicated that cordycepin augmented phospho-AMP-activated protein kinase (p-AMPK) and inhibited p-AKT expression. Collectively, cordycepin has the ability to prevent testosterone-induced BPH in rats. This is mediated, at least partially, by its antiproliferative, antioxidant, anti-inflammatory, and pro-apoptotic actions in addition to its modulation of AMPK and AKT activation. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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15 pages, 2613 KiB

Open AccessArticle

Novel Fusidic Acid Cream Containing Metal Ions and Natural Products against Multidrug-Resistant Bacteria

by Hani Naseef, Yousef Sahoury, Mohammad Farraj, Moammal Qurt, Abdallah D. Abukhalil, Nidal Jaradat, Israr Sabri, Abdullah K. Rabba and Mahmmoud Sbeih

Pharmaceutics 2022, 14(8), 1638; https://doi.org/10.3390/pharmaceutics14081638 - 05 Aug 2022

Cited by 3 | Viewed by 2932

Abstract

Background: Drug design and development to overcome antimicrobial resistance continues to be an area of research due to the evolution of microbial resistance mechanisms and the necessity for new treatments. Natural products have been used since the dawn of medicine to heal skin [...] Read more.

Background: Drug design and development to overcome antimicrobial resistance continues to be an area of research due to the evolution of microbial resistance mechanisms and the necessity for new treatments. Natural products have been used since the dawn of medicine to heal skin infections. The antimicrobial properties of fusidic acid, zinc sulfate, and copper sulfate have been studied and are well known. Furthermore, these compounds have different mechanisms of action in targeting microorganisms, either by inhibiting protein synthesis or bacterial cell walls. Therefore, their combination is expected to have synergistic activity in killing bacteria. However, the synergistic antimicrobial activity has not been evaluated in a cream formulation. Therefore, the objectives of this in vitro study were to develop and evaluate the synergistic efficacy of fusidic acid in combinations with natural products, including oleuropein, thyme oil, zinc sulfate, and copper sulfate, as a cream to eradicate fusidic-acid-resistant microorganisms in skin infections. Methods: Three different cream formulations were developed, compared, and labeled F1, F2, and F3. The compounds were studied for their antibacterial activity. In addition, the stability of the cream was investigated at 25 °C and 40 °C in plastic jars over three months. Results: The F2 formula has adequate physicochemical properties. Furthermore, it displays stable and better results than the marketed trade product and has potential inhibition zones (ZOI). Interestingly, considerable numbers (9.5%) of fusidic-acid-resistant Staphylococcus aureus (FRSA) isolates possessed a high resistance pattern with MIC ≥ 128 μg/mL. In contrast, most tested FRSA isolates (90.5%) had a low resistance pattern with MIC ≤ 8 μg/mL. Conclusion: In conclusion, the F2 cream made with fusidic acid, oleuropein, thyme oil, zinc sulfate, and copper sulfate in the right amounts has stable physical and chemical properties and has potential against FRSA as an antimicrobial agent. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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12 pages, 2624 KiB

Open AccessArticle

Chemical Composition and Antimicrobial Activity of Essential Oils from Three Mediterranean Plants against Eighteen Pathogenic Bacteria and Fungi

by Soukaina Razzouk, Mouaad Amine Mazri, Lamya Jeldi, Bacem Mnasri, Lahcen Ouahmane and Mohamed Najib Alfeddy

Pharmaceutics 2022, 14(8), 1608; https://doi.org/10.3390/pharmaceutics14081608 - 01 Aug 2022

Cited by 8 | Viewed by 1919

Abstract

The chemical composition and antimicrobial activity of essential oils (EOs) obtained from three medicinal plants of the Moroccan flora were evaluated. The chemical composition of EOs of Thymus leptobotrys, Laurus nobilis and Syzygium aromaticum was determined using a gas chromatograph coupled with [...] Read more.

The chemical composition and antimicrobial activity of essential oils (EOs) obtained from three medicinal plants of the Moroccan flora were evaluated. The chemical composition of EOs of Thymus leptobotrys, Laurus nobilis and Syzygium aromaticum was determined using a gas chromatograph coupled with mass spectrometry. Carvacrol (75.05%) was the main constituent of T. leptobotrys EOs, while 1,8-cineole (31.48%) and eugenol (82.16%) were the predominant components of L. nobilis and S. aromaticum EOs, respectively. The antimicrobial activity of the EOs was evaluated qualitatively and quantitatively against 18 microbial strains pathogenic to humans by using the disc diffusion method, and by measuring the minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC). The EOs of T. leptobotrys were the most active against the strains tested, with inhibitory zone values ranging from 7.00 to 45.00 mm, and MIC and MMC values ranging from 0.312 to 80.00 mg/mL. In many cases, these EOs exhibited higher antibacterial and antifungal activities than the chemical compounds ciprofloxacin and fluconazole, respectively. This high antimicrobial activity can be ascribed to their richness in carvacrol. The EOs of T. leptobotrys, L. nobilis, and S. aromaticum could be considered a promising alternative to replace chemical antimicrobials, and a readily available natural source of bioactive compounds. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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18 pages, 2672 KiB

Open AccessArticle

Polyphenols-Rich Fraction from Annona muricata Linn. Leaves Attenuates Oxidative and Inflammatory Responses in Neutrophils, Macrophages, and Experimental Lung Injury

by André Lopes Saraiva, Allisson Benatti Justino, Rodrigo Rodrigues Franco, Heitor Cappato Guerra Silva, Felipe dos Santos Arruda, Sandra Gabriela Klein, Mara Rúbia Nunes Celes, Luiz Ricardo Goulart and Foued Salmen Espindola

Pharmaceutics 2022, 14(6), 1182; https://doi.org/10.3390/pharmaceutics14061182 - 31 May 2022

Cited by 1 | Viewed by 1893

Abstract

Annona muricata Linn. is a common plant found in the warmest regions of South and Central America and its use in traditional medicine has been reported for the treatment of various illnesses. In the current study, we investigate the antioxidant and anti-inflammatory activities [...] Read more.

Annona muricata Linn. is a common plant found in the warmest regions of South and Central America and its use in traditional medicine has been reported for the treatment of various illnesses. In the current study, we investigate the antioxidant and anti-inflammatory activities of crude extract and fractions from A. muricata L. leaves in isolated murine phagocytic immune cells as well as experimental LPS-induced acute lung injury (ALI). In a luminol-dependent chemiluminescence assay, we showed that ethyl acetate (EtOAc.f) and n-butanol (BuOH.f) fractions—both rich in polyphenols—reduced the generation of reactive oxygen species (ROS) by neutrophils stimulated with opsonized zymosan; similar results were found in culture of bone marrow-derived macrophages (BMDMs). By evaluating anti-inflammatory activity in BMDMs, EtOAc.f and BuOH.f reduced secretion of IL-6 and expression of the co-stimulatory molecule CD40. Furthermore, in LPS-induced ALI, oral administration of EtOAc.f reduced myeloperoxidase (MPO) activity in lung tissue. In addition, on a mechanism dependent on glutathione levels, the oxidative damage was also attenuated. These findings revealed direct antioxidant and anti-inflammatory activities of polyphenols-rich fractions of A. muricata L. leaves on neutrophils and macrophages. Moreover, the reduced oxidative damage and levels of inflammatory markers in experimental ALI suggest that these fractions might be explored for the development of new therapies for inflammatory conditions. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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20 pages, 4108 KiB

Open AccessArticle

The Antitumoral/Antimetastatic Action of the Flavonoid Brachydin A in Metastatic Prostate Tumor Spheroids In Vitro Is Mediated by (Parthanatos) PARP-Related Cell Death

by Diego Luis Ribeiro, Katiuska Tuttis, Larissa Cristina Bastos de Oliveira, Juliana Mara Serpeloni, Izabela Natalia Faria Gomes, André van Helvoort Lengert, Cláudia Quintino da Rocha, Rui Manuel Reis, Ilce Mara de Syllos Cólus and Lusânia Maria Greggi Antunes

Pharmaceutics 2022, 14(5), 963; https://doi.org/10.3390/pharmaceutics14050963 - 29 Apr 2022

Cited by 10 | Viewed by 2196

Abstract

Metastatic prostate cancer (mPCa) is resistant to several chemotherapeutic agents. Brachydin A (BrA), a glycosylated flavonoid extracted from Fridericia platyphylla, displays a remarkable antitumoral effect against in vitro mPCa cells cultured as bidimensional (2D) monolayers. Considering that three-dimensional (3D) cell cultures provide [...] Read more.

Metastatic prostate cancer (mPCa) is resistant to several chemotherapeutic agents. Brachydin A (BrA), a glycosylated flavonoid extracted from Fridericia platyphylla, displays a remarkable antitumoral effect against in vitro mPCa cells cultured as bidimensional (2D) monolayers. Considering that three-dimensional (3D) cell cultures provide a more accurate response to chemotherapeutic agents, this study investigated the antiproliferative/antimetastatic effects of BrA and the molecular mechanisms underlying its action in mPCa spheroids (DU145) in vitro. BrA at 60–100 μM was cytotoxic, altered spheroid morphology/volume, and suppressed cell migration and tumor invasiveness. High-content analysis revealed that BrA (60–100 µM) reduced mitochondrial membrane potential and increased apoptosis and necrosis markers, indicating that it triggered cell death mechanisms. Molecular analysis showed that (i) 24-h treatment with BrA (80–100 µM) increased the protein levels of DNA disruption markers (cleaved-PARP and p-γ-H2AX) as well as decreased the protein levels of anti/pro-apoptotic (BCL-2, BAD, and RIP3K) and cell survival markers (p-AKT1 and p-44/42 MAPK); (ii) 72-h treatment with BrA increased the protein levels of effector caspases (CASP3, CASP7, and CASP8) and inflammation markers (NF-kB and TNF-α). Altogether, our results suggest that PARP-mediated cell death (parthanatos) is a potential mechanism of action. In conclusion, BrA confirms its potential as a candidate drug for preclinical studies against mPCa. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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Review

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14 pages, 1983 KiB

Open AccessReview

Chemical and Biological Properties of Biochanin A and Its Pharmaceutical Applications

by Zhen-Jie Feng and Wing-Fu Lai

Pharmaceutics 2023, 15(4), 1105; https://doi.org/10.3390/pharmaceutics15041105 - 30 Mar 2023

Cited by 6 | Viewed by 1943

Abstract

Biochanin A (BCA), an isoflavone derived from various plants such as chickpea, red clover and soybean, is attracting increasing attention and is considered to have applications in the development of pharmaceuticals and nutraceuticals due to its anti-inflammatory, anti-oxidant, anti-cancer and neuroprotective properties. To [...] Read more.

Biochanin A (BCA), an isoflavone derived from various plants such as chickpea, red clover and soybean, is attracting increasing attention and is considered to have applications in the development of pharmaceuticals and nutraceuticals due to its anti-inflammatory, anti-oxidant, anti-cancer and neuroprotective properties. To design optimised and targeted BCA formulations, on one hand there is a need for more in-depth studies on the biological functions of BCA. On the other hand, further studies on the chemical conformation, metabolic composition and bioavailability of BCA need to be conducted. This review highlights the various biological functions, extraction methods, metabolism, bioavailability, and application prospects of BCA. It is hoped that this review will provide a basis for understanding the mechanism, safety and toxicity of BCA and implementing the development of BCA formulations. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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30 pages, 1592 KiB

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Mechanism and Antibacterial Activity of Gold Nanoparticles (AuNPs) Functionalized with Natural Compounds from Plants

by Anna Timoszyk and Renata Grochowalska

Pharmaceutics 2022, 14(12), 2599; https://doi.org/10.3390/pharmaceutics14122599 - 25 Nov 2022

Cited by 11 | Viewed by 2294

Abstract

Recently, the biosynthesis of gold nanoparticles (AuNPs) has been widely studied and described. In the age of bacterial drug resistance, an intensive search for new agents with antibacterial properties or a new form of antibiotics with effective action is necessary. As a result, [...] Read more.

Recently, the biosynthesis of gold nanoparticles (AuNPs) has been widely studied and described. In the age of bacterial drug resistance, an intensive search for new agents with antibacterial properties or a new form of antibiotics with effective action is necessary. As a result, the antibacterial activity of AuNPs functionalized with natural compounds is being investigated more frequently. AuNPs biosynthesized with plant extract or functionalized with bioactive compounds isolated from plants could be particularly useful for pharmaceutical applications. The biosynthesized AuNPs are stabilized by an envelope, which may consist of flavonoids, phenolic acids, lipids and proteins as well as carbohydrates and vitamins. The composition of the natural coating affects the size, shape and stability of the AuNPs and is also responsible for interactions with the bacterial cell wall. Recently, several mechanisms of AuNP interactions with bacterial cells have been identified. Nevertheless, they are not yet well understood, due to the large diversity of plants and biosynthesized AuNPs. Understanding the antibacterial mechanisms allows for the creation of pharmaceutical formulations in the most useful form. Utilizing AuNPs functionalized with plant compounds as antibacterial agents is still a new concept. However, the unique physicochemical and biological properties of AuNPs emphasises their potential for a broad range of applications in the future. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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Open AccessReview

Nanoscale Delivery Systems of Lutein: An Updated Review from a Pharmaceutical Perspective

by Aslihan Hilal Algan, Ayca Gungor-Ak and Aysegul Karatas

Pharmaceutics 2022, 14(9), 1852; https://doi.org/10.3390/pharmaceutics14091852 - 02 Sep 2022

Cited by 17 | Viewed by 2372

Abstract

Carotenoids are natural lipid-soluble pigments that produce yellow to red colors in plants as well as providing bright coloration in vegetables and fruits. Lutein belongs to the xanthophyll subgroup of the carotenoid family, which plays an essential role in photosynthesis and photoprotection in [...] Read more.

Carotenoids are natural lipid-soluble pigments that produce yellow to red colors in plants as well as providing bright coloration in vegetables and fruits. Lutein belongs to the xanthophyll subgroup of the carotenoid family, which plays an essential role in photosynthesis and photoprotection in nature. In the human body, lutein, together with its isomer zeaxanthin and its metabolite meso-zeaxanthin, accumulates in the macula of the eye retina, which is responsible for central, high-resolution, and color vision. As a bioactive phytochemical, lutein has essential physiological functions, providing photoprotection against damaging blue light, along with the neutralization of oxidants and the preservation of the structural and functional integrity of cellular membranes. As a potent antioxidant and anti-inflammatory agent, lutein unfortunately has a low bioavailability because of its lipophilicity and a low stability as a result of its conjugated double bonds. In order to enhance lutein stability and bioavailability and achieve its controlled delivery to a target, nanoscale delivery systems, which have great potential for the delivery of bioactive compounds, are starting to be employed. The current review highlights the advantages and innovations associated with incorporating lutein within promising nanoscale delivery systems, such as liposomes, nanoemulsions, polymer nanoparticles, and polymer–lipid hybrid nanoparticles, as well as their unique physiochemical properties. Full article

(This article belongs to the Special Issue Bioactive Molecules from Plants: Discovery and Pharmaceutical Applications (Volume II))

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