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Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Plant-Derived Antibiotics".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 26254

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Prof. Dr. Marcello Iriti

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Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, 20133 Milan, Italy
Interests: essential oils; bioactive phytochemicals; ethnopharmacology; antimicrobial resistance; one health; food security
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Dr. Elena Varoni

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Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy
Interests: oral medicine; biomaterials; nutrition; oral health
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Dr. Sara Vitalini

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Department of Agricultural and Environmental Sciences, Università degli Studi di Milano, Milan, Italy
Interests: crop protection; plant diseases; bioactivity; phytochemistry; ethnopharmacology; natural products
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Special Issue Information

Dear Colleagues,

The urgent need for novel antimicrobial drugs to reduce the global burden of infectious diseases has greatly stimulated the exploration of plant products as a source of novel and effective phytotherapeutic agents. Indeed, plant products represent a nearly unlimited source of (multitarget) active ingredients, consisting of complex mixtures of hundreds of different compounds that may be additively or synergistically active once administered. In addition, plant extracts, essential oils and phytochemicals can be useful in adjuvant therapy for improving the efficacy of conventional antimicrobials, decreasing their adverse effects, and reversing multidrug resistance, the latter being a global threat due to the genetic plasticity and environmental adaptability of pathogenic microorganisms. Not least, selected phytochemicals can also be used as templates for the development of new scaffolds for antimicrobial drugs.

Prof. Dr. Marcello Iriti
Prof. Dr. Elena Maria Varoni
Prof. Dr. Sara Vitalini
Guest Editors

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Keywords

plant products
marine drugs
infectious diseases
antibiotics
fungicides
antibacterial agents
antifungal/antimycotic agents
crop protection
pesticides
antibiotic resistance
multidrug resistance
cross resistance
ethnopharmacology
preclinical (in vitro/in vivo) studies
clinical/in-human studies
evidence-based phytotherapy
systematic reviews and meta-analyses

Published Papers (10 papers)

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Research

23 pages, 9527 KiB

Open AccessArticle

Anti-Biofilm and Antibacterial Activities of Cycas media R. Br Secondary Metabolites: In Silico, In Vitro, and In Vivo Approaches

by Nashwah G. M. Attallah, Omnia Momtaz Al-Fakhrany, Engy Elekhnawy, Ismail A. Hussein, Moataz A. Shaldam, Najla Altwaijry, Moneerah J. Alqahtani and Walaa A. Negm

Antibiotics 2022, 11(8), 993; https://doi.org/10.3390/antibiotics11080993 - 24 Jul 2022

Cited by 19 | Viewed by 1851

Abstract

Enterococcus species possess many virulence factors that have an essential role in exacerbating the infections caused by them. The current study aimed to evaluate the effect of the secondary metabolites ginkgetin (GINK) and sotetsuflavone (SOTE), isolated from Cycas media R. Br dichloromethane fraction, on Enterococcus faecalis (E. faecalis) isolates for the first time. The antibacterial and antivirulence activities of the isolated compounds were investigated using docking studies and in vitro by determination of the minimum inhibitory concentrations (MICs). Additionally, flow cytometry and scanning electron microscope (SEM) were utilized to assess the effect of SOTE on the tested bacteria. Moreover, crystal violet assay and qRT-PCR were used to test the effect of SOTE on the biofilm-forming ability of E. faecalis isolates. In addition, a systemic infection model was utilized in vivo to investigate the antibacterial activity of SOTE. We found that both GINK and SOTE showed a good affinity for the five proteins enrolled in the virulence of E. faecalis, with SOTE being the highest, suggesting the possible mechanisms for the antivirulence activity of both ligands. In addition, SOTE exhibited a higher antibacterial activity than GINK, as the values of the MICs of SOTE were lower than those of GINK. Thus, we performed the in vitro and in vivo assays on SOTE. However, they did not exhibit any significant variations (p > 0.05) in the membrane depolarization of E. faecalis isolates. Moreover, as evaluated by SEM, SOTE caused distortion and deformation in the treated cells. Regarding its impact on the biofilm formation, it inhibited the biofilm-forming ability of the tested isolates, as determined by crystal violet assay and qRT-PCR. The in vivo experiment revealed that SOTE resulted in a reduction of the inflammation of the liver and spleen with an increase in the survival rate. SOTE also improved the liver-function tests and decreased tumor necrosis factor-alpha using immunostaining and the inflammation markers, interleukins (IL-1β and IL-6), using ELISA. Thus, we can conclude that SOTE could be a promising compound that should be investigated in future preclinical and clinical studies. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)

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21 pages, 4005 KiB

Open AccessArticle

Investigating the Antituberculosis Activity of Selected Commercial Essential Oils and Identification of Active Constituents Using a Biochemometrics Approach and In Silico Modeling

by Katyna J. Boussamba-Digombou, Maxleene Sandasi, Guy P. Kamatou, Sandy van Vuuren, Rafal Sawicki, Zeynab Fakhar and Alvaro M. Viljoen

Antibiotics 2022, 11(7), 948; https://doi.org/10.3390/antibiotics11070948 - 14 Jul 2022

Cited by 1 | Viewed by 1770

Abstract

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis which has become prevalent due to the emergence of resistant M. tuberculosis strains. The use of essential oils (EOs) as potential anti-infective agents to treat microbial infections, including TB, offers promise due to their long historical use and low adverse effects. The current study aimed to investigate the in vitro anti-TB activity of 85 commercial EOs, and identify compounds responsible for the activity, using a biochemometrics approach. A microdilution assay was used to determine the antimycobacterial activity of the EOs towards some non-pathogenic Mycobacterium strains. In parallel, an Alamar blue assay was used to investigate antimycobacterial activity towards the pathogenic M. tuberculosis strain. Chemical profiling of the EOs was performed using gas chromatography-mass spectrometry (GC-MS) analysis. Biochemometrics filtered out putative biomarkers using orthogonal projections to latent structures discriminant analysis (OPLS-DA). In silico modeling was performed to identify potential therapeutic targets of the active biomarkers. Broad-spectrum antimycobacterial activity was observed for Cinnamomum zeylanicum (bark) (MICs = 1.00, 0.50, 0.25 and 0.008 mg/mL) and Levisticum officinale (MICs = 0.50, 0.5, 0.5 and 0.004 mg/mL) towards M. smegmatis, M. fortuitum, M. gordonae and M. tuberculosis, respectively. Biochemometrics predicted cinnamaldehyde, thymol and eugenol as putative biomarkers. Molecular docking demonstrated that cinnamaldehyde could serve as a scaffold for developing a novel class of antimicrobial compounds by targeting FtsZ and PknB from M. tuberculosis. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)

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21 pages, 2113 KiB

Open AccessArticle

Antibacterial Screening, Biochemometric and Bioautographic Evaluation of the Non-Volatile Bioactive Components of Three Indigenous South African Salvia Species

by Margaux Lim Ah Tock, Sandra Combrinck, Guy Kamatou, Weiyang Chen, Sandy Van Vuuren and Alvaro Viljoen

Antibiotics 2022, 11(7), 901; https://doi.org/10.3390/antibiotics11070901 - 06 Jul 2022

Cited by 4 | Viewed by 1644

Abstract

Salvia africana-lutea L., S. lanceolata L., and S. chamelaeagnea L. are used in South Africa as traditional medicines to treat infections. This paper describes an in-depth investigation into their antibacterial activities to identify bioactive compounds. Methanol extracts from 81 samples were screened against seven bacterial pathogens, using the microdilution assay. Biochemometric models were constructed using data derived from minimum inhibitory concentration (MIC) and ultra-performance liquid chromatography-mass spectrometry data. Active molecules in selected extracts were tentatively identified using high-performance thin layer chromatography (HPTLC), combined with bioautography, and finally, by analysis of active zone eluates by mass spectrometry (MS) via a dedicated interface. Salvia chamelaeagnea displayed notable activity towards all seven pathogens, and the activity, reflected by MICs, was superior to that of the other two species, as confirmed through ANOVA. Biochemometric models highlighted potentially bioactive compounds, including rosmanol methyl ether, epiisorosmanol methyl ether and carnosic acid. Bioautography assays revealed inhibition zones against A. baumannii, an increasingly multidrug-resistant pathogen. Mass spectral data of the eluted zones correlated to those revealed through biochemometric analysis. The study demonstrates the application of a biochemometric approach, bioautography, and direct MS analysis as useful tools for the rapid identification of bioactive constituents in plant extracts. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)

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21 pages, 1854 KiB

Open AccessArticle

Antibacterial and Antioxidant Activity of Dysphania ambrosioides (L.) Mosyakin and Clemants Essential Oils: Experimental and Computational Approaches

by Fahd Kandsi, Amine Elbouzidi, Fatima Zahra Lafdil, Nada Meskali, Ali Azghar, Mohamed Addi, Christophe Hano, Adil Maleb and Nadia Gseyra

Antibiotics 2022, 11(4), 482; https://doi.org/10.3390/antibiotics11040482 - 05 Apr 2022

Cited by 39 | Viewed by 3443

Abstract

Dysphania ambrosioides (L.) Mosyakin and Clemants, also known as Mexican tea, and locally known as Mkhinza, is a polymorphic annual and perennial herb, and it is widely used in folk medicine to treat a broad range of illnesses in Morocco. The aim of this study was to determine the phytochemical content and the antioxidant and the antibacterial properties of essential oils isolated from D. ambrosioides aerial components, growing in Eastern Morocco (Figuig). Hydrodistillation was used to separate D. ambrosioides essential oils, and the abundance of each phytocompound was determined by using Gas Chromatography coupled with Mass Spectrometry (GC–MS). In vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and inhibition of β-carotene/linoleic acid bleaching assays were used to determine D. ambrosioides essential oils’ antioxidant activity. The findings revealed relative antioxidative power and modest radical scavenging. The antibacterial activity of the essential oils was broad-spectrum, with Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis as the most susceptible strains tested. To elucidate the physicochemical nature, drug-likeness, and the antioxidant and antibacterial action of the identified phytocomponents, computational techniques, such as ADMET analysis, and molecular docking were used. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)

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14 pages, 3413 KiB

Open AccessArticle

Characterization and Antimicrobial Activity of Nigella sativa Extracts Encapsulated in Hydroxyapatite Sodium Silicate Glass Composite

by Salima Tiji, Mohammed Lakrat, Yahya Rokni, El Miloud Mejdoubi, Christophe Hano, Mohamed Addi, Abdeslam Asehraou and Mostafa Mimouni

Antibiotics 2022, 11(2), 170; https://doi.org/10.3390/antibiotics11020170 - 28 Jan 2022

Cited by 5 | Viewed by 3008

Abstract

N. sativa is an interesting source of bioactive compounds commonly used for various therapeutic purposes. Associate its seeds extracts with biomaterials to improve their antimicrobial properties are highly demanded. This study aims to investigate the encapsulation of NS extracts in hydroxyapatite nanoparticle sodium silicate glass (nHap/SSG) scaffold. NS essential oil (HS) was extracted by hydrodistillation, while hexane (FH) and acetone extracts (FA) were obtained using Soxhlet extraction. (FH) was the most abundant (34%) followed by (FA) (2.02%) and (HS) (1.2%). GC-MS chromatography showed that the (HS) contained beta cymene, alpha thujene, β-pinene and thymoquinone, while (FH) had mostly fatty acids and (FA) decane, 2.9-dimethyl, benzene 1,3,3-trimethylnonyl and beta cymene. Loaded nHap/SGG scaffolds with various amount of (FH), (HS) and (FA) at 1.5, 3, and 6 wt%; were elaborated then characterized by ATR-FTIR, X-ray and SEM techniques and their antimicrobial activity was studied. Samples loaded with 1.5 wt% HE was highly active against C. albicans (19 mm), and at 3 wt% on M. luteus (20 mm) and S. aureus (20 mm). Additionally, loaded scaffolds with 1.5 wt% AE had an important activity against M. luteus (18.9 mm) and S. aureus (19 mm), while the EO had low activities on all bacterial strains. The outcome of this finding indicated that loaded scaffolds demonstrated an important antimicrobial effect that make them promising materials for a wide range of medical applications. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)

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14 pages, 1376 KiB

Open AccessArticle

Protective Effects of Grape Seed Oligomeric Proanthocyanidins in IPEC-J2–Escherichia coli/Salmonella Typhimurium Co-Culture

by Dóra Kovács, Nikolett Palkovicsné Pézsa, Ákos Jerzsele, Miklós Süth and Orsolya Farkas

Antibiotics 2022, 11(1), 110; https://doi.org/10.3390/antibiotics11010110 - 15 Jan 2022

Cited by 11 | Viewed by 2282

Abstract

Intestinal epithelium provides the largest barrier protecting mammalian species from harmful external factors; however, it can be severely compromised by the presence of bacteria in the gastrointestinal (GI) tract. Antibiotics have been widely used for the prevention and treatment of GI bacterial infections, leading to antimicrobial resistance in human and veterinary medicine alike. In order to decrease antibiotic usage, natural substances, such as flavonoids, are investigated to be used as antibiotic alternatives. Proanthocyanidins (PAs) are potential candidates for this purpose owing to their various beneficial effects in humans and animals. In this study, protective effects of grape seed oligomeric proanthocyanidins (GSOPs) were tested in IPEC-J2 porcine intestinal epithelial cells infected with Escherichia coli and Salmonella enterica ser. Typhimurium of swine origin. GSOPs were able to alleviate oxidative stress, inflammation and barrier integrity disruption inflicted by bacteria in the co-culture. Furthermore, GSOPs could decrease the adhesion of both bacteria to IPEC-J2 cells. Based on these observations, GSOPs seem to be promising candidates for the prevention and treatment of gastrointestinal bacterial infections. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)

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15 pages, 3344 KiB

Open AccessArticle

Sanguiin H-6 Fractionated from Cloudberry (Rubus chamaemorus) Seeds Can Prevent the Methicillin-Resistant Staphylococcus aureus Biofilm Development during Wound Infection

by John Jairo Aguilera-Correa, Sara Fernández-López, Iskra Dennisse Cuñas-Figueroa, Sandra Pérez-Rial, Hanna-Leena Alakomi, Liisa Nohynek, Kirsi-Marja Oksman-Caldentey, Juha-Pekka Salminen, Jaime Esteban, Juan Cuadros, Riitta Puupponen-Pimiä, Ramon Perez-Tanoira and Teemu J. Kinnari

Antibiotics 2021, 10(12), 1481; https://doi.org/10.3390/antibiotics10121481 - 03 Dec 2021

Cited by 8 | Viewed by 3846

Abstract

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)

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14 pages, 8832 KiB

Open AccessArticle

Silver Nanoparticles Biosynthesized with Spruce Bark Extract—A Molecular Aggregate with Antifungal Activity against Candida Species

by Anca Delia Mare, Adrian Man, Cristina Nicoleta Ciurea, Felicia Toma, Anca Cighir, Mihai Mareș, Lavinia Berța and Corneliu Tanase

Antibiotics 2021, 10(10), 1261; https://doi.org/10.3390/antibiotics10101261 - 17 Oct 2021

Cited by 13 | Viewed by 2427

Abstract

Due to their high content of biomolecules, combined with silver’s well known antimicrobial potential, silver nanoparticles biosynthesized using spruce bark (AgNP SBEs) demonstrate antibacterial and antioxidant activity, making them a versatile option for developing new antimicrobial agents that might be used for medical treatment or as adjuvants for the classical agents. This study aims to analyze if silver nanoparticles (AgNPs) mediated by spruce bark extract (SBE) and silver salts (AgNP SBE Acetate, AgNP SBE Nitrate) presents antifungal activity against five different Candida spp., synergistic activity with fluconazole, and if they interact with some virulence factors of C. albicans. AgNP SBEs presented MICs (minimum inhibitory concentrations) for all the five tested Candida spp. AgNP SBEs inhibited the growth of C. parapsilosis, C. krusei, and C. guilliermondii, exerted synergistic activity with fluconazole for C. parapsilosis and C. guilliermondii, and inhibited biofilm production for C. albicans, C. auris, and C. guilliermondii. MICs of AgNP SBE Acetate significantly inhibited the production of germ tubes of C. albicans. The expression of C. albicans SAP2 gene was down-regulated by the short-time treatment with MICs of AgNP SBE Acetate, while ALS3 and HSP70 genes were up-regulated by the AgNPs MICs. These results emphasize the potential of using the AgNP SBEs as treatments/adjuvants options, not only against the redundant C. albicans but also for the non-albicans Candida species (which are not as frequently involved in human pathologies, but, sometimes, can be more aggressive). Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)

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14 pages, 2934 KiB

Open AccessArticle

Iriflophenone-3-C-β-d Glucopyranoside from Dryopteris ramosa (Hope) C. Chr. with Promising Future as Natural Antibiotic for Gastrointestinal Tract Infections

by Muhammad Ishaque, Yamin Bibi, Samha Al Ayoubi, Saadia Masood, Sobia Nisa and Abdul Qayyum

Antibiotics 2021, 10(9), 1128; https://doi.org/10.3390/antibiotics10091128 - 18 Sep 2021

Cited by 7 | Viewed by 2285 | Correction

Abstract

Ethnopharmacological approaches provide clues for the search of bioactive compounds. Dryopteris ramosa (Hope) C. Chr. (plant family: Dryopteridaceae) is an ethnomedicinal plant of the Galliyat region of Pakistan. The aqueous fraction (AqF) of D. ramosa is being used by inhabitants of the Galliyat region of Pakistan to treat their gastrointestinal tract ailments, especially those caused by bacteria. The aims of the present study were as follows: (i) to justify the ethnomedicinal uses of the AqF of D. ramosa; (ii) to isolate a bioactive compound from the AqF of D. ramosa; and (iii) to evaluate the antibacterial and cytotoxic potential of the isolated compound. Column chromatography (CC) techniques were used for the isolation studies. Spectroscopic techniques (UV–Vis, MS, 1&2D NMR) were used for structural elucidation. The agar-well diffusion method was used to evaluate the antibacterial potential of “i3CβDGP” against five bacterial strains, and compare it with the known antibiotic “Cefixime”. The brine shrimp lethality test (BSLT) was used for cytotoxic studies. The AqF of D. ramosa afforded “iriflophenone-3-C-β-D glucopyranoside (i3CβDGP)” when subjected to LH20 Sephadex, followed by MPLC silica gel₆₀, and purified by preparative TLC. The “i3CβDGP” showed a strong potential (MIC = 31.1 ± 7.2, 62.5 ± 7.2, and 62.5 ± 7.2 µg/mL) against Klebsiella pneumoniae, Staphylococcus aureus, and Escherichia coli, respectively. On the other hand, the least antibacterial potential was shown by “i3CβDGP” (MIC = 125 ± 7.2 µg/mL), against Bacillus subtilis, in comparison to Cefixime (MIC = 62.5 ± 7.2 µg/mL). The cytotoxicity of “i3CβDGP” was significantly low (LD₅₀ = 10.037 ± 2.8 µg/mL) against Artemia salina nauplii. This study not only justified the ethnomedicinal use of D. ramosa, but also highlighted the importance of ethnomedicinal knowledge. Further studies on AqF and other fractions of D. ramosa are in progress. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)

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10 pages, 300 KiB

Open AccessArticle

Synergistic Anticandidal Effects of Six Essential Oils in Combination with Fluconazole or Amphotericin B against Four Clinically Isolated Candida Strains

by Bouchra Soulaimani, Elena Varoni, Marcello Iriti, Nour-Eddine Mezrioui, Lahcen Hassani and Abdelaziz Abbad

Antibiotics 2021, 10(9), 1049; https://doi.org/10.3390/antibiotics10091049 - 27 Aug 2021

Cited by 7 | Viewed by 2151

Abstract

The development of opportunistic pathogenic Candida strains insensitive to several classes of antifungals has emerged as a major health care problem during the last years. Combinational therapy of natural products (e.g., essential oils, EOs) with conventional antifungals has been suggested as a promising alternative to overcome this medical problem. The present study investigates the potential antifungal activity of EOs extracted from some selected medicinal plants, alone and in combination with two common conventional antifungals (fluconazole and amphotericin B) against four clinical Candida isolates. MIC assays indicated that EOs induced strong anticandidal activities with MIC values ranging from 0.162 to 4.950 mg/mL. The combination of amphotericin B with Thymus leptobotrys, Origanum compactum and Artemisia herba alba EOs provided a synergistic effect against C. krusei only, with MIC gain of four-fold, and additive effect against remaining strains (MIC gain = two-fold). Interesting synergistic interactions were observed by combining all studied EOs with fluconazole, with reduction rates of their MICs ranging from 16 to 512-fold. This synergistic effect was very pronounced with the combination of T. leptobotrys EO and fluconazole. These findings indicate that studied EOs can be used as anti-candidals in combination with antifungals, particularly fluconazole, to counteract the emergence of resistant Candida spp. Full article

(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)

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