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34 pages, 4842 KiB

Open AccessArticle

Globularia alypum L. and Related Species: LC-MS Profiles and Antidiabetic, Antioxidant, Anti-Inflammatory, Antibacterial and Anticancer Potential

by Maja Friščić, Roberta Petlevski, Ivan Kosalec, Josip Madunić, Maja Matulić, Franz Bucar, Kroata Hazler Pilepić and Željan Maleš

Pharmaceuticals 2022, 15(5), 506; https://doi.org/10.3390/ph15050506 - 21 Apr 2022

Cited by 8 | Viewed by 3038

Abstract

Species from the genus Globularia L. have been used as healing agents for various ailments, with utilization of Globularia alypum L. being most frequently reported. The aim of this study was to evaluate the antidiabetic, antioxidant, anti-inflammatory, antibacterial and anticancer potential of G. [...] Read more.

Species from the genus Globularia L. have been used as healing agents for various ailments, with utilization of Globularia alypum L. being most frequently reported. The aim of this study was to evaluate the antidiabetic, antioxidant, anti-inflammatory, antibacterial and anticancer potential of G. alypum and three related species, G. punctata Lapeyr., G. cordifolia L. and G. meridionalis (Podp.) O.Schwarz, in relation to their phytochemical compositions. Globularin and verbascoside were identified using LC-PDA-ESI-MSⁿ as the major metabolites of G. alypum with known biological activities. G. alypum demonstrated the greatest α-glucosidase inhibitory activity and DPPH radical scavenging activity (IC₅₀ = 17.25 μg/mL), while its anti-inflammatory activity was not significantly different from those of related species. All investigated species showed considerable antibacterial activity against methicillin-resistant Staphylococcus aureus in the broth microdilution method (MIC = 1.42–3.79 mg/mL). G. punctata also showed antibacterial activities against Escherichia coli (MIC = 1.42 mg/mL), Bacillus subtilis (MIC = 1.89 mg/mL), B. cereus (MIC = 2.84 mg/mL) and Enterococcus faecalis (MBC = 5.68 mg/mL). G. punctata, G. cordifolia and G. meridionalis showed greater anticancer potential than G. alypum. Obtained results indicate investigated Globularia species could serve as sources of diverse bioactive molecules, with G. punctata having the greatest antibacterial potential. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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15 pages, 3014 KiB

Open AccessArticle

Harpagophytum procumbens Root Extract Mediates Anti-Inflammatory Effects in Osteoarthritis Synoviocytes through CB2 Activation

by Alessia Mariano, Irene Bigioni, Roberto Mattioli, Antonella Di Sotto, Martina Leopizzi, Stefania Garzoli, Pier Francesco Mariani, Pietro Dalla Vedova, Sergio Ammendola and Anna Scotto d’Abusco

Pharmaceuticals 2022, 15(4), 457; https://doi.org/10.3390/ph15040457 - 09 Apr 2022

Cited by 8 | Viewed by 3364

Abstract

The endocannabinoid system is involved in the nociceptive and anti-inflammatory pathways, and a lowered expression of CB2 receptors has been associated with inflammatory conditions, such as osteoarthritis (OA). This suggests that CB2 modulators could be novel therapeutic tools to treat OA. In the [...] Read more.

The endocannabinoid system is involved in the nociceptive and anti-inflammatory pathways, and a lowered expression of CB2 receptors has been associated with inflammatory conditions, such as osteoarthritis (OA). This suggests that CB2 modulators could be novel therapeutic tools to treat OA. In the present study, the involvement of Harpagophytum procumbens root extract, a common ingredient of nutraceuticals used to treat joint disorders, in CB2 modulation has been evaluated. Moreover, to clarify the effects of the pure single components, the bioactive constituent, harpagoside, and the main volatile compounds were studied alone or in a reconstituted mixture. Human fibroblast-like synoviocytes, extracted by joints of patients, who underwent a total knee replacement, were treated with an H. procumbens root extract dissolved in DMSO (HPE_DMSO). The effectiveness of HPE_DMSO to affect CB2 pathways was studied by analyzing the modulation of cAMP, the activation of PKA and ERK MAP kinase, and the modulation of MMP-13 production. HPE_DMSO was able to inhibit the cAMP production and MAP kinase activation and to down-regulate the MMP-13 production. Pure compounds were less effective than the whole phytocomplex, thus suggesting the involvement of synergistic interactions. Present findings encourage further mechanistic studies and support the scientific basis of the use of H. procumbens in joint disorders. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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15 pages, 1156 KiB

Open AccessArticle

Plectranthus zeylanicus: A Rich Source of Secondary Metabolites with Antimicrobial, Disinfectant and Anti-Inflammatory Activities

by Mayuri Napagoda, Jana Gerstmeier, Hannah Butschek, Sybille Lorenz, Sudhara De Soyza, Mallique Qader, Ajith Nagahawatte, Gaya Bandara Wijayaratne, Bernd Schneider, Aleš Svatoš, Lalith Jayasinghe, Andreas Koeberle and Oliver Werz

Pharmaceuticals 2022, 15(4), 436; https://doi.org/10.3390/ph15040436 - 31 Mar 2022

Cited by 2 | Viewed by 2268

Abstract

Plectranthus zeylanicus Benth is used in Sri Lankan folk medicine as a remedy for inflammatory conditions and microbial infections. Our previous investigations revealed potent 5-lipoxygenase (5-LO) inhibitory activity in lipophilic extracts of this plant, supporting its anti-inflammatory potential. In-depth studies on the antimicrobial [...] Read more.

Plectranthus zeylanicus Benth is used in Sri Lankan folk medicine as a remedy for inflammatory conditions and microbial infections. Our previous investigations revealed potent 5-lipoxygenase (5-LO) inhibitory activity in lipophilic extracts of this plant, supporting its anti-inflammatory potential. In-depth studies on the antimicrobial activity have not been conducted and the bioactive ingredients remained elusive. As a continuation of our previous work, the present investigation was undertaken to evaluate the antimicrobial activity of different extracts of P. zeylanicus and to isolate and characterize bioactive secondary metabolites. Different organic extracts of this plant were analyzed for their antibacterial activity, and the most active extract, i.e., dichloromethane extract, was subjected to bioactivity-guided fractionation, which led to the isolation of 7α-acetoxy-6β-hydroxyroyleanone. This compound displayed strong antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimum inhibitory concentration of 62.5 µg/mL, and its disinfectant capacity was comparable to the potency of a commercial disinfectant. Moreover, 7α-acetoxy-6β-hydroxyroyleanone inhibits 5-LO with IC₅₀ values of 1.3 and 5.1 µg/mL in cell-free and cell-based assays, respectively. These findings rationalize the ethnopharmacological use of P. zeylanicus as antimicrobial and anti-inflammatory remedy. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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13 pages, 2756 KiB

Open AccessArticle

Euphorbia supina Extracts Block NADPH Oxidase-Mediated, Ceramide-Induced Apoptosis Initiated by Diesel Particulate Matter

by Kyong-Oh Shin, Sungeun Kim, Bokyung Kim, Hye-Yoon Park, Eunhee Jung, Garyun Kim, Donghee Kim, Hwang Eui Cho, Yoshikazu Uchida and Kyungho Park

Pharmaceuticals 2022, 15(4), 431; https://doi.org/10.3390/ph15040431 - 31 Mar 2022

Cited by 3 | Viewed by 2021

Abstract

Air pollutants contribute to the development of diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary cancer, cardiovascular problems, and some skin diseases. We recently found that a major air pollutant, diesel particulate matter (DPM), induces apoptosis in human keratinocytes by increasing [...] Read more.

Air pollutants contribute to the development of diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary cancer, cardiovascular problems, and some skin diseases. We recently found that a major air pollutant, diesel particulate matter (DPM), induces apoptosis in human keratinocytes by increasing a proapoptotic lipid mediator, ceramide. DPM activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), which stimulates sphingomyelinase, leading to an increased conversion of sphingomyelin to ceramide. Interestingly, we characterized that although NOX is a reactive oxygen species (ROS) generator, the activation of sphingomyelinases by NOX is an ROS-independent mechanism. A Korean weed, prostrate spurge Euphorbia supina Rafin (ESR), has been used for centuries as a folk medicine to treat bronchitis, hepatitis, hemorrhage, and skin inflammation. Flavonoids, terpenes and tannins are enriched in ESR, and although ESR has proven antioxidative activity, its biological activities are largely unknown. Here, we investigate whether and how ESR protects keratinocytes against DPM-mediated apoptosis. We found that ESR-extracts (ESR-Ex) protect keratinocytes from DPM-induced apoptosis by inhibiting NOX activation in keratinocytes in response to DPM. We also demonstrated that ESR-Ex suppresses NOX activation via a blockage of the aryl hydrocarbon receptor (AhR) activation-mediated transcription of neutrophil cytosolic factor 1 (NCF1)/p47phox, a subunit of NOX. Our study reveals previously uncharacterized biological activity of ESR-Ex; i.e., its inhibition of Ahr and NOX activation. Thus, because the inhibition of NOX has already been developed to treat NOX-mediated diseases, including various types of cardiovascular diseases and cancers, initiated by air pollutants and because AhR activation contributes to the development of chronic inflammatory diseases, our study provides further advantages for the medical use of ESR. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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14 pages, 1498 KiB

Open AccessArticle

Daphne jejudoensis Attenuates LPS-Induced Inflammation by Inhibiting TNF-α, IL-1β, IL-6, iNOS, and COX-2 Expression in Periodontal Ligament Cells

by Ji-Yeong Bae, Dong-Seol Lee, You Kyoung Cho, Ji-Yeon Lee, Joo-Hwang Park and Sang Ho Lee

Pharmaceuticals 2022, 15(4), 387; https://doi.org/10.3390/ph15040387 - 22 Mar 2022

Cited by 6 | Viewed by 2467

Abstract

Periodontitis is a common disease involving inflammation and tissue destruction in the periodontal region. Although uncontrolled long-term inflammation in the gingiva may lead to loss of the periodontal ligament, treatments or preventive solutions for periodontitis are scarce. The aim of this study is [...] Read more.

Periodontitis is a common disease involving inflammation and tissue destruction in the periodontal region. Although uncontrolled long-term inflammation in the gingiva may lead to loss of the periodontal ligament, treatments or preventive solutions for periodontitis are scarce. The aim of this study is to find anti-inflammatory material from a natural source that can be used to treat or protect against periodontitis. Daphne species (Thymelaeaceae) are important and popular components of traditional Chinese medicine and are used as anti-inflammatory agents. Daphne jejudoensis is an endemic plant that grows on Jeju Island and was identified as a new species in 2013. In this study, for the first time, we investigated the anti-inflammatory effect of D. jejudoensis leaf extract (DJLE) on human periodontal ligament cells. The gene expression levels of pro-inflammatory cytokines (interleukin-1β and 6 and tumor necrosis factor-α) and inflammation-inducible enzymes (inducible nitric oxide synthase and cyclooxygenase-2) were reduced after DJLE treatment with/without lipopolysaccharide stimulation. The findings of this study indicate that D. jejudoensis possesses anti-inflammatory activities, suggesting that DJLE may be a potential preventive and therapeutic agent for periodontitis. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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21 pages, 3036 KiB

Open AccessArticle

Polyphenols as Inhibitors of Antibiotic Resistant Bacteria—Mechanisms Underlying Rutin Interference with Bacterial Virulence

by Marija Ivanov, Katarina Novović, Milka Malešević, Miroslav Dinić, Dejan Stojković, Branko Jovčić and Marina Soković

Pharmaceuticals 2022, 15(3), 385; https://doi.org/10.3390/ph15030385 - 21 Mar 2022

Cited by 23 | Viewed by 3942

Abstract

The rising incidence of antibiotic resistant microorganisms urges novel antimicrobials development with polyphenols as appealing potential therapeutics. We aimed to reveal the most promising polyphenols among hesperetin, hesperidin, naringenin, naringin, taxifolin, rutin, isoquercitrin, morin, chlorogenic acid, ferulic acid, p-coumaric acid, and gallic [...] Read more.

The rising incidence of antibiotic resistant microorganisms urges novel antimicrobials development with polyphenols as appealing potential therapeutics. We aimed to reveal the most promising polyphenols among hesperetin, hesperidin, naringenin, naringin, taxifolin, rutin, isoquercitrin, morin, chlorogenic acid, ferulic acid, p-coumaric acid, and gallic acid based on antimicrobial capacity, antibiofilm potential, and lack of cytotoxicity towards HaCaT, and to further test its antivirulence mechanisms. Although the majority of studied polyphenols were able to inhibit bacterial growth and biofilm formation, the most promising activities were observed for rutin. Further investigation proved rutin’s ability to prevent/eradicate Pseudomonas aeruginosa and MRSA urinary catheter biofilms. Besides reduction of biofilm biomass, rutin antibiofilm mechanisms included reduction of cell viability, exopolysaccharide, and extracellular DNA levels. Moderate reduction of bacterial adhesion to human keratinocytes upon treatment was observed. Rutin antivirulence mechanisms included an impact on P. aeruginosa protease, pyocyanin, rhamnolipid, and elastase production and the downregulation of the lasI, lasR, rhlI, rhlR, pqsA and mvfR genes. Rutin also interfered with membrane permeability. Polyphenols could repress antibiotic resistant bacteria. Rutin has shown wide antimicrobial and antibiofilm capacity employing a range of mechanisms that might be used for the development of novel antimicrobials. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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13 pages, 7422 KiB

Open AccessArticle

Quercetin and Quercitrin from Agrimonia pilosa Ledeb Inhibit the Migration and Invasion of Colon Cancer Cells through the JNK Signaling Pathway

by Nguyet-Tran Trinh, Thi Minh Ngoc Nguyen, Jong-In Yook, Sang-Gun Ahn and Soo-A Kim

Pharmaceuticals 2022, 15(3), 364; https://doi.org/10.3390/ph15030364 - 17 Mar 2022

Cited by 11 | Viewed by 2493

Abstract

Considering the high metastatic potential of colorectal cancer (CRC), the inhibition of metastasis is important for anti-CRC therapy. Agrimonia pilosa Ledeb (A. pilosa) is a perennial herbaceous plant that is widely distributed in Asia. The extracts of A. pilosa have shown [...] Read more.

Considering the high metastatic potential of colorectal cancer (CRC), the inhibition of metastasis is important for anti-CRC therapy. Agrimonia pilosa Ledeb (A. pilosa) is a perennial herbaceous plant that is widely distributed in Asia. The extracts of A. pilosa have shown diverse pharmacological properties, such as antimicrobial, anti-inflammatory, and antitumor activities. In the present study, the antimetastatic activity of A. pilosa was evaluated. Methanol extraction from the roots of A. pilosa was performed by high-performance liquid chromatography (HPLC) and 12 fractions were obtained. Among these, fraction 4 showed the most potent inhibitory effect on the migration of colon cancer cells. Using LC-HR MS analysis, quercetin and quercitrin were identified as flavonoids contained in fraction 4. Like fraction 4, quercetin and quercitrin effectively inhibited the migration and invasion of RKO cells. While the level of E-cadherin was increased, the levels of N-cadherin and vimentin were decreased by the same agents. Although they all activate the p38, JNK, and ERK signaling pathways, only SP600125, an inhibitor of the JNK pathway, specifically inhibited the effect of fraction 4, quercetin, and quercitrin on cell migration. An in vivo experiment also confirmed the antitumor activity of quercetin and quercitrin. Collectively, these results suggest that A. pilosa and its two flavonoids, quercetin and quercitrin, are candidates for the antimetastatic treatment of CRC. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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15 pages, 2865 KiB

Open AccessArticle

Pharmacological Effects of Gami-Yukmijihwang-Tang on the Lipopolysaccharide-Induced Hippocampus Oxidation and Inflammation via Regulation of Sirt6

by Jie-Yoon Kang, Jong-Suk Lee, In-Chan Seol, Yoon-Sik Kim, Miso S. Park and Ho-Ryong Yoo

Pharmaceuticals 2022, 15(3), 293; https://doi.org/10.3390/ph15030293 - 28 Feb 2022

Cited by 2 | Viewed by 2609

Abstract

Yukmijihwang-Tang is widely used in traditional Korean medicine to treat age-related disorders. In the present study, we re-prescribed Gami-Yukmijihwang-Tang (YJT), which is slightly modified from Yukmijihwang-Tang by adding more medicinal plants to evaluate its pharmacological effects on underlying mechanisms against repeated lipopolysaccharide (LPS)-injection-induced [...] Read more.

Yukmijihwang-Tang is widely used in traditional Korean medicine to treat age-related disorders. In the present study, we re-prescribed Gami-Yukmijihwang-Tang (YJT), which is slightly modified from Yukmijihwang-Tang by adding more medicinal plants to evaluate its pharmacological effects on underlying mechanisms against repeated lipopolysaccharide (LPS)-injection-induced neuroinflammation in the hippocampus regions. C57BL/6J male mice (16–24 weeks old) were divided into six groups: (1) the control group (DW with 0.9% saline injection), (2) LPS group (DW with LPS injection), YJT groups ((3) 100, (4) 200, or (5) 400 mg/kg of YJT with LPS injection), and (6) glutathione (GSH) group (100 mg/kg of GSH with LPS injection), respectively. Mice were orally administrated with various doses of YJT or glutathione (GSH) for the first five days. Neuroinflammation in the hippocampus region was induced by repeated injection of LPS during the last three days. As predicted, LPS not only increased oxidative stress–related markers including malondialdehyde, 4-hydroxynonenal, nitrotryptophan, and hydrogen peroxide, but also drastically enhanced inflammatory reactions including nitric oxide, inducible nitric oxide synthase, p65, and toll-like receptor 4, respectively. YJT administration, on the other hand, notably decreased the above pathological alterations by enhancement of antioxidant capacities such as superoxide dismutase and catalase activities. To explain the underlying pharmacological actions of YJT, we focused on a representative epigenetic regulator, a nicotinamide adenine dinucleotide + (NAD+)–dependent chromatin enzyme, Sirtuin 6 (Sirt6). Neuroinflammation in hippocampus regions depleted Sirt6 at the protein level and this alteration directly affected the nuclear factor erythroid 2–related factor (Nrf2)/hemeoxygenase (HO)-1 signaling pathway in the LPS group; however, YJT significantly recovered the Sirt6 protein levels, and it could recover the abnormal status of Nrf2/HO-1 signaling pathways in the hippocampus regions. Additionally, Sirt6 led to the up-regulation of GSH sub-enzymes of mRNA expression and protein levels of total GSH content. These findings suggest that YJT can protect against LPS-induced neuroinflammation and oxidative stress by regulating the Sirt6-related pathways and normalizing the GSH redox cycle. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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13 pages, 2951 KiB

Open AccessArticle

Ointment-Based Combination of Dittrichia viscosa L. and Marrubium vulgare L. Accelerate Burn Wound Healing

by Ibrahim Mssillou, Abdelkrim Agour, Meryem Slighoua, Mohamed Chebaibi, Fatima Ez-Zahra Amrati, Samar Zuhair Alshawwa, Omkulthom Al kamaly, Abdelfattah El Moussaoui, Badiaa Lyoussi and Elhoussine Derwich

Pharmaceuticals 2022, 15(3), 289; https://doi.org/10.3390/ph15030289 - 25 Feb 2022

Cited by 18 | Viewed by 3222

Abstract

Burns constitute a major challenge in medical science, and plants can be part of the solution. Dittrichia viscosa L. (Asteraceae) and Marrubium vulgare L. (Lamiaceae) are widely used in Moroccan traditional medicine to treat several diseases and possess high potency to cure wounds. [...] Read more.

Burns constitute a major challenge in medical science, and plants can be part of the solution. Dittrichia viscosa L. (Asteraceae) and Marrubium vulgare L. (Lamiaceae) are widely used in Moroccan traditional medicine to treat several diseases and possess high potency to cure wounds. This study aimed to investigate in vivo the analgesic, anti-inflammatory, and burn-healing effects of both plants and their mixture. The hydro-ethanolic extract of both plants was analyzed using high-performance liquid chromatography with diode-array detection (HPLC-DAD). Burns were conducted on dorsal part of rats, and the wound healing process was evaluated during 21 days. Gallic acid, caffeic acid, ferulic acid, and quercetin were identified in M. vulgare extract. The analysis recorded the presence of caffeic acid, rosmarinic acid, rutin, and quercetin in D. viscosa. The group treated with the mixture showed the lowest abdominal contractions (30.4 ± 7.52) with the highest percentage of inhibition (69.12 ± 7.04%). The inhibition of paw inflammation for M. vulgare was 47.65%, followed by D. viscosa (33.86%) and the mixture (30.41%). The mixture showed the highest wound contraction at day 7 (33.16 ± 14.33%) and day 14 (87.54 ± 3.98%). D. viscosa showed the highest wound contraction on the 21st day (99.28 ± 0.44%). In conclusion, both plants and their combination showed promising results for burn healing. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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20 pages, 3256 KiB

Open AccessArticle

Rhynchosia volubilis Promotes Cell Survival via cAMP-PKA/ERK-CREB Pathway

by Sang-Hyun Ahn, Jung-Soo Suh, Yoon-Kwan Jang, Heon-Su Kim, Gyu-Ho Choi, Eunhye Kim and Tae-Jin Kim

Pharmaceuticals 2022, 15(1), 73; https://doi.org/10.3390/ph15010073 - 06 Jan 2022

Cited by 3 | Viewed by 2142

Abstract

Rhynchosia volubilis, a small black bean, has been used as a traditional remedy to treat diseases and maintain health in East Asia, but its cellular effects and molecular mechanisms are not fully understood. The purpose of this study was to investigate the [...] Read more.

Rhynchosia volubilis, a small black bean, has been used as a traditional remedy to treat diseases and maintain health in East Asia, but its cellular effects and molecular mechanisms are not fully understood. The purpose of this study was to investigate the effect of ethanol extract from Rhynchosia volubilis (EERV) on cell survival and to elucidate the biochemical signaling pathways. Our results showed that EERV stimulated the cyclic AMP (cAMP) signal revealed by a fluorescent protein (FP)-based intensiometric sensor. Using a Förster resonance energy transfer (FRET)-based sensor, we further revealed that EERV could activate PKA and ERK signals, which are downstream effectors of cAMP. In addition, we reported that EERV could induce the phosphorylation of CREB, a key signal for cell survival. Thus, our results suggested that EERV protects against apoptosis by activating the cell survival pathway through the cAMP-PKA/ERK-CREB pathway. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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17 pages, 2123 KiB

Open AccessArticle

Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

by Muhammad Waleed Baig, Humaira Fatima, Nosheen Akhtar, Hidayat Hussain, Mohammad K. Okla, Abdulrahman Al-Hashimi, Wahidah H. Al-Qahtani, Hamada AbdElgawad and Ihsan-ul Haq

Pharmaceuticals 2021, 14(12), 1248; https://doi.org/10.3390/ph14121248 - 30 Nov 2021

Cited by 10 | Viewed by 2639

Abstract

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s [...] Read more.

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC₅₀) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC₅₀ values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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17 pages, 3796 KiB

Open AccessArticle

Pharmacognostic Study on Elsholtzia ciliata (Thumb.) Hyl: Anatomy, Phytochemistry and Pharmacological Activities

by Qian Zhang, Niara Moura Porto, Carolina Carvalho Guilhon, Thais Biondino Sardella Giorno, Daniela Sales Alviano, Maria de Fatima Agra, Patricia Dias Fernandes and Fabio Boylan

Pharmaceuticals 2021, 14(11), 1152; https://doi.org/10.3390/ph14111152 - 12 Nov 2021

Cited by 11 | Viewed by 3348

Abstract

Elsholtzia ciliata (Thunb.) Hyl, family Lamiaceae, is an important and popular anti-bacterial and anti-inflammatory Traditional Chinese Medicine (TCM). However, there are limited scientific studies on its anatomy and pharmacological activities. Moreover, the information of chemical constituents in relation to its non-volatile constituents are [...] Read more.

Elsholtzia ciliata (Thunb.) Hyl, family Lamiaceae, is an important and popular anti-bacterial and anti-inflammatory Traditional Chinese Medicine (TCM). However, there are limited scientific studies on its anatomy and pharmacological activities. Moreover, the information of chemical constituents in relation to its non-volatile constituents are still missing. The current study aimed to evaluate the anatomic, pharmacological and phytochemical profile of Elsholtzia ciliata, providing means for the quality control of this herbal drug. The methodology designed for this study included the preparation of anatomic sections and their description, extraction, chromatography, structural elucidation of isolated compounds by NMR techniques and their quantification by HPLC using pharmacological assays (Formalin, hot plate, DPPH, antimicrobial-Gram positive, Gram Negative and fungus, and MTT assays) to confirm the activities described for this species. Results of the anatomic study are aligned with the pattern expected for plants belonging to the Lamiaceae family; Ursolic acid and Oroxylin were isolated from this plant species. The findings observed in this study indicate that Elsholtzia ciliata possess anti-inflammatory, antinociceptive, antioxidant, antimicrobial and anticancer activities. The chemical compounds isolated from its leaves and the anatomy profile of its parts provide the basis for further quality control for this plant. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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11 pages, 1136 KiB

Open AccessArticle

Stability of Rosmarinic Acid and Flavonoid Glycosides in Liquid Forms of Herbal Medicinal Products—A Preliminary Study

by Agnieszka Bodalska, Adam Kowalczyk and Izabela Fecka

Pharmaceuticals 2021, 14(11), 1139; https://doi.org/10.3390/ph14111139 - 10 Nov 2021

Cited by 1 | Viewed by 1614

Abstract

Peppermint leaf, sage leaf, thyme herb, and their preparations are common components of herbal medicinal products (HMPs). According to the European Pharmacopoeia guidelines, the above-mentioned plant substances are standardized for the content of essential oils, omitting polyphenols, which also have a significant impact [...] Read more.

Peppermint leaf, sage leaf, thyme herb, and their preparations are common components of herbal medicinal products (HMPs). According to the European Pharmacopoeia guidelines, the above-mentioned plant substances are standardized for the content of essential oils, omitting polyphenols, which also have a significant impact on their activities. The aim of this study was to evaluate the stability of the predominant polyphenols—rosmarinic acid, luteolin-7-O-β-glucuronide, and eriocitrin—in selected commercial liquid HMPs containing thyme, sage, and peppermint under long-term, intermediate, and accelerated testing conditions. Qualitative and quantitative analyses of these polyphenols were performed by the previously optimized and validated HPLC-DAD method. Rosmarinic acid stability was better in hydroethanolic than in an aqueous solution. The effect of the solvent on the stability of luteolin-7-O-β-glucuronide and eriocitrin could not be determined and requires further investigation. The present study is the first to analyze the stability of these compounds in commercial herbal medicinal products. The expiration dates proposed by the manufacturers of the tested HMPs did not guarantee stable levels of all analyzed polyphenols throughout the stated period. However, this study is preliminary and requires continuation on a larger number of medicinal products. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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15 pages, 3804 KiB

Open AccessArticle

Gardenia jasminoides Attenuates Allergic Rhinitis-Induced Inflammation by Inhibiting Periostin Production

by Bo-Jeong Pyun, Joo Young Lee, Yu Jin Kim, Kon-Young Ji, Dong Ho Jung, Ki-Sun Park, Kyuhyung Jo, Susanna Choi, Myung-A Jung, Yun Hee Kim and Taesoo Kim

Pharmaceuticals 2021, 14(10), 986; https://doi.org/10.3390/ph14100986 - 28 Sep 2021

Cited by 3 | Viewed by 3174

Abstract

Allergic rhinitis (AR) is a chronic inflammatory condition affecting the nasal mucosa of the upper airways. Herein, we investigated the effects of extracts from Gardenia jasminoides (GJ), a traditional herbal medicine with anti-inflammatory properties, on AR-associated inflammatory responses that cause epithelial damage. We [...] Read more.

Allergic rhinitis (AR) is a chronic inflammatory condition affecting the nasal mucosa of the upper airways. Herein, we investigated the effects of extracts from Gardenia jasminoides (GJ), a traditional herbal medicine with anti-inflammatory properties, on AR-associated inflammatory responses that cause epithelial damage. We investigated the inhibitory effects of water- and ethanol-extracted GJ (GJW and GJE, respectively) in an ovalbumin-induced AR mouse model and in splenocytes, differentiated Th2 cells, and primary human nasal epithelial cells (HNEpCs). Administering GJW and GJE to ovalbumin-induced AR mice improved clinical symptoms including behavior (sneezing and rubbing), serum cytokine levels, immune cell counts, and histopathological marker levels. Treatment with GJW and GJE reduced the secretion of Th2 cytokines in Th2 cells isolated and differentiated from the splenocytes of these mice. To investigate the underlying molecular mechanisms of AR, we treated IL-4/IL-13-stimulated HNEpCs with GJW and GJE; we found that these extracts significantly reduced the production of mitochondrial reactive oxygen species via the uncoupling protein-2 and periostin, a biomarker of the Th2 inflammatory response. Our results suggest that GJ extracts may potentially serve as therapeutic agents to improve the symptoms of AR by regulating the Th2 inflammatory response of the nasal epithelium. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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16 pages, 6362 KiB

Open AccessArticle

Anti-Cancer Potential of Afzelin towards AGS Gastric Cancer Cells

by Iwona Radziejewska, Katarzyna Supruniuk, Robert Czarnomysy, Kamila Buzun and Anna Bielawska

Pharmaceuticals 2021, 14(10), 973; https://doi.org/10.3390/ph14100973 - 25 Sep 2021

Cited by 7 | Viewed by 2207

Abstract

Afzelin demonstrates anti-inflammatory and anti-cancer properties. Our purpose was to assess its influence on apoptosis, Bax, caspases, MUC1, cancer-related carbohydrate antigens, enzymes participating in their formation, and galectin-3 in AGS gastric cancer cells. A total of 60 and 120 μM afzelin was used [...] Read more.

Afzelin demonstrates anti-inflammatory and anti-cancer properties. Our purpose was to assess its influence on apoptosis, Bax, caspases, MUC1, cancer-related carbohydrate antigens, enzymes participating in their formation, and galectin-3 in AGS gastric cancer cells. A total of 60 and 120 μM afzelin was used in all experiments. Flow cytometry was applied to determine apoptotic response. Western blotting and RT PCR were used to detect the expression of mentioned factors. Flavonoid at higher concentration revealed slight apoptotic respond. Bax, caspase-3, -8, -9 increased upon afzelin action. Stimulatory effect of the flavonoid on MUC1 cytoplasmic tail and extracellular domain in cell lysates and on MUC1 gene was revealed. MUC1 release into the culture medium was inhibited by the flavonoid. The 60 μM afzelin dose stimulated GalNAcTL5 protein expression and inhibited C1GalT1. ST6GalNAcT mRNA was inhibited by both flavonoid doses. ST3GalT was inhibited by 120 μM afzelin on protein and mRNA level. Lewis^a/b protein was reduced by both afzelin concentrations. FUT3 and FUT4 mRNA was inhibited by 120 μM dose of afzelin. Galectin-3 protein increased in cell lysates and decreased in culture supernatant by 60 and 120 μM flavonoid. Galectin-3 gene expression was stimulated by two used concentrations of afzelin in comparison to control. We conclude that afzelin can be considered as the potential anti-cancer agent, supporting conventional cancer treatment. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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20 pages, 1619 KiB

Open AccessArticle

Chicory Extracts and Sesquiterpene Lactones Show Potent Activity against Bacterial and Fungal Pathogens

by Suvi T. Häkkinen, Marina Soković, Liisa Nohynek, Ana Ćirić, Marija Ivanov, Dejan Stojković, Irina Tsitko, Melanie Matos, João P. Baixinho, Viktoriya Ivasiv, Naiara Fernández, Claudia Nunes dos Santos and Kirsi-Marja Oksman-Caldentey

Pharmaceuticals 2021, 14(9), 941; https://doi.org/10.3390/ph14090941 - 20 Sep 2021

Cited by 22 | Viewed by 5136

Abstract

Chicory (Cichorium intybus L.) is an important industrial crop cultivated mainly to extract the dietary fiber inulin. However, chicory also contains bioactive compounds such as sesquiterpene lactones and certain polyphenols, which are currently discarded as waste. Plants are an important source of [...] Read more.

Chicory (Cichorium intybus L.) is an important industrial crop cultivated mainly to extract the dietary fiber inulin. However, chicory also contains bioactive compounds such as sesquiterpene lactones and certain polyphenols, which are currently discarded as waste. Plants are an important source of active pharmaceutical ingredients, including novel antimicrobials that are urgently needed due to the global spread of drug-resistant bacteria and fungi. Here, we tested different extracts of chicory for a range of bioactivities, including antimicrobial, antifungal and cytotoxicity assays. Antibacterial and antifungal activities were generally more potent in ethyl acetate extracts compared to water extracts, whereas supercritical fluid extracts showed the broadest range of bioactivities in our assays. Remarkably, the chicory supercritical fluid extract and a purified fraction thereof inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Pseudomonas aeruginosa IBRS P001. Chicory extracts also showed higher antibiofilm activity against the yeast Candida albicans than standard sesquiterpene lactone compounds. The cytotoxicity of the extracts was generally low. Our results may thus lead to the development of novel antibacterial and antifungal preparations that are both effective and safe for human use. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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17 pages, 889 KiB

Open AccessArticle

Antifungal Activity of Extracts, Fractions, and Constituents from Coccoloba cowellii Leaves

by Daniel Méndez, Julio C. Escalona-Arranz, Enrique Molina Pérez, Kenn Foubert, An Matheeussen, Emmy Tuenter, Ann Cuypers, Paul Cos and Luc Pieters

Pharmaceuticals 2021, 14(9), 917; https://doi.org/10.3390/ph14090917 - 10 Sep 2021

Cited by 3 | Viewed by 2678

Abstract

Coccoloba cowellii Britton (Polygonaceae, order Caryophyllales) is an endemic and critically endangered plant species that only grows in the municipality of Camagüey, a province of Cuba. A preliminary investigation of its total methanolic extract led to the discovery of promising antifungal activity. In [...] Read more.

Coccoloba cowellii Britton (Polygonaceae, order Caryophyllales) is an endemic and critically endangered plant species that only grows in the municipality of Camagüey, a province of Cuba. A preliminary investigation of its total methanolic extract led to the discovery of promising antifungal activity. In this study, a bioassay-guided fractionation allowed the isolation of quercetin and four methoxyflavonoids: 3-O-methylquercetin, myricetin 3,3′,4′-trimethyl ether, 6-methoxymyricetin 3,4′-dimethyl ether, and 6-methoxymyricetin 3,3′,4′-trimethyl ether. The leaf extract, fractions, and compounds were tested against various fungi and showed strong in vitro antifungal activity against Cryptococcus neoformans and various Candida spp. with no cytotoxicity (CC₅₀ > 64.0 µg/mL) on MRC-5 SV2 cells, determined by a resazurin assay. A Candida albicans SC5314 antibiofilm assay indicated that the antifungal activity of C. cowellii extracts and constituents is mainly targeted to planktonic cells. The total methanolic extract showed higher and broader activity compared with the fractions and mixture of compounds. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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17 pages, 2756 KiB

Open AccessArticle

A Design of Experiment (DoE) Approach to Model the Yield and Chemical Composition of Ajowan (Trachyspermum ammi L.) Essential Oil Obtained by Microwave-Assisted Extraction

by Eugenia Mazzara, Serena Scortichini, Dennis Fiorini, Filippo Maggi, Riccardo Petrelli, Loredana Cappellacci, Giuseppe Morgese, Mohammad Reza Morshedloo, Giovanni Filippo Palmieri and Marco Cespi

Pharmaceuticals 2021, 14(8), 816; https://doi.org/10.3390/ph14080816 - 19 Aug 2021

Cited by 7 | Viewed by 2656

Abstract

Ajowan (Trachyspermum ammi L.) is a spice traditionally used in Middle Eastern medicine and contains a valuable essential oil (EO) exploited in different fields, such as pharmaceutics, agrochemicals and food additives. This EO is mostly characterized by the thymol to which most [...] Read more.

Ajowan (Trachyspermum ammi L.) is a spice traditionally used in Middle Eastern medicine and contains a valuable essential oil (EO) exploited in different fields, such as pharmaceutics, agrochemicals and food additives. This EO is mostly characterized by the thymol to which most of its biological properties are related. Given the economic value of ajowan and its increasing demand across the globe, the extraction method used for its EO is of paramount importance in terms of quality and quantity of the final product. In the present study, we used the design of experiment (DoE) approach to study and optimize the extraction of the ajowan EO using the microwave-assisted extraction (MAE), a novel extraction technique with high efficiency, low energy consumption, short process length and low environmental impact. A two-step DoE (screening followed by surface response methodology) was used to reduce the number of experiments and to improve the cost/benefit ratio. Reliable mathematical models, relating the more relevant EO features with the extraction conditions, were obtained and used to identify the best experimental conditions able to maximize the yield and thymol concentration. The optimized MAE procedure assures an EO with a higher yield and thymol amount compared with the standard hydrodistillation procedure. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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18 pages, 5338 KiB

Open AccessArticle

Formulation and Evaluation of Helichrysum italicum Essential Oil-Based Topical Formulations for Wound Healing in Diabetic Rats

by Marijana Andjić, Biljana Božin, Nevena Draginić, Aleksandar Kočović, Jovana N. Jeremić, Marina Tomović, Andjela Milojević Šamanović, Nebojša Kladar, Ivan Čapo, Vladimir Jakovljević and Jovana V. Bradić

Pharmaceuticals 2021, 14(8), 813; https://doi.org/10.3390/ph14080813 - 19 Aug 2021

Cited by 23 | Viewed by 6135

Abstract

As proper wound management is crucial to reducing morbidity and improving quality of life, this study evaluated for the first time the wound healing potential of H. italicum essential oil (HIEO) prepared in the form of ointment and gel in streptozotocin-induced diabetic wound [...] Read more.

As proper wound management is crucial to reducing morbidity and improving quality of life, this study evaluated for the first time the wound healing potential of H. italicum essential oil (HIEO) prepared in the form of ointment and gel in streptozotocin-induced diabetic wound models in rats. After creating full-thickness cutaneous wounds, forty-eight diabetic rats were divided into six groups: (1) negative control; (2) positive control; (3) ointment base; (4) gel base; (5) 0.5% HIEO ointment (6) 0.5% HIEO gel. Wound healing potential was determined by the percentage of wound contraction, hydroxyproline content, redox status, and histological observation. A significant decrease in the wound size was observed in animals treated with HIEO formulations compared with other groups. The HIEO groups also showed a higher level of total hydroxyproline content, and more pronounced restitution of adnexal structures with only the underlying muscle defect indicating the incision site. Hence, our results legitimate the traditional data of the pro-healing effect of HIEO because HIEO in both formulations such as gel and ointment exhibited the significant wound repairing effect in the incision wound model. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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23 pages, 5292 KiB

Open AccessArticle

A High-Content Screen for the Identification of Plant Extracts with Insulin Secretion-Modulating Activity

by Roland Hager, Johannes Pitsch, Jakob Kerbl-Knapp, Cathrina Neuhauser, Nicole Ollinger, Marcus Iken, Josef Ranner, Verena Mittermeier-Kleßinger, Corinna Dawid, Peter Lanzerstorfer and Julian Weghuber

Pharmaceuticals 2021, 14(8), 809; https://doi.org/10.3390/ph14080809 - 17 Aug 2021

Cited by 11 | Viewed by 3544

Abstract

Bioactive plant compounds and extracts are of special interest for the development of pharmaceuticals. Here, we describe the screening of more than 1100 aqueous plant extracts and synthetic reference compounds for their ability to stimulate or inhibit insulin secretion. To quantify insulin secretion [...] Read more.

Bioactive plant compounds and extracts are of special interest for the development of pharmaceuticals. Here, we describe the screening of more than 1100 aqueous plant extracts and synthetic reference compounds for their ability to stimulate or inhibit insulin secretion. To quantify insulin secretion in living MIN6 β cells, an insulin–Gaussia luciferase (Ins-GLuc) biosensor was used. Positive hits included extracts from Quillaja saponaria, Anagallis arvensis, Sapindus mukorossi, Gleditsia sinensis and Albizia julibrissin, which were identified as insulin secretion stimulators, whereas extracts of Acacia catechu, Myrtus communis, Actaea spicata L., Vaccinium vitis-idaea and Calendula officinalis were found to exhibit insulin secretion inhibitory properties. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were used to characterize several bioactive compounds in the selected plant extracts, and these bioactives were retested for their insulin-modulating properties. Overall, we identified several plant extracts and some of their bioactive compounds that may be used to manipulate pancreatic insulin secretion. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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22 pages, 2018 KiB

Open AccessFeature PaperArticle

Antimicrobial and Immunomodulating Activities of Two Endemic Nepeta Species and Their Major Iridoids Isolated from Natural Sources

by Neda Aničić, Uroš Gašić, Feng Lu, Ana Ćirić, Marija Ivanov, Bojan Jevtić, Milena Dimitrijević, Boban Anđelković, Marijana Skorić, Jasmina Nestorović Živković, Yingle Mao, Jia Liu, Chunping Tang, Marina Soković, Yang Ye and Danijela Mišić

Pharmaceuticals 2021, 14(5), 414; https://doi.org/10.3390/ph14050414 - 28 Apr 2021

Cited by 20 | Viewed by 3073

Abstract

Two Balkan Peninsula endemics, Nepeta rtanjensis and N. argolica subsp. argolica, both characterized by specialized metabolite profiles predominated by iridoids and phenolics, are differentiated according to the stereochemistry of major iridoid aglycone nepetalactone (NL). For the first time, the present study provides [...] Read more.

Two Balkan Peninsula endemics, Nepeta rtanjensis and N. argolica subsp. argolica, both characterized by specialized metabolite profiles predominated by iridoids and phenolics, are differentiated according to the stereochemistry of major iridoid aglycone nepetalactone (NL). For the first time, the present study provides a comparative analysis of antimicrobial and immunomodulating activities of the two Nepeta species and their major iridoids isolated from natural sources—cis,trans-NL, trans,cis-NL, and 1,5,9-epideoxyloganic acid (1,5,9-eDLA), as well as of phenolic acid rosmarinic acid (RA). Methanol extracts and pure iridoids displayed excellent antimicrobial activity against eight strains of bacteria and seven strains of fungi. They were especially potent against food-borne pathogens such as L. monocytogenes, E. coli, S. aureus, Penicillium sp., and Aspergillus sp. Targeted iridoids were efficient agents in preventing biofilm formation of resistant P. aeruginosa strain, and they displayed additive antimicrobial interaction. Iridoids are, to a great extent, responsible for the prominent antimicrobial activities of the two Nepeta species, although are probably minor contributors to the moderate immunomodulatory effects. The analyzed iridoids and RA, individually or in mixtures, have the potential to be used in the pharmaceutical industry as potent antimicrobials, and in the food industry to increase the shelf life and safety of food products. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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18 pages, 2915 KiB

Open AccessFeature PaperArticle

Identification of Anti-Inflammatory and Anti-Proliferative Neolignanamides from Warburgia ugandensis Employing Multi-Target Affinity Ultrafiltration and LC-MS

by Xiao-Cui Zhuang, Yong-Li Zhang, Gui-Lin Chen, Ye Liu, Xiao-Lan Hu, Na Li, Jian-Lin Wu and Ming-Quan Guo

Pharmaceuticals 2021, 14(4), 313; https://doi.org/10.3390/ph14040313 - 01 Apr 2021

Cited by 9 | Viewed by 3411

Abstract

Previous reports have illustrated that the incidence and mortality of cancer are increasing year by year worldwide. In addition, the occurrence, development, recurrence and metastasis of cancer are closely related to inflammation, which is a kind of defensive response of human body to [...] Read more.

Previous reports have illustrated that the incidence and mortality of cancer are increasing year by year worldwide. In addition, the occurrence, development, recurrence and metastasis of cancer are closely related to inflammation, which is a kind of defensive response of human body to various stimuli. As an important medicinal plant in Africa, Warburgia ugandensis has been reported to have certain anti-inflammatory and anti-proliferative activities, but its specific components and mechanisms of action remain elusive. To tackle this challenge, affinity ultrafiltration with drug targets of interest coupled to high-performance liquid chromatography-mass spectrometry (AUF-HPLC-MS/MS) could be utilized to quickly screen out bioactive constituents as ligands against target enzymes from complex extracts of this plant. AUF-HPLC-MS/MS with four drug targets, i.e., cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), topoisomerase I (Top I) and topoisomerase II (Top II) were used to rapidly screen and characterize the anti-inflammatory and anti-proliferative natural ligands from W. ugandensis, and the resulting potential active compounds as ligands with specific binding affinity to COX-2, 5-LOX, Top I and Top II, were isolated with modern separation and purification techniques and identified with spectroscopic method like NMR, and then their antiinflammatory and anti-proliferative activities were tested to verify the screening results from AUF-HPLC-MS/MS. Compounds 1 and 2, which screened out and identified from W. ugandensis showed remarkable binding affinity to COX-2, 5-LOX, Top I and Top II with AUF-HPLC-MS/MS. In addition, 1 new compound (compound 3), together with 5 known compounds were also isolated and identified from W. ugandensis. The structure of compound 3 was elucidated by extensive 1D, 2D NMR data and UPLC-QTOF-MS/MS. Furthermore, compounds 1 and 2 were further proved to possess both anti-inflammatory and anti-proliferative activities which are in good agreement with the screening results using AUF-HPLC-MS/MS. This work showcased an efficient method for quickly screening out bioactive components with anti-inflammatory and anti-proliferative activity from complex medicinal plant extracts using AUF-HPLC-MS/MS with target enzymes of interest, and also demonstrated that neolignanamides (compounds 1 and 2) from W. ugandensis would be the active components responsible for its anti-inflammatory and anti-proliferative activity with the potential to treat cancer and inflammation. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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13 pages, 1267 KiB

Open AccessArticle

In Vitro Effects of Low Doses of β-Caryophyllene, Ascorbic Acid and d-Glucosamine on Human Chondrocyte Viability and Inflammation

by Elena Mattiuzzo, Alessia Faggian, Rina Venerando, Andrea Benetti, Elisa Belluzzi, Giovanni Abatangelo, Pietro Ruggieri and Paola Brun

Pharmaceuticals 2021, 14(3), 286; https://doi.org/10.3390/ph14030286 - 23 Mar 2021

Cited by 9 | Viewed by 3140

Abstract

β-caryophyllene (BCP), a plant-derived sesquiterpene, has been reported to have anti-inflammatory and antioxidant effects. The purpose of this study is to evaluate the effects of BCP in combination with ascorbic acid (AA) and d-glucosamine (GlcN) against macrophage-mediated inflammation on in vitro primary [...] Read more.

β-caryophyllene (BCP), a plant-derived sesquiterpene, has been reported to have anti-inflammatory and antioxidant effects. The purpose of this study is to evaluate the effects of BCP in combination with ascorbic acid (AA) and d-glucosamine (GlcN) against macrophage-mediated inflammation on in vitro primary human chondrocytes. Changes in cell viability, intracellular ROS generation, gene expression of pro-inflammatory mediators, metalloproteinases (MMPs), collagen type II and aggrecan were analyzed in primary human chondrocytes exposed to the conditioned medium (CM) of activated U937 monocytes and subsequently treated with BCP alone or in combination with AA and GlcN. The CM-induced chondrocyte cytotoxicity was reduced by the presence of low doses of BCP alone or in combination with AA and GlcN. The exposure of cells to CM significantly increased IL-1β, NF-κB1 and MMP-13 expression, but when BCP was added to the inflamed cells, alone or in combination with AA and GlcN, gene transcription for all these molecules was restored to near baseline values. Moreover, chondrocytes increased the expression of collagen type II and aggrecan when stimulated with AA and GlcN alone or in combination with BCP. This study showed the synergistic anti-inflammatory and antioxidative effects of BCP, AA and GlcN at low doses on human chondrocyte cultures treated with the CM of activated U937 cells. Moreover, the combination of the three molecules was able to promote the expression of collagen type II and aggrecan. All together, these data could suggest that BCP, AA and GlcN exert a chondro-protective action. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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14 pages, 2201 KiB

Open AccessCommunication

A Novel Pro-Melanogenic Effect of Standardized Dry Olive Leaf Extract on Primary Human Melanocytes from Lightly Pigmented and Moderately Pigmented Skin

by Shilpi Goenka and Sanford R. Simon

Pharmaceuticals 2021, 14(3), 252; https://doi.org/10.3390/ph14030252 - 11 Mar 2021

Cited by 7 | Viewed by 2788

Abstract

Benolea^® (EFLA^®943) is a standardized dry olive leaf extract (DOLE) considered safe for food consumption and has demonstrated superior pharmaceutical benefits such as antioxidant, anti-obesity, and anti-hypertensive activities. However, there is no study on its effects on melanogenesis yet. Disruption [...] Read more.

Benolea^® (EFLA^®943) is a standardized dry olive leaf extract (DOLE) considered safe for food consumption and has demonstrated superior pharmaceutical benefits such as antioxidant, anti-obesity, and anti-hypertensive activities. However, there is no study on its effects on melanogenesis yet. Disruption in the sequence of steps in melanogenesis can lead to hypopigmentary disorders which occur due to reduced production or export of pigment melanin in the skin. There is a need for safe and nontoxic therapeutics for the treatment of hypopigmentation disorders. Herein, we studied the effects of DOLE over a concentration range of 10–200 µg/mL on melanin synthesis and melanin secretion in B16F10 mouse melanoma cells and MNT-1 human melanoma cells and validated our results in primary human melanocytes (obtained from lightly pigmented (LP) and moderately pigmented (MP) cells) as well as their cocultures with keratinocytes. The capacity of melanocytes to export melanosomes was also estimated indirectly by the quantitation of melanocyte dendrite lengths and numbers. Our results show that DOLE significantly enhanced levels of extracellular melanin in the absence of effects on intracellular melanin, demonstrating that this plant extract’s pro-melanogenic activity is primarily based on its capacity to augment melanin secretion and stimulate melanocyte dendricity. In summary, our preliminary results demonstrate that DOLE may hold promise as a pro-pigmenting agent for vitiligo therapy and gray hair treatment by its exclusive and novel mechanism of functioning as a dendrite elongator. Further studies to elucidate the mechanisms of action of the pro-melanogenic activity and effects of DOLE on melanosome export as well as the last steps of melanogenesis are warranted. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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16 pages, 3669 KiB

Open AccessArticle

Chemical Composition, Larvicidal Activity, and Enzyme Inhibition of the Essential Oil of Lippia grata Schauer from the Caatinga Biome against Dengue Vectors

by Stênio Freitas Felix, Alzeir Machado Rodrigues, Ana Livya Moreira Rodrigues, José Claudio Carneiro de Freitas, Daniela Ribeiro Alves, Alice Araújo da Silva, Dayanne Lima dos Santos, Kethelly Rayne Lima de Oliveira, Renato Almeida Montes, Marcus Vinicius Ferreira da Silva, Francisco Flávio da Silva Lopes and Selene Maia de Morais

Pharmaceuticals 2021, 14(3), 250; https://doi.org/10.3390/ph14030250 - 10 Mar 2021

Cited by 9 | Viewed by 3260

Abstract

Insect resistance and environmental pollution are among the drawbacks of continuous use of synthetic insecticides against the vectors of dengue, Aedesaegypti and Aedes albopictus. The objective of this study was to analyze the composition of the essential oil of Lippia grata [...] Read more.

Insect resistance and environmental pollution are among the drawbacks of continuous use of synthetic insecticides against the vectors of dengue, Aedesaegypti and Aedes albopictus. The objective of this study was to analyze the composition of the essential oil of Lippia grata Schauer collected from plants, in three periods of the year, to compare the larvicidal activity and enzymatic inhibition of the dengue vectors. The oilsanalyzed by gas chromatography coupled to mass spectrometry (GC-MS), presented thymol and 1,8-cineole, as the main constituents, in all three periods. This composition was different from that found in previous studies of the species from different places, thus, suggesting a new chemotype of Lippia grata. Larvicidal tests were performed at concentrations of 100, 75, 50, 25, and 12.5 μg.mL⁻¹ and the essential oil from the rainy season showed the best results, with LC₅₀ of 22.79 μg.mL⁻¹ and 35.36 μg.mL⁻¹ against Ae. aegypti and Ae. albopictus, respectively; this result was better than other reports. In the rainy period, however, there was a greater variety of components, which led to a better larvicidal effect, possibly due to synergistic action with minor constituents. Total proteins, amylases, and acetylcholinesterase of both species were inhibited by the oils. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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10 pages, 1390 KiB

Open AccessArticle

Carnosic Acid Induces Apoptosis and Inhibits Akt/mTOR Signaling in Human Gastric Cancer Cell Lines

by Waseem El-Huneidi, Khuloud Bajbouj, Jibran Sualeh Muhammad, Arya Vinod, Jasmin Shafarin, Ghalia Khoder, Mohamed A. Saleh, Jalal Taneera and Eman Abu-Gharbieh

Pharmaceuticals 2021, 14(3), 230; https://doi.org/10.3390/ph14030230 - 08 Mar 2021

Cited by 21 | Viewed by 3103

Abstract

Gastric cancer is among the most common malignancies worldwide. Due to limited availability of therapeutic options, there is a constant need to find new therapies that could target advanced, recurrent, and metastatic gastric cancer. Carnosic acid is a naturally occurring polyphenolic abietane diterpene [...] Read more.

Gastric cancer is among the most common malignancies worldwide. Due to limited availability of therapeutic options, there is a constant need to find new therapies that could target advanced, recurrent, and metastatic gastric cancer. Carnosic acid is a naturally occurring polyphenolic abietane diterpene derived from Rosmarinus officinalis and reported to have numerous pharmacological effects. In this study, the cytotoxicity assay, Annexin V-FITC/PI, caspases 3, 8, and 9, cell cycle analysis, and Western blotting were used to assess the effect of carnosic acid on the growth and survival of human gastric cancer cell lines (AGS and MKN-45). Our findings showed that carnosic acid inhibited human gastric cancer cell proliferation and survival in a dose-dependent manner. Additionally, carnosic acid is found to inhibit the phosphorylation/activation of Akt and mTOR. Moreover, carnosic acid enhanced the cleavage of PARP and downregulated survivin expression, both being known markers of apoptosis. In conclusion, carnosic acid exhibits antitumor activity against human gastric cancer cells via modulating the Akt-mTOR signaling pathway that plays a crucial role in gastric cancer cell proliferation and survival. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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12 pages, 2587 KiB

Open AccessArticle

Up-Regulated Vitamin D Receptor by Pelargonium sidoides Extract EPs^® 7630 Contributes to Rhinovirus Defense in Bronchial Epithelial Cells

by Michael Roth, Qingzhu Sun and Michael Tamm

Pharmaceuticals 2021, 14(2), 172; https://doi.org/10.3390/ph14020172 - 22 Feb 2021

Cited by 12 | Viewed by 2943

Abstract

EPs^®7630, extracted from Pelargonium sidoides, reduces the severity of viral upper respiratory tract infections. Vitamin D also improves anti-viral host defense through similar signaling pathways. This study assessed if EPs^®7630 modifies vitamin D receptor (VDR) expression and function [...] Read more.

EPs^®7630, extracted from Pelargonium sidoides, reduces the severity of viral upper respiratory tract infections. Vitamin D also improves anti-viral host defense through similar signaling pathways. This study assessed if EPs^®7630 modifies vitamin D receptor (VDR) expression and function by human bronchial epithelial cells. Bronchial epithelial cells were incubated with EPs^®7630 over 48 h before calcitriol stimulation and/or infection with Rhinovirus (RV)-16. Protein expression was determined by Western-blotting. Intracellular signaling of mitogen activated protein kinases (MAPK) was studied by chemical inhibitors. The anti-viral effect was assessed by immunofluorescence for RV-16 protein. EPs^®7630 upregulated VDR expression through Erk1/2 MAPK and thereby increased the cell’s sensitivity to calcitriol. Compared ton untreated cells, the shift of the VDR into the nucleus at 5.3 times lower calcitriol concentration. EPs^®7630 increased Erk1/2 MAPK signaling, but reduced p38 phosphorylation, and had no effect on Jun N-terminal kinase (JNK). EPs^®7630 improved the anti-viral effect of vitamin D on RV-16 infection by 2.1 folds compared to vitamin D alone or to untreated cells. Furthermore, EPs^®7630 improved the differentiation of epithelial cells by upregulating E-cadherin expression through Erk1/2. In conclusion, EPs^®7630 increased host defense against Rhinovirus infection by upregulating the VDR and the differentiation of epithelial cells. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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12 pages, 1433 KiB

Open AccessArticle

Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity

by Marija Ivanov, Abhilash Kannan, Dejan S. Stojković, Jasmina Glamočlija, Ricardo C. Calhelha, Isabel C. F. R. Ferreira, Dominique Sanglard and Marina Soković

Pharmaceuticals 2021, 14(1), 27; https://doi.org/10.3390/ph14010027 - 30 Dec 2020

Cited by 38 | Viewed by 3593

Abstract

Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, [...] Read more.

Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, apigenin), flavonols (quercetin), and their glycosylated derivatives (quercitrin, isoquercitrin, rutin, and apigetrin) along with their impact on genes encoding efflux pumps (CDR1) and ergosterol biosynthesis enzyme (ERG11) has been the subject of this study. Cytotoxicity of flavonoids towards primary liver cells has also been addressed. Luteolin, quercitrin, isoquercitrin, and rutin inhibited growth of Candida albicans with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced C. albicans biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, apigetrin, and quercitrin has downregulated CDR1. Contrary to rutin and apigenin, isoquercitrin has upregulated ERG11. Except apigetrin and quercitrin (90 µg/mL and 73 µg/mL, respectively inhibited 50% of the net cell growth), the examined flavonoids did not exhibit cytotoxicity. The reduction of both fungal virulence and expression of antifungal resistance-linked genes was the most pronounced for apigenin and apigetrin; these results indicate flavonoids’ indispensable capacity for further development as part of an anticandidal therapy or prevention strategy. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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17 pages, 2947 KiB

Open AccessArticle

Additive Effect of a Combination of Artocarpus lakoocha and Glycyrrhiza glabra Extracts on Tyrosinase Inhibition in Melanoma B16 Cells

by Tasanee Panichakul, Teerapat Rodboon, Prasit Suwannalert, Chanchai Tripetch, Rittipun Rungruang, Nattaporn Boohuad and Piyawan Youdee

Pharmaceuticals 2020, 13(10), 310; https://doi.org/10.3390/ph13100310 - 14 Oct 2020

Cited by 18 | Viewed by 3468

Abstract

Artocarpus lakoocha (Al) and Glycyrrhiza glabra (Gg) extracts have been reported to show tyrosinase inhibitory activity and melanin pigment reduction. This is the first study to assess the combination of Al and Gg extracts in enhancing inhibition of tyrosinase and reduction of melanin [...] Read more.

Artocarpus lakoocha (Al) and Glycyrrhiza glabra (Gg) extracts have been reported to show tyrosinase inhibitory activity and melanin pigment reduction. This is the first study to assess the combination of Al and Gg extracts in enhancing inhibition of tyrosinase and reduction of melanin pigments. Al and Gg extracted by maceration in 70% and 95% ethanol were analyzed for oxyresveratrol and glabridin using Ultra High Performance Liquid Chromatography. Extracts of Al and Gg singly and combinations of Al95 and Gg95 were tested for cytotoxicity, tyrosinase inhibitory activity, and reduction of melanin pigments in melanoma B16 cells. Al95 had higher antioxidant, tyrosinase inhibitory activity and reduced more melanin pigments in B16 cells compared to Al70, and exhibited higher levels of oxyresveratrol. Gg95 inhibited oxidative stress and mushroom tyrosinase better than Gg70, and exhibited higher levels of glabridin. Combinations of Al95 and Gg95 at various ratios (concentration of 0.1 mg/mL) were not cytotoxic to B16 cells. Interestingly, Al95 and Gg95 combined at a ratio 9:1 reduced melanin pigment up to 53% in B16 cells. This combination of Al95 and Gg95 extracts exhibited the additive effect of reducing melanin pigments by suppressing the expression of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein-2 (TRP-2) in B16 cells. The combination of Al and Gg extracts could be developed as skin care products for hyperpigmentation treatment. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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Review

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14 pages, 334 KiB

Open AccessReview

Insects as Diet and Therapy: Perspectives on Their Use for Combating Diabetes Mellitus in Tanzania

by Geert René Verheyen, Luc Pieters, Sheila Maregesi and Sabine Van Miert

Pharmaceuticals 2021, 14(12), 1273; https://doi.org/10.3390/ph14121273 - 06 Dec 2021

Cited by 7 | Viewed by 2876

Abstract

More than 450 million people worldwide are suffering from diabetes and this number is expected to increase. In developing countries, such as Tanzania, the number of patients suffering from diabetes and associated diseases is increasing as well. Up to 80% of the Tanzanian [...] Read more.

More than 450 million people worldwide are suffering from diabetes and this number is expected to increase. In developing countries, such as Tanzania, the number of patients suffering from diabetes and associated diseases is increasing as well. Up to 80% of the Tanzanian people rely on traditional medicines for their health care services. The nature of Tanzanian is very rich in different plant and insect species, and this could be exploited through their implementation in preventive and/or curative approaches in the battle against diabetes. The implementation of healthy insects in the diets of people may help in the prevention of obesity, which is a risk factor in the etiology of diabetes, while the identification of small molecules in insects may help in the discovery of potential new drugs that can be used in the treatment of diabetes. In this paper, an overview on the potential implementation of insects against diabetes is presented. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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18 pages, 527 KiB

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Psilocybin, a Naturally Occurring Indoleamine Compound, Could Be Useful to Prevent Suicidal Behaviors

by Robertas Strumila, Bénédicte Nobile, Laura Korsakova, Aiste Lengvenyte, Emilie Olie, Jorge Lopez-Castroman, Sébastien Guillaume and Philippe Courtet

Pharmaceuticals 2021, 14(12), 1213; https://doi.org/10.3390/ph14121213 - 24 Nov 2021

Cited by 15 | Viewed by 10848

Abstract

The available interventions for people who are at risk of suicide have limited efficacy. Recently, research on new mental health treatments has started to consider psychedelic compounds, particularly psilocybin, a molecule with a few thousand years of history of use in human societies. [...] Read more.

The available interventions for people who are at risk of suicide have limited efficacy. Recently, research on new mental health treatments has started to consider psychedelic compounds, particularly psilocybin, a molecule with a few thousand years of history of use in human societies. The possible effects of psilocybin on suicidal ideation and behaviors have not been specifically studied yet; however, the current knowledge on the suicidal process and the available data on es/ketamine suggest that psylocibin could be used to modulate the thoughts and behavioral patterns in individuals who are at risk of suicidal behaviors. Here, we summarize the available evidence on the possible mechanisms underlying psilocybin positive effects on suicide risk. Major pathways related to suicidal behaviors that might be modulated by psylocibin include serotonin receptors. Specifically, psylocibin directly stimulates the serotonin 2A receptor (5HT_2A), targeting the inflammatory and oxidative stress pathways and leading to a rapid increase in brain plasticity and inflammation suppression and increases in cognitive flexibility, spirituality, and empathy. We also present preliminary epidemiological data and provide a rationale for studying psilocybin in individuals with suicidal ideation or who are at risk of suicidal behaviors. This review presents a framework to understand the basis for psilocybin use in individuals who are at risk of suicidal behaviors and calls for clinical studies. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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18 pages, 3959 KiB

Open AccessReview

Antiviral Activities of Eucalyptus Essential Oils: Their Effectiveness as Therapeutic Targets against Human Viruses

by Daniel Mieres-Castro, Sunny Ahmar, Rubab Shabbir and Freddy Mora-Poblete

Pharmaceuticals 2021, 14(12), 1210; https://doi.org/10.3390/ph14121210 - 23 Nov 2021

Cited by 29 | Viewed by 11799

Abstract

Given the limited therapeutic management of infectious diseases caused by viruses, such as influenza and SARS-CoV-2, the medicinal use of essential oils obtained from Eucalyptus trees has emerged as an antiviral alternative, either as a complement to the treatment of symptoms caused by [...] Read more.

Given the limited therapeutic management of infectious diseases caused by viruses, such as influenza and SARS-CoV-2, the medicinal use of essential oils obtained from Eucalyptus trees has emerged as an antiviral alternative, either as a complement to the treatment of symptoms caused by infection or to exert effects on possible pharmacological targets of viruses. This review gathers and discusses the main findings on the emerging role and effectiveness of Eucalyptus essential oil as an antiviral agent. Studies have shown that Eucalyptus essential oil and its major monoterpenes have enormous potential for preventing and treating infectious diseases caused by viruses. The main molecular mechanisms involved in the antiviral activity are direct inactivation, that is, by the direct binding of monoterpenes with free viruses, particularly with viral proteins involved in the entry and penetration of the host cell, thus avoiding viral infection. Furthermore, this review addresses the coadministration of essential oil and available vaccines to increase protection against different viruses, in addition to the use of essential oil as a complementary treatment of symptoms caused by viruses, where Eucalyptus essential oil exerts anti-inflammatory, mucolytic, and spasmolytic effects in the attenuation of inflammatory responses caused by viruses, in particular respiratory diseases. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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46 pages, 2503 KiB

Open AccessReview

Phytochemicals from Plant Foods as Potential Source of Antiviral Agents: An Overview

by Tapan Behl, Gabriele Rocchetti, Swati Chadha, Gokhan Zengin, Simona Bungau, Arun Kumar, Vineet Mehta, Md Sahab Uddin, Gaurav Khullar, Dhruv Setia, Sandeep Arora, Kouadio Ibrahime Sinan, Gunes Ak, Predrag Putnik, Monica Gallo and Domenico Montesano

Pharmaceuticals 2021, 14(4), 381; https://doi.org/10.3390/ph14040381 - 19 Apr 2021

Cited by 49 | Viewed by 9732

Abstract

To date, the leading causes of mortality and morbidity worldwide include viral infections, such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow [...] Read more.

To date, the leading causes of mortality and morbidity worldwide include viral infections, such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus. Recently, drugs used in the past especially against ebolavirus, such as remdesivir and favipiravir, have been considered for the treatment of COVID-19 disease. However, even if these drugs represent important tools against viral diseases, they are certainly not sufficient to defend us from the multitude of viruses present in the environment. This represents a huge problem, especially considering the unprecedented global threat due to the advancement of COVID-19, which represents a potential risk to the health and life of millions of people. The demand, therefore, for new and effective antiviral drugs is very high. This review focuses on three fundamental points: (1) presents the main threats to human health, reviewing the most widespread viral diseases in the world, thus describing the scenario caused by the disease in question each time and evaluating the specific therapeutic remedies currently available. (2) It comprehensively describes main phytochemical classes, in particular from plant foods, with proven antiviral activities, the viruses potentially treated with the described phytochemicals. (3) Consideration of the various applications of drug delivery systems in order to improve the bioavailability of these compounds or extracts. A PRISMA flow diagram was used for the inclusion of the works. Taking into consideration the recent dramatic events caused by COVID-19 pandemic, the cry of alarm that denounces critical need for new antiviral drugs is extremely strong. For these reasons, a continuous systematic exploration of plant foods and their phytochemicals is necessary for the development of new antiviral agents capable of saving lives and improving their well-being. Full article

(This article belongs to the Special Issue Natural Pharmacons: Biologically Active Plant Based Pharmaceuticals)

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