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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Chemical and Molecular Sciences".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 39654

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Dr. Hari Prasad Devkota

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Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8555, Japan
Interests: bioactive natural products; phytochemistry; inflammation; flavonoids; functional foods
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Dear Colleagues,

Medicinal plants have been used for the maintenance of human health since ancient times in the form of food, spices, and traditional medicines. Medicinal plant-based traditional medicines serve as the primary healthcare systems in various countries even at present. Along with that, medicinal plants have also served as the one of the main sources for the discovery of new therapeutic agents. At present, various plant extracts and their isolated phytochemicals are screened and evaluated for their diverse pharmacological activities related to both communicable and non-communicable diseases. However, comparatively little focus is given to the detailed mechanism of action of these agents on the molecular level. Molecular mechanism-based studies are essential for the development of evidence- based traditional medicines as well as for the development of isolated natural products as the lead candidates for novel drug discovery.

This Special Issue of the journal Applied Sciences, “Plant-based Bioactive Natural Products: Insights into Molecular Mechanisms of Action” aims to cover the recent advances in science related to the molecular mechanisms of action of natural products. Original articles, communications, and reviews related to these topics are welcome for submission.

Dr. Hari Prasad Devkota
Guest Editor

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Keywords

Natural products
bioactive compounds
medicinal plants
bioactivity
mechanism of action
traditional medicines

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Editorial

Jump to: Research, Review

3 pages, 188 KiB

Open AccessEditorial

Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action

by Hari Prasad Devkota

Appl. Sci. 2021, 11(21), 10220; https://doi.org/10.3390/app112110220 - 1 Nov 2021

Cited by 2 | Viewed by 1621

Abstract

Medicinal plants have been used for the maintenance of human health since ancient times in the form of food, spices, and traditional medicines [...] Full article

(This article belongs to the Special Issue Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action)

Research

Jump to: Editorial, Review

12 pages, 11557 KiB

Open AccessArticle

Vepris macrophylla Essential Oil Produces Notable Antiproliferative Activity and Morphological Alterations in Human Breast Adenocarcinoma Cells

by Marisa Colone, Filippo Maggi, Rianasoambolanoro Rakotosaona and Annarita Stringaro

Appl. Sci. 2021, 11(10), 4369; https://doi.org/10.3390/app11104369 - 12 May 2021

Cited by 1 | Viewed by 1918

Abstract

Medicinal plants contain numerous bioactive molecules that synergistically provide therapeutic benefits. We have devoted our attention to various EOs without toxicity to normal cells, studying their activities against human cancer cells. In particular, we have studied the cytotoxicity of Vepris macrophylla (Baker) I. Verd. EO. V. macrophylla is an evergreen tree of Madagascar where is much appreciated as a source of traditional remedies. Its major volatile components are citral, i.e., a mixture of neral and geranial, citronellol and myrcene. The antiproliferative activities of V. macrophylla EO were studied against human breast adenocarcinoma cell line SKBR3. Cellular metabolism was analyzed by MTT assay at different concentrations of EO and at different times of incubation (24, 48 and 72 h). Moreover, morphological and ultrastructural analyses were performed to study its antiproliferative effects against human adenocarcinoma cells, demonstrating the ability of V. macrophylla EO, stored inside numerous intracellular vesicles, to damage both plasma membranes and disorganize the cytoskeleton protein as actin filaments. Full article

(This article belongs to the Special Issue Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action)

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12 pages, 2867 KiB

Open AccessArticle

Scrophularia buergeriana Extract (Brainon) Improves Scopolamine-Induced Neuronal Impairment and Cholinergic Dysfunction in Mice through CREB-BDNF Signaling Pathway

by Hae-Jin Lee, Hae-Lim Kim, Dae-Young Lee, Dong-Ryung Lee, Bong-Keun Choi and Seung-Hwan Yang

Appl. Sci. 2021, 11(9), 4286; https://doi.org/10.3390/app11094286 - 10 May 2021

Cited by 10 | Viewed by 3066

Abstract

We evaluated the effectiveness of Scrophularia buergeriana extract (Brainon) on cognitive dysfunction and determined its underlying mechanisms in a scopolamine (SCO)-treated mouse model of memory impairment. Brainon treatment for 28 days ameliorated the symptoms of memory impairment as indicated by the results of both passive avoidance performance and the Morris water mazes. Brainon lowered acetylcholinesterase activity and raised acetylcholine levels in the hippocampus. The treatment elevated the protein levels of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding (CREB). Additionally, the excessive generation of SCO-induced reactive oxygen species (ROS) and subsequent oxidative stress were suppressed by the enhancement of superoxide dismutase (SOD)-1 and SOD-2 proteins. mRNA levels of upregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, as well as the apoptotic protein Bcl-2-associated X protein (Bax), cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase (PARP) expression after SCO injection were downregulated by Brainon treatment. Collectively, these findings suggested that Brainon possesses anti-amnesic effects through the CREB-BDNF pathway. Moreover, it exerted antioxidant, anti-inflammatory, and anti-apoptotic effects in SCO-induced mice exhibiting cognitive impairment and memory loss. Full article

(This article belongs to the Special Issue Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action)

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13 pages, 1004 KiB

Open AccessArticle

Artichoke By-Products as Natural Source of Phenolic Food Ingredient

by Lucía López-Salas, Isabel Borrás-Linares, David Quintin, Presentación García-Gomez, Rafael Giménez-Martínez, Antonio Segura-Carretero and Jesús Lozano-Sánchez

Appl. Sci. 2021, 11(9), 3788; https://doi.org/10.3390/app11093788 - 22 Apr 2021

Cited by 21 | Viewed by 3137

Abstract

Nowadays, the transformation activity of the food industry results in the generation of a huge amount of daily discarded vegetables wastes. One of those undervalued by-products are produced during the post-harvesting and processing process of artichokes. In the present research, the potential of artichokes’ bracts and stalks have been evaluated as a natural source of phenolic compounds which could be used as bioactive food ingredients, among others. In this study, the bioactive composition of those wastes has been evaluated using recent advances in extraction and analytical technologies, concretely, pressurized liquid extraction (PLE) followed by high-performance liquid chromatography (HPLC) coupled to electrospray time-of flight mass spectrometry (ESI-TOF/MS) analysis. To achieve this goal, first, the extraction process was evaluated by a comparative study using GRAS (Generally Recognized As Safe) solvents (mixtures of ethanol and water) at different temperatures (40–200 °C). The second step was to deeply characterize the composition of individual polyphenols by HPLC-ESI-TOF/MS in order to establish a comparison among the different PLE conditions applied to extract the phenolic fraction. The analysis revealed a wide variety of phenolic-composition, mainly phenolic acids and flavonoids. The results also highlighted that high percentages of ethanol and medium-high temperatures pointed out to be useful PLE conditions for recovering this kind of phytochemicals, which could be used in different applications, such as functional food ingredients, cosmetics, or nutraceuticals. Full article

(This article belongs to the Special Issue Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action)

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17 pages, 3815 KiB

Open AccessArticle

A Molecular Insight into the Synergistic Mechanism of Nigella sativa (Black Cumin) with β-Lactam Antibiotics against Clinical Isolates of Methicillin-Resistant Staphylococcus aureus

by Lorina I. Badger-Emeka, Promise Madu Emeka and Hairul Islam M. Ibrahim

Appl. Sci. 2021, 11(7), 3206; https://doi.org/10.3390/app11073206 - 2 Apr 2021

Cited by 8 | Viewed by 3454

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infection is detrimental to hospitalized patients. With diminishing choices of antibiotics and the worry about resistance to colistin in synergistic combined therapy, there are suggestions for the use of herbal derivatives. This investigation evaluated the synergistic effects of Nigella sativa (NS) in combination with beta-lactam (β-lactam) antibiotics on extreme drug-resistant (XDR) MRSA isolates. NS concentrations of 10, 7.5, 5.0, 2.5, 1.0, and 0.1 µg/mL, alone and in combination with β-lactam antibiotics, were used to determine the antimicrobial susceptibility of MRSA isolates by the well diffusion method. Time–kill assays were performed using a spectrophotometer, with time–kill curves plotted and synergism ascertained by the fractional inhibitory concentration (FIC). Scanning and transmission electron microscopy were used to gain insight into the mechanism of action of treated groups. Isolates were inhibited by the NS concentrations, with differences in the zones of inhibition being statistically insignificant at p < 0.05. There were statistically significant differences in the time–kill assay for the MRSA isolates. In addition, NS combined with augmentin showed better killing than oxacillin and cefuroxime. The mechanism of action shown by the SEM and TEM results revealed cell wall disruption, which probably created interference that led to bacterial lysis. Full article

(This article belongs to the Special Issue Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action)

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11 pages, 1904 KiB

Open AccessFeature PaperArticle

Liensinine Prevents Vascular Inflammation by Attenuating Inflammatory Mediators and Modulating VSMC Function

by Moon Young Jun, Rajendra Karki, Keshav Raj Paudel, Nisha Panth, Hari Prasad Devkota and Dong-Wook Kim

Appl. Sci. 2021, 11(1), 386; https://doi.org/10.3390/app11010386 - 3 Jan 2021

Cited by 9 | Viewed by 2857

Abstract

Liensinine is a bisbenzylisoquinoline alkaloid found in various parts of the lotus (Nelumbo nucifera Gaertn.) including seeds. In this study, we explored the preventive activity of liensinine on vascular inflammation via attenuation of inflammatory mediators in macrophage and targeting the proliferation and migration of human vascular smooth muscle cells (VSMC). Anti-oxidative activity was evaluated by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay method and measuring the peroxidation of serum lipid. Inflammatory markers were studied by evaluating the release of nitric oxide (NO) and the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in macrophage cells (RAW264.7) and interleukin (IL)-6 production in VSMC. Similarly, anti-proliferative activity in VSMC was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The enzymatic activity of matrix metalloproteinase (MMP)-9 in VSMC was evaluated by gelatin zymography. Liensinine possesses significant anti-oxidative activity as revealed by the DPPH assay and inhibition of serum lipid peroxidation. Likewise, liensinine decreased NO generation in RAW 264.7 cells. In VSMC, liensinine suppressed platelet-derived growth factor stimulated proliferation and tumor necrosis factor-α (TNF-α) induced MMP-9 enzymatic activity as well as IL-6 expression. Our results revealed the potential preventive effect of liensinine on vascular inflammation, suggesting it as a promising compound for the prevention of vascular inflammation. Full article

(This article belongs to the Special Issue Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action)

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18 pages, 4100 KiB

Open AccessArticle

Anti-Osteoarthritic Effects of Terminalia Chebula Fruit Extract (AyuFlex^®) in Interleukin-1β-Induced Human Chondrocytes and in Rat Models of Monosodium Iodoacetate (MIA)-Induced Osteoarthritis

by Hae Lim Kim, Hae Jin Lee, Dong-Ryung Lee, Bong-Keun Choi and Seung Hwan Yang

Appl. Sci. 2020, 10(23), 8698; https://doi.org/10.3390/app10238698 - 4 Dec 2020

Cited by 7 | Viewed by 4036

Abstract

Osteoarthritis (OA) is a general joint illness caused by the destruction of joint cartilage, and is common in the population of old people. Its occurrence is related to inflammatory reactions and cartilage degradation. AyuFlex^® is an aqueous extract of Terminalia chebula fruit, and T. chebula has been utilized extensively in several traditional oriental medications for the management of diverse diseases. Pre-clinical and clinical research has shown its antioxidant and anti-inflammatory effectiveness. Nevertheless, the mechanism underlying the anti-arthritic effects of AyuFlex^® remains unclear. In the current research, we proposed the ameliorating effects of AyuFlex^® with respect to the incidence of OA and described the latent signalization in interleukin (IL)-1β-treated chondrocytes and MIA-incurred OA in a rat model. In vitro, AyuFlex^® decreased oxidative stress and induction of pro-inflammatory cytokines and mediators as well as matrix metalloproteinases (MMPs), while also increasing the levels of collagen synthesis-related proteins. Mechanistically, we identified that AyuFlex^® disrupted nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation via the inhibition of NF-κB p65 and extracellular regulated protein kinase (ERK) phosphorylation. The ameliorating effects of AyuFlex^® were also observed in vivo. AyuFlex^® significantly inhibited the MIA-incurred increase in OA symptoms such as oxidative stress, cartilage damage, and changes in cytokines and MMPs revelation in arthrodial cartilage. Therefore, our results suggest that AyuFlex^® attenuates OA progression in vivo, indicating that AyuFlex^® can be suggested as an excellent therapeutic remedy for the care of OA. Full article

(This article belongs to the Special Issue Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action)

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13 pages, 2162 KiB

Open AccessArticle

Scrophularia buergeriana Extract Improves Memory Impairment via Inhibition of the Apoptosis Pathway in the Mouse Hippocampus

by Hae Jin Lee, Dae Young Lee, Hae Lim Kim and Seung Hwan Yang

Appl. Sci. 2020, 10(22), 7987; https://doi.org/10.3390/app10227987 - 11 Nov 2020

Cited by 9 | Viewed by 2780

Abstract

Scrophularia buergeriana (SB) Miq. (Scrophulariaceae) has been used to help cure swelling and fever and has reported antioxidant and neuro-protective effects. However, few mechanism–based studies have evaluated the memory-improving effects in a beta-amyloid induced memory loss model. As a result of Scrophularia buergeriana extract (SBE) administration (30 and 100 mg/kg) for 28 days significantly recovered beta-amyloid-induced amnesia in the passive avoidance test and improved the impairment of spatial memory in the Morris Water Maze (MWM) task. Furthermore, SBE up-regulated superoxide dismutase-1 (SOD)-1, SOD-2, glutathione peroxidase-1, and B-cell lymphoma (Bcl)-2 protein expression levels. Additionally, SBE downregulated Bcl-2-associated X protein, cleaved caspase-9, cleaved poly (adenosine diphosphate-ribose) polymerase, and Aβ protein expression levels and inhibited the phosphorylation of the tau protein of Aβ-treated mice hippocampus. These results demonstrate that SBE improved memory impairment by reducing beta-amyloid induced neurotoxicity and regulated oxidative stress, anti-apoptotic pathways. Full article

(This article belongs to the Special Issue Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action)

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Review

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19 pages, 1922 KiB

Open AccessFeature PaperReview

Vaccinium Species (Ericaceae): From Chemical Composition to Bio-Functional Activities

by Rosa Tundis, Maria C. Tenuta, Monica R. Loizzo, Marco Bonesi, Federica Finetti, Lorenza Trabalzini and Brigitte Deguin

Appl. Sci. 2021, 11(12), 5655; https://doi.org/10.3390/app11125655 - 18 Jun 2021

Cited by 28 | Viewed by 4879

Abstract

The genus Vaccinium L. (Ericaceae) includes more than 450 species, which mainly grow in cooler areas of the northern hemisphere. Vaccinium species have been used in traditional medicine of different cultures and the berries are widely consumed as food. Indeed, Vaccinium supplement-based herbal medicine and functional food, mainly from V. myrtillus and V. macrocarpon, are used in Europe and North America. Biological studies support traditional uses since, for many Vaccinium components, important biological functions have been described, including antioxidant, antitumor, anti-inflammatory, antidiabetic and endothelium protective activities. Vaccinium components, such as polyphenols, anthocyanins and flavonoids, are widely recognized as modulators of cellular pathways involved in pathological conditions, thus indicating that Vaccinium may be an important source of bioactive molecules. This review aims to better describe the bioactivity of Vaccinium species, focusing on anti-inflammatory and endothelial protective cellular pathways, modulated by their components, to better understand their importance for public health. Full article

(This article belongs to the Special Issue Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action)

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35 pages, 681 KiB

Open AccessFeature PaperReview

Potential Role of Plant Extracts and Phytochemicals Against Foodborne Pathogens

by Farhat Ullah, Muhammad Ayaz, Abdul Sadiq, Farman Ullah, Ishtiaq Hussain, Muhammad Shahid, Zhanibek Yessimbekov, Anjana Adhikari-Devkota and Hari Prasad Devkota

Appl. Sci. 2020, 10(13), 4597; https://doi.org/10.3390/app10134597 - 2 Jul 2020

Cited by 41 | Viewed by 10280

Abstract

Foodborne diseases are one of the major causes of morbidity and mortality, especially in low-income countries with poor sanitation and inadequate healthcare facilities. The foremost bacterial pathogens responsible for global outbreaks include Salmonella species, Campylobacter jejuni, Escherichia coli, Shigella sp., Vibrio, Listeria monocytogenes and Clostridium botulinum. Among the viral and parasitic pathogens, norovirus, hepatitis A virus, Giardia lamblia, Trichinella spiralis, Toxoplasma and Entamoeba histolytica are commonly associated with foodborne diseases. The toxins produced by Staphylococcus aureus, Bacillus cereus and Clostridium perfringens also cause these infections. The currently available therapies for these infections are associated with various limited efficacy, high cost and side-effects. There is an urgent need for effective alternative therapies for the prevention and treatment of foodborne diseases. Several plant extracts and phytochemicals were found to be highly effective to control the growth of these pathogens causing foodborne infections in in vitro systems. The present review attempts to provide comprehensive scientific information on major foodborne pathogens and the potential role of phytochemicals in the prevention and treatment of these infections. Further detailed studies are necessary to evaluate the activities of these extracts and phytochemicals along with their mechanism of action using in vivo models. Full article

(This article belongs to the Special Issue Plant-Based Bioactive Natural Products: Insights into Molecular Mechanisms of Action)

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