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Molecular Research in Bioactivity of Natural Products

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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 18035

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Dr. Magdalena Bartnik

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Department of Pharmacognosy with Medicinal Plants Garden, Medical University of Lublin, Chodźki 1 Street, 20-093 Lublin, Poland
Interests: pharmacognosy; phytochemistry; natural products; HPLC; secondary metabolites; coumarins; flavonoids; phenolic acids; antioxidant activity; glycosides; LC-MS; antioxidants; anticancer activity
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Wirginia Kukula-Koch

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Department of Pharmacognosy with Medicinal Plants Garden, Medical University of Lublin, Chodzki str., 20-093 Lublin, Poland
Interests: natural products chemistry; chromatography; bioactivity testing in vitro and in vivo; mass spectrometry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products, especially those of plant origin, due to the diversity of their chemical structure, provide an opportunity to discover new compounds that can be transformed into drugs. These compounds can influence various metabolic pathways in the body, helping to maintain homeostasis processes, improving antioxidant mechanisms, protecting the central nervous system, and having anticancer effects, both as apoptosis inducers and antiangiogenic chemicals. All of these mechanisms are extremely important for maintaining and restoring human health. In this Special Issue, we encourage researchers to publish their latest discoveries in this field, highlighting the importance of naturally derived active metabolites and their associated molecular mechanisms of bioactivity.

Entries related to the topic of this Special Issue do not have to be limited to the areas mentioned in the keywords.

We look forward to receiving your contributions.

Dr. Magdalena Bartnik
Prof. Dr. Wirginia Kukula-Koch
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Issues in Molecular Biology is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

molecular research
molecular properties
metabolic pathway
phytochemicals
natural products
apoptosis
bioactivity assessment
chemical composition
therapeutic targets

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Published Papers (11 papers)

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Research

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13 pages, 3568 KiB

Open AccessArticle

The Root Extract of Rosa multiflora Ameliorates Nonalcoholic Steatohepatitis Development via Blockade of De Novo Lipogenesis and Inflammation

by Nam-Hee Kim, Seung-Jin Lee, Kyeong-Jin Lee, Ae Ri Song, Hyun-Je Park, Jong Soo Kang, Joo Young Cha and Yong-Hyun Han

Curr. Issues Mol. Biol. 2024, 46(6), 5881-5893; https://doi.org/10.3390/cimb46060351 - 12 Jun 2024

Cited by 1 | Viewed by 898

Abstract

Nonalcoholic steatohepatitis (NASH) is characterized by severe inflammation and fibrosis due to an excessive accumulation of triglycerides (TGs) in the liver with a dysregulated de novo lipogenesis (DNL) pathway. In this study, we aimed to evaluate the effectiveness of YC-1102, an extract obtained from the roots of Rosa multiflora, as a nutritional supplement in a diet-induced NASH mouse model. C57BL/6 wild-type mice were fed a fructose, palmitate, and cholesterol (FPC)-containing diet for 16 weeks to induce experimental NASH. A daily oral gavage of YC-1102 and obetichoic acid (OCA) was conducted for 9 weeks. After sacrifice, disease parameters related to hepatic lipids, inflammation, and fibrosis were evaluated. The treatment with YC-1102 significantly decreased the liver/body weight ratio, epididymal fat weight, and plasma ALT and AST levels, which are indicators of NASH injuries. YC-1102 attenuated hepatic lipid accumulation by inhibiting the transcription of DNL genes in the livers exhibiting NASH. Additionally, we found that YC-1102 blocked the development of hepatic inflammation and fibrosis by directly disturbing macrophage activation, resulting in an amelioration of hepatic fibrosis. Our findings suggest that YC-1102 could ameliorate NASH progression by inhibiting uncontrolled DNL and inflammation. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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19 pages, 3459 KiB

Open AccessArticle

Black Chokeberry (Aronia melanocarpa) Juice Supplementation Improves Oxidative Stress and Aging Markers in Testis of Aged Rats

by Elena Daskalova, Mina Pencheva and Petko Denev

Curr. Issues Mol. Biol. 2024, 46(5), 4452-4470; https://doi.org/10.3390/cimb46050270 - 8 May 2024

Viewed by 1252

Abstract

Spermatogenesis is a process that continues until the end of an individual’s life, although with reduced activity with advancing age. Inflammation, oxidation, and apoptosis are events considered as predictors of pathogenesis and the development of age-related diseases observed in aged testes. The use of natural compounds with antioxidant and anti-inflammatory properties has a beneficial effect on the inflammatory and oxidative status of the aged testis. The aim of this study was to determine the effect of supplementation with antioxidant-rich black chokeberry (Aronia melanocarpa) juice on several markers of oxidative stress and aging in rat testis. In total, 24 male Wistar rats were divided into three experimental groups: young controls aged 2 months, old controls aged 27 months, and 27-month-old rats supplemented with black chokeberry juice at a dose of 10 mL/kg for 3 months. A. melanocarpa juice supplementation led to reduced oxidative stress, manifested by increased immunoexpression of nNOS, eNOS, and MAS1 in the seminiferous tubules and in the Leydig cells. The morphometrically determined tubule structure data showed no significant differences between the three groups. However, the intensity of the immunoreaction for TRK-C and NT3 in Leydig cells was demonstrably higher in the supplemented old animals compared with the old controls. There was a significantly higher number of blood vessels around the seminiferous tubules in the supplemented animals compared to the old controls. These data indicate that supplementation with A. melanocarpa juice slows down aging processes in the testis and preserves the functional activity of Leydig cells. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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14 pages, 2858 KiB

Open AccessArticle

A Computational Approach for the Discovery of Novel DNA Methyltransferase Inhibitors

by Eftichia Kritsi, Paris Christodoulou, Thalia Tsiaka, Panagiotis Georgiadis and Maria Zervou

Curr. Issues Mol. Biol. 2024, 46(4), 3394-3407; https://doi.org/10.3390/cimb46040213 - 16 Apr 2024

Cited by 1 | Viewed by 1260

Abstract

Nowadays, the explosion of knowledge in the field of epigenetics has revealed new pathways toward the treatment of multifactorial diseases, rendering the key players of the epigenetic machinery the focus of today’s pharmaceutical landscape. Among epigenetic enzymes, DNA methyltransferases (DNMTs) are first studied as inhibition targets for cancer treatment. The increasing clinical interest in DNMTs has led to advanced experimental and computational strategies in the search for novel DNMT inhibitors. Considering the importance of epigenetic targets as a novel and promising pharmaceutical trend, the present study attempted to discover novel inhibitors of natural origin against DNMTs using a combination of structure and ligand-based computational approaches. Particularly, a pharmacophore-based virtual screening was performed, followed by molecular docking and molecular dynamics simulations in order to establish an accurate and robust selection methodology. Our screening protocol prioritized five natural-derived compounds, derivatives of coumarins, flavones, chalcones, benzoic acids, and phenazine, bearing completely diverse chemical scaffolds from FDA-approved “Epi-drugs”. Their total DNMT inhibitory activity was evaluated, revealing promising results for the derived hits with an inhibitory activity ranging within 30–45% at 100 µM of the tested compounds. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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12 pages, 1207 KiB

Open AccessCommunication

The Combination of Oolonghomobisflavan B and Diallyl Disulfide Induces Apoptotic Cell Death via 67-kDa Laminin Receptor/Cyclic Guanosine Monophosphate in Acute Myeloid Leukemia Cells

by Jaehoon Bae and Su-Jin Park

Curr. Issues Mol. Biol. 2024, 46(3), 2444-2455; https://doi.org/10.3390/cimb46030154 - 14 Mar 2024

Cited by 1 | Viewed by 1203

Abstract

Diallyl disulfide (DADS) is a well-known principal functional component derived from garlic (Allium sativum) that has various health benefits. Previously, we identified a 67-kDa laminin receptor, a receptor for oolong tea polyphenol oolonghomobisflavan B (OHBFB). However, its molecular mechanisms still remain to be elucidated. Here, we show that DADS synergistically enhanced the effect of the oolong tea polyphenol oolonghomobisflavan B (OHBFB), which induces apoptosis in acute myeloid leukemia (AML) cancer cells without affecting normal human peripheral blood mononuclear cells (PBMCs). The underlying mechanism of OHBFB-induced anti-AML effects involves the upregulation of the 67-kDa laminin receptor/endothelial nitric oxide synthase/cyclic guanosine monophosphate (cGMP)/protein kinase c delta (PKCδ)/acid sphingomyelinase (ASM)/cleaved caspase-3 signaling pathway. In conclusion, we show that the combination of OHBFB and DADS synergistically induced apoptotic cell death in AML cells through activation of 67LR/cGMP/PKCδ/ASM signaling pathway. Moreover, in this mechanism, we demonstrate DADS may reduce the enzyme activity of phosphodiesterase, which is a negative regulator of cGMP that potentiates OHBFB-induced AML apoptotic cell death without affecting normal PBMCs. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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13 pages, 21447 KiB

Open AccessArticle

Production of Mature Recombinant Human Activin A in Transgenic Rice Cell Suspension Culture

by Van Giap Do and Moon-Sik Yang

Curr. Issues Mol. Biol. 2024, 46(2), 1164-1176; https://doi.org/10.3390/cimb46020074 - 30 Jan 2024

Cited by 1 | Viewed by 1748

Abstract

Activin A belongs to the transforming growth factor (TGF) family member, which exhibits a wide range of biological activities, including the regulation of cellular proliferation and differentiation and the promotion of neuronal survival. The isolation of AA from natural sources can only produce limited quantities of this bioactive protein. In this study, the whole gene of the precursor form of recombinant human activin A (rhAA) contains a signal peptide, and a pro-region and a mature region were cloned into an expression vector under the control of the rice α-amylase 3D (RAmy3D) promoter. To obtain the mature (active) form of rhAA, an enterokinase cleavage site was inserted between the pro-region and mature region of rhAA. The rice seed (Oryza sativa L. cv. Dongjin) was transformed with recombinant vectors by the Agrobacterium-mediated method, and the integration of the target gene into the plant genome was confirmed by genomic PCR. The transcript expression of rhAA in transgenic rice calli was confirmed by a Northern blot analysis of mRNA. The production of rhAA was verified by Western blot analysis and ELISA. The accumulation of secreted rhAA in the culture medium was purified by Ni²⁺—NTA. The mature form of AA was released from the precursor form of rhAA after proteolytically processing with enterokinase. Western blot shows that the mature AA was split into monomer and homodimer with molecular weights of 14 kDa and 28 kDa under reducing and non-reducing conditions, respectively. These results suggest that the mature form of rhAA could be produced and purified using transgenic rice cell suspension culture. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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12 pages, 2946 KiB

Open AccessArticle

Anti-Neuroinflammatory Effects of Arecae pericarpium on LPS-Stimulated BV2 Cells

by Hyeon-gyu Cho, Dong-Uk Kim, Jin-Young Oh, Sung-Joo Park, Bitna Kweon and Gi-Sang Bae

Curr. Issues Mol. Biol. 2024, 46(1), 884-895; https://doi.org/10.3390/cimb46010056 - 19 Jan 2024

Cited by 1 | Viewed by 1665

Abstract

Arecae pericarpium (AP), the fruit peel of the betel palm, is a traditional Oriental herbal medicine. AP is used to treat various diseases and conditions, such as ascites, edema, and urinary retention, in traditional Korean medicine. Recent studies have demonstrated its anti-obesity and antibacterial effects; however, its anti-neuroinflammatory effects have not yet been reported. Therefore, we investigated the anti-neuroinflammatory effects of AP on lipopolysaccharide (LPS)-stimulated mouse microglia in this study. To determine the anti-neuroinflammatory effects of AP on BV2 microglial cells, we examined the production of nitric oxide (NO) using Griess assay and assessed the mRNA expression levels of inflammatory mediators, such as inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, and pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, using a real-time reverse transcription-polymerase chain reaction. Furthermore, we determined the levels of mitogen-activated protein kinases and IκBα via Western blotting to understand the regulating mechanisms of AP. AP treatment decreased NO production in LPS-stimulated BV2 cells. Additionally, AP suppressed the expression of iNOS and COX-2 and the production of pro-inflammatory cytokines. AP also inhibited the activation of p38 and nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells. Therefore, AP exerts anti-neuroinflammatory effects via inactivation of the p38 and NF-κB pathways. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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15 pages, 5358 KiB

Open AccessArticle

Cytotoxic Effect of Andrographis paniculata Associated with 2-Aminoethyl Dihydrogen Phosphate in Triple-Negative Breast Cells

by Rosa Andrea Nogueira Laiso, Julia Carolina Ferreira, Rose Eli Grassi Rici, Laertty Garcia de Sousa Cabral and Durvanei Augusto Maria

Curr. Issues Mol. Biol. 2024, 46(1), 527-541; https://doi.org/10.3390/cimb46010034 - 5 Jan 2024

Cited by 1 | Viewed by 2084

Abstract

Cancer stands out as a major global public health concern and a significant impediment to increasing life expectancy worldwide. Natural bioactives derived from plants are renowned for their efficacy in treating various types of cancer. Andrographis paniculata (Burm.f.) is a well-known plant traditionally employed in diverse medical systems across the globe. The 2-AEH₂P monophosphoester, a molecule intricately involved in phospholipid turnover, demonstrates antiproliferative effects across a broad spectrum of cancer types. This study aims to assess the antitumor, antiproliferative, and pharmacological effects of andrographolide at different concentrations, both individually and in conjunction with 2-aminoethyl dihydrogen phosphate. The cytotoxicity of the treatments was evaluated using the colorimetric MTT method, cell cycle phases, mitochondrial electrical potential, and markers expression via flow cytometry, while the pharmacological effects were assessed using SynergyFinder software 3.0. Treatments with A. paniculata, isolated at concentrations of 10%, 30%, and 50% of andrographolide, induced cell death in tumor cells, resulting in a reduction in mitochondrial electrical potential and alterations in cell cycle phases, particularly a decrease in the population of MDA MB-231 cells in the G0/G1 phase. The combination treatments exhibited significant cytotoxicity toward tumor cells, with minimal toxicity observed in normal fibroblast cells FN1. This led to a reduction in mitochondrial electrical potential and cell cycle arrest in the S phase for MDA MB-231 cells. Across all concentrations, the combined treatments demonstrated a synergistic pharmacological effect, underscoring the efficacy of the association. There was a change in the markers involved in cell death, such as p53, caspase 3, Bcl-2, and cytochrome c, suggesting the induction of regulated cell death. Markers associated with progression and proliferation, such as cyclin D1 and p21, corroborate the findings for cytotoxicity and cell cycle arrest. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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Review

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22 pages, 2141 KiB

Open AccessReview

A Comprehensive View on the Impact of Chlorogenic Acids on Colorectal Cancer

by Andreea-Adriana Neamțu, Teodor Andrei Maghiar, Violeta Turcuș, Paula Bianca Maghiar, Anca-Maria Căpraru, Bianca-Andreea Lazar, Cristina-Adriana Dehelean, Ovidiu Laurean Pop, Carmen Neamțu, Bogdan Dan Totolici and Endre Mathe

Curr. Issues Mol. Biol. 2024, 46(7), 6783-6804; https://doi.org/10.3390/cimb46070405 - 2 Jul 2024

Cited by 1 | Viewed by 1119

Abstract

Chlorogenic acids are plant secondary metabolites, chemically—polyphenols with similar biological activity, formed through the esterification of quinic acid and hydrocinnamic acid moieties. They are best known for their high concentration in coffee and other dietary sources and the antioxidant properties that they exhibit. Both chlorogenic acids and plant extracts containing significant amounts of the compounds show promising in vitro activity against colorectal cancer. With coffee being the most popular drink in the world, and colorectal cancer at an unfortunate peak in incidence and mortality, the mechanisms through which the anti-tumorigenic effect of chlorogenic acids could be functionalized for CRC prevention seem appealing to study. Therefore, this review aims to enable a better understanding of the modes of action of chlorogenic acids in combating carcinogenesis, with a focus on cell cycle arrest, the induction of apoptosis, and the modulation of Wnt, Pi3K/Akt, and MAPK signal transduction pathways, alongside the reduction in the number of inflammatory cytokines and chemokines and the counterintuitive beneficial elevation of oxidative stress. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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17 pages, 2669 KiB

Open AccessReview

Actinomycetes Associated with Arthropods as a Source of New Bioactive Compounds

by Carlos Olano and Miriam Rodríguez

Curr. Issues Mol. Biol. 2024, 46(5), 3822-3838; https://doi.org/10.3390/cimb46050238 - 24 Apr 2024

Cited by 4 | Viewed by 1455

Abstract

Antimicrobial resistance is one of the main global threats to human health in the 21st century due to the rapid appearance of bacterial resistance and the lack of novel bioactive compounds. Natural products, especially from Actinomycetes, remain the best source to refill the drug industry pipeline. Different strategies have been pursued to increase the chances of discovering new molecules, such as studying underexplored environments like arthropod symbionts, which represent a relevant reservoir for active metabolites. This review summarizes recent research on the identification of bioactive molecules produced by Actinomycetes associated with arthropods’ microbiome. The metabolites have been categorized based on their structural properties and host, highlighting that multidisciplinary approaches will be the key to fully understanding this complex relationship. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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42 pages, 13572 KiB

Open AccessReview

Advances in Flavonoid Research: Sources, Biological Activities, and Developmental Prospectives

by Baocheng Hao, Zhen Yang, Haoyu Liu, Yu Liu and Shengyi Wang

Curr. Issues Mol. Biol. 2024, 46(4), 2884-2925; https://doi.org/10.3390/cimb46040181 - 26 Mar 2024

Cited by 9 | Viewed by 2789

Abstract

At present, the occurrence of a large number of infectious and non-communicable diseases poses a serious threat to human health as well as to drug development for the treatment of these diseases. One of the most significant challenges is finding new drug candidates that are therapeutically effective and have few or no side effects. In this respect, the active compounds in medicinal plants, especially flavonoids, are potentially useful compounds with a wide range of pharmacological activities. They are naturally present in nature and valuable in the treatment of many infectious and non-communicable diseases. Flavonoids are divided into fourteen categories and are mainly derived from plant extraction, chemical synthesis and structural modification, and biosynthesis. The structural modification of flavonoids is an important way to discover new drugs, but biosynthesis is currently considered the most promising research direction with the potential to revolutionize the new production pipeline in the synthesis of flavonoids. However, relevant problems such as metabolic pathway analyses and cell synthesis protocols for flavonoids need to be addressed on an urgent basis. In the present review, new research techniques for assessing the biological activities of flavonoids and the mechanisms of their biological activities are elucidated and their modes of interaction with other drugs are described. Moreover, novel drug delivery systems, such as nanoparticles, bioparticles, colloidals, etc., are gradually becoming new means of addressing the issues of poor hydrophilicity, lipophilicity, poor chemical stability, and low bioavailability of flavonoids. The present review summarizes the latest research progress on flavonoids, existing problems with their therapeutic efficacy, and how these issues can be solved with the research on flavonoids. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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28 pages, 2974 KiB

Open AccessReview

Methoxyfuranocoumarins of Natural Origin–Updating Biological Activity Research and Searching for New Directions—A Review

by Magdalena Bartnik

Curr. Issues Mol. Biol. 2024, 46(1), 856-883; https://doi.org/10.3390/cimb46010055 - 19 Jan 2024

Cited by 4 | Viewed by 1681

Abstract

Plant secondary metabolites, including furanocoumarins, have attracted attention for decades as active molecules with therapeutic potential, especially those occurring in a limited number of species as evolutionarily specific and chemotaxonomically important. The most famous methoxyfuranocoumarins (MFCs), bergapten, xanthotoxin, isopimpinellin, phellopterin, byakangelicol, byakangelicin, isobergapten, pimpinellin, sphondin, as well as rare ones such as peucedanin and 8-methoxypeucedanin, apaensin, cnidilin, moellendorffiline and dahuribiethrins, have recently been investigated for their various biological activities. The α-glucosidase inhibitory activity and antioxidant potential of moellendorffiline, the antiproliferative and proapoptotic properties of non-UV-activated bergapten and xanthotoxin, the effect of MFC on the activity of tyrosinase, acetyl- and butylcholinesterase, and the role of these compounds as adjuvants in anticancer and antibacterial tests have been confirmed. The anticonvulsant effects of halfordin, the antidepressant effects of xanthotoxin, and the antiadipogenic, neuroprotective, anti-amyloid-β, and anti-inflammatory (via increasing SIRT 1 protein expression) properties of phellopterin, as well as the activity of sphondin against hepatitis B virus, have also attracted interest. It is worth paying attention to the agonistic effect of xanthotoxin on bitter taste receptors (TAS2Rs) on cardiomyocytes, which may be important in the future treatment of tachycardia, as well as the significant anti-inflammatory activity of dahuribiethrins. It should be emphasized that MFCs, although in many cases isolated for the first time many years ago, are still of great interest as bioactive molecules. The aim of this review is to highlight key recent developments in the study of the diverse biological activities of MFCs and attempt to highlight promising directions for their further research. Where possible, descriptions of the mechanisms of action of MFC are provided, which is related to the constantly discovered therapeutic potential of these molecules. The review covers the results of experiments from the last ten years (2014–2023) conducted on isolated natural cMFCs and includes the activity of molecules that have not been activated by UV rays. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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