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Natural Products in Biomedicine and Pharmacotherapy

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

Deadline for manuscript submissions: 30 April 2024 | Viewed by 13704

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Special Issue Editor

Dr. Ahmed Ezat El Zowalaty

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Guest Editor

1. Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, 405 30 Gothenburg, Sweden
2. Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden
Interests: natural compounds; cellular toxicology; pharmacogenomics; toxicogenomics; metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bioactive compounds from natural products and their structural analogues have been used for long time for biomedical and pharmacotherapeutic applications such as cancer, cardiovascular diseases and infectious diseases. In this Special Issue, we invite researchers to present primary research papers, reviews, visionary perspectives, or retrospective analyses that address recent advances in understanding the contribution of natural products to biological processes as well as development of new therapeutics with consequences to human health and drug safety. Studies addressing pharmacokinetic and pharmacodynamic properties of natural products as well as studies utilizing novel analytical tools, genome mining of novel natural products, genetic engineering of natural products’ biosynthetic genes, structure-based methods, molecular dynamics simulations and computational tools for analysis of bioactive compounds from natural products are welcome. Studies utilizing rational genetic engineering, promoter engineering, targeted gene manipulation and heterologous expression for improving the pharmacological properties of bioactive compounds as well as improving the immunomodulatory properties of natural products would be an asset.

Dr. Ahmed Ezat El Zowalaty
Guest Editor

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

natural products
genetic engineering
pharmacotherapy
anticancer
antimicrobials

Published Papers (7 papers)

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Research

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14 pages, 5607 KiB

Open AccessArticle

In Silico and In Vitro Study of Isoquercitrin against Kidney Cancer and Inflammation by Triggering Potential Gene Targets

by Safia Iqbal, Md. Rezaul Karim, Shahnawaz Mohammad, Jong Chan Ahn, Anjali Kariyarath Valappil, Ramya Mathiyalagan, Deok-Chun Yang, Dae-Hyo Jung, Hyocheol Bae and Dong Uk Yang

Curr. Issues Mol. Biol. 2024, 46(4), 3328-3341; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb46040208 - 12 Apr 2024

Viewed by 386

Abstract

Kidney cancer has emerged as a major medical problem in recent times. Multiple compounds are used to treat kidney cancer by triggering cancer-causing gene targets. For instance, isoquercitrin (quercetin-3-O-β-d-glucopyranoside) is frequently present in fruits, vegetables, medicinal herbs, and foods and drinks made from plants. Our previous study predicted using protein-protein interaction (PPI) and molecular docking analysis that the isoquercitrin compound can control kidney cancer and inflammation by triggering potential gene targets of IGF1R, PIK3CA, IL6, and PTGS2. So, the present study is about further in silico and in vitro validation. We performed molecular dynamic (MD) simulation, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, cytotoxicity assay, and RT-PCR and qRT-PCR validation. According to the MD simulation (250 ns), we found that IGF1R, PIK3CA, and PTGS2, except for IL6 gene targets, show stable binding energy with a stable complex with isoquercitrin. We also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the final targets to determine their regulatory functions and signaling pathways. Furthermore, we checked the cytotoxicity effect of isoquercitrin (IQ) and found that 5 μg/mL and 10 μg/mL doses showed higher cell viability in a normal kidney cell line (HEK 293) and also inversely showed an inhibition of cell growth at 35% and 45%, respectively, in the kidney cancer cell line (A498). Lastly, the RT-PCR and qRT-PCR findings showed a significant decrease in PTGS2, PIK3CA, and IGF1R gene expression, except for IL6 expression, following dose-dependent treatments with IQ. Thus, we can conclude that isoquercitrin inhibits the expression of PTGS2, PIK3CA, and IGF1R gene targets, which in turn controls kidney cancer and inflammation. Full article

(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)

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14 pages, 3282 KiB

Open AccessArticle

Molecular Docking Integrated with Network Pharmacology Explores the Therapeutic Mechanism of Cannabis sativa against Type 2 Diabetes

by Juan Manuel Guzmán-Flores, Victoriano Pérez-Vázquez, Fernando Martínez-Esquivias, Mario Alberto Isiordia-Espinoza and Juan Manuel Viveros-Paredes

Curr. Issues Mol. Biol. 2023, 45(9), 7228-7241; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45090457 - 01 Sep 2023

Viewed by 2288

Abstract

The incidence of type 2 diabetes (T2D) is rising, and finding new treatments is important. C. sativa is a plant suggested as a potential treatment for T2D, but how it works needs to be clarified. This study explored the pharmacological mechanism of C. sativa in treating T2D. We identified the active compounds in C. sativa and their targets. From there, we examined the genes associated with T2D and found overlapping genes. We conducted an enrichment analysis and created a protein–protein and target–compound interactions network. We confirmed the binding activities of the hub proteins and compounds with molecular docking. We identified thirteen active compounds from C. sativa, which have 150 therapeutic targets in T2D. The enrichment analysis showed that these proteins are involved in the hormone, lipid, and stress responses. They bind transcription factors and metals and participate in the insulin, PI3K/Akt, HIF-1, and FoxO signaling pathways. We found four hub proteins (EGFR, ESR1, HSP90AA1, and SRC) that bind to the thirteen bioactive compounds. This was verified using molecular docking. Our findings suggest that C. sativa’s antidiabetic action is carried out through the insulin signaling pathway, with the participation of HIF-1 and FoxO. Full article

(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)

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32 pages, 9561 KiB

Open AccessArticle

Anti-Inflammatory Effects of Serotonin Receptor and Transient Receptor Potential Channel Ligands in Human Small Intestinal Epithelial Cells

by Gregory Ian Robinson, Dongping Li, Bo Wang, Yeva Zahoruiko, Marta Gerasymchuk, Darryl Hudson, Olga Kovalchuk and Igor Kovalchuk

Curr. Issues Mol. Biol. 2023, 45(8), 6743-6774; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45080427 - 15 Aug 2023

Cited by 6 | Viewed by 3180

Abstract

Intestinal inflammation and dysbiosis can lead to inflammatory bowel diseases (IBD) and systemic inflammation, affecting multiple organs. Developing novel anti-inflammatory therapeutics is crucial for preventing IBD progression. Serotonin receptor type 2A (5-HT2A) ligands, including psilocybin (Psi), 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), and ketanserin (Ket), along with transient receptor potential (TRP) channel ligands like capsaicin (Cap), curcumin (Cur), and eugenol (Eug), show promise as anti-inflammatory agents. In this study, we investigated the cytotoxic and anti-inflammatory effects of Psi, 4-AcO-DMT, Ket, Cap, Cur, and Eug on human small intestinal epithelial cells (HSEIC). HSEIC were exposed to tumor necrosis factor (TNF)-α and interferon (IFN)-γ for 24 h to induce an inflammatory response, followed by treatment with each compound at varying doses (0–800 μM) for 24 to 96 h. The cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and protein expression by Western blot (WB) analysis. As single treatments, Psi (40 μM), Cur (0.5 μM), and Eug (50 μM) significantly reduced COX-2 levels without cytotoxic effects. When combined, Psi (40 μM) and Cur (0.5 μM) exhibited synergy, resulting in a substantial decrease in COX-2 protein levels (−28× fold change), although the reduction in IL-6 was less pronounced (−1.6× fold change). Psi (20 μM) and Eug (25 μM) demonstrated the most favorable outcomes, with significant decreases in COX-2 (−19× fold change) and IL-6 (−10× fold change) protein levels. Moreover, the combination of Psi and Eug did not induce cytotoxic effects in vitro at any tested doses. This study is the first to explore the anti-inflammatory potential of psilocybin and 4-AcO-DMT in the intestines while highlighting the potential for synergy between the 5-HT2A and TRP channel ligands, specifically Psi and Eug, in alleviating the TNF-α/IFN-γ-induced inflammatory response in HSEIC. Further investigations should evaluate if the Psi and Eug combination has the therapeutic potential to treat IBD in vivo. Full article

(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)

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12 pages, 2932 KiB

Open AccessCommunication

Escin Activates Canonical Wnt/β-Catenin Signaling Pathway by Facilitating the Proteasomal Degradation of Glycogen Synthase Kinase-3β in Cultured Human Dermal Papilla Cells

by Jae Young Shin, Jaeyoon Kim, Yun-Ho Choi, Sanghwa Lee and Nae-Gyu Kang

Curr. Issues Mol. Biol. 2023, 45(7), 5902-5913; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45070373 - 14 Jul 2023

Viewed by 1149

Abstract

Abnormal inactivation of the Wnt/β-catenin signaling pathway is involved in skin diseases like androgenetic alopecia, vitiligo and canities, but small-molecule activators are rarely described. In this study, we investigated the stimulatory effects of escin on the canonical Wnt/β-catenin signaling pathway in cultured human dermal papilla cells (hDPCs). Escin stimulated Wnt/β-catenin signaling, resulting in increased β-catenin and lymphoid enhancer-binding factor 1 (LEF1), the accumulation of nuclear β-catenin and the enhanced expression of Wnt target genes in cultured hDPCs. Escin drastically reduced the protein level of glycogen synthase kinase (GSK)-3β, a key regulator of the Wnt/β-catenin signaling pathway, while the presence of the proteasome inhibitor MG-132 fully restored the GSK-3β protein level. The treatment of secreted frizzled-related proteins (sFRPs) 1 and 2 attenuated the activity of escin in Wnt reporter assays. Our data demonstrate that escin is a natural agonist of the canonical Wnt/β-catenin signaling pathway and downregulates GSK-3β protein expression by facilitating the proteasomal degradation of GSK-3β in cultured hDPCs. Our data suggest that escin likely stimulates Wnt signaling through direct interactions with frizzled receptors. This study underscores the therapeutic potential of escin for Wnt-related diseases such as androgenetic alopecia, vitiligo and canities. Full article

(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)

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19 pages, 4710 KiB

Open AccessArticle

Pharmacological and Pathological Effects of Mulberry Leaf Extract on the Treatment of Type 1 Diabetes Mellitus Mice

by Liru Luo, Wei Fan, Jingping Qin, Shiyin Guo, Hang Xiao and Zhonghai Tang

Curr. Issues Mol. Biol. 2023, 45(7), 5403-5421; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45070343 - 29 Jun 2023

Cited by 1 | Viewed by 2275

Abstract

This study investigated the pharmacological and pathological effects of aqueous mulberry leaf extract on type 1 diabetes mellitus mice induced with an intraperitoneal injection of streptozotocin (STZ). Diabetic mice were randomized into six groups: control (normal group), model, metformin-treated mice, and high-dose, medium-dose, and low-dose mulberry. The mulberry-treated mice were divided into high-, medium-, and low-dose groups based on the various doses of aqueous mulberry leaf extract during gavage. The efficacy of the six-week intervention was evaluated by measuring levels of fasting plasma glucose, alkaline phosphatase, alanine aminotransferase, aspartate transaminase, blood urea nitrogen, gamma-glutamyl transferase, glucose, high-density lipoprotein cholesterol, lactate dehydrogenase, and low-density lipoprotein cholesterol and recording body weight. Results revealed that mulberry leaf extract exhibited an ideal hypoglycemic effect, and the high-dose group was the most affected. Histology analysis, glycogen staining and apoptosis detection were used to study the extract’s effects on the liver, kidney, and pancreatic cells of diabetic mice, enabling the assessment of its effectiveness and complications on a clinical and theoretical basis. It was shown that a certain concentration of aqueous mulberry leaf extract repaired the islet cells of type 1 diabetes mellitus mice, promoting normal insulin secretion. Herein, it was confirmed that mulberry leaf could be used to develop new hypoglycemic drugs or functional health food with broad applicability. Full article

(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)

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11 pages, 5550 KiB

Open AccessCommunication

Protective Effects of Apamin on Acetaminophen-Induced Hepatotoxicity in Mice

by Hyo-Jeong Jang, Jaechan Leem and Gyun Moo Kim

Curr. Issues Mol. Biol. 2023, 45(5), 4389-4399; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45050279 - 17 May 2023

Cited by 2 | Viewed by 1635

Abstract

Acetaminophen (APAP) overdose can cause severe liver damage, but therapeutic options are limited. Apamin is a natural peptide present in bee venom and has antioxidant and anti-inflammatory properties. Accumulating evidence suggests that apamin has favorable actions in rodent models of inflammatory disorders. Here, we examined the effect of apamin on APAP-evoked hepatotoxicity. Intraperitoneal administration of apamin (0.1 mg/kg) alleviated histological abnormalities and reduced serum levels of liver enzymes in mice injected with APAP. Apamin inhibited oxidative stress through an increase in the amount of glutathione and activation of the antioxidant system. Apamin also attenuated apoptosis with inhibition of caspase-3 activation. Moreover, apamin reduced serum and hepatic levels of cytokines in APAP-injected mice. These effects were accompanied by suppression of NF-κB activation. Furthermore, apamin inhibited chemokine expression and inflammatory cell infiltration. Our results suggest that apamin dampens APAP-evoked hepatotoxicity through inhibiting oxidative stress, apoptosis, and inflammation. Full article

(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)

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Review

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15 pages, 4480 KiB

Open AccessReview

Recent Trends in the Antidiabetic Prominence of Natural and Synthetic Analogues of Aurones

by Rammohan Aluru, Anindita Mukherjee, Grigory V. Zyryanov, Adinath Majee and Sougata Santra

Curr. Issues Mol. Biol. 2023, 45(10), 8461-8475; https://0-doi-org.brum.beds.ac.uk/10.3390/cimb45100533 - 19 Oct 2023

Cited by 1 | Viewed by 1318

Abstract

Natural products are a boundless source for the development of pharmaceutical agents against a wide range of human diseases. Accordingly, naturally occurring aurones possess various biological benefits, such as anticancer, antioxidant, antimicrobial, antidiabetic, anti-inflammatory, antiviral and neuroprotective effects. In addition, various studies have revealed that aurones are potential templates for the regulation of diabetes mellitus and its associated complications. Likewise, certain aurones and their analogues have been found to be remarkable kinase inhibitors of DARK2, PPAR-γ, PTPM1, AGE, α-amylase and α-glucosidase, which represents a promising approach for the treatment of chronic metabolic disorders such as diabetes. Therefore, in our present study, we provide a detailed account of the advances in aurones as antidiabetic agents over the past decade. Full article

(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)

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