Submit to CIMB Review for CIMB Propose a Special Issue

Journal Menu

Journal Browser

Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

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

Deadline for manuscript submissions: closed (31 December 2025) | Viewed by 13252

Share This Special Issue

Special Issue Editor

Dr. Hidayat Hussain

E-Mail Website
Guest Editor

Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany
Interests: natural product; chemistry; medicinal chemistry; cancer biology; bioorganic chemistry; pharmacology; diabetes; synthetic chemistry; biology oriented synthesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products (NPs) and NP-based semi-synthetic compounds have been attracting increased attention from the scientific community due to their great structural and chemical diversity. Notably, NP-based molecules are valid sources of drug lead compounds, because 60% of chemotherapeutic agents originate from natural products. On the other hand, pseudo‐natural products (PNPs) combine natural product (NP) fragments in novel and intriguing arrangements that are not accessible via biosynthesis pathways. Moreover, they can be regarded as non‐biogenic fusions of NP‐derived fragments. Scientists have established new synthesis principles to advance beyond the chemical space explored by nature by combining the principles of biology-orientated synthesis (BIOS) and fragment-based compound design. Interestingly, scaffolds from different NPs can be combined and reconnected to create new alternative molecular scaffolds: so-called pseudo-natural products.

The aim of this Special Issue on natural product (NP)- and pseudo‐natural product (PNP)-based drug discovery is to underline the most recent discoveries and progress in all fields of biological sciences dealing with NPs and PNPs. This Special Issue will mainly focus on biological studies on NPs and PNPs on a molecular level. In addition, this Special Issue will also focus on the development of new NP- and PNP-based therapeutic agents for the treatment of numerous diseases, employing the newest techniques in pharmacology, biotechnology, and genetic engineering. For this Special Issue, we welcome original articles, communications, and reviews exploring drug discovery and development.

Dr. Hidayat Hussain
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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.

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
pseudo-natural products
drug discovery
molecular level
in vitro studies
in vivo studies
computational methods
mode of action
computational methods

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (9 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

21 pages, 14108 KB

Open AccessArticle

Levistolide A Alleviates Myocardial Ischemia–Reperfusion Injury Partly by Improving Calcium Homeostasis via the ADORA2B/cAMP/PKA/PLB/SERCA2α Signaling Axis

by Yaofeng Li, Yuxin Lu, Xiangyun Chen and Mengyue Guo

Curr. Issues Mol. Biol. 2026, 48(2), 125; https://doi.org/10.3390/cimb48020125 - 23 Jan 2026

Viewed by 330

Abstract

This study aims to investigate the protective effect of the natural phthalide compound Levistolide A (LA) against myocardial ischemia–reperfusion injury (MIRI) and to elucidate its underlying mechanisms. Utilizing network pharmacology, potential targets of LA in the treatment of MIRI were predicted. Subsequently, a hypoxia/reoxygenation (H/R) model was established using rat H9C2 cardiomyocytes to simulate MIRI, and the mechanisms of action were validated through cellular experiments. Network pharmacology analysis indicated that the potential targets of LA in treating MIRI were significantly enriched in calcium signaling pathways, with the adenosine A2B receptor (ADORA2B), a G protein-coupled receptor (GPCR), identified as a key protein. Cellular experiments demonstrated that 24 μM LA significantly alleviated H/R-induced damage in H9C2 cells, enhanced cell viability, and reduced the release of lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), and cardiac troponin I (cTnI). Pre-treatment with LA significantly activated the ADORA2B/Cyclic adenosine monophosphate (cAMP)/Protein kinase A (PKA) signaling axis, promoting the phosphorylation of phospholamban (PLB), enhancing the activity and protein expression of sarco/endoplasmic reticulum Ca²⁺-ATPase 2 alpha (SERCA2α), and effectively mitigating intracellular calcium overload induced by H/R. However, the ADORA2B antagonist MRS 1754 partially reverses the aforementioned protective effects of LA. The findings of this study reveal a novel mechanism by which LA exerts cardioprotective effects through the ADORA2B/cAMP/PKA/PLB/SERCA2α signaling axis, preventing calcium overload and improving calcium homeostasis, and identify potential candidate compounds and precise targets for the treatment of MIRI. Full article

(This article belongs to the Special Issue Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025)

► Show Figures

Figure 1

16 pages, 1968 KB

Open AccessArticle

Effect of Different Prebiotic Saccharides on Listeria monocytogenes Adherence to Human Adenocarcinoma Caco-2 Cell Line

by Tereza Kodešová, Ivo Doskočil, Eva Vlková and Hana Šubrtová Salmonová

Curr. Issues Mol. Biol. 2025, 47(11), 891; https://doi.org/10.3390/cimb47110891 - 28 Oct 2025

Viewed by 602

Abstract

Listeria monocytogenes (LM) is one of the most emerging pathogens responsible for the serious foodborne disease listeriosis. The risk of disease outbreaks can be reduced by suppressing the adherence of LM to the intestinal epithelial cells. This effect can be achieved by prebiotic supplementation. The aim of this work was to determine the effect of prebiotics beta-(1,3)-D-glucan, inulin, fructooligosaccharides, galactooligosaccharides, lactulose, raffinose, stachyose, human milk oligosaccharides (HMOs), and 2’-fucosyllactose on the ability of LM to adhere to the human adenocarcinoma Caco-2 cell line. Despite strain-specific variability, a statistically significant reduction in LM adhesion to intestinal epithelial cells was observed in the presence of beta-(1,3)-D-glucan (~60% reduction), inulin (~46%), and HMOs (~44%). In contrast, the remaining tested prebiotics did not show a significant impact on LM adhesion. These findings highlight the potential of specific prebiotics, especially beta-glucans, to limit LM adherence, suggesting a protective effect for the host. Full article

(This article belongs to the Special Issue Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025)

► Show Figures

Figure 1

14 pages, 4433 KB

Open AccessArticle

Saucerneol D Suppresses the Growth of Helicobacter pylori and Their Virulence Factors

by Su Man Kim, Hyun Jun Woo, Zhongduo Yang, Tiankun Zhao, Ji Yeong Yang and Sa-Hyun Kim

Curr. Issues Mol. Biol. 2025, 47(10), 828; https://doi.org/10.3390/cimb47100828 - 9 Oct 2025

Viewed by 888

Abstract

Helicobacter pylori infects the human stomach and causes various gastrointestinal diseases. Saucerneol D is a type of lignan, which is a polyphenol compound that exists naturally in plants, and it is abundant in flaxseed, sesame seeds, whole grains, vegetables, and fruits. Saucerneol D is found in Saurus chinensis extract and has been reported to exert a variety of effects, such as antioxidant and anti-inflammatory abilities. However, its antibacterial effect against H. pylori has not been reported; therefore, we analyzed the effect of saucerneol D on H. pylori in the present study. Changes in the expression of pathogenic factors and gene transcription in H. pylori were observed after treatment with saucerneol D using Western blotting and RT-PCR. It was confirmed that saucerneol D suppressed the growth of H. pylori by decreasing the expression of the genes dnaN and polA, which are required for bacterial replication. Saucerneol D also reduced the secretion of the major pathogenic toxin protein, CagA, by downregulating the expression of type IV secretion system-composing proteins. Furthermore, saucerneol D reduced ammonia production by inhibiting the expression of urease proteins, which are essential for the survival of H. pylori in the acidic gastric environment. Additionally, saucerneol D decreased the expression of flaB, potentially reducing motility. Finally, it was confirmed that the expression of the sabA gene, associated with cell adhesion, was reduced. These results suggest that saucerneol D inhibits the growth of H. pylori and the expression of several pathogenic factors, indicating that saucerneol D has an antimicrobial effect against H. pylori. Full article

(This article belongs to the Special Issue Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025)

► Show Figures

Graphical abstract

23 pages, 4307 KB

Open AccessArticle

Cinnamomum migao H.W. Li Ethanol-Water Extract Suppresses IL-6 Production in Cardiac Fibroblasts: Mechanisms Elucidated via UPLC-Q-TOF-MS, Network Pharmacology, and Experimental Assays

by Yuxin Lu, Yaofeng Li, Can Zhu, Mengyue Guo, Xia Liu and Xiangyun Chen

Curr. Issues Mol. Biol. 2025, 47(10), 798; https://doi.org/10.3390/cimb47100798 - 26 Sep 2025

Viewed by 949

Abstract

This study aims to elucidate the active components and underlying molecular mechanisms by which the ethanol-water extract of Cinnamomum migao H.W. Li (MG-EWE) inhibits cardiac fibroblast (CF) transdifferentiation and IL-6 production, providing insights into its anti-myocardial fibrosis effects. The chemical composition of MG-EWE was characterized using UPLC-Q-TOF-MS. Network pharmacology analysis identified active constituents and their mechanisms in inhibiting IL-6 production in CFs. An isoproterenol (ISO)-induced rat CF model was established to evaluate the effects of MG-EWE and its main monomers, Laurolitsine and Hecogenin, on cell proliferation, migration, collagen metabolism, IL-6 production, and key proteins in the ADRB2/JNK signaling pathway. A total of 173 compounds were identified in MG-EWE, with 14 core constituents regulating IL-6 synthesis via 16 key targets, including ADRB2 and MAPK9. Gene Ontology enrichment indicated that MG-EWE affects phosphorylation and the JNK signaling cascade. Molecular docking showed strong binding affinities between Laurolitsine, Hecogenin, and their targets ADRB2 and JNK. Experimentally, MG-EWE, Laurolitsine, and Hecogenin significantly inhibited ISO-induced CF proliferation, migration, and hydroxyproline synthesis, as well as the expression of p-ADRB2, p-JNK, p-c-Jun, and IL-6. MG-EWE inhibits CF transdifferentiation and IL-6 production via the ADRB2/JNK/c-Jun signaling axis, mediated by its constituents Laurolitsine and Hecogenin, highlighting its potential for drug development targeting myocardial fibrosis. Full article

(This article belongs to the Special Issue Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025)

► Show Figures

Figure 1

21 pages, 1652 KB

Open AccessArticle

Comparative Molecular Profiling and Bioactivity Analysis of Algerian Propolis: Antioxidant, Antibacterial Activities, and In Silico NRF2-KEAP1 Pathway Modulation

by Amel Reguig, Ahmed Messai, Ibtissam Kahina Bedaida, Diana C. G. A. Pinto, Chawki Bensouici, Abdelmoneim Tarek Ouamane, Artur M. S. Silva and Jean-Philippe Roy

Curr. Issues Mol. Biol. 2025, 47(9), 761; https://doi.org/10.3390/cimb47090761 - 15 Sep 2025

Cited by 1 | Viewed by 1295

Abstract

Propolis, a natural bee-derived product rich in diverse phytochemicals with potential therapeutic benefits, remains underexplored in Algeria. This study investigated the molecular profile, antioxidant capacity, and antibacterial activity of propolis sourced from two bioclimatically distinct Algerian regions (humid subtropical Batna and hot desert Biskra) using electrospray ionization mass spectrometry, ultra-high-performance liquid chromatography with diode array detection, and gas chromatography–mass spectrometry. Significant regional variations were observed, with propolis extract 2 (PE2) exhibiting a higher bioactive content, including a constituent not previously reported in propolis. Antioxidant assays (2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), ferric reducing antioxidant power, and phenanthroline) demonstrated that PE2 consistently outperformed propolis extract 1 and the reference standards (DPPH IC₅₀: 27.74 µg/mL; FRAP: 5.16 µg/mL). Antibacterial testing demonstrated potent bactericidal effects, particularly for PE2, with minimum inhibitory concentration values equivalent to the minimum bactericidal concentrations required against Staphylococcus aureus ATCC 25923 (18.75 µg/mL) and Escherichia coli ATCC 25922 (133 µg/mL). Molecular docking identified nine bioactive compounds with high KEAP1 binding affinity, with 1,3-O-caffeoyl-dihydrocaffeoylglycerol (first time reported in propolis) showing the strongest binding affinity (−11.02 Kcal/mol). In silico pharmacokinetic predictions further verified its drug-like properties. These findings suggest the tested Algerian propolis samples, as a source of natural alternative antioxidants and antimicrobials, provide a basis for future research in drug discovery and development. Full article

(This article belongs to the Special Issue Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025)

► Show Figures

Figure 1

9 pages, 635 KB

Open AccessArticle

Osteogenic Potential of Osteolforte: Gene and Protein-Level Evaluation in Human Bone Marrow Stromal Cells

by Da-Sol Kim, Soo-Kyung Bae, Yeon-Ju Kwak, Geum-Joung Youn and Hye-Ock Jang

Curr. Issues Mol. Biol. 2025, 47(8), 588; https://doi.org/10.3390/cimb47080588 - 24 Jul 2025

Viewed by 973

Abstract

Osteolforte, a compound with potential bone-regenerative properties, was investigated for its effects on human bone marrow stromal cells (hBMSCs). This study aimed to evaluate its impact on cell viability, osteogenic differentiation, and both gene and protein expression using a combination of assays, including CCK-8, Alizarin Red S staining, Quantitative Real-Time PCR (qRT-PCR), and Western blot analysis. The results demonstrated that Osteolforte significantly enhanced osteogenic differentiation in hBMSCs. Alizarin Red S staining revealed increased mineralization, indicating elevated calcium deposition. Gene expression analysis showed an upregulation of key osteogenic markers, including runt-related transcription factor-2 (RUNX-2), collagen type I (COL-1), and bone morphogenetic protein-2 (BMP-2), supporting the role of Osteolforte in promoting osteoblastic activity. In particular, the elevated expression of RUNX-2—a master transcription factor in osteoblast differentiation along with COL-1, a major bone matrix component, and BMP-2, a key bone morphogenetic protein—highlights the compound’s osteogenic potential. In conclusion, Osteolforte enhances early-stage osteogenesis and mineralization in hBMSCs and represents a promising candidate for bone regeneration. Full article

(This article belongs to the Special Issue Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025)

► Show Figures

Figure 1

Review

Jump to: Research

18 pages, 1823 KB

Open AccessReview

Molecular Diversity, Structure–Function Relationship, Mechanism of Action, and Transformative Potential of Black Soldier Fly Antimicrobial Peptides Against Multidrug-Resistant Pathogens

by Ru-Xi Yuan, Xiao-Yang Ma, Yang Lv and Hong-Bin Si

Curr. Issues Mol. Biol. 2026, 48(1), 62; https://doi.org/10.3390/cimb48010062 - 5 Jan 2026

Cited by 1 | Viewed by 634

Abstract

This review aims to systematically synthesize recent research advances on the antimicrobial peptides (AMPs) derived from the black soldier fly (Hermetia illucens). Against the backdrop of the escalating global crisis of antimicrobial resistance (AMR), AMPs have emerged as pivotal candidates to replace conventional antibiotics. As a unique saprophagous insect, H. illucens has evolved a robust and efficient innate immune system to thrive in its pathogen-rich environment. The AMPs it produces demonstrate remarkable broad-spectrum activity, high stability, and a low propensity for inducing resistance. Based on cutting-edge research available up to 2025, this article will provide an in-depth exploration of the astounding molecular diversity of H. illucens AMPs, their key structure–function relationships, and their multifaceted mechanisms of action, ranging from membrane disruption to immunomodulation. It will also highlight engineering strategies driven by artificial intelligence (AI). Finally, the review will assess the significant translational potential of these AMPs in combating multidrug-resistant bacteria, analyzing the current status of research in animal models, the challenges for industrial production, and viable future development pathways. The goal is to provide a solid theoretical foundation and forward-looking perspective to facilitate the translation of this valuable biological resource from basic research to clinical and agricultural applications. Full article

(This article belongs to the Special Issue Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025)

► Show Figures

Figure 1

31 pages, 1423 KB

Open AccessReview

The Pathogenesis of Chronic Kidney Disease (CKD) and the Preventive and Therapeutic Effects of Natural Products

by Yuxin Dong and Yanqing Tong

Curr. Issues Mol. Biol. 2025, 47(10), 853; https://doi.org/10.3390/cimb47100853 - 16 Oct 2025

Cited by 3 | Viewed by 4709

Abstract

Chronickidney disease (CKD) poses a major global public health challenge, driven by a complex pathogenesis involving multiple interconnected processes—including metabolic disturbances, chronic inflammation, oxidative stress, endoplasmic reticulum stress, and ferroptosis—which collectively contribute to progressive and often irreversible loss of renal function. Although current standard therapies can ameliorate CKD progression, a substantial number of patients still advance to end-stage renal disease, highlighting the urgent need for innovative treatment strategies. Natural products have shown great promise in the prevention and management of CKD, largely attributable to their multi-target and multi-pathway synergistic effects. This review systematically outlines the core pathogenic mechanisms underlying CKD and elucidates the molecular mechanisms through which bioactive natural compounds exert renoprotective effects. Despite robust preclinical evidence, the clinical translation of these compounds remains hindered by limitations such as poor bioavailability and a lack of large-scale clinical trials. Moving forward, research should prioritize clinical translation of these compounds, aiming to provide novel therapeutic perspectives for CKD management. Full article

(This article belongs to the Special Issue Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025)

► Show Figures

Figure 1

17 pages, 1782 KB

Open AccessReview

Quinoa and Colonic Health: A Review of Bioactive Components and Mechanistic Insights

by Yan Pan, Jimin Zheng, Zhixuan Wang, Shaohua Lin, Hongliang Jia, Hairun Pei and Ronghui Ju

Curr. Issues Mol. Biol. 2025, 47(10), 815; https://doi.org/10.3390/cimb47100815 - 2 Oct 2025

Cited by 1 | Viewed by 2190

Abstract

Quinoa (Chenopodium quinoa Willd.) is an ancient Andean crop renowned for its exceptional nutritional profile and diverse bioactive compounds, including polysaccharides, polyphenols, saponins, and essential fatty acids. As global incidence of colonic diseases such as inflammatory bowel disease (IBD), colorectal cancer (CRC), and celiac disease continues to rise, the therapeutic potential of quinoa has garnered increasing scientific attention. This review systematically examines the role of quinoa, with focus on quinoa polysaccharides (QPs), in maintaining and improving colonic health. It summarizes the molecular structure, functional properties, and gut microbiota-modulating effects of QPs, alongside emerging findings on their anti-inflammatory, antioxidant, immunomodulatory, and anticancer activities. Furthermore, the review explores quinoa’s auxiliary effects in mitigating CRC progression and chemotherapy resistance, alleviating intestinal inflammation, and supporting gastrointestinal integrity in celiac patients. By integrating evidence from multi-omics technologies, cell and animal models, and limited clinical studies with mechanistic insights, this review provides a focused synthesis of quinoa bioactive compounds in relation to colonic health. It highlights how precision nutrition and multi-omics approaches could guide future applications of quinoa as a novel functional food-based intervention for colonic diseases. Full article

(This article belongs to the Special Issue Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025)

► Show Figures

Journal Menu

Journal Browser

Applications of Natural and Pseudo-Natural Products in Drug Discovery and Development 2025

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI