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Molecular Mechanisms and Therapeutic Potential of Natural Compounds

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 2093

Special Issue Editors


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Guest Editor
Department of Cell Biology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland
Interests: cell culture; cell signaling; cell cycle; carcinogenesis; metastasis; oxidative stress

Special Issue Information

Dear Colleagues,

In recent years, there has been an increased interest in natural products, and in many cases the new drugs being designed have pharmacophores based on those specific to natural substances.

Bioactive compounds isolated from natural sources are characterized by relatively low systemic toxicity compared to synthetic drugs and exhibit a variety of pharmacological activities, such as antimicrobial, anti-inflammatory, anticancer, and anti-Alzheimer's properties, as well as affecting the nervous system, modulating enzyme activity, etc. Studies on the biological activity of single compounds in comparison with whole extracts, including studies of synergistic interactions of active ingredients, provide a potential foundation for the development of new therapeutic strategies.

In this Special Issue, we would like to present methods for studying the biological activity of isolated and characterized active natural compounds, with particular emphasis on analyzing the mechanisms underlying these activities. Studies of single substances alone or/and in synergistic studies are particularly welcome.

We invite contributions of both original and review papers to this Special Issue.

Dr. Magdalena Bartnik
Dr. Adrianna Sławińska-Brych
Guest Editors

Manuscript Submission Information

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Keywords

  • natural products
  • biological activity
  • bioactive compounds
  • mechanistic study
  • mechanism of action
  • drug discovery
  • pharmacological activity
  • synergism

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Published Papers (2 papers)

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Research

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20 pages, 4807 KB  
Article
The Natural Triterpenoid Alisol B Overcomes Temozolomide Resistance in Glioblastoma Through Multi-Target Mechanisms: Coordinated Epigenetic, Metabolic, and Cell-Cycle Reprogramming
by Yamin Zhang, Bingfang Shen, Chaoqun Zhang, Ziting Li, Lisha Li, Xiaomei Xu, Hongwei Li and Wenjin Lin
Int. J. Mol. Sci. 2026, 27(5), 2138; https://doi.org/10.3390/ijms27052138 - 25 Feb 2026
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Abstract
Glioblastoma (GBM) is a highly aggressive and therapy-resistant brain tumor, necessitating innovative multi-target strategies. Natural compounds like the triterpenoid Alisol B from Alisma orientale hold promise due to their polypharmacological potential, yet their system-level mechanisms are unclear. Using an integrated multi-omics approach (transcriptomics, [...] Read more.
Glioblastoma (GBM) is a highly aggressive and therapy-resistant brain tumor, necessitating innovative multi-target strategies. Natural compounds like the triterpenoid Alisol B from Alisma orientale hold promise due to their polypharmacological potential, yet their system-level mechanisms are unclear. Using an integrated multi-omics approach (transcriptomics, proteomics, lysine acetyl-proteomics) in resistant GBM cells and validating findings in vitro and in AB strain zebrafish (Danio rerio) xenografts, we found that Alisol B induces endoplasmic reticulum stress and G2/M arrest, initiated by extensive lysine acetylation reprogramming on histones and metabolic enzymes (e.g., FASN, FDFT1). This epigenetic rewiring leads to disrupted cholesterol biosynthesis, characterized by transcriptional activation of the mevalonate pathway alongside post-transcriptional suppression of terminal enzymes (DHCR7, CYP51A1), suggestive of toxic intermediate accumulation. Alisol B also downregulated the oncogenic axis (BIRC5-FOXM1-ITGA4) and SCD5. This study delineates Alisol B’s novel multi-mechanistic action through concurrent epigenetic rewiring, metabolic dysfunction induction, and survival network dismantling. Our work elucidates the molecular pharmacology of a natural compound and provides a framework for developing polypharmacological therapies against resistant cancers, exemplifying natural products as tools to reveal new therapeutic paradigms. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Potential of Natural Compounds)
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Review

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50 pages, 3024 KB  
Review
Unveiling the Therapeutic Potential of Gallic Acid: Mechanistic Insights into the Management of Pathogenesis: A Narrative Review
by Hajed Obaid A. Alharbi, Tarique Sarwar and Arshad Husain Rahmani
Int. J. Mol. Sci. 2026, 27(3), 1536; https://doi.org/10.3390/ijms27031536 - 4 Feb 2026
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Abstract
Gallic acid (GA) is a natural polyphenol abundantly found in a variety of fruits, including blackberries, apples, pineapples, strawberries, bananas, and grapes. With prominent anti-inflammatory and antioxidant properties, GA effectively mitigates inflammation and oxidative stress. Furthermore, it plays a significant role in modulating [...] Read more.
Gallic acid (GA) is a natural polyphenol abundantly found in a variety of fruits, including blackberries, apples, pineapples, strawberries, bananas, and grapes. With prominent anti-inflammatory and antioxidant properties, GA effectively mitigates inflammation and oxidative stress. Furthermore, it plays a significant role in modulating various cellular processes and biological activities, ultimately inhibiting the progression of pathogenesis. This review explores the multifaceted health benefits of GA, highlighting its role as antidiabetic, anti-obesity, anti-arthritis, hepatoprotective, cardioprotective, and neuroprotective effects. Additionally, its impact on the respiratory, digestive, and reproductive systems, along with its related pathogenesis, is described. Additionally, its role as an antimicrobial is defined primarily through mechanisms such as disruption of microbial cell membranes, inhibition of efflux pumps, and antibiofilm activity. Moreover, this review provides a novel, integrative analysis of GA by unifying its mechanistic roles across various pathogenesis. It further describes the role of GA in cancer management via the modulation of signaling pathways. In addition, it demonstrates the synergistic effects of GA when used in combination with other drugs/compounds and discusses nanoformulation approaches that improve its therapeutic efficacy. However, despite significant preclinical outcomes, the clinical application of GA is limited by a shortage of human trials, low bioavailability, and an inadequate understanding of its mechanisms of action and optimal dosage. To overcome these limitations, well-designed clinical trials, in vivo studies, and advanced nanoformulation approaches are required to enhance bioavailability, elucidate mechanisms of action, and increase knowledge of safety and long-term toxicity. Addressing these gaps will enable the full exploration of GA’s benefits in disease prevention and management. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Potential of Natural Compounds)
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