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Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products
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Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products

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: 30 June 2025 | Viewed by 6097

Special Issue Editor

Dr. Premalatha Balachandran

E-Mail Website
Guest Editor
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677, USA
Interests: natural products research; drug discovery and development; signaling pathways; target identification; immune modulation; cancer treatment and prevention; diabetic nephropathy

Special Issue Information

Dear Colleagues,

The Special Issue titled "Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products" aims to delve into the intricate molecular mechanisms that govern the diverse biological activities of natural products. It seeks to provide a comprehensive understanding of how these compounds interact with molecular targets, cellular components, and signaling pathways, while also influencing gene expression and metabolic processes to elicit physiological responses in organisms. Through elucidating these mechanisms, researchers aim to comprehend the broad spectrum of biological effects exerted by natural products, including, but not limited to, immune modulation, antidiabetic, antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. Molecular studies offer insights into the structural features of natural products that contribute to their pharmacological properties, informing drug discovery, nutraceutical development, and therapeutic interventions. This understanding is crucial for maximizing the therapeutic potential of natural products and advancing their use in medicine and other fields.

Topics of interest include, but are not limited to, the pharmacodynamics, pharmacokinetics, target identification, and mode of action of natural products. By uncovering these molecular insights, this Special Issue strives to shed light on the therapeutic potential of natural products in various fields such as medicine, agriculture, and environmental science. Researchers are encouraged to contribute original research articles, reviews, and perspectives that contribute to our understanding of the molecular basis underlying the biological activities of natural products.

Dr. Premalatha Balachandran
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 100 words) can be sent to the Editorial Office for announcement on this website.

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
  • molecular mechanisms
  • biological activities
  • pharmacodynamics
  • drug discovery
  • therapeutic potential
  • signaling pathways
  • target identification
  • pharmacological properties
  • bioactive compounds

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Published Papers (6 papers)

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Research

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30 pages, 6234 KiB  
Article
Molecular Effects of Cornelian Cherry Fruit (Cornus mas L.) Extract on Sleep Deprivation-Induced Oxidative Stress, Cytokine Dysregulation, and Behavioural Changes in Wistar Rats
by Vlad Sever Neculicioiu, Ioana Colosi, Alexandra Sevastre-Berghian, Dan Alexandru Toc, Horațiu Alexandru Colosi, Luminita David, Mara Muntean, Remus Moldovan, Ana-Maria Vlase, Vlad Alexandru Toma, Carmen Costache, Şoimiţa Mihaela Suciu and Simona Clichici
Curr. Issues Mol. Biol. 2025, 47(6), 399; https://doi.org/10.3390/cimb47060399 - 28 May 2025
Abstract
Sleep deprivation (SD) induces significant neurobiological changes, including oxidative stress, neuroinflammation, and behavioural impairments. This study was designed as a proof of concept to assess the potential for modulating the effects of SD through a short-term seven-day administration of Cornus mas (C. [...] Read more.
Sleep deprivation (SD) induces significant neurobiological changes, including oxidative stress, neuroinflammation, and behavioural impairments. This study was designed as a proof of concept to assess the potential for modulating the effects of SD through a short-term seven-day administration of Cornus mas (C. mas) in a rapid eye movement (REM) SD rodent paradigm. Adult male Wistar rats were randomised in four groups (n = 7): control, C. mas (CM), sleep deprivation (SD), and sleep deprivation with C. mas (SD + CM). Behaviourally, SD induced hyperactivity and hyperlocomotion. SD determined histological alterations in the prefrontal cortex and corpus callosum myelin coupled with ultrastructural mitochondrial and cellular abnormalities in the prefrontal cortex, hippocampus, and pineal gland. Despite evidence of systemic oxidative stress coupled with decreased serum GABA and BDNF following SD, no significant changes were observed in redox markers or inflammatory cytokine levels (TNF-α, IL-1β) within the prefrontal cortex or hippocampus. C. mas extract has shown an overall modest modulatory action, mainly evidenced on behavioural, histological, and ultrastructural parameters. Taken together, these findings highlight behavioural changes and region-specific molecular and structural abnormalities following prolonged REM SD in rats. Full article
(This article belongs to the Special Issue Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products)
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17 pages, 1402 KiB  
Article
A Comparative Study on the Mycelium and Fruiting Body of Meripilus giganteus: Chemical Composition and Biological Activity
by Katarzyna Sułkowska-Ziaja, Mateusz Korczyński, Monika Trepa, Agnieszka Galanty, Jan Lazur, Paweł Kubica, Katarzyna Kała, Paweł Paśko and Bożena Muszyńska
Curr. Issues Mol. Biol. 2025, 47(5), 302; https://doi.org/10.3390/cimb47050302 - 25 Apr 2025
Viewed by 315
Abstract
Meripilus giganteus (Pers.) P. Karst. is a basidiomycete fungus known for its bioactive properties, including antioxidant, antimicrobial, and cytotoxic effects. Although research has largely focused on fruiting bodies, mycelium obtained through in vitro culture offers a sustainable and potentially scalable source of bioactive [...] Read more.
Meripilus giganteus (Pers.) P. Karst. is a basidiomycete fungus known for its bioactive properties, including antioxidant, antimicrobial, and cytotoxic effects. Although research has largely focused on fruiting bodies, mycelium obtained through in vitro culture offers a sustainable and potentially scalable source of bioactive metabolites. This study aimed to compare the chemical composition and biological activity of extracts from the fruiting bodies and mycelium of M. giganteus. Key compound groups were analyzed using high-performance liquid chromatography (HPLC), and biological activity was assessed through DPPH and ABTS antioxidant assays and MTT-based cytotoxicity testing on human gastrointestinal cancer and normal colon epithelial cell lines. The results revealed distinct metabolite profiles between fungal forms and demonstrated that solvent type strongly influenced extraction efficiency. Cytotoxicity assays indicated moderate activity of both extract types, with some selectivity towards colorectal cancer cell lines. These findings suggest that M. giganteus mycelium may serve as a promising alternative to fruiting bodies for the production of antioxidant and potentially chemopreventive compounds. Further studies are recommended to optimize cultivation and extraction conditions to enhance both metabolite yield and biological activity. Full article
(This article belongs to the Special Issue Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products)
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12 pages, 2768 KiB  
Article
Prevention of Muscle Atrophy by Low-Molecular-Weight Fraction from Hirsutella sinensis Mycelium
by Yi-Wen Chen, Tsung-Ju Li, Li-Ching Wang, Bi-Hua Yang, Yen-Lien Chen, Chin-Chu Chen and Hsin-Tang Lin
Curr. Issues Mol. Biol. 2024, 46(12), 14033-14044; https://doi.org/10.3390/cimb46120839 - 12 Dec 2024
Viewed by 912
Abstract
Muscle atrophy, an age-related condition, presents a growing healthcare concern within the context of global population aging. While studies have investigated Hirsutella sinensis for its potential antifatigue properties, reports on its active components remain limited. This study evaluated the efficacy of H. sinensis [...] Read more.
Muscle atrophy, an age-related condition, presents a growing healthcare concern within the context of global population aging. While studies have investigated Hirsutella sinensis for its potential antifatigue properties, reports on its active components remain limited. This study evaluated the efficacy of H. sinensis mycelium extract on muscle health, utilizing a 1:1 water–ethanol preparation administered to C57BL/6 mice exhibiting acute hind leg atrophy. The results indicated no adverse effects, with significant improvements in muscle endurance and soleus muscle mass observed over a 14-day period. To further elucidate the mechanisms and effects of H. sinensis mycelium on dexamethasone-induced muscle atrophy, the water extract was fractionated into components of <3.5 kDa, 3.5–10 kDa, and >10 kDa using dialysis membranes. The investigation utilized a C2C12 cell atrophy model, induced by dexamethasone, to analyze the expression of relevant genes via qPCR. The results demonstrated that the <3.5 kDa and >10 kDa fractions significantly upregulated the expression of Myh2 and Myh7 genes while simultaneously downregulating the expression of MuRF-1 and Atrogin-1. It is noteworthy that the <3.5 kDa fraction exclusively enhanced MYHC protein expression and suppressed AMPK expression, as confirmed by Western blot analysis. This comprehensive pilot study suggests that the low-molecular-weight fraction of H. sinensis mycelium exhibits considerable potential for muscle mass preservation and atrophy mitigation. As a result, it offers a promising direction for the development of supplements aimed at addressing fatigue and preventing muscle atrophy. Full article
(This article belongs to the Special Issue Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products)
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14 pages, 2606 KiB  
Article
Alliin Induces Reconstitution of Testes Damaged by Estrogen Overstimulation by Regulating Apoptosis
by Dae-Seung Kim, Min-Jee Oh and Sang-Hwan Kim
Curr. Issues Mol. Biol. 2024, 46(11), 13021-13034; https://doi.org/10.3390/cimb46110776 - 16 Nov 2024
Viewed by 755
Abstract
We analyzed the effect of alliin on the recovery of mouse testicular function and structure following estradiol treatment as well as on apoptosis regulation. During the cultivation of testicular cells, high-concentration estradiol suppressed Casp-3; PCNA, mTOR, and PI3K signaling increased; and cell proliferation [...] Read more.
We analyzed the effect of alliin on the recovery of mouse testicular function and structure following estradiol treatment as well as on apoptosis regulation. During the cultivation of testicular cells, high-concentration estradiol suppressed Casp-3; PCNA, mTOR, and PI3K signaling increased; and cell proliferation in the testes was abnormally increased. Therefore, estradiol treatment increased the proportion of abnormal cells. The estradiol and 2.5 μM of alliin treatment increased Casp-3 levels and suppressed Bcl-2, PCNA, mTOR, and PI3K expression. Additionally, treatment with estradiol caused tissue loss. Furthermore, Ca2+ deposition decreased, TNF-r protein expression increased, and the levels of other protein markers of cell survival and death decreased. Tissue recovery and restoration of the testes occurred after alliin treatment; the gene expression of cell survival and death markers, except for TNF-r, increased with increasing Ca2+ deposition. Cell proliferation and tissue reorganization may correlate with an increased signal of intrinsic apoptosis owing to increased Ca2+ deposition. Therefore, treatment with alliin may regulate the apoptosis of cells with normal or abnormal signal transduction and help to revert testicular dysfunction. Full article
(This article belongs to the Special Issue Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products)
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19 pages, 3071 KiB  
Article
Effects of Heat-Induced Oxidative Stress and Astaxanthin on the NF-kB, NFE2L2 and PPARα Transcription Factors and Cytoprotective Capacity in the Thymus of Broilers
by Donna Lee Kuehu, Yuanyuan Fu, Masaki Nasu, Hua Yang, Vedbar S. Khadka and Youping Deng
Curr. Issues Mol. Biol. 2024, 46(8), 9215-9233; https://doi.org/10.3390/cimb46080544 - 22 Aug 2024
Cited by 1 | Viewed by 2014
Abstract
The thymus, a central lymphoid organ in animals, serves as the site for T cell development, differentiation and maturation, vital to adaptive immunity. The thymus is critical for maintaining tissue homeostasis to protect against tumors and tissue damage. An overactive or prolonged immune [...] Read more.
The thymus, a central lymphoid organ in animals, serves as the site for T cell development, differentiation and maturation, vital to adaptive immunity. The thymus is critical for maintaining tissue homeostasis to protect against tumors and tissue damage. An overactive or prolonged immune response can lead to oxidative stress from increased production of reactive oxygen species. Heat stress induces oxidative stress and overwhelms the natural antioxidant defense mechanisms. This study’s objectives were to investigate the protective properties of astaxanthin against heat-induced oxidative stress and apoptosis in the chicken thymus, by comparing the growth performance and gene signaling pathways among three groups: thermal neutral, heat stress, and heat stress with astaxanthin. The thermal neutral temperature was 21–22 °C, and the heat stress temperature was 32–35 °C. Both heat stress groups experienced reduced growth performance, while the astaxanthin-treated group showed a slightly lesser decline. The inflammatory response and antioxidant defense system were activated by the upregulation of the NF-kB, NFE2L2, PPARα, cytoprotective capacity, and apoptotic gene pathways during heat stress compared to the thermal neutral group. However, expression levels showed no significant differences between the thermal neutral and heat stress with antioxidant groups, suggesting that astaxanthin may mitigate inflammation and oxidative stress damage. Full article
(This article belongs to the Special Issue Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products)
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Review

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36 pages, 2809 KiB  
Review
The Therapeutic Potential of Baicalin and Baicalein in Breast Cancer: A Systematic Review of Mechanisms and Efficacy
by Bartłomiej Zieniuk and Şuheda Uğur
Curr. Issues Mol. Biol. 2025, 47(3), 181; https://doi.org/10.3390/cimb47030181 - 11 Mar 2025
Cited by 1 | Viewed by 1398
Abstract
Cancer remains a leading cause of death globally, with breast cancer being the most commonly diagnosed cancer in women. This systematic review focuses on the therapeutic potential of baicalin and baicalein, two bioactive flavonoids derived from Scutellaria baicalensis, in breast cancer treatment. [...] Read more.
Cancer remains a leading cause of death globally, with breast cancer being the most commonly diagnosed cancer in women. This systematic review focuses on the therapeutic potential of baicalin and baicalein, two bioactive flavonoids derived from Scutellaria baicalensis, in breast cancer treatment. These compounds exhibit anticancer properties through mechanisms such as apoptosis induction, cell cycle arrest, and inhibition of metastasis. Baicalin and baicalein modulate key signaling pathways, including NF-κB, PI3K/AKT/mTOR, and Wnt/β-catenin, and have shown efficacy in both in vitro and in vivo models. Their synergy with chemotherapy agents and incorporation into nanotechnology-based delivery systems highlight opportunities to enhance therapeutic outcomes. However, current evidence is predominantly preclinical, with limited clinical trials to validate their safety and efficacy in humans. Challenges such as poor bioavailability and rapid metabolism also underscore the need for advanced formulation strategies. This review synthesizes current evidence on the molecular mechanisms, therapeutic efficacy, and potential applications of baicalin and baicalein in breast cancer research. Full article
(This article belongs to the Special Issue Molecular Insights: Mechanisms Underlying the Biological Activities of Natural Products)
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