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Functions and Applications of Natural Products: 2nd Edition

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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: 25 June 2026 | Viewed by 6225

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Special Issue Editor

Prof. Dr. Seung-Hong Lee

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Guest Editor

Department of Pharmaceutical Engineering, Soonchunhyang University, Asan, Republic of Korea
Interests: natural products nutraceuticals; cosmeceuticals; pharmaceuticals; bioactive compounds; marine organisms; phytomedicine
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Special Issue Information

Dear Colleagues,

Natural products are small molecules produced naturally by living organisms, encompassing both primary and secondary metabolites. They exhibit a wide range of possible applications in biomedicine and pharmacotherapy and are valuable for the treatment and management of numerous human diseases due to their remarkable biological properties. Furthermore, bioactive compounds and pharmaceuticals derived from natural products have attracted increasing attention for their considerable benefits to human health.

This Special Issue aims to shape future research direction in the field of natural products and related bioactives. Our goal is to feature high-quality, cutting-edge research and insights from research groups worldwide working on the functional and medicinal properties of natural products. We invite the submission of original research articles and comprehensive reviews exploring the functional and medicinal properties of natural products.

Topics of interest include, but are not limited to, the following:

Natural products for preventing and managing human diseases;
The importance of nutraceuticals and cosmeceuticals derived from natural products for human health and skin aging;
Bioactivity and mechanism of action of natural products; new strategies of using natural drugs for promoting human health;
Biotechnology for yielding bioactive components from the natural products.

Prof. Dr. Seung-Hong Lee
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.

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Keywords

natural products
biomedicine/phytomedicine
biologically active extracts and compounds
pharmacological and toxicological mechanisms of action

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Published Papers (6 papers)

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Research

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19 pages, 2371 KB

Open AccessArticle

Ethanolic Extract of Padina arborescens Suppresses Melanogenesis and Attenuates UVB-Induced Photodamage in Cellular and Zebrafish Models

by Yun-Su Lee, Wook-Chul Kim, Kyeong Min Lee, Seo-Rin Jung, Seung Tae Im, Min-Cheol Kang and Seung-Hong Lee

Int. J. Mol. Sci. 2026, 27(8), 3382; https://doi.org/10.3390/ijms27083382 - 9 Apr 2026

Viewed by 387

Abstract

Ultraviolet (UV) irradiation induces complex skin damage, including hyperpigmentation, oxidative stress, and alterations in proteins related to keratinocyte differentiation and epidermal barrier-associated status. This study investigated the multifunctional protective effects of Padina arborescens ethanolic extract (PAEE) against skin damage in melanocytes, keratinocytes, and zebrafish. In alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells, PAEE effectively suppressed the protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) signaling pathway, which was associated with reduced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, leading to decreased melanin synthesis. PAEE also exhibited photoprotective properties by reducing reactive oxygen species (ROS), inhibiting interleukin-1 beta (IL-1β), and attenuating matrix metalloproteinase-1 (MMP-1) upregulation associated with UVB (ultraviolet B)-induced photodamage in HaCaT keratinocytes. Notably, PAEE restored the UVB-reduced expression of filaggrin and involucrin, representative markers of keratinocyte differentiation and epidermal barrier-associated status, in HaCaT keratinocytes. In zebrafish embryos, PAEE suppressed α-MSH-induced melanin accumulation and UVB-induced ROS generation at non-toxic concentrations. Taken together, these results suggest that PAEE exerts anti-melanogenic and photoprotective effects in cellular and zebrasfish models and may serve as a promising marine-derived ingredient for cosmeceutical applications targeting UVB-related skin damage. Full article

(This article belongs to the Special Issue Functions and Applications of Natural Products: 2nd Edition)

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18 pages, 2070 KB

Open AccessArticle

Neuroprotective Effect of the Combined Extract of Mentha piperita and Cornus officinalis Against Neuronal Cell Death and Scopolamine-Induced Memory Impairment

by Kang-Il Oh, Junhwan Jeong, Hyesoo Jeong, Yoonjoong Yong, Subin Yeo, Eunkuk Park and Seon-Yong Jeong

Int. J. Mol. Sci. 2026, 27(5), 2508; https://doi.org/10.3390/ijms27052508 - 9 Mar 2026

Viewed by 622

Abstract

Mild cognitive impairment (MCI) represents an intermediate stage between normal aging and Alzheimer’s disease. This study investigated the neuroprotective effects of a combined extract of Mentha piperita (MP) and Cornus officinalis (CO) (MC) using in vitro and in vivo models. In SK-N-SH cells, pretreatment with MC (50–150 μg/mL) significantly attenuated H₂O₂-induced cellular injury, as evidenced by a reduction in Annexin V-positive cells and an increase in brain-derived neurotrophic factor (BDNF) mRNA expression. Rosmarinic acid and loganin, the marker compounds of MP and CO, alone or combined at a 6:4 ratio, mitigated H₂O₂-induced decreases in cell viability and BDNF mRNA. In the in vivo study, male Sprague–Dawley rats were orally administered MC (50, 100, or 200 mg/kg/day) for 28 days, with phosphatidylserine (50 mg/kg/day) serving as a positive control. MC administration significantly improved cognitive performance in rats with scopolamine-induced memory impairment, as demonstrated by increased step-through latency in the passive avoidance test and reduced escape latency in the Morris water maze. Furthermore, in the probe trial, MC-treated rats spent significantly more time in the target quadrant, indicating enhanced spatial memory retention. Mechanistically, MC restored hippocampal acetylcholine levels and reversed the scopolamine-induced decrease in BDNF and its downstream signaling. Specifically, MC upregulated hippocampal BDNF expression and enhanced the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and cAMP response element-binding protein (CREB). In conclusion, these results demonstrate that the MC extract possesses potent neuroprotective and learning- and memory-enhancing effects, highlighting its potential as a therapeutic candidate for managing age-related cognitive decline and MCI. Full article

(This article belongs to the Special Issue Functions and Applications of Natural Products: 2nd Edition)

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19 pages, 1304 KB

Open AccessArticle

Protective Effects of Schinus terebinthifolius Leaf Supercritical Fluid Extract Against UVC-Induced Oxidative Stress: A Com-Prehensive Gene Expression Study

by Tanakarn Chaithep, Anurak Muangsanguan, Juan M. Castagnini, Francisco J. Marti-Quijal, Pornchai Rachtanapun, Chaiwat Arjin, Korawan Sringarm, Francisco J. Barba and Warintorn Ruksiriwanich

Int. J. Mol. Sci. 2026, 27(5), 2092; https://doi.org/10.3390/ijms27052092 - 24 Feb 2026

Viewed by 581

Abstract

Ultraviolet (UV) exposure accelerates skin aging by inducing oxidative stress, extracellular matrix (ECM) degradation, and epidermal barrier dysfunction. This study investigated the protective effects of Brazilian pepper tree (SB), neem (SD), and Vietnamese coriander (PP) leaf extracts obtained by supercritical fluid extraction (SFE) using CO₂ with ethanol as a co-solvent against radiation-induced cellular damage. Among these, SB yielded the greatest amount of extract and exhibited the highest levels of phenolic and flavonoid constituents, including naringin, epicatechin gallate, and rosmarinic acid. These compounds, identified through HPLC profiling, were associated with strong inhibition of collagenase, elastase, and hyaluronidase, and exhibited potent antioxidant activity in the DPPH assay. Under UVC-induced oxidative stress in HaCaT keratinocytes, SB markedly enhanced the mRNA expression of key genes involved in ECM integrity (COL1A1, 3.04 ± 0.15-fold), epidermal barrier and hydration (FLG, 4.66 ± 0.17-fold; HAS1, 1.90 ± 0.14-fold), and cellular defense mechanisms (SIRT1, 3.83 ± 0.54-fold), demonstrating superior efficacy to reference antioxidants (EGCG and ascorbic acid) in upregulating key barrier genes like FLG. Overall, the findings highlight SB as the extract with the most comprehensive photoprotective properties and support the use of SFE-derived botanical extracts as promising agents for natural and photoprotective skincare applications. Full article

(This article belongs to the Special Issue Functions and Applications of Natural Products: 2nd Edition)

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31 pages, 1112 KB

Open AccessReview

The Ethnopharmacological Use of Mescaline for Psychiatric Disorders: A Systematic Review

by Jonathan Shaw, Aidan Yong, Jacky Lee, Justin Cheng, Anton Andricioaei, Jen-Yeu Wang, Yaara Zisman-Ilani and Robert Bota

Int. J. Mol. Sci. 2026, 27(7), 3081; https://doi.org/10.3390/ijms27073081 - 28 Mar 2026

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Abstract

Mescaline, the primary bioactive alkaloid found in Peyote and San Pedro cactus, has been used in traditional medicine for centuries and is now attracting renewed interest for clinical applications. The purpose of this systematic review was to search the literature for studies reporting the use of mescaline to address the gap in our understanding of mescaline use and its impact. References were exported from PubMed, Scopus, Embase, and Cochrane. Included studies contained patient data pertaining to mescaline, primary sources for beliefs on the use of mescaline as traditional medicine, and a range of psychiatric conditions. Excluded studies included unpublished studies, animal studies, and studies without English full-texts available. Of 2770 imported references, 66 met the inclusion criteria, with only 10 being found suitable for analysis. Studies reported therapeutic effects such as improvements in depression scales, well-being, nicotine dependence, alcohol use, and obsessions. Bayesian analysis found that certain effects were frequently reported, such as hypertension, headache, nausea, and vomiting. The existing literature on mescaline is limited and of highly variable quality, preventing definitive conclusions regarding the prevalence of psychological and somatic effects from mescaline and mescaline-containing ethnobotanicals. Additional research is needed to determine the safety profile of mescaline. Given the prevalence of Peyote use in the Native American Church, the collaboration of the Native American Church and regional hospitals/poison centers is recommended to create a registry to allow for standardized and clinically applicable data collection on the effects of mescaline in prevalent populations. Full article

(This article belongs to the Special Issue Functions and Applications of Natural Products: 2nd Edition)

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22 pages, 1521 KB

Open AccessReview

The Women’s Microbiome: Molecular Insights, Clinical Gaps, and Future Frontiers in Precision Health with Implications for Gulf Cooperation Council Populations

by Muriel Tahtouh Zaatar, Rima Othman, Mohammed Abushawish, Michel Akl, Mohamad Taha Alachkar, Ghaya Almatboona, Fatma Alriyami, Aljoud Alshaibani, Dana Ashkanani, Munira Basharova, Mohammad Imam, Nadia Khassay, Mila Souha Mikhael, Rozhin Naderi Far, Sophia Shaqra, Kiara Verwey, Alika Suleimanova, Mariam Yousafzada and Yuliya Burmagina

Int. J. Mol. Sci. 2026, 27(6), 2521; https://doi.org/10.3390/ijms27062521 - 10 Mar 2026

Viewed by 1095

Abstract

The human microbiome has emerged as a central regulator of health and disease; however, women-specific microbiome research has only recently gained focused scientific attention. Accumulating evidence demonstrates that microbial ecosystems across the gut, vagina, skin, breast tissue, and reproductive tract are dynamically shaped by female hormones, life-stage transitions, and environmental exposures. These interactions influence immune regulation, metabolic homeostasis, reproductive outcomes, mental health, and cancer risk, in part through microbiome-mediated endocrine pathways such as the estrobolome. Advances in high-resolution molecular technologies—including metagenomics, metabolomics, spatial and single-cell profiling, and artificial intelligence-driven modeling—have shifted microbiome research from descriptive taxonomy toward functional, mechanistic, and predictive science. These approaches highlight microbial function and metabolite production as stronger determinants of health outcomes than taxonomic composition alone. Nonetheless, major gaps persist, including limited causal evidence, methodological heterogeneity, underrepresentation of non-Western populations, and barriers to clinical translation. Microbiome-targeted interventions, including probiotics, prebiotics, postbiotics, and emerging microbiota-based therapies, have garnered increasing interest in women’s health. Select Lactobacillus and Bifidobacterium strains show potential in modulating vaginal and gastrointestinal health, pregnancy outcomes, and immune function; however, clinical effects remain highly strain-specific and context-dependent. Discrepancies between experimental findings, commercial claims, and validated clinical use underscore the need for rigorous, women-centered trials and standardized outcome measures. This narrative review synthesizes current molecular insights into the women’s microbiome across endocrine interactions, pregnancy, reproductive and metabolic health, lifestyle influences, and microbiome-based therapeutic strategies. We integrate clinical perspectives to identify diagnostic and translational challenges and propose future directions emphasizing precision microbiome medicine, validated biomarkers, careful evaluation of microbiome-targeted interventions, and inclusive research frameworks, including populations from the Gulf Cooperation Council (GCC). Collectively, this review positions the microbiome as a critical yet underutilized axis in women’s health and outlines a roadmap toward personalized, evidence-based care across the female lifespan. Full article

(This article belongs to the Special Issue Functions and Applications of Natural Products: 2nd Edition)

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39 pages, 7473 KB

Open AccessReview

Current Research on the Control Mechanisms of Cell Survival and Proliferation as Potential Interaction Sites with Pentacyclic Triterpenoids in Ovarian Cancer

by Arkadiusz Orchel, Jonasz Skrobek, Anna Kaps, Piotr Paduszyński and Ewa Chodurek

Int. J. Mol. Sci. 2025, 26(23), 11622; https://doi.org/10.3390/ijms262311622 - 30 Nov 2025

Viewed by 1379

Abstract

The treatment of gynecological cancers is challenging because they are often diagnosed at the advanced stages. Furthermore, available chemotherapeutics increasingly imply the development of resistance in cancer patients. This necessitates the search for alternative solutions that could be used in therapy. One of the possibilities to consider is the use of pentacyclic triterpenoids. They are naturally occurring compounds characterized by a wide range of biological activities. They can also be modified to improve their pharmacological properties. Terpenoids based on oleanane, ursane, and lupane skeletons can modulate the numerous processes occurring in both normal and transformed cells. To develop effective anti-cancer therapy, it is essential to understand the processes regulating the progression and suppression of a given type of cancer. For this reason, it is necessary to assess the influence of the tested compounds on cellular processes such as the cell cycle, epithelial–mesenchymal transition, autophagy, and apoptosis. This article summarizes available information on the effects of pentacyclic triterpenoids on the PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Notch, HIF-1α, TGF-β, Wnt/β-catenin, Hippo, and Hedgehog signaling pathways in ovarian cancer cells. Full article

(This article belongs to the Special Issue Functions and Applications of Natural Products: 2nd Edition)

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