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The Role of Bioactive Natural Products in Human Health

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A Special Issue of International Journal of Molecular Sciences (ISSN 1422-0067) belonging to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (20 June 2026) | Viewed by 7056

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Dr. Eleonora Di Salvo

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Department of Biomedical, Dental, Morphological, and Functional Image Sciences (BIOMORF), University of Messina, 98100 Messina, Italy
Interests: bioactive compound; essential oil; polyphenol; natural product; nutraceutical; antioxidant; bioactivity; functional foods; food analysis; waste by-products
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Special Issue Information

Dear Colleagues,

Bioactive natural products are derived from natural sources and have a wide range of biological activities. This highlights their potential as therapeutic agents and functional food ingredients in healthcare and nutrition. In recent years, there has been a growing understanding of the close correlation between therapeutic benefits and the role in human health. These compounds are also effective and relatively safe compared to synthetic alternatives. Their natural origins often align with traditional medicinal practices, validating the use of natural products based on centuries of traditional knowledge.

The theme of this Special Issue is "The Role of Bioactive Natural Products in Human Health". Original articles and broad reviews covering natural products, their by-products and chemical analogues are invited for submission.

The topics of considerable interest encompass the novel methodology for the assessment of bio-natural products, which has resulted in the development of functional foods derived from active biomolecules, which have anti-oxidative, anti-microbial and anti-inflammatory properties, and their novel applications in the field of human health.

This Special Issue is supervised by Dr. Eleonora Di Salvo, Department of Biomedical, Dental, Morphological, and Functional Image Sciences (BIOMORF), University of Messina.

Dr. Eleonora Di Salvo
Guest Editor

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Keywords

bioactive compound
human health
functional foods
nutraceutical products
food toxicology
antioxidant properties
anti-inflammation
antimicrobial molecules

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Published Papers (5 papers)

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Research

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24 pages, 12869 KB

Open AccessArticle

Baicalein Attenuates High Glucose and Sodium Palmitate-Induced Ferroptosis in Cardiomyocytes via the Nrf2/SLC7A11/GPX4 Signaling Pathway

by Huan Wang, Yuhan Xu, Lei Wang, Wanting Meng, Yanwu Xu and Haidong Guo

Int. J. Mol. Sci. 2026, 27(14), 6391; https://doi.org/10.3390/ijms27146391 - 18 Jul 2026

Cited by 2 | Viewed by 730

Abstract

Diabetes mellitus (DM) is increasing rapidly worldwide, and diabetic cardiomyopathy (DCM) has become a leading cause of death in diabetic patients. Therefore, effective strategies for the prevention and treatment of DCM are urgently needed. Ferroptosis, a form of regulated cell death, has been implicated in the pathogenesis of DCM. This study integrated network pharmacology, data mining, molecular docking, molecular dynamics simulations, and in vitro experiments to investigate whether baicalein inhibits high glucose and sodium palmitate (HG + PA)-induced ferroptosis in cardiomyocytes and to elucidate the underlying mechanisms. Baicalein significantly improved the viability of H9c2 and AC16 cells, reduced cell death, and decreased LDH release under HG + PA conditions. Network pharmacology predicted that the protective effects of baicalein against HG + PA-induced cardiomyocyte injury were associated with ferroptosis regulation. Transcriptomic data mining further identified ferroptosis-related pathway enrichment in complementary in vitro and diabetic rat cardiac datasets. Molecular docking predicted favorable binding poses of baicalein with Nrf2, SLC7A11, and GPX4, while molecular dynamics simulations suggested general stability of the modeled complexes. In vitro experiments further confirmed ferroptosis involvement, as the ferroptosis inhibitor Ferrostatin-1 (Fer-1) reversed the HG + PA-induced decline in cell viability. Conversely, the ferroptosis inducer Erastin diminished cell survival and antagonized the protection conferred by baicalein, indicating that baicalein acts by inhibiting ferroptosis. Baicalein reduced lipid peroxidation, MDA and Fe²⁺ levels, and the mRNA expression of ACSL4 and PTGS2, while restoring the GSH/GSSG ratio and the protein expression of Nrf2, SLC7A11, and GPX4. These protective effects were partially reversed by the Nrf2 inhibitor ML385. In conclusion, baicalein protects cardiomyocytes from HG + PA-induced injury by activating the Nrf2/SLC7A11/GPX4 signaling pathway and inhibiting ferroptosis. Full article

(This article belongs to the Special Issue The Role of Bioactive Natural Products in Human Health)

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15 pages, 2612 KB

Open AccessArticle

Chemical Characterization and Biological Activity of Astaxanthin Extracted from Callinectes sapidus By-Products: Implications for Oxidative Stress and Inflammatory Skin Disorders

by Marco Casciaro, Roberta Tardugno, Filomena Corbo, Angelica Spano, Paola Lucia Minciullo, Eleonora Di Salvo, Sebastiano Gangemi and Nicola Cicero

Int. J. Mol. Sci. 2026, 27(9), 3912; https://doi.org/10.3390/ijms27093912 - 28 Apr 2026

Cited by 1 | Viewed by 699

Abstract

Astaxanthin (AST) is a carotenoid with powerful antioxidant and anti-inflammatory properties and increasing interest in dermatological and nutraceutical applications. In this study, AST-rich extracts were obtained from by-products of the blue crab Callinectes sapidus and chemically characterized using HPLC-DAD analysis. The antioxidant activity of the extracts was assessed through complementary spectrophotometric assays (DPPH and FRAP). Comparable AST contents were detected in the two extracts, with values of 1.269 ± 0.006 and 1.219 ± 0.015 mg/100 g dry weight for EtOH and IPrOH, respectively. However, the EtOH extract exhibited higher antioxidant activity, reaching 0.10 ± 0.01 mg Trolox equivalents (TE)/g in the DPPH assay and 0.27 ± 0.02 mg TE/g in the FRAP assay, compared with 0.08 ± 0.01 and 0.11 ± 0.03 mg TE/g for the IPrOH extract. The biological activity of AST extracts was further evaluated against the opportunistic pathogen Staphylococcus aureus and beneficial lactic acid bacteria. AST exhibited moderate antibacterial activity against S. aureus, with an MIC value of 50 μg/mL and inhibition zones up to 14 mm at 200 μg/disc, while promoting the proliferation of Lactobacillus plantarum, Lactobacillus casei, and Lactobacillus reuteri. These findings highlight the prospective valorization of blue crab by-products as a sustainable supply of antioxidant and microbiota-modulating compounds with possible applications in skin health and cosmetic formulations. Full article

(This article belongs to the Special Issue The Role of Bioactive Natural Products in Human Health)

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13 pages, 1131 KB

Open AccessArticle

From By-Product to Bioactive Molecular Ingredient: The Impact of Cranberry Pomace on Antioxidant Properties and Enzyme Modulation in Functional Biscuits

by Natalia Matłok, Tomasz Piechowiak, Ireneusz Kapusta and Maciej Balawejder

Int. J. Mol. Sci. 2025, 26(18), 9002; https://doi.org/10.3390/ijms26189002 - 16 Sep 2025

Cited by 7 | Viewed by 1583

Abstract

Large-fruited cranberry (Vaccinium macrocarpon Ait.) is a rich source of polyphenolic compounds, including anthocyanins, flavonols, and unique A-type proanthocyanidins, which exhibit strong antioxidant and health-promoting properties. Cranberry pomace, a by-product generated during juice and concentrate production, remains underutilized despite being abundant in dietary fiber and non-extractable polyphenols (NEPPs). In this study, cranberry pomace was characterized phytochemically and applied as a functional ingredient in biscuits at levels of 5%, 10%, and 15% substitution of wheat flour. Total polyphenol content (TPC) and antioxidant activity (ABTS^•+, DPPH^•) were significantly higher in pomace compared to whole fruit values reported in the literature, which can be attributed to the concentration of polymeric proanthocyanidins and flavonols in skins and seeds. Biscuits enriched with pomace exhibited a dose-dependent increase in TPC and antioxidant capacity, with the 15% variant showing up to 6-fold higher polyphenol content and over 30-fold higher ABTS^•+ activity after in vitro digestion compared to control. Digestion also released NEPP bound to the fiber matrix, improving bioaccessibility. Moreover, extracts from digested biscuits reduced oxidative stress in Saccharomyces cerevisiae and inhibited COX-1, COX-2, and AChE activities, suggesting potential anti-inflammatory and neuroprotective effects. These findings highlight cranberry pomace as a sustainable, high-value ingredient for functional foods, aligning with circular economy strategies. Full article

(This article belongs to the Special Issue The Role of Bioactive Natural Products in Human Health)

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20 pages, 4066 KB

Open AccessReview

Potential Health Benefits of Bee Bread from Stingless Bees on Reproductive Health: A Review

by Nurul Ain Kamar Bashah, Adila A. Hamid, Farah Hanan Fathihah Jaffar, Mohd Zulkifli Mustafa, Siti Hajar Adam, Siti Sarah Mohamad Zaid, Wan Iryani Wan Ismail, Muhammad Adib Dwi Tamma Putra and Mohd Helmy Mokhtar

Int. J. Mol. Sci. 2026, 27(12), 5511; https://doi.org/10.3390/ijms27125511 - 18 Jun 2026

Viewed by 1273

Abstract

Bees are social insects belonging to the Apidae family, which includes stingless bees, honeybees, and related groups. Their ability to produce various products, such as bee bread, bee pollen, propolis, beeswax, and royal jelly, has attracted scientific interest due to their nutritional composition, biological activities, and potential therapeutic value. Bee bread is a fermented mixture of pollen, honey, and salivary bee enzymes, rich in bioactive compounds with potential benefits for reproductive health and other biological activities. However, bee bread remains one of the least explored bee products in relation to reproductive health. This narrative review summarises the potential health benefits of bee bread from stingless bees for male and female reproductive function. Evidence from animal studies shows that bee bread has promising effects on reproductive function, possibly through its antioxidant properties, support of spermatogenesis and steroidogenesis, improvement of pregnancy outcomes, enhancement of ovarian function, regulation of metabolism, and modulation of inflammatory activity. Findings from animal studies suggest potential benefits for both male and female reproductive health. However, well-designed randomised controlled trials are needed to evaluate its efficacy, optimal dosage, safety profile, and long-term effects on reproductive outcomes in both males and females. Full article

(This article belongs to the Special Issue The Role of Bioactive Natural Products in Human Health)

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37 pages, 1347 KB

Open AccessReview

Natural Bioactive Compounds in Polycystic Ovary Syndrome: Properties, Molecular Mechanisms, and Therapeutic Potential

by Rosa Linares, Gabriela Rosas, Elizabeth Vieyra, Andrea Chaparro, Julieta-Azucena Espinoza, Deyra de los Angeles Ramírez, Carlos-Camilo Silva, Patricia Rosas, Víctor-Manuel Macías and Leticia Morales-Ledesma

Int. J. Mol. Sci. 2026, 27(11), 4715; https://doi.org/10.3390/ijms27114715 - 23 May 2026

Viewed by 2038

Abstract

Polycystic ovary syndrome (PCOS) is one of the most common metabolic–endocrine disorders affecting women of reproductive age and represents a significant public health concern due to its clinical heterogeneity. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, and is frequently associated with hyperinsulinemia, obesity, dyslipidemia, chronic low-grade inflammation, and an increased risk of type 2 diabetes and cardiovascular disease. Conventional treatments, including combined oral contraceptives, metformin, and ovulation-inducing agents, primarily target symptoms and present limitations in efficacy, tolerability, and their ability to address underlying metabolic dysfunction. In this context, naturally derived bioactive compounds have emerged as promising complementary therapeutic strategies. Various phytochemicals exhibit antioxidant, anti-inflammatory, hypoglycemic, and reproductive axis-modulating effects by targeting key molecular pathways involved in insulin resistance, hyperandrogenism, and follicular dysfunction. Emerging preclinical and clinical evidence suggests that these compounds may improve metabolic, hormonal, and reproductive outcomes in women with PCOS. Full article

(This article belongs to the Special Issue The Role of Bioactive Natural Products in Human Health)

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