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The Role of Natural Products in Treating Human Diseases

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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: 20 March 2026 | Viewed by 5176

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Special Issue Editor

Dr. Luís R. Silva

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Guest Editor

CPIRN-UDI/IPG, Center of Potential and Innovation of Natural Resources, Research for Inland Developments (UDI), Polytechnic Institute of Guarda, 6300-559 Guarda, Portugal
Interests: bioactive compounds as health promoters; natural products; medicinal plants; bioactivity; in vivo assays; clinical trials
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Special Issue Information

Dear Colleagues,

Natural products originating from living organisms have a long history of use in the treatment of numerous human diseases and are now being actively researched for their potential therapeutic benefits. Plants, animals, fungi, and microorganisms are examples of a wide variety of organisms that can be used for natural products. Plant-derived phytochemicals, in particular, are being extensively studied for their potential in treating chronic disorders. They may provide solutions to these problems since they contain a variety of components that can exhibit unexpected biological properties. Furthermore, individual ingredients derived from natural sources are expected to have synergistic effects when employed in traditional medicine. Natural products have shown promise in treating a range of human diseases, including cancer, infectious diseases, cardiovascular diseases, neurological disorders, and others. Their potential for preventing, alleviating, and curing a variety of illnesses is still being researched. Many drugs currently used to treat diseases, including cancer and infectious diseases, are derived from natural sources, and research continues to identify new compounds with therapeutic potential. Natural products are valuable resources for drug discovery due to their structural diversity and complexity. They can serve as lead compounds for the development of new drugs, and synthetic analogs of natural products with improved efficacy and safety can also be created. This Special Issue focusses on the previously unknown therapeutic benefits of natural products against various diseases.

Dr. Luís R. Silva
Guest Editor

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Keywords

natural products
phytochemicals
biological potential
pharmacological activity
health promoters
chronic diseases

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Published Papers (5 papers)

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Research

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17 pages, 2907 KB

Open AccessArticle

Potential Anti-Inflammatory Effects of Gintonin-Enriched Fraction in TNF-α-Stimulated Keratinocytes

by Rami Lee, Kyung-Jong Won, Ji-Hun Kim, Sun-Hye Choi, Sung-Hee Hwang and Seung-Yeol Nah

Int. J. Mol. Sci. 2025, 26(24), 11864; https://doi.org/10.3390/ijms262411864 - 9 Dec 2025

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Abstract

Gintonin-enriched fraction (GEF), a bioactive glycolipoprotein derived from Panax ginseng is known for its potential as a natural anti-inflammatory agent. Keratinocytes are closely related to the development and progression of various inflammatory skin conditions. However, the effect of GEF on inflammation-related responses in keratinocytes remains unclear. This study aimed to investigate whether GEF modulates key inflammatory responses in keratinocytes stimulated by tumor necrosis factor (TNF)-α. The effect of GEF on biological activities in TNF-α-stimulated keratinocytes (HaCaT cells) was evaluated using water-soluble tetrazolium salt, enzyme-linked immunosorbent, immunostaining, and immunoblotting assays. In TNF-α-stimulated HaCaT cells, GEF attenuated reactive oxygen species production, nitric oxide release, and inducible nitric oxide synthase expression. Moreover, GEF reduced the release of interleukin (IL)-6 and RANTES, while increasing the release of IL-10 in TNF-α-exposed HaCaT cells. Additionally, GEF treatment resulted in reduced cyclooxygenase-2 expression and prostaglandin E₂ release and inhibited TNF-α-induced translocation of nuclear factor-κB in HaCaT cells. Furthermore, TNF-α and IL-6 levels in ultraviolet B-irradiated HaCaT cells were reduced by GEF treatment. These findings indicated that GEF exerts anti-inflammatory effects on keratinocytes. This study provides a basis for the development of novel therapeutic approaches for the prevention and treatment of inflammatory skin disorders. Full article

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

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23 pages, 6819 KB

Open AccessArticle

Pomegranate and Cherry Leaf Extracts as Stabilizers of Magnetic Hydroxyapatite Nanocarriers for Nucleic Acid Delivery

by Hina Inam, Simone Sprio, Federico Pupilli, Marta Tavoni and Anna Tampieri

Int. J. Mol. Sci. 2025, 26(23), 11562; https://doi.org/10.3390/ijms262311562 - 28 Nov 2025

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Abstract

Small interfering RNAs (siRNAs) provide strong therapeutic potential due to their efficient gene-silencing properties; however, their instability limits clinical application. Nanoparticle carriers may overcome this problem; in particular, magnetic nanoparticles show great promise as they can be directed to the target sites by external magnetic fields, thus improving delivery efficiency and reducing off-target effects. In addition, magnetic nanoparticles offer a novel nanoplatform for theranostic applications, integrating siRNA delivery with magnetic resonance imaging and magnetic hyperthermia for synergistic diagnostic and therapeutic advantages. The present work reports the development of a novel platform based on biomimetic magnetic nanoparticles made of Fe(II)/Fe(III)-doped apatite (FeHA) nucleated and grown in the presence of cherry and pomegranate leaf extracts to enhance the colloidal stability and make it suitable for nucleic acid delivery under the guidance of magnetic fields. This approach allowed the obtention of FeHA suspension with increased negative zeta potential leading to very good stability. In addition, the functionalization with natural extracts conferred antioxidant properties also favoring the maintenance of the Fe(III)/Fe(II) ratio in the apatitic structure, inducing the superparamagnetic properties. To evaluate the delivery capability of the system, a model GAPDH-targeting siRNA molecule was employed. Its interaction with the nanoplatform was characterized by assessing loading capacity and release kinetics, which were further interpreted using mathematical modeling to elucidate the underlying release mechanisms. Full article

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

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25 pages, 7422 KB

Open AccessArticle

Vitamin B1 Involved in Dendrobium Taiseed Tosnobile Extract Mediates Protection Against Cancer-Induced Muscle Wasting by Suppressing IL-6 Pathogenicity and Enhancing Myoblast Fusion

by Chen-Chu Lin, Wan-Ting Liao, Tsung-Ying Yang, Jing-Hua Tsai, Yi-Ju Lee, Chi-Luan Wen, Shih-Lan Hsu and Chun-Chi Wu

Int. J. Mol. Sci. 2025, 26(21), 10704; https://doi.org/10.3390/ijms262110704 - 3 Nov 2025

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Abstract

In this report, we showed that oral administration of Dendrobium Taiseed Tosnobile (DTT, also known as Taiwan Emperor No.1) allowed Lewis Lung Carcinoma (LLC) tumor-bearing mice to maintain body weight and grip strength in a dose-dependent manner. Histological analysis showed that treatment with DTT water extract significantly reduced muscle fiber damage by inducing muscle regeneration and improved the cross-sectional area of the rectus femoris, soleus, and gastrocnemius of LLC tumor-bearing C57BL/6 female mice. Further studies revealed that DTT water extract also reduced the expression of inflammatory cytokines such as IL-6 and TNF-α, both in vitro and in vivo. Other analyses showed that DTT water extract promoted the differentiation of C2C12 myoblasts with or without IL-6 by maintaining Myosin Heavy Chain (MyHC) levels. This suggests that DTT water extract acts against muscle wasting via multiple mechanisms. Interestingly, vitamin B1 was identified as an ingredient in DTT water extract through an HPLC analysis. Vitamin B1 was shown to ameliorate IL-6 but not TNF-α generation in active THP-1 cells and protected C2C12 myotubes against IL-6. Further studies showed that DTT and vitamin B1 promoted the multi-nucleus fusion step of C2C12 differentiation by inducing E-cadherin-β-catenin expression with or without IL-6 treatment. In summary, DTT water extract protects muscle cells under cancer conditions through direct and indirect mechanisms, with vitamin B1 being a key functional ingredient that reduces IL-6 generation and aids muscle cell fusion against IL-6 treatment. Full article

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

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22 pages, 615 KB

Open AccessArticle

Effects of Cherry Consumption on Metabolic Health: A Pilot Clinical Study on Healthy Adults

by Filomena Carvalho, Alexandra Varges, Radhia Aitfella Lahlou, Eduardo Bárbara, Isa Santos, Cecília Fonseca and Luís R. Silva

Int. J. Mol. Sci. 2025, 26(18), 8891; https://doi.org/10.3390/ijms26188891 - 12 Sep 2025

Viewed by 2493

Abstract

Cherry consumption has been associated with several metabolic health benefits, due to their rich profile of bioactive compounds, including anthocyanins. This pilot clinical study, which is, to our knowledge, the first evaluating consumption of whole cherries, aimed to evaluate the effects of daily cherry consumption on oxidative stress, inflammation, glycaemic regulation, and other metabolic health markers in healthy adults. A total of 27 volunteers consumed 280 g of sweet cherries daily for 42 days, followed by a two-week post-intervention period. Significant improvements were observed in glucose regulation, including reduced HbA1c and estimated average glucose levels. Markers of inflammation, such as IL-6 and AGP-1 were significantly reduced during the intervention period. In addition, reductions in GGT and LDH indicated potential hepatoprotective effects. These results suggest that regular cherry consumption may serve as a preventive strategy against early metabolic dysfunction, highlighting the need for further investigation with larger, long-term clinical trials. Full article

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

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Review

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61 pages, 7437 KB

Open AccessReview

Investigating the Epigenetic Therapeutic Potential of Natural Compounds in Cancer

by Agnieszka Zaczek and Aleksandra Rodacka

Int. J. Mol. Sci. 2025, 26(21), 10776; https://doi.org/10.3390/ijms262110776 - 5 Nov 2025

Viewed by 1017

Abstract

Natural compounds, including alkaloids, terpenes, and polyphenols, are increasingly recognized for their potential to modulate epigenetic mechanisms and influence cellular function, particularly in cancer. Studies have shown that diverse phytochemicals impact epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA expression. Epigenetics is critical in cancer and can dysregulate crucial cellular processes, such as cell proliferation, apoptosis, and differentiation. In cancer, aberrant epigenetic patterns can silence tumor suppressor genes and activate oncogenes, contributing to uncontrolled cell growth and metastasis. Understanding the precise mechanisms by which these natural compounds interact with the epigenetic machinery holds significant promise for developing novel therapeutic strategies for cancer and other diseases. Future research, including basic studies and well-designed clinical trials, will be crucial in validating these findings and developing effective clinical applications of natural compounds. Full article

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

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