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Molecular Mechanism Study of Natural Products for Human Health

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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: closed (10 April 2024) | Viewed by 8906

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Dr. Hyeung-Jin Jang

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Professor, Head of Department of Biochemistry, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Interests: nutrition and dietary components; herbal medicine; immunomodulatory potential of natural compounds; novel gene regulation; diabetes-related diseases; metabolic disease; inflammation; COPD; cancer therapy; cancer biology; regulation of p53; regulation of c-Myc
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Dear Colleagues,

Plant natural products have been used medically since the past, but most of the pharmaceutical market is mainly composed of synthetic drugs. Recently, interest in natural has been increasing, and various studies on their efficacy and molecular biological mechanisms have been conducted. Interestingly, natural drugs also serve as substitute for existing drugs and have the result of further enhancing the therapeutic effect. In addition, when it no longer works as a conventional treatment, natural products or herbal medicine can be effective as an alternative treatment. We invite all scientists working on molecular mechanism study of natural products to participate in this Special Issue. Original research articles or reviews on all aspects of the molecular and cellular mechanisms modulated by natural compounds are welcome. We look forward to your contributions.

Prof. Dr. Hyeung-Jin Jang
Guest Editor

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Keywords

drug discovery
natural compound
chemoprevention
herbal medicine
plant extract
novel gene

Published Papers (7 papers)

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Research

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17 pages, 1612 KiB

Open AccessArticle

Polyphenolic Characterization and Anti-Inflammatory Effect of In Vitro Digested Extracts of Echinacea purpurea L. Plant Parts in an Inflammatory Model of Human Colon Cells

by María Ángeles Ávila-Gálvez, Juan Antonio Giménez-Bastida, Bulent Karadeniz, Salvador Romero-Reyes, Juan Carlos Espín, Ebru Pelvan and Antonio González-Sarrías

Int. J. Mol. Sci. 2024, 25(3), 1744; https://doi.org/10.3390/ijms25031744 - 01 Feb 2024

Viewed by 822

Abstract

Echinacea purpurea L. (EP) preparations are globally popular herbal supplements known for their medicinal benefits, including anti-inflammatory activities, partly related to their phenolic composition. However, regarding their use for the management of inflammation-related intestinal diseases, the knowledge about the fate of orally ingested constituents throughout the human gastrointestinal tract and the exposition of in vitro digested extracts in relevant inflammatory models are unknown. This study investigated for the first time the impact of in vitro gastrointestinal digestion (INFOGEST) on the phenolic composition and anti-inflammatory properties of EP extracts from flowers (EF), leaves (EL), and roots (ER) on IL-1β-treated human colon-derived CCD-18Co cells. Among the seven hydroxycinnamic acids identified using HPLC-UV-MS/MS, chicoric and caftaric acids showed the highest concentrations in EL, followed by EF and ER, and all extracts exerted significant reductions in IL-6, IL-8, and PGE₂ levels. After digestion, despite reducing the bioaccessibility of their phenolics, the anti-inflammatory effects were preserved for digested EL and, to a lesser extent, for EF, but not for digested ER. The lower phenolic content in digested EF and ER could explain these findings. Overall, this study emphasizes the potential of EP in alleviating intestinal inflammatory conditions and related disorders. Full article

(This article belongs to the Special Issue Molecular Mechanism Study of Natural Products for Human Health)

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13 pages, 2040 KiB

Open AccessArticle

Menadione Contribution to the In Vitro Radical Scavenging Potential of Phytochemicals Naringenin and Lignin

by Zvezdelina Yaneva, Donika Ivanova, Monika Toneva, Milena Tzanova, Vanya Marutsova and Neli Grozeva

Int. J. Mol. Sci. 2023, 24(22), 16268; https://doi.org/10.3390/ijms242216268 - 13 Nov 2023

Viewed by 764

Abstract

Vitamin K₃ (menadione), classified as a pro-vitamin, is a synthetic form of the fat-soluble family of vitamin K compounds. The combination of the vitamin with other molecules sharing structural and/or functional similarities, such as naturally occurring polyphenols, vitamins, or biopolymers, could potentiate mutual improvement of their antioxidant activity. The aim of the present study was to evaluate the role and contribution of vitamin K₃ to the in vitro radical scavenging capacity of double and triple combinations with the phytochemicals naringenin and lignin, as well as assess possible intermolecular interactions between the bioactive compounds. Comparative analyses of the DPPH and ABTS radical scavenging activity of the pure substances vitamin K₃, naringenin, and lignin; the two-component systems lignin/vitamin K₃ and vitamin K₃/naringenin; and the triple combination vitamin K₃/flavonoid/lignin were carried out. The experimental results demonstrated increased DPPH and ABTS activities of the vitamin in combination with lignin compared to those of the two pure substances, i.e., a synergistic effect was observed. The registered significant increases in the radical scavenging activity of the triple combination determined via both methods are indicative of a remarkable potentiation effect, i.e., higher antioxidant potential exceeding the additive activity of the three pure substances. Full article

(This article belongs to the Special Issue Molecular Mechanism Study of Natural Products for Human Health)

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13 pages, 2543 KiB

Open AccessArticle

Novel Combination of Choline with Withania somnifera (L.) Dunal, and Bacopa monnieri (L.) Wetts Reduced Oxidative Stress in Microglia Cells, Promoting Neuroprotection

by Vittoria Borgonetti and Nicoletta Galeotti

Int. J. Mol. Sci. 2023, 24(18), 14038; https://doi.org/10.3390/ijms241814038 - 13 Sep 2023

Cited by 1 | Viewed by 1018

Abstract

Memory deficit is one of the major negative outcomes of chronic stress. Cholinergic system modulates memory not only through the neuronal cells, but also via interactions with non-neuronal cells, suggesting that microglia can influence synaptic function and plasticity, contributing to cognition and memory function. Withania somnifera (L.) Dunal (WS) and Bacopa monnieri (L.) Wettst (BM), are traditional herbal medicinal products used for the temporary relief of symptoms of stress. The aim of this study was to investigate whether choline (CLN) activity could be enhanced via an association with adaptogens: WS and BM extracts. First, we optimized an in vitro model of corticotropin-releasing hormone (CRH)-induced oxidative stress on microglial BV2 cells. CRH 100 nM reduced BV2 cell viability and induced morphological changes and neurotoxicity after 24 h of microglia stimulation. Moreover, it induced an increase in the production of reactive oxygen species (ROS) and dysregulated antioxidant protein (i.e., SIRT-1 and NRF-2). The association between choline and adaptogens (CBW) 10 μg/mL counteracted the effect of CRH on BV2 cells and reduced the neurotoxicity produced by BV2 CRH-conditioned medium in the SH-SY5Y cell lines. CBW 200 mg/kg produced an ameliorative effect on recognition memory in the novel object recognition test (NORT) test in mice. In conclusion, combining choline with adaptogen plant extracts might represent a promising intervention in chronic stress associated with memory disturbances through the attenuation of microglia-induced oxidative stress. Full article

(This article belongs to the Special Issue Molecular Mechanism Study of Natural Products for Human Health)

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20 pages, 4068 KiB

Open AccessArticle

Soybean (Glycine max) INFOGEST Colonic Digests Attenuated Inflammatory Responses Based on Protein Profiles of Different Varieties

by Jennifer Kusumah, Erick Damian Castañeda-Reyes, Neal A. Bringe and Elvira Gonzalez de Mejia

Int. J. Mol. Sci. 2023, 24(15), 12396; https://doi.org/10.3390/ijms241512396 - 03 Aug 2023

Cited by 1 | Viewed by 1725

Abstract

Soybean compounds have been established to modulate inflammation, but less is known about how whole soybean compositions work together after digestion. The objective was to evaluate and compare the anti-inflammatory responses of different soybean varieties under simulated gastrointestinal digestion, with additional consideration of the glycinin:β-conglycinin ratio (GBR). Soybean colonic digests (SCD) inhibited cyclooxygenase (COX)-2 (25–82%), 5-lipoxidase (LOX) (18–35%), and inducible nitric oxide (iNOS) (8–61%). Varieties 88, GN3, and 93 were the most effective inhibitors. SCD (1 mg/mL) of varieties 81 and GN1 significantly (p < 0.05) reduced nitrite production by 44 and 47%, respectively, compared to lipopolysaccharide (LPS)-stimulated macrophages. SCD effectively reduced pro-inflammatory cytokine interleukin (IL)-6 (50 and 80% for 96 and GN1, respectively). Western blot results showed a decrease in the expression of iNOS, p65, and p50. The GBR was in the range of 0.05–1.57. Higher ratio correlated with higher production of IL-1β (r = 0.44) and tumor necrosis factor-alpha (TNF-α, r = 0.56). Inflammatory microarray results showed a significant decrease in expression of markers granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-6 in cells treated with GN1 SCD compared to LPS. The results suggested that SCD exerted its anti-inflammatory potential through nuclear factor kappa B (NF-κΒ) pathway inhibition by decreasing the levels of NF-κB-dependent cytokines and subunits, and inhibition of pro-inflammatory enzyme activity. Full article

(This article belongs to the Special Issue Molecular Mechanism Study of Natural Products for Human Health)

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13 pages, 2831 KiB

Open AccessArticle

Viscum album Induces Apoptosis by Regulating STAT3 Signaling Pathway in Breast Cancer Cells

by Ye-Rin Park, Wona Jee, So-Mi Park, Seok Woo Kim, Hanbit Bae, Ji Hoon Jung, Hyungsuk Kim, Sangki Kim, Jong Sup Chung and Hyeung-Jin Jang

Int. J. Mol. Sci. 2023, 24(15), 11988; https://doi.org/10.3390/ijms241511988 - 26 Jul 2023

Cited by 3 | Viewed by 1082

Abstract

In this study, we investigated the potential anticancer effects of Viscum album, a parasitic plant that grows on Malus domestica (VaM) on breast cancer cells, and explored the underlying mechanisms. VaM significantly inhibited cell viability and proliferation and induced apoptosis in a dose-dependent manner. VaM also regulated cell cycle progression and effectively inhibited activation of the STAT3 signaling pathway through SHP-1. Combining VaM with low-dose doxorubicin produced a synergistic effect, highlighting its potential as a promising therapeutic. In vivo, VaM administration inhibited tumor growth and modulated key molecular markers associated with breast cancer progression. Overall, our findings provide strong evidence for the therapeutic potential of VaM in breast cancer treatment and support further studies exploring clinical applications. Full article

(This article belongs to the Special Issue Molecular Mechanism Study of Natural Products for Human Health)

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11 pages, 1800 KiB

Open AccessCommunication

Inhibition of Soluble Epoxide Hydrolase Activity by Components of Glycyrrhiza uralensis

by Jang Hoon Kim, Yun-Chan Huh, Mok Hur, Woo Tae Park, Youn-Ho Moon, Tae Il Kim, Yong Il Kim, Seon Mi Kim, Jeonghoon Lee and Ik Soo Lee

Int. J. Mol. Sci. 2023, 24(7), 6485; https://doi.org/10.3390/ijms24076485 - 30 Mar 2023

Cited by 1 | Viewed by 1101

Abstract

Soluble epoxide hydrolase (sEH) is a target enzyme for the treatment of inflammation and cardiovascular disease. A Glycyrrhiza uralensis extract exhibited ~50% inhibition of sEH at 100 μg/mL, and column chromatography yielded compounds 1–11. Inhibitors 1, 4–6, 9, and 11 were non-competitive; inhibitors 3, 7, 8, and 10 were competitive. The IC₅₀ value of inhibitor 10 was below 2 μM. Molecular simulation was used to identify the sEH binding site. Glycycoumarin (10) requires further evaluation in cells and animals. Full article

(This article belongs to the Special Issue Molecular Mechanism Study of Natural Products for Human Health)

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Review

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25 pages, 9278 KiB

Open AccessReview

Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer

by Wonyoung Park, Jung Ho Han, Shibo Wei, Eun-Sun Yang, Se-Yun Cheon, Sung-Jin Bae, Dongryeol Ryu, Hwan-Suck Chung and Ki-Tae Ha

Int. J. Mol. Sci. 2024, 25(2), 807; https://doi.org/10.3390/ijms25020807 - 09 Jan 2024

Cited by 1 | Viewed by 1299

Abstract

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Targeted therapy against the epidermal growth factor receptor (EGFR) is a promising treatment approach for NSCLC. However, resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a major challenge in its clinical management. EGFR mutation elevates the expression of hypoxia-inducible factor-1 alpha to upregulate the production of glycolytic enzymes, increasing glycolysis and tumor resistance. The inhibition of glycolysis can be a potential strategy for overcoming EGFR-TKI resistance and enhancing the effectiveness of EGFR-TKIs. In this review, we specifically explored the effectiveness of pyruvate dehydrogenase kinase inhibitors and lactate dehydrogenase A inhibitors in combating EGFR-TKI resistance. The aim was to summarize the effects of these natural products in preclinical NSCLC models to provide a comprehensive understanding of the potential therapeutic effects. The study findings suggest that natural products can be promising inhibitors of glycolytic enzymes for the treatment of EGFR-TKI-resistant NSCLC. Further investigations through preclinical and clinical studies are required to validate the efficacy of natural product-based glycolytic inhibitors as innovative therapeutic modalities for NSCLC. Full article

(This article belongs to the Special Issue Molecular Mechanism Study of Natural Products for Human Health)

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