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Natural Products as Multitarget Agents in Human Diseases
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Natural Products as Multitarget Agents in Human Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 March 2025 | Viewed by 7343

Special Issue Editors

Dr. Andrey Marchev

E-Mail Website
Guest Editor
Laboratory of Metabolomics, Department of Biotechnology, The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 139 Ruski Blvd, 4000 Plovdiv, Bulgaria
Interests: natural products; plant-derived extracts and molecules; medicinal plants; plant in vitro systems; natural products pharmacology
Special Issues, Collections and Topics in MDPI journals
Dr. Nikolina Mihaylova

E-Mail Website
Guest Editor
Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
Interests: autoimmunity; osteoarthritis; B cells; T cells; cell signaling; mouse models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to share your scientific achievements in the field of natural products (extracts and/or pure molecules derived from natural sources) that are utilized as potential novel therapeutic agents targeting wide spectrum of human diseases.

For centuries, natural products (NPs) have been proven as agents with numerous health benefits for humans and explored as a pool for the development of novel therapeutic drugs. Because of the side effects associated with conventional therapies, the search for novelty and safety from NPs with proven therapeutic qualities is increasingly imperative. It is absolutely necessary to validate the bioactivity of the NPs studied, to prove their quality, effectiveness, and safety, while simultaneously clarify their possible molecular mechanism, including interactions with conventional drugs.

The aim of this Special Issue (SI) is to present high-quality novel research findings that evaluate the therapeutic effects of NPs with focus on the physiological, biochemical, and molecular processes underlying their mechanism of activity in in vitro and in vivo studies related to human health. The SI will accept original research articles, short communications, and reviews.

Dr. Andrey Marchev
Dr. Nikolina Mihaylova
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • bioactive compounds
  • human health
  • disease prevention and treatment
  • molecular and physiological mechanism
  • inflammatory diseases
  • cancer
  • arthritic diseases
 

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Published Papers (4 papers)

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Research

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21 pages, 5361 KiB  
Article
Mangiferin Represses Inflammation in Macrophages Under a Hyperglycemic Environment Through Nrf2 Signaling
by Ravichandran Jayasuriya, Kumar Ganesan and Kunka Mohanram Ramkumar
Int. J. Mol. Sci. 2024, 25(20), 11197; https://doi.org/10.3390/ijms252011197 - 18 Oct 2024
Cited by 1 | Viewed by 1090
Abstract
Inflammation in macrophages is exacerbated under hyperglycemic conditions, contributing to chronic inflammation and impaired wound healing in diabetes. This study investigates the potential of mangiferin, a natural polyphenol, to alleviate this inflammatory response by targeting a redox-sensitive transcription factor, nuclear factor erythroid 2-related [...] Read more.
Inflammation in macrophages is exacerbated under hyperglycemic conditions, contributing to chronic inflammation and impaired wound healing in diabetes. This study investigates the potential of mangiferin, a natural polyphenol, to alleviate this inflammatory response by targeting a redox-sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2). Mangiferin, a known Nrf2 activator, was evaluated for its ability to counteract the hyperglycemia-induced inhibition of Nrf2 and enhance antioxidant defenses. The protective effects of mangiferin on macrophages in a hyperglycemic environment were assessed by examining the expression of Nrf2, NF-κB, NLRP3, HO-1, CAT, COX-2, IL-6, and IL-10 through gene and protein expression analyses using qPCR and immunoblotting, respectively. The mangiferin-mediated nuclear translocation of Nrf2 was evidenced, leading to a robust antioxidant response in macrophages exposed to a hyperglycemic microenvironment. This activation suppressed NF-κB signaling, reducing the expression of pro-inflammatory mediators such as COX-2 and IL-6. Additionally, mangiferin decreased NLRP3 inflammasome activation and reactive oxygen species accumulation in hyperglycemia exposed macrophages. Our findings revealed that mangiferin alleviated hyperglycemia-induced reductions in AKT phosphorylation, highlighting its potential role in modulating key signaling pathways. Furthermore, mangiferin significantly enhanced the invasiveness and migration of macrophages in a hyperglycemic environment, indicating its potential to improve wound healing. In conclusion, this study suggests that mangiferin may offer a promising therapeutic approach for managing inflammation and promoting wound healing in diabetic patients by regulating Nrf2 activity in hyperglycemia-induced macrophages. Full article
(This article belongs to the Special Issue Natural Products as Multitarget Agents in Human Diseases)
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19 pages, 6692 KiB  
Article
Leonurine Inhibits Hepatic Lipid Synthesis to Ameliorate NAFLD via the ADRA1a/AMPK/SCD1 Axis
by Wen Fan, Maoxing Pan, Chuiyang Zheng, Haiyan Shen, Dajin Pi, Qingliang Song, Zheng Liang, Jianwei Zhen, Jinyue Pan, Lianghao Liu, Qinhe Yang and Yupei Zhang
Int. J. Mol. Sci. 2024, 25(19), 10855; https://doi.org/10.3390/ijms251910855 - 9 Oct 2024
Cited by 1 | Viewed by 1608
Abstract
Leonurine is a natural product unique to the Lamiaceae plant Leonurus japonicus Houtt., and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic [...] Read more.
Leonurine is a natural product unique to the Lamiaceae plant Leonurus japonicus Houtt., and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms, but its mechanism of action remains to be elucidated. Therefore, this study aims to preliminarily explore the mechanisms of action of leonurine in NAFLD. Mice were randomly divided into four groups: the normal control (NC) group, the Model (M) group, the leonurine treatment (LH) group, and the fenofibrate treatment (FB) group. The NAFLD model was induced by a high-fat high-sugar diet (HFHSD) for 12 weeks, and liver pathological changes and biochemical indices were observed after 12 weeks. Transcriptomic analysis results indicated that leonurine intervention reversed the high-fat high-sugar diet-induced changes in lipid metabolism-related genes such as stearoyl-CoA desaturase 1 (Scd1), Spermine Synthase (Sms), AP-1 Transcription Factor Subunit (Fos), Oxysterol Binding Protein Like 5 (Osbpl5), and FK506 binding protein 5 (Fkbp5) in liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results suggest that leonurine may exert its lipid-lowering effects through the AMP-activated protein kinase (AMPK) signaling pathway. Liver lipidomic analysis showed that leonurine could alter the abundance of lipid molecules related to fatty acyl (FAs) and glycerophospholipids (GPs) such as TxB3, carnitine C12-OH, carnitine C18:1-OH, and LPC (20:3/0:0). Molecular biology experiments and molecular docking techniques verified that leonurine might improve hepatic lipid metabolism through the alpha-1A adrenergic receptor (ADRA1a)/AMPK/SCD1 axis. In summary, the present study explored the mechanism by which leonurine ameliorated NAFLD by inhibiting hepatic lipid synthesis via the ADRA1a/AMPK/SCD1 axis. Full article
(This article belongs to the Special Issue Natural Products as Multitarget Agents in Human Diseases)
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18 pages, 8366 KiB  
Article
Isorhamnetin Alleviates Mitochondrial Injury in Severe Acute Pancreatitis via Modulation of KDM5B/HtrA2 Signaling Pathway
by Xiaojuan Li, Tao Wang, Qilong Zhou, Fan Li, Ting Liu, Kun Zhang, Ao Wen, Lijuan Feng, Xiaoling Shu, Simin Tian, Yijiang Liu, Yu Gao, Qing Xia, Guang Xin and Wen Huang
Int. J. Mol. Sci. 2024, 25(7), 3784; https://doi.org/10.3390/ijms25073784 - 28 Mar 2024
Cited by 3 | Viewed by 1566
Abstract
Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately [...] Read more.
Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately linked to the modulation of mitochondrial function. However, the specific protective impact of ISO on SAP remains to be fully elucidated. In this study, we demonstrated that ISO treatment significantly alleviated pancreatic damage and reduced serum lipase and amylase levels in the mouse model of SAP induced by sodium taurocholate (STC) or L-arginine. Utilizing an in vitro SAP cell model, we found that ISO co-administration markedly prevented STC-induced pancreatic acinar cell necrosis, primarily by inhibiting mitochondrial ROS generation, preserving ATP production, maintaining mitochondrial membrane potential, and preventing the oxidative damage and release of mitochondrial DNA. Mechanistically, our investigation identified that high-temperature requirement A2 (HtrA2) may play a central regulatory role in mediating the protective effect of ISO on mitochondrial dysfunction in STC-injured acinar cells. Furthermore, through an integrated approach involving bioinformatics analysis, molecular docking analysis, and experimental validation, we uncovered that ISO may directly impede the histone demethylation activity of KDM5B, leading to the restoration of pancreatic HtrA2 expression and thereby preserving mitochondrial function in pancreatic acinar cells following STC treatment. In conclusion, this study not only sheds new light on the intricate molecular complexities associated with mitochondrial dysfunction during the progression of SAP but also underscores the promising value of ISO as a natural therapeutic option for SAP. Full article
(This article belongs to the Special Issue Natural Products as Multitarget Agents in Human Diseases)
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Review

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24 pages, 2336 KiB  
Review
Natural Product-Derived Compounds Targeting Keratinocytes and Molecular Pathways in Psoriasis Therapeutics
by Yu Geon Lee, Younjung Jung, Hyo-Kyoung Choi, Jae-In Lee, Tae-Gyu Lim and Jangho Lee
Int. J. Mol. Sci. 2024, 25(11), 6068; https://doi.org/10.3390/ijms25116068 - 31 May 2024
Cited by 1 | Viewed by 1851
Abstract
Psoriasis is a chronic autoimmune inflammatory skin disorder that affects approximately 2–3% of the global population due to significant genetic predisposition. It is characterized by an uncontrolled growth and differentiation of keratinocytes, leading to the formation of scaly erythematous plaques. Psoriasis extends beyond [...] Read more.
Psoriasis is a chronic autoimmune inflammatory skin disorder that affects approximately 2–3% of the global population due to significant genetic predisposition. It is characterized by an uncontrolled growth and differentiation of keratinocytes, leading to the formation of scaly erythematous plaques. Psoriasis extends beyond dermatological manifestations to impact joints and nails and is often associated with systemic disorders. Although traditional treatments provide relief, their use is limited by potential side effects and the chronic nature of the disease. This review aims to discuss the therapeutic potential of keratinocyte-targeting natural products in psoriasis and highlight their efficacy and safety in comparison with conventional treatments. This review comprehensively examines psoriasis pathogenesis within keratinocytes and the various related signaling pathways (such as JAK-STAT and NF-κB) and cytokines. It presents molecular targets such as high-mobility group box-1 (HMGB1), dual-specificity phosphatase-1 (DUSP1), and the aryl hydrocarbon receptor (AhR) for treating psoriasis. It evaluates the ability of natural compounds such as luteolin, piperine, and glycyrrhizin to modulate psoriasis-related pathways. Finally, it offers insights into alternative and sustainable treatment options with fewer side effects. Full article
(This article belongs to the Special Issue Natural Products as Multitarget Agents in Human Diseases)
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