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Pharmaceuticals
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Multi-Targeted Natural Products as Therapeutics, 2nd Edition
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Multi-Targeted Natural Products as Therapeutics, 2nd Edition

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 4343

Special Issue Editors

Dr. Elena Y. Enioutina

E-Mail Website
Guest Editor
Division of Clinical Pharmacology, Pediatrics Department, School of Medicine, University of Utah, 295 Chipeta Way, Salt Lake City, UT, USA
Interests: effectiveness and safety of natural products; herbal-drug interactions; pediatric clinical pharmacology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Catherine M. T. Sherwin

E-Mail Website
Guest Editor
Internal Medicine, UWA Medical School, The University of Western Australia, Perth, WA, Australia
Interests: clinical pharmacology; clinical toxicology; pharmacometrics; pediatric pharmacology; maternal-fetal pharmacology; population pharmacokinetics; interventional trials; optimal trial design
Special Issues, Collections and Topics in MDPI journals
Dr. Kathleen M. Job

E-Mail Website
Guest Editor
Division of Clinical Pharmacology, Pediatrics Department, School of Medicine, University of Utah, 295 Chipeta Way, Salt Lake City, UT, USA
Interests: effectiveness and safety of natural products; herbal-drug interactions; pediatric clinical pharmacology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

For centuries, humans have used medicinal herbs and other natural products to treat and prevent various diseases. In the 20th century, many new drugs, approved by regulatory agencies worldwide, had been isolated from natural products, demonstrating the importance of medicinal herbs and other natural products as a valuable resource in drug development.

Nowadays, we are aware that the pathogenesis of many diseases is multifactorial. Therefore, for the successful treatment and management of these diseases, we should target multiple pathways. Conventional drugs, which are single-molecule medicines, usually target a single pathway or specific body function. Unlike conventional drugs, traditional medicine traditionally uses one or more natural product to prepare extracts, infusions, and decoctions. Preparations using even one medicinal herb may contain hundreds, if not thousands, of bioactive molecules. These molecules target functions of different organs and systems and potentiate or antagonize the functions of the preparation's other bioactive molecules. For example, many, if not all, antibacterial and antiviral drugs also possess immunomodulatory properties. Another example is that anti-cancer remedies may activate or suppress various pathways involved in cancer development and progression.

The Special Issue “The 20th Anniversary of Pharmaceuticals—Multi-Targeted Natural Products as Therapeutics” has enjoyed great success, with 25 articles published. This Special Issue aimed to summarize and examine the latest research findings in identifying natural products targeting multiple pathways and body functions to successfully treat multifactorial diseases. As of September 2025, articles published in this Special Issue had been cited 189 times. It appears that there is considerable interest in investigating the effects of purified extracts prepared from natural products or bioactive molecules from these extracts. We as Guest Editors hope that the second edition of the Special Issue will be successful, and we welcome our colleagues in this field to be part of it through the publication of research results.

Dr. Elena Y. Enioutina
Prof. Dr. Catherine M. T. Sherwin
Dr. Kathleen M. Job
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 250 words) can be sent to the Editorial Office for assessment.

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. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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
  • medicinal herbs
  • marine products
  • animal products
  • bioactive compounds
  • multifactorial diseases
  • multi-targeting phytochemicals

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Related Special Issue

Published Papers (4 papers)

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Research

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16 pages, 1954 KB  
Article
Calamagrostis arundinacea Extract Mitigates Testosterone Induced Prostatic Hyperplasia in Rats
by Poornima Kumbukgahadeniya, Eun-Bok Baek, Seung-Hoon Lee, Dae-In Ha, Eun-Ju Hong, Jun-Yeop Song, Won-Kee Yoon and Hyo-Jung Kwun
Pharmaceuticals 2026, 19(3), 453; https://doi.org/10.3390/ph19030453 - 11 Mar 2026
Viewed by 664
Abstract
Background: Benign prostatic hyperplasia (BPH) is an age-associated urological condition defined by abnormal multiplication of both stromal and epithelial components within the prostate. Calamagrostis arundinacea (CA), a species of perennial grass native to East Asia, has been recognized for its anti-inflammatory and [...] Read more.
Background: Benign prostatic hyperplasia (BPH) is an age-associated urological condition defined by abnormal multiplication of both stromal and epithelial components within the prostate. Calamagrostis arundinacea (CA), a species of perennial grass native to East Asia, has been recognized for its anti-inflammatory and antioxidant biological activities. The present study examined whether CA extract could attenuate prostatic enlargement induced by testosterone propionate (TP) in rats. Methodology: To establish the experimental model, rats received subcutaneous TP injections (3 mg/kg/day) for four consecutive weeks. During the same period, an extract of CA (150 mg/kg/day) was orally administered. Results: TP-treated animals developed significant prostatic enlargement, whereas CA supplementation markedly reduced prostate weight and significantly decreased circulating dihydrotestosterone (DHT) and testosterone levels. Microscopic analysis demonstrated that CA mitigated glandular epithelial thickening and suppressed hyperplastic alterations. In addition, CA reduced proliferating cell nuclear antigen (PCNA) expression and increased apoptotic cell numbers, as evidenced by TUNEL staining. Gene expression analysis further revealed significant downregulation of insulin-like growth factor-2 (Igf-2), transforming growth factor-β (Tgf-β), and vascular endothelial growth factor (Vegf), in CA-treated prostates. Moreover, CA inhibited activation of the PI3K/Akt/mTOR signaling cascades by reducing phosphorylation of Akt and mTOR. Conclusions: Overall, these results indicate that CA extract alleviates testosterone-induced BPH through suppression of growth-related signaling cascades and induction of apoptosis, suggesting its potent value as a phytotherapeutic strategy for BPH management. Full article
(This article belongs to the Special Issue Multi-Targeted Natural Products as Therapeutics, 2nd Edition)
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17 pages, 11836 KB  
Article
Wanshi Shachong Xiaoji Pills Alleviate Functional Dyspepsia in Mice and Exhibit Lipid-Lowering Effects in a Hepatocyte Steatosis Model
by Xiaoyue Wang, Xinrong Ren, Rui Zhao, Junming Tu, Minghui Wang, Fanfan Wang, Yuanyuan Duan, Tao Tang, Wuxian Zhou, Qingfang Wang and Jingmao You
Pharmaceuticals 2026, 19(3), 448; https://doi.org/10.3390/ph19030448 - 10 Mar 2026
Viewed by 493
Abstract
Objective: To investigate the therapeutic effects and safety profile of Wanshi Shachong Xiaoji Pills (WSXPs) on a functional dyspepsia (FD) mouse model and to preliminarily explore its potential mechanism and impact on associated hepatic metabolism. Methods: An FD model was established [...] Read more.
Objective: To investigate the therapeutic effects and safety profile of Wanshi Shachong Xiaoji Pills (WSXPs) on a functional dyspepsia (FD) mouse model and to preliminarily explore its potential mechanism and impact on associated hepatic metabolism. Methods: An FD model was established in mice using L-arginine. Gastrointestinal motility was assessed by measuring gastric emptying and intestinal propulsion rates. Serum levels of gastrointestinal hormones (MTL, GAS, VIP, CCK) and gut microbiota composition were analyzed. A one-month repeated-dose toxicity study was conducted in normal mice to evaluate safety. The effects of WSXPs on lipid metabolism and inflammation were further examined in a hepatocyte steatosis model in vitro, and network pharmacology was employed to predict potential mechanisms. Results: WSXPs significantly alleviated FD symptoms by improving gastrointestinal motility, bidirectionally regulating gut hormone levels, and increasing the abundance of beneficial bacteria (Akkermansia muciniphila). Long-term administration showed no significant toxicity. In vitro, WSXPS reduced lipid accumulation and inflammation in hepatocytes. Network analysis identified the PI3K-Akt signaling pathway as a potentially central common target, providing a hypothesis for future mechanistic studies. Conclusions: WSXPs effectively improve FD symptoms, modulates gut microbiota, and exhibits potential benefits on hepatic lipid metabolism in vitro, possibly via the PI3K-Akt pathway. This hepatocyte-level finding, combined with its in vivo efficacy in FD, suggests a promising avenue for future research into its potential applications in metabolic-associated conditions. This study provides a scientific foundation for the further development and clinical application of WSXPs in treating FD. Full article
(This article belongs to the Special Issue Multi-Targeted Natural Products as Therapeutics, 2nd Edition)
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28 pages, 35644 KB  
Article
Multi-Targeted Therapeutic Mechanisms of Huangqi Guizhi Wuwu Decoction Against Rheumatoid Arthritis: An Integrated Approach Combining Serum Pharmacochemistry, Network Pharmacology, Metabolomics, and Experimental Validation
by Zihua Xu, Zhenshu Li, Jiameng Qu, Chen Liang, Yingshi Zhang, Qingchun Zhao and Qing Li
Pharmaceuticals 2026, 19(2), 236; https://doi.org/10.3390/ph19020236 - 29 Jan 2026
Viewed by 1173
Abstract
Background: The pathogenesis of rheumatoid arthritis (RA) is closely related to multiple disorders in the immune and metabolic systems, which indicates that a multi-target therapy strategy may have advantages over traditional single-target therapy. Huangqi Guizhi Wuwu Decoction (HGWD), as a classic traditional [...] Read more.
Background: The pathogenesis of rheumatoid arthritis (RA) is closely related to multiple disorders in the immune and metabolic systems, which indicates that a multi-target therapy strategy may have advantages over traditional single-target therapy. Huangqi Guizhi Wuwu Decoction (HGWD), as a classic traditional Chinese medicine formula that has been used to treat RA in clinic, is a potential source of multi-target natural medicine. However, its active components and mechanism of action still need further research. Methods: This study combined serum pharmacochemistry, non-targeted metabonomics, network pharmacology, and experimental verification and comprehensively analyzed the therapeutic mechanism and pharmacodynamic basis of HGWD. Results: Through HPLC-Q-TOF-MS/MS, a total of 99 chemical components were identified. Among them, 25 prototype compounds were absorbed into the systemic circulation. The study of network pharmacology indicates that these compounds are concentrated in TNF, IL-17, and MAPK signaling pathways. In collagen-induced arthritis rats, HGWD can effectively alleviate joint inflammation, inhibit the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17), block the activation of the MAPK pathway, and restore 13 abnormal metabolic markers related to lipid and amino acid metabolism. In addition, the researchers identified and verified the combination of four active components (calycosin, paeoniflorin, 6-gingerol, and formononetin) in vitro, and its anti-inflammatory and anti-migration activities were equivalent to or stronger than those of the complete extract. Pharmacokinetic analysis also confirmed that these components were fully exposed in vivo. Conclusions: These findings reveal the mechanism of multi-component therapy of HGWD and identify the potential bioactive components, which can be used to develop multi-target therapeutic drugs for RA based on natural products. Full article
(This article belongs to the Special Issue Multi-Targeted Natural Products as Therapeutics, 2nd Edition)
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Review

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39 pages, 2259 KB  
Review
Innovations in the Delivery of Bioactive Compounds for Cancer Prevention and Therapy: Advances, Challenges, and Future Perspectives
by Carlos A. Ligarda-Samanez, Mary L. Huamán-Carrión, Jackson M’coy Romero Plasencia, Dante Fermín Calderón Huamaní, Bacilia Vivanco Garfias, Jenny C. Muñoz-Saenz, Maria Magdalena Bautista Gómez, Jaime A. Martinez-Hernandez and Wilber Cesar Calsina-Ponce
Pharmaceuticals 2026, 19(1), 60; https://doi.org/10.3390/ph19010060 - 27 Dec 2025
Cited by 3 | Viewed by 1530
Abstract
Naturally occurring bioactive compounds represent a promising option for cancer prevention and therapy due to their ability to modulate apoptosis, angiogenesis, inflammation, oxidative stress, and cell signaling. However, their clinical impact is limited by low bioavailability, chemical instability, rapid metabolism, and poor tumor [...] Read more.
Naturally occurring bioactive compounds represent a promising option for cancer prevention and therapy due to their ability to modulate apoptosis, angiogenesis, inflammation, oxidative stress, and cell signaling. However, their clinical impact is limited by low bioavailability, chemical instability, rapid metabolism, and poor tumor microenvironment accumulation. Innovative delivery platforms, including lipid and polymeric nanoparticles, liposomes, micelles, nanoemulsions, hydrogels, and stimulus-responsive systems, have been developed to improve stability, absorption, tumor specificity, and therapeutic efficacy. This review integrates molecular mechanisms, preclinical and clinical evidence, and recent technological advances, highlighting both potential and limitations. Although several compounds show encouraging results in cell and animal models, only a small number have progressed to early clinical trials, where outcomes remain heterogeneous and often fail to replicate preclinical magnitudes. Regulatory barriers, a lack of formulation standardization, and the absence of predictive biomarkers persist. Sustainability is also addressed through the valorization of agrifood by-products and green extraction processes. This review provides an integrative framework linking molecular mechanisms, advanced delivery technologies, clinical translation, and sustainability, offering a broader perspective than conventional reviews. Future perspectives emphasize multicenter trials, comparative designs, and the development of regulatory guidelines for nanoformulated bioactive compounds. Full article
(This article belongs to the Special Issue Multi-Targeted Natural Products as Therapeutics, 2nd Edition)
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