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The Modes of Action of Herbal Medicines and Natural Products,...
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The Modes of Action of Herbal Medicines and Natural Products, 2nd Edition

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

Deadline for manuscript submissions: 15 October 2025 | Viewed by 1440

Special Issue Editor

Dr. Hongnan Cao

E-Mail Website
Guest Editor
Department of Biochemistry, Alumni of University of California, Riverside, CA, USA
Interests: protein chemistry; structural biology; crystallography; drug discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We invite researchers and scholars to contribute to our upcoming Special Issue, "The Modes of Action of Herbal Medicines and Natural Products, 2nd Edition". This interdisciplinary collection aims to explore the intricate mechanisms through which herbal medicines and natural products exert their health benefits and/or therapeutic effects.

With growing global interest in alternative medicine, understanding the mechanisms of how herbal remedies work is essential. We encourage submissions that delve into the molecular, cellular, and systemic interactions between bioactive compounds in herbs and their targets within the human body.

Potential topics include, but are not limited to, the following:

  • Molecular pathways and signaling cascades influenced by herbal compounds;
  • Computational methods for predicting the mode of actions of natural products and herbal medicines;
  • Experimental methods for elucidating and/or investigating the mode of actions of natural products and herbal medicines;
  • Pharmacokinetics and pharmacodynamics of natural products;
  • Cellular and physiological responses to herbal interventions;
  • Novel approaches to integrating traditional knowledge with modern research methods;
  • Case studies on the mechanisms of specific herbal medicines;
  • Ethnopharmacology and the cultural context of herbal therapies.

Contributions from diverse perspectives and research methodologies are welcome. Join us in advancing our understanding of the therapeutic potential inherent in herbal medicines and natural products. Submissions are invited from researchers, clinicians, and academics across disciplines. Together, let us unravel the mysteries behind the efficacy of nature's pharmacopeia.

Dr. Hongnan Cao
Guest Editor

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. 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

  • herbal compounds
  • natural products
  • pharmacokinetics and pharmacodynamics of natural products
  • herbal medicines
  • herbal therapies

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  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
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Further information on MDPI's Special Issue policies can be found here.

Published Papers (3 papers)

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Research

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36 pages, 8683 KB  
Article
Shentong Zhuyu Decoction Alleviates Neuropathic Pain in Mice by Inhibiting the NMDAR-2B Receptor-Mediated CaMKII/CREB Signaling Pathway in GABAergic Neurons of the Interpeduncular Nucleus
by Ying Liu, Rujie Li, Haojie Cheng, Yuxin Wang, Jian Sun and Meiyu Zhang
Pharmaceuticals 2025, 18(10), 1456; https://doi.org/10.3390/ph18101456 - 28 Sep 2025
Abstract
Background: Shentong Zhuyu Decoction (STZYD) is a traditional Chinese medicine formula that has shown promise in alleviating neuropathic pain (NPP), yet its central mechanisms remain unclear. Methods: We investigated the STZYD effects on NPP using network pharmacology, in vivo assays, and [...] Read more.
Background: Shentong Zhuyu Decoction (STZYD) is a traditional Chinese medicine formula that has shown promise in alleviating neuropathic pain (NPP), yet its central mechanisms remain unclear. Methods: We investigated the STZYD effects on NPP using network pharmacology, in vivo assays, and analytical chemistry, focusing on molecular pathways and GABAergic neuronal modulation. Results: Network pharmacology revealed 254 potential STZYD targets enriched in calcium signaling and GABAergic synapse pathways, especially the NMDAR-2B/CaMKII/CREB axis. High-dose STZYD (1.25 g·mL−1) and ifenprodil (6 mg·kg−1) reversed hyperalgesia and anxiety-like behaviors in spared nerve injury (SNI) mice, and microdialysis showed that STZYD and ifenprodil reduced the glutamate, D-serine, aspartate, glycine, and gamma-aminobutyric acid levels in the interpeduncular nucleus (IPN). Immunofluorescence and fiber photometry showed reduced c-Fos expression and suppressed GCaMP signals in IPN GABAergic neurons, with chemogenetic experiments confirming their role in pain modulation. Multimodal molecular biology experiments demonstrated that STZYD and ifenprodil significantly downregulated the GluN2B, p-CaMKII, and p-CREB expressions within the IPN. We identified 145 constituents in STZYD through high-resolution mass spectrometry analysis, among which 40 were absorbed into plasma and 7 were able to cross the blood–brain barrier and accumulate in the IPN. Molecular docking revealed the strong binding of licoricesaponin K2 and senkyunolide F to NMDAR-2B. Conclusions: STZYD exerts dose-dependent antinociceptive effects by modulating IPN GABAergic neuronal activity through the inhibition of the NMDAR-2B-mediated CaMKII/CREB pathway. Full article
(This article belongs to the Special Issue The Modes of Action of Herbal Medicines and Natural Products, 2nd Edition)
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15 pages, 2669 KB  
Article
Integrative Study of Dipsaci Radix and Phlomidis Radix: Nomenclature, Morphology, DNA-Based Authentication, and Comparative Effects on Osteoclastogenesis
by Jun-Ho Song, Yun-Soo Seo, Yeseul Kim, Sohee Jeong, Sungyu Yang, Goya Choi, Joong-Sun Kim and Inkyu Park
Pharmaceuticals 2025, 18(9), 1418; https://doi.org/10.3390/ph18091418 - 20 Sep 2025
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Abstract
Background/Objectives: Dipsaci Radix (Dipsacus asper) and Phlomidis Radix (Phlomoides umbrosa) are both traditional medicines used in Korea and China for various bone-associated diseases. However, the two are misused due to similarities in name and appearance. Additionally, D. japonicus [...] Read more.
Background/Objectives: Dipsaci Radix (Dipsacus asper) and Phlomidis Radix (Phlomoides umbrosa) are both traditional medicines used in Korea and China for various bone-associated diseases. However, the two are misused due to similarities in name and appearance. Additionally, D. japonicus root frequently contaminates Dipsaci Radix in Korean herbal markets. Methods: We examined morphological plant traits and performed a DNA barcoding analysis using ITS2 and matK sequences to differentiate between these three species. The effects of root extracts on bone resorption and osteoclast differentiation, measured as tartrate-resistant acid phosphatase (TRAP)-positive cell formation, were evaluated using mouse (5 weeks male ICR mice) bone marrow-derived macrophages. Cytotoxicity assays were conducted to assess extract safety. Results: Phlomoides umbrosa is easily distinguished by its verticillaster inflorescences and 2-labiate corollas. Dipsacus asper and D. japonicus, which share globose inflorescences, are distinguishable by flower color and leaf lobation. The ITS2 and matK sequences clearly differentiated the three species, with haplotype analysis supporting their genetic distinctiveness, enabling robust species discrimination. All three extracts decreased osteoclastic bone resorption and inhibited TRAP-positive cell formations in a dose-dependent manner. Only the D. japonicus extract demonstrated toxicity. Conclusions: This integrative study provides the current scientific names of the original species and proposes their use in the Korean Herbal Pharmacopoeia. Moreover, a reasonable molecular method for authenticating medicinal materials is suggested. Dipsacus japonicus shows promise as an additional origin species in the Korean Pharmacopoeia. However, processing methods that reduce toxicity must be discovered. Full article
(This article belongs to the Special Issue The Modes of Action of Herbal Medicines and Natural Products, 2nd Edition)
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Review

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31 pages, 4245 KB  
Review
Modulation of Macrophage Polarization by Traditional Chinese Medicine in HFpEF: A Review of Mechanisms and Therapeutic Potentials
by Chunqiu Liu, Jinfeng Yuan, Peipei Cheng, Tao Yang, Qian Liu, Tianshu Li, Chuyi Li, Huiyan Qu and Hua Zhou
Pharmaceuticals 2025, 18(9), 1317; https://doi.org/10.3390/ph18091317 - 2 Sep 2025
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Abstract
Heart failure with preserved ejection fraction (HFpEF) is a multifactorial cardiovascular disorder characterized by diastolic dysfunction, systemic inflammation, and myocardial fibrosis. Emerging evidence indicates that macrophage polarization imbalance plays a central role in HFpEF pathogenesis. Traditional Chinese medicine (TCM) has demonstrated therapeutic potential [...] Read more.
Heart failure with preserved ejection fraction (HFpEF) is a multifactorial cardiovascular disorder characterized by diastolic dysfunction, systemic inflammation, and myocardial fibrosis. Emerging evidence indicates that macrophage polarization imbalance plays a central role in HFpEF pathogenesis. Traditional Chinese medicine (TCM) has demonstrated therapeutic potential in modulating macrophage activity through pathways such as NO/cGMP/PKG, TGF-β/Smads, and PI3K/Akt, thereby exerting anti-inflammatory, antifibrotic, and antioxidant effects. In this review, we conducted a literature search in PubMed, Google Scholar, Web of Science, and CNKI for studies published up to May 2025, using the terms “HFpEF”, “Traditional Chinese Medicine”, and “macrophage”. A total of 19 relevant studies were included. We highlight representative TCM metabolites and TCM formulas, such as resveratrol, Qishen Yiqi Pill, Shenfu Injection, etc. And we summarize their mechanisms in regulating M1/M2 macrophage polarization. Finally, we identify current challenges, including limited HFpEF-specific models and insufficient mechanistic validation, and propose directions for future research. Full article
(This article belongs to the Special Issue The Modes of Action of Herbal Medicines and Natural Products, 2nd Edition)
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