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Pharmaceuticals
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Advances in Smooth Muscle Pharmacology
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Advances in Smooth Muscle Pharmacology

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

Deadline for manuscript submissions: 30 June 2026 | Viewed by 4577

Special Issue Editors

Dr. Beata Modzelewska

E-Mail Website
Guest Editor
Department of Biophysics, Medical University of Bialystok, 15-089 Bialystok, Poland
Interests: smooth muscles; gastric motility; uterine contractions; potassium channels; nitric oxide; polyphenols; quercetin; resveratrol; beta-adrenoceptor
Dr. Tomasz Kleszczewski

E-Mail Website
Guest Editor
Department of Biophysics, Medical University of Bialystok, 15-089 Bialystok, Poland
Interests: smooth muscles; gastric motility; uterine contractions; potassium channels; polyphenols
Dr. Jacek Kapała

E-Mail Website
Guest Editor
Department of Biophysics, Medical University of Bialystok, 15-089 Bialystok, Poland
Interests: smooth muscles; bisphenols; air pollution; environmental monitoring; soil radioactivity

Special Issue Information

Dear Colleagues,

Smooth muscle tissue is essential for regulating a wide range of physiological processes, including vascular tone regulation, gastrointestinal motility, airway constriction, and urogenital functions. Dysfunctions in smooth muscle contribute to significant clinical conditions such as hypertension, aneurysms, coronary artery spasms, asthma, irritable bowel syndrome, gastroparesis, urinary incontinence, erectile dysfunction, dysmenorrhea, or infertility.

This Special Issue entitled "Advances in Smooth Muscle Pharmacology" aims to highlight cutting-edge research in smooth muscle pharmacology, focusing on novel signaling pathways, receptor–ligand interactions, ion channel regulation, and the development of new therapeutic agents. Emphasis is also placed on translational approaches that bridge basic research with clinical applications, providing insights into how innovative pharmacological strategies can address unmet medical needs.

The Special Issue explores the recent breakthroughs in studying smooth muscle function, regulation, and therapeutic targeting. By bringing together interdisciplinary contributions from molecular biology, biophysics, and pharmacology, this Special Issue seeks to advance our understanding of smooth muscle pathophysiology and stimulate the development of targeted therapies.

Dr. Beata Modzelewska
Dr. Tomasz Kleszczewski
Dr. Jacek Kapała
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

  • smooth muscle regulation
  • pharmacological interventions
  • ion channel modulation
  • receptor–ligand dynamics
  • therapeutic drug development
  • vascular tone regulation
  • smooth muscle disorders
  • translational pharmacology
  • cellular signaling pathways
  • pathophysiology

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Published Papers (4 papers)

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Research

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28 pages, 31042 KB  
Article
Danggui Buxue Decoction and Its Active Constituents Inhibit Drug-Induced Uterine Contractions via L-Type Calcium Channels and the IP3/Ca2+ Pathway
by Mingming Liu, Taiping He, Wenqiao An, Pengmei Guo, Tang Zhou, Yufei Chen, Xiaojuan Tian, Mingxu Wu, Ting Zhang and Sanyin Zhang
Pharmaceuticals 2026, 19(3), 520; https://doi.org/10.3390/ph19030520 - 23 Mar 2026
Viewed by 672
Abstract
Background/Objectives: Primary dysmenorrhea is a common gynecological disorder characterized by painful uterine contractions. Danggui Buxue Decoction (DBD) is used to treat menstrual irregularities, but its mechanism in primary dysmenorrhea remains unclear. This study investigated the efficacy of DBD against dysmenorrhea and its [...] Read more.
Background/Objectives: Primary dysmenorrhea is a common gynecological disorder characterized by painful uterine contractions. Danggui Buxue Decoction (DBD) is used to treat menstrual irregularities, but its mechanism in primary dysmenorrhea remains unclear. This study investigated the efficacy of DBD against dysmenorrhea and its calcium signaling-related mechanism. Methods: DBD components were analyzed by UPLC–Orbitrap MS. Isolated uterine muscle strips precontracted with oxytocin (OT, 50 ng/mL) or KCl (60 mM) were used to assess the effects of DBD and its active compounds (Quercetin, Formononetin, Ononin, Ferulic acid, Senkyunolide I, Calycosin, Ligustilide, Calycosin-7-O-β-D-glucoside). Ca2+-dependent experiments, intracellular calcium release assays, and inhibitor treatments (Nifedipine, 2-APB) were performed to evaluate the involvement of L-type calcium channels and the IP3R pathway. A primary dysmenorrhea model induced by estradiol benzoate and oxytocin was used to assess the analgesic effects, histopathology, inflammatory factors, and IP3/Ca2+-related proteins and genes following DBD and Quercetin treatment. Results: A total of 161 compounds were identified in DBD. DBD and its eight active constituents relaxed OT (50 ng/mL) or KCl (60 mM)-induced uterine contractions, with Quercetin, Calycosin, and Ligustilide showing particularly prominent relaxant activity. These three compounds suppressed extracellular calcium influx and intracellular calcium release through the blockade of L-type calcium channels and IP3R. In vivo, DBD and Quercetin alleviated pain, reduced inflammation, and decreased uterine Ca2+ and IP3 levels in dysmenorrhea mice. Conclusions: DBD and its active component Quercetin promote uterine relaxation by lowering Ca2+ levels, which is achieved through suppression of L-type calcium channels and the IP3/Ca2+ pathway. This contributes to their therapeutic action against primary dysmenorrhea. Full article
(This article belongs to the Special Issue Advances in Smooth Muscle Pharmacology)
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16 pages, 2325 KB  
Article
ACE Inhibitors Boost Mobility and Muscle Strength by Reducing Intestinal Permeability in Older Adults with Alzheimer’s Disease
by Rizwan Qaisar, Asima Karim, M. Shahid Iqbal, Firdos Ahmad, Khalid Saeed and Shaea A. Alkahtani
Pharmaceuticals 2026, 19(2), 304; https://doi.org/10.3390/ph19020304 - 12 Feb 2026
Viewed by 779
Abstract
Objectives: Hypertension is common in Alzheimer’s disease (AD) and contributes to functional decline. While ACE inhibitors are widely used for hypertension, their systemic effects on intestinal permeability and physical capacity in AD patients remain unclear. Materials and Methods: We investigated the potential contribution [...] Read more.
Objectives: Hypertension is common in Alzheimer’s disease (AD) and contributes to functional decline. While ACE inhibitors are widely used for hypertension, their systemic effects on intestinal permeability and physical capacity in AD patients remain unclear. Materials and Methods: We investigated the potential contribution of increased intestinal permeability to handgrip strength (HGS) and physical capacity in patients with Alzheimer’s disease (AD) taking ACE inhibitors. We investigated hypertensive AD patients taking ACE inhibitors (n = 55) or other anti-hypertensive medications (n = 57) at baseline and one year later, along with age-matched controls (n = 64) and normotensive AD patients (n = 61). We measured plasma zonulin, a marker of intestinal permeability, and HGS, and performed the short physical performance battery (SPPB). Results: AD patients had lower HGS, gait speed, SPPB, and higher plasma zonulin than controls at baseline (all p < 0.05). The use of ACE inhibitors was associated with increased HGS and gait speed, and reduced plasma zonulin in AD patients. Conversely, AD patients on other anti-hypertensive medications had higher zonulin and lower HGS but no change in gait speed and SPPB after one year. The patients taking ACE inhibitors also exhibited significant dynamic correlations of zonulin with HGS, gait speed, and SPPB (p < 0.05). ACE inhibitors also reduced plasma C-reactive proteins and 8-isoprostanes as markers of oxidative stress and inflammation. Conclusions: ACE inhibitors may improve physical performance and cognitive function in hypertensive AD patients, primarily through vascular smooth muscle modulation, leading to better perfusion. These effects may indirectly support intestinal barrier and muscle function, highlighting a novel gut–vascular–muscle interface relevant to therapeutic strategies. Full article
(This article belongs to the Special Issue Advances in Smooth Muscle Pharmacology)
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Review

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16 pages, 837 KB  
Review
K2P Channels as Key Regulators of Cardiovascular and Pulmonary Vascular Function
by Hala Y. Abdelnasser, Xinchun Pi, Lavannya M. Pandit and Bradley K. McConnell
Pharmaceuticals 2026, 19(4), 533; https://doi.org/10.3390/ph19040533 - 25 Mar 2026
Viewed by 539
Abstract
Two-pore domain potassium (K2P) channels are the most recently identified family of potassium channels. They are regarded as the largest group of background “leak” channels, encoded by 15 mammalian KCNK genes, and divided into six subfamilies (TWIK, TREK, TASK, TALK, THIK, [...] Read more.
Two-pore domain potassium (K2P) channels are the most recently identified family of potassium channels. They are regarded as the largest group of background “leak” channels, encoded by 15 mammalian KCNK genes, and divided into six subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). These channels have a role in stabilizing the resting membrane potential. Their widespread presence in the heart and vasculature supports cellular homeostasis by regulating cardiac rhythm, vascular tone, and protection against ischemic stress. The TASK, TWIK, and TREK subfamilies are the most abundantly expressed K2P channel subfamilies in the cardiovascular system, and dysregulation of specific members has been strongly linked to the development of major cardiovascular diseases. Mutations in TASK-1 have been identified in patients with pulmonary arterial hypertension, providing human genetic evidence linking K2P dysfunction to pulmonary vascular disease. While alterations in other K2P channels, such as TREK-1, have been demonstrated in preclinical studies where reduced channel activity is associated with ischemia–reperfusion injury and promotes cardiac arrhythmias. Growing evidence suggests that K2P channels could serve as promising therapeutic targets, with pharmacological activation of TASK-1 and TREK-1, for instance, that might help restore vascular tone, reduce remodeling, and offer cardioprotection. Their unique leak-channel properties enable the development of highly selective treatments. This review addresses the molecular biology, physiological roles, and disease relevance of K2P channels in the cardiovascular and pulmonary systems, emphasizing their potential as targets for innovative therapies in cardiovascular diseases. Full article
(This article belongs to the Special Issue Advances in Smooth Muscle Pharmacology)
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30 pages, 2981 KB  
Review
Polyphenols as Modulators of Gastrointestinal Motility: Mechanistic Insights from Multi-Model Studies
by Andrzej Chomentowski, Krzysztof Drygalski, Tomasz Kleszczewski, Marta Berczyńska, Marzena Tylicka, Jacek Kapała, Agnieszka Raciborska, Przemysław Zubrzycki, Hady Razak Hady and Beata Modzelewska
Pharmaceuticals 2025, 18(10), 1564; https://doi.org/10.3390/ph18101564 - 16 Oct 2025
Cited by 4 | Viewed by 2054
Abstract
Dietary polyphenols are recognized as crucial modulators of gastrointestinal motility, holding therapeutic promise for conditions like irritable bowel syndrome, postoperative ileus, and functional dyspepsia. However, their reported effects are heterogeneous, ranging from spasmolytic to prokinetic. This review aims to clarify these inconsistencies by [...] Read more.
Dietary polyphenols are recognized as crucial modulators of gastrointestinal motility, holding therapeutic promise for conditions like irritable bowel syndrome, postoperative ileus, and functional dyspepsia. However, their reported effects are heterogeneous, ranging from spasmolytic to prokinetic. This review aims to clarify these inconsistencies by synthesizing experimental evidence on structure–activity relationships and underlying mechanisms. Relevant publications were identified in PubMed and Google Scholar using terms related to polyphenols and gastrointestinal motility. References were selected for relevance, and the narrative review integrates findings from in vitro, ex vivo, in vivo, and clinical studies. Across various experimental models, polyphenols function as multi-target modulators of gastrointestinal smooth muscle. The primary mechanisms identified involve the blockade of voltage-dependent L-type Ca2+ channels, activation of K+ channels (BK, KATP), and modulation of the NO/cGMP and cAMP/PKA pathways. Flavones and multiple flavonols consistently demonstrate spasmolytic activity via Ca2+ channel antagonism. In contrast, flavanones engage BK and KATP channels to induce membrane hyperpolarization. Complex extracts from plants like ginger and turmeric exhibit mixed pro- or antimotility effects, reflecting the diverse profiles of their constituent compounds. While robust ex vivo pharmacology and some in vivo and human data exist, a high degree of dataset heterogeneity and inconsistent reporting impedes direct translational efforts. Polyphenols are promising multi-mechanistic modulators of gastrointestinal motility with clear structure–activity patterns. To advance their clinical application, future research must focus on establishing standardized in vivo pharmacokinetics, conducting targeted structure–activity studies, employing bioassay-guided fractionation, and designing rigorous clinical trials. Full article
(This article belongs to the Special Issue Advances in Smooth Muscle Pharmacology)
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