Submit to Special Issue Submit Abstract to Special Issue Review for Pharmaceuticals Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Pharmacological Activities of Flavonoids and Their Analogues, Third Edition

Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

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

Deadline for manuscript submissions: 25 December 2026 | Viewed by 8999

Share This Special Issue

Special Issue Editors

Dr. Fernando Calzada

E-Mail Website
Guest Editor

Medical Research Unit in Pharmacology, Speciality Hospital, National Medical Center Siglo XXI, Av. Cuauhtémoc 330 Col Doctores, México City 06725, CP, Mexico
Interests: pharmacognosy of Mexican medicinal plants; diabetes mellitus; cancer; diarrhea; molecular docking; secondary metabolites
Special Issues, Collections and Topics in MDPI journals

Dr. Miguel Valdes

E-Mail Website
Guest Editor

Medical Research Unit in Pharmacology, Speciality Hospital, National Medical Center Siglo XXI, Av. Cuauhtémoc 330 Col Doctores, Mexico City CP 06725, Mexico
Interests: pharmacology; pharmacognosy; phytochemistry; medicinal plants; diabetes mellitus; cancer; diarrhea; drug development; isolation of natural compounds; terpenoids; flavonoids; molecular docking; molecular mechanism elucidation; pharmacological evaluation of natural compounds isolated from plants used in traditional Mexican medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The development of new drugs continues to be important for the health of global society. In recent years, there has been increased interest in the study of polyphenols due to the multiple pharmacological activities that they demonstrate. Flavonoids are a class of polyphenols that have been widely studied; they are characterized as having a 15-C skeleton with a 2-phenylbenzopyranone core structure. They are classified as flavones, isoflavones, flavonols, anthocyanidins, flavanones, flavanols, chalcones, and aurones. Within the various classes, further differentiation is possible based on the number and nature of substituent groups attached to the rings. Moreover, flavonoids can exist as free aglycones or conjugated glycosidic bonds. Flavonoids are present in almost all types of nourishment, and recent studies have focused on their biological, nutritional, pharmacological, and medicinal relevance. These kind of molecules and their analogues are of the utmost relevance due to their multiple applications. Considering the above, we invite researchers to publish their findings regarding the pharmacological applications of flavonoids and their analogs, while also highlighting the importance of using these molecules as a basis for the development of new drugs.

We look forward to your contributions.

Dr. Fernando Calzada
Dr. Miguel Valdes
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
polyphenols
flavonoids
medicinal chemistry
traditional medicine
flavonoids isolation
flavonoids identification
flavonoids pharmacology
flavonoids as prodrugs
in vivo, in vitro, and in silico studies
molecular modeling studies

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (8 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Other

22 pages, 19219 KB

Open AccessArticle

Total Flavonoids from Snow Chrysanthemum Exert Synergistic Vascular and Neuroprotective Effects in Hypertensive Vascular Dementia Rats

by Xinyan Wu, Kangmeng Sun, Xinyu Wang, Mengying Hu, Xinyuan Sun, Baoping Jiang, Yuhua Sun and Chunnian He

Pharmaceuticals 2026, 19(5), 700; https://doi.org/10.3390/ph19050700 - 29 Apr 2026

Viewed by 471

Abstract

Background/Objectives: Snow Chrysanthemum (Coreopsis tinctoria Nutt.), a traditional medicinal and edible plant rich in flavonoids (TFSC) with antihypertensive and neuroprotective activities, has unclear effects and mechanisms on vascular dementia (VaD) comorbid with hypertension, a key risk factor accelerating VaD. This study aimed to investigate TFSC’s ameliorative effects on cognitive impairment in hypertensive VaD rats and elucidate its holistic therapeutic mechanisms. Methods: Spontaneously hypertensive rats (SHRs) with unilateral common carotid artery ligation were used to establish the hypertensive VaD model. TFSC was intragastrically administered for 11 weeks. Systolic blood pressure (BP) and cerebral blood flow (CBF) were monitored; cognitive function was assessed via open field, novel object recognition and Morris water maze tests. Histopathological changes were evaluated by H&E and Nissl staining, serum oxidative stress and inflammatory markers were measured, and hippocampal transcriptome sequencing plus RT-qPCR was performed to identify key pathways and genes. Results: The chemical profile of TFSC was characterized, showing a total flavonoid content of 84.96%; 49 compounds were identified, 39 of which were flavonoids. TFSC reduced BP, improved CBF, alleviated cognitive dysfunction and neuronal damage, enhanced antioxidant capacity (increased SOD, CAT, GSH; decreased ROS), and exerted anti-inflammatory effects (reduced TNF-α, IL-1β, IL-6, Ang-II). It modulated multiple pathways, with the PI3K-Akt and MAPK pathways enriched, and validated key differentially expressed genes. Conclusions: This study provides preliminary evidence for the holistic therapeutic potential of TFSC against hypertensive VaD. With integrated vascular regulatory and neuroprotective effects, TFSC serves as a promising candidate for VaD by targeting both vascular risk factors and neuropathological damage. Full article

(This article belongs to the Special Issue Pharmacological Activities of Flavonoids and Their Analogues, Third Edition)

► Show Figures

Figure 1

16 pages, 7402 KB

Open AccessArticle

Diosmetin Alleviates MRSA-Induced Pneumonia in Mice by Inhibiting NLRP3 Inflammasome Activation and NF-κB Signaling Pathway

by Chenxi Wu, Huiguo Xie, Xiaofei Liang, Lujie Yang, Zhengxiao Ren, Ping Wu and Yingying Zhang

Pharmaceuticals 2026, 19(5), 674; https://doi.org/10.3390/ph19050674 - 25 Apr 2026

Viewed by 451

Abstract

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a major public health concern. It predominantly infects immunocompromised individuals and is frequently associated with severe pulmonary complications, including acute lung injury. Diosmetin, a natural flavonoid, known for its anti-inflammatory, antioxidant, and anti-infective properties. Nevertheless, its therapeutic mechanism in the treatment of acute pneumonia induced by MRSA remains unclear. Methods: In this study, we employed network pharmacology and molecular docking to elucidate the mechanisms underlying the therapeutic effect of diosmetin against MRSA-induced pneumonia. An MRSA pneumonia model was established in Balb/c mice. The impacts of diosmetin on murine pneumonia were evaluated by detecting biochemical indicators via HE staining, ELISA, RT-qPCR, and WB. In vitro experiments utilized RAW264.7 macrophages to establish an MRSA infection model for further validation of the therapeutic mechanisms of diosmetin. Results: In vivo results demonstrated that diosmetin alleviated MRSA-induced lung injury and reduced mortality by inhibiting the release of pro-inflammatory cytokines. Furthermore, compared with model mice, diosmetin-treated mice showed reduced phosphorylation levels of NLRP3, pro-caspase-1, ASC, and NF-κB p65, along with an increased level of IκBα in lung tissue. In vitro experiments indicated that diosmetin effectively reduced the levels of pro-inflammatory cytokines in MRSA-infected RAW264.7 macrophages and exerted anti-inflammatory effects by modulating the expression of NLRP3, pro-caspase-1, ASC, IκBα, and NF-κB p65. Conclusions: Our results demonstrate that diosmetin alleviates MRSA-induced pneumonia in mice, and this protective effect is achieved through dual inhibition of the NF-κB/NLRP3 inflammasome axis. Full article

(This article belongs to the Special Issue Pharmacological Activities of Flavonoids and Their Analogues, Third Edition)

► Show Figures

Figure 1

20 pages, 5022 KB

Open AccessArticle

Kaempferol-7-O-Glucoside Ameliorates Atopic Dermatitis via the TSLP-Mediated JAK2/STAT5 Signaling Axis

by Xingmei Lan, Jing Liu, Yijie Shi, Yonghua Zhou, Cheng Yang and Bingtian Zhao

Pharmaceuticals 2026, 19(4), 580; https://doi.org/10.3390/ph19040580 - 4 Apr 2026

Viewed by 607

Abstract

Background/Objectives: Thymic stromal lymphopoietin (TSLP) is central to the pathogenesis of atopic dermatitis (AD) and a promising therapeutic target. However, developing small-molecule TSLP inhibitors is challenging due to the difficulty in disrupting the TSLP-TSLPR interface. This study aimed to explore naturally sourced blockers of the TSLP-TSLPR interaction and identify novel candidate compounds for AD treatment. Methods: HuT78 cells were stimulated with PMA, ionomycin, and TSLP to establish an AD model. Inflammatory cytokines were measured by qRT-PCR and ELISA. JAK/STAT signaling was analyzed by Western blot. In female BALB/c mice, DNCB-induced AD-like skin lesions were topically treated with test compounds, followed by histopathological and immunohistochemical assessment. Results: Eight compounds were screened, and their key structural features were elucidated via structure–activity relationship (SAR) analysis. Among them, kaempferol-7-O-glucoside (K-7-G) emerged as the most potent candidate. It interfered with the TSLP-TSLPR interaction, selectively inhibited TSLP-mediated JAK2/STAT5 phosphorylation, and significantly downregulated IL-4 (p < 0.0001) and IL-13 (p < 0.001) levels. Topical application of 1% K-7-G significantly alleviated AD-like symptoms in a mouse model, decreasing dorsal skin thickness, dermatitis score, and scratching frequency while restoring the expression of filaggrin, loricrin, and occludin (p < 0.0001). Meanwhile, it significantly reduced key inflammatory mediators in a concentration-dependent manner, including TSLP, IL-4, IL-13, TNF-α, IFN-γ, and IgE. Conclusions: This study demonstrates that K-7-G is a novel natural TSLP inhibitor capable of blocking the TSLP-TSLPR signaling pathway and effectively improving AD symptoms. Further research may explore its therapeutic potential in other inflammatory diseases. Full article

(This article belongs to the Special Issue Pharmacological Activities of Flavonoids and Their Analogues, Third Edition)

► Show Figures

Graphical abstract

18 pages, 24132 KB

Open AccessArticle

Myricetin Inhibits Osteosarcoma Cell Viability and Modulates EMT-Related Genes Associated with the SNAI1/MMP-9 Axis

by Isabela Santos, Hélio M. T. Albuquerque, Marta Teixeira Pinto, Nuno Mendes, José Miguel P. Ferreira de Oliveira and Eduarda Fernandes

Pharmaceuticals 2026, 19(3), 499; https://doi.org/10.3390/ph19030499 - 18 Mar 2026

Viewed by 535

Abstract

Background/Objectives: Osteosarcoma treatment options remain limited due to tumor metastasis and the toxicity of conventional chemotherapy, warranting new therapeutic strategies. A well-founded strategy is the use of flavonoids, a class of phytochemicals possessing pharmaceutical properties that contribute to anticancer effects, including antioxidant and anti-inflammatory properties. This study aimed to evaluate the anticancer potential of flavonoids in osteosarcoma and investigate their interaction with doxorubicin. Methods: In this study, five flavonoids were screened for cytotoxicity and selectivity across four osteosarcoma cell lines and healthy fibroblasts (MRC-5). The interaction between myricetin and doxorubicin was assessed using a fixed-ratio combination approach. Cell migration and invasion were evaluated using cell exclusion/wound healing and 2D co-culture assays. EMT-related gene expressions were assessed by RT-qPCR. Antitumor activity was evaluated in vivo using a chick chorioallantoic membrane (CAM) xenograft model. Results: Myricetin emerged as the most selective compound, exhibiting cytotoxicity against osteosarcoma cells while sparing MRC-5 fibroblasts. Notably, myricetin synergized with doxorubicin (ratio 69:1), enhancing its cytotoxicity and significantly reducing osteosarcoma cell migration in vitro. Myricetin downregulated SNAI1 and MMP9, suggesting modulation of epithelial–mesenchymal transition (EMT)-related pathways. Complementarily, in the CAM xenograft model, myricetin reduced xenograft tumor size, confirming its anticancer activity in vivo. Conclusions: Collectively, these findings emphasize the anticancer potential of myricetin in osteosarcoma through inhibition of the SNAI1/MMP-9 signaling axis. Full article

(This article belongs to the Special Issue Pharmacological Activities of Flavonoids and Their Analogues, Third Edition)

► Show Figures

Figure 1

16 pages, 7586 KB

Open AccessArticle

Chemical Class–Driven Polyphenolic Profiles Shape In Vitro Regenerative Activity of Four Medicinal Plants Relevant to Burn Wound Healing

by Oana-Janina Roșca, Alexandra Mioc, Livia-Nicoleta Deveseleanu-Corici, Roxana Racoviceanu, Roxana Negrea-Ghiulai, Cristina Adriana Dehelean, Ersilia Alexa, Liliana Cseh and Codruta Soica

Pharmaceuticals 2026, 19(2), 245; https://doi.org/10.3390/ph19020245 - 30 Jan 2026

Viewed by 709

Abstract

Background: Burn wound repair is driven by oxidative balance and keratinocyte regeneration. Polyphenol-rich botanicals are considered promising due to combined antioxidant and pro-regenerative properties. This study compares four ethnopharmacologically relevant species—Boswellia serrata (BS), Sambucus nigra (SN), Ocimum basilicum (OB), and Galium verum (GV)—to determine how their polyphenolic class profiles relate to in vitro regenerative activity. Methods: Ethanolic (E—99.5%) and hydroalcoholic (H—70%) extracts were profiled by LC–MS, total polyphenol content (TPC), and DPPH assays. Biological effects were assessed in HaCaT keratinocytes using Alamar Blue (24/48 h) and scratch wound closure (24 h), and results were correlated with chemical profiles. Results: The H extract of OB (OB-H) and of GV (GV-H) had the highest TPC (62.6 and 63.9 mg GAE/g) and lowest DPPH IC₅₀ (18.7 and 17.1 μg/mL), aligning with the strongest biological responses—HaCaT viability up to 169.1% and wound closure up to 414%. SN extracts, dominated by rutin, promoted moderate migration with preserved viability, whereas BS produced modest viability gains. Conclusions: Polyphenolic composition—particularly the dominance of phenolic acids—correlates strongly with in vitro regenerative responses in HaCaT keratinocytes. O. basilicum and G. verum hydroalcoholic extracts displayed the most favorable profiles. Full article

(This article belongs to the Special Issue Pharmacological Activities of Flavonoids and Their Analogues, Third Edition)

► Show Figures

Graphical abstract

25 pages, 3468 KB

Open AccessArticle

Baicalin–Myricetin-Coated Selenium Nanoparticles Mitigate Pathology in an Aβ1-42 Mice Model of Alzheimer’s Disease

by Rosa Martha Pérez Gutiérrez, Julio Téllez Gómez, José María Mota Flores, Mónica Corea Téllez and Alethia Muñiz Ramírez

Pharmaceuticals 2025, 18(9), 1391; https://doi.org/10.3390/ph18091391 - 17 Sep 2025

Cited by 2 | Viewed by 1373

Abstract

Background: Current Alzheimer’s disease (AD) treatments primarily focus on symptom management and offer limited potential to arrest disease progression. To address this limitation, we developed baicalin–myricetin (BM) functionalized selenium nanoparticles (SeNPs), termed BMSe@BSA, aimed at multi-targeted neuroprotection. Materials and Methods: BMSe@BSA nanoparticles were synthesized via a gel–sol technique using bovine serum albumin (BSA), ascorbic acid, selenous acid, and BM. Interactions among BSA, BM, and SeNPs were characterized by microscopy and spectrometry. Cytotoxicity was assessed on RAW 264.7 and PC12 cells to determine biocompatibility. Neuroinflammation and cognitive function were evaluated in C57BL6/J mice challenged with Aβ1-42. Recognition memory was tested through open-field exploration, novel object recognition (NOR), and T-maze assays. Inflammatory markers (IL-1β and TNF-α) and microglial changes in the cerebral cortex were quantified, while amyloid fibril morphology was assessed using atomic force microscopy (AFM). Results: Spectroscopic analysis verified successful BM functionalization. Transmission electron microscopy revealed a spherical morphology with an average particle size of 90.57 nm, zeta potential of 27.2 mV, and a polydispersity index (PDI) of 0.270. BM entrapment efficiency reached approximately 90%. Cytotoxicity assays confirmed the nanoparticles’ safety, with no toxicity observed at concentrations up to 400 µg/mL after 4 h of incubation. BMSe@BSA effectively inhibited amyloid fibril formation, downregulated pro-inflammatory cytokine expression, preserved neuronal integrity, and significantly enhanced cognitive performance in AD mouse models. Conclusion: BMSe@BSA appear as a potential nanotherapeutic approach for targeted brain delivery and multi-pathway intervention in Alzheimer’s disease. Full article

(This article belongs to the Special Issue Pharmacological Activities of Flavonoids and Their Analogues, Third Edition)

► Show Figures

Figure 1

36 pages, 11682 KB

Open AccessArticle

Isoliquiritigenin as a Neuronal Radiation Mitigant: Mitigating Radiation-Induced Anhedonia Tendency Targeting Grik3/Grm8/Grin3a via Integrated Proteomics and AI-Driven Discovery

by Boyang Li, Suqian Cheng, Han Zhang and Bo Li

Pharmaceuticals 2025, 18(9), 1307; https://doi.org/10.3390/ph18091307 - 30 Aug 2025

Cited by 1 | Viewed by 1437

Abstract

Background/Objectives: Radiotherapy can cause severe and irreversible brain damage, including cognitive impairment, increased dementia risk, debilitating depression, and other neuropsychiatric disorders. Current radioprotective drugs face limitations, such as single-target inefficacy or manufacturing hurdles. Isoliquiritigenin (ISL), a natural flavonoid derived from licorice root, exhibits broad bioactivities. It exhibits anti-inflammatory, anti-cancer, immunoregulatory, hepatoprotective, and cardioprotective activities. This study aimed to elucidate ISL’s neuronal radiation mitigation effects and key targets. Methods: In vitro and in vivo models of radiation-induced neuronal injury were established. ISL’s bioactivities were evaluated through cellular cytotoxicity assays, LDH release, ROS, ATP, glutamate, and GSH levels. In vivo, ISL’s radiation mitigation effect was evaluated with sucrose preference test, IL-β level, histopathological analysis, and Golgi-Cox staining analysis. Proteomics, pathway enrichment, and ensemble models (four machine learning models, weighted gene co-expression network, protein–protein interaction) identified core targets. Molecular docking and dynamic simulations validated ISL’s binding stability with key targets. Results: ISL attenuated radiation-induced cellular cytotoxicity, reduced LDH/ROS, restored ATP, elevated GSH, and mitigated glutamate accumulation. In rats, ISL alleviated anhedonia-like phenotypes and hippocampal synaptic loss. ISL also significantly suppressed radiation-induced neuroinflammation, as evidenced by reduced levels of the pro-inflammatory cytokine IL-1β. Proteomic analysis revealed that ISL’s main protective pathways included the synaptic vesicle cycle, glutamatergic synapse, MAPK signaling pathway, SNARE interactions in vesicular transport, insulin signaling pathway, and insulin secretion. Grm8, Grik3, and Grin3a were identified as key targets using the integrated models. The expression of these targets was upregulated post-radiation and restored by ISL. Molecular docking and dynamic simulations indicated that ISL showed stable binding to these receptors compared to native ligands. Conclusions: ISL demonstrates multi-scale radiation mitigation activities in vitro and in vivo by modulating synaptic and inflammatory pathways, with glutamate receptors as core targets. This work nominates ISL as an important natural product for mitigating radiotherapy-induced neural damage. Full article

(This article belongs to the Special Issue Pharmacological Activities of Flavonoids and Their Analogues, Third Edition)

► Show Figures

Figure 1

Other

Jump to: Research

38 pages, 2064 KB

Open AccessSystematic Review

Humulus lupulus (Hop)-Derived Chemical Compounds Present Antiproliferative Activity on Various Cancer Cell Types: A Meta-Regression Based Panoramic Meta-Analysis

by Georgios Tsionkis, Elisavet M. Andronidou, Panagiota I. Kontou, Ioannis A. Tamposis, Konstantinos Tegopoulos, Panagiotis Pergantas, Maria E. Grigoriou, George Skavdis, Pantelis G. Bagos and Georgia G. Braliou

Pharmaceuticals 2025, 18(8), 1139; https://doi.org/10.3390/ph18081139 - 31 Jul 2025

Cited by 3 | Viewed by 2457

Abstract

Background/Objectives: Humulus lupulus (hops) are a perennial, dioecious plant widely cultivated for beer production, used for their distinguishing aroma and bitterness—traits that confer high added value status. Various hop-derived compounds have been reported to exhibit antioxidant, antimicrobial, antiproliferative and other bioactive effects. This systematic review and meta-analysis assesses the impact of hop compounds on the viability of diverse cancer cell lines. Methods: A comprehensive literature search was performed following PRISMA guidelines. Data were synthesized via multivariate meta-analysis and meta-regression, using IC₅₀ values as the effect size. Key variables included assay type (SRB, tetrazolium salt-based, crystal violet), exposure duration (24, 48, 72 h), specific hop compound and cancer cell line. Results: Of 622 articles identified, 61 met eligibility criteria, yielding 354 individual experiments. Meta-regression of xanthohumol (XN) IC₅₀ values across SRB, tetrazolium and crystal violet assays revealed no statistically significant differences at 24 h (p = 0.77), 48 h (p = 0.35) and 72 h (p = 0.70), supporting the interchangeability of the methods. Meta-analysis confirmed that hop constituents inhibit cancer cell proliferation; XN emerged as the most potent flavonoid (IC₅₀ = 16.89 μM at 72 h), while lupulone was the strongest compound overall (IC₅₀ = 5.00 μM at 72 h). Crude hop extracts demonstrated greater antiproliferative selectivity for cancer versus non-cancer cells (IC₅₀ = 35.23 vs. 43.80 μg/mL at 72 h). Conclusions: Hop compounds, and particularly bitter acids, demonstrate promising antiproliferative activity against cancer cells with comparatively low toxicity to healthy cells. Furthermore, our analysis confirms the comparability of SRB, tetrazolium-based and crystal violet assays, supporting the robust integration of antiproliferative data. Full article

(This article belongs to the Special Issue Pharmacological Activities of Flavonoids and Their Analogues, Third Edition)

► Show Figures

Journal Menu

Journal Browser

Pharmacological Activities of Flavonoids and Their Analogues, Third Edition

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (8 papers)

Research

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI