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Pharmaceuticals
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Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts
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Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts

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

Deadline for manuscript submissions: closed (30 June 2025) | Viewed by 10612

Special Issue Editor

Dr. Luis Apaza Ticona

E-Mail Website
Guest Editor
Organic Chemistry Unit, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, University Complutense of Madrid, Plza. Ramón y Cajal s/n, 28040 Madrid, Spain
Interests: phytomedicine; phytochemistry; natural products; drug discovery; organic and medicinal chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

I am pleased to inform you that I am organizing a Special Issue titled “Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts” for the journal Pharmaceuticals (ISSN: 1424-8247, https://www.mdpi.com/journal/pharmaceuticals). Given your distinguished expertise in this field, I warmly invite you to submit articles, short communications, or letters for this Special Issue.

Below is a brief introduction to the focus we are seeking for this Special Issue:

Inflammation is a physiological response triggered by various factors, such as pathogens or injuries. Additionally, environmental factors, including dietary choices, can contribute to lifestyle-related diseases, where chronic inflammation plays a crucial role. These diseases include cardiovascular conditions, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease, neurodegenerative disorders, and autoimmune diseases, among others.

Chronic inflammation often creates an environment conducive to oxidative stress, and vice versa. Oxidative stress results from an imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the body's antioxidant defenses. This imbalance, combined with the action of pro-inflammatory agents, can trigger harmful inflammatory processes.

The increasing prevalence of chronic inflammatory diseases over the recent decade has intensified the search for natural compounds that exhibit both antioxidant and anti-inflammatory properties. These compounds are being explored as potential safe and effective alternatives to conventional pharmaceuticals.

Natural product extracts stand out for their chemical diversity and therapeutic potential. For instance, phenolic compounds and flavonoids have shown effectiveness in modulating inflammatory pathways and neutralizing free radicals. Similarly, terpenoids and saponins have demonstrated the ability to inhibit key enzymes involved in inflammatory processes, such as cyclooxygenases and lipoxygenases. Additional compounds, such as alkaloids and glycosides, exhibit notable antioxidant and anti-inflammatory properties by influencing specific biological pathways and regulating cellular responses.

Furthermore, natural products targeting key pharmacological pathways, such as Interleukins (IL), NF-κB, TNF-α, Nrf2, HIF-1α, SOD, and Catalase, offer significant therapeutic promise. Some extracts can modulate IL levels, affecting cytokine production and inflammatory responses. Others may impact the NF-κB signaling pathway, which is crucial for regulating inflammatory genes. Compounds that activate Nrf2 enhance antioxidant defenses, while those affecting SOD and Catalase help reduce oxidative stress and inflammation.

Finally, the application of advanced screening techniques and OMIC technologies, including lipidomics, proteomics, genomics, and metabolomics, has enabled the identification of new natural compounds with significant antioxidant and anti-inflammatory properties. These technologies provide a deeper understanding of how these compounds interact with biological systems and how they can be optimized for therapeutic applications.

This field represents unexplored potential and is a rich source of opportunities for researchers interested in discovering and developing new therapies based on natural products. We invite you to contribute your research and findings to this exciting and promising area of science.

Dr. Luis Apaza Ticona
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

  • inflammation
  • oxidative stress
  • natural products
  • antioxidant properties
  • anti-inflammatory properties
  • omic technologies

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Published Papers (7 papers)

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Research

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22 pages, 2577 KiB  
Article
Characterization of the Compounds Present in Bougainvillea x buttiana (var. Rose) with Healing Activity in a Murine Model
by Luís Martínez-Cuevas, Mayra Cedillo-Cortezano, Blanca Nury Echeverria Guerrero, Rodolfo Abarca-Vargas and Vera L. Petricevich
Pharmaceuticals 2025, 18(5), 752; https://doi.org/10.3390/ph18050752 - 19 May 2025
Viewed by 712
Abstract
Background/Objective: Bougainvillea x buttiana of the Nyctagenaceae family is widely used in traditional Mexican medicine for treating different diseases. This study was planned to estimate the healing effect of the acetonic extract obtained from Bougainvillea x buttiana (var. Rose). Methods: The bracts [...] Read more.
Background/Objective: Bougainvillea x buttiana of the Nyctagenaceae family is widely used in traditional Mexican medicine for treating different diseases. This study was planned to estimate the healing effect of the acetonic extract obtained from Bougainvillea x buttiana (var. Rose). Methods: The bracts with flowers were subjected to extraction using maceration and concentrated in vacuo. Fractionation with a similar profile resulted in 11 fractions, which were determined using TLC. A mouse wound excision model was tested to evaluate the wound healing effect of the topical treatment pre-formulated with fractions of acetonic extract, which were determined using image analysis techniques. Cytokine levels present in the sera of mice treated or not treated with the acetonic extract were determined using the ELISA method. Results: The results obtained showed that the crude acetonic extract of B. x buttiana and/or its fractions in a pre-formulated hydrogel had wound healing capacity. The wound contraction rate and the healing speed in groups of animals treated with the pre-formulated crude extract and/or its fractions were significantly higher compared with the negative control (p < 0.001). Fraction 2 demonstrated more significant healing, reduced the production of cytokines such as IL-6 and TNF-α, and enhanced the levels of IL-10. Conclusion: The present study showed that the fractions obtained from the acetonic extract of B. x buttiana bracts were able to accelerate the wound healing process through anti-inflammatory mechanisms by regulating inflammatory cytokines. The results presented demonstrate that the extracts from B. x buttiana contain compounds that may be responsible for their healing properties. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts)
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21 pages, 2427 KiB  
Article
Neuroprotective Potential of Tetraselmis chuii Compounds: Insights into Blood–Brain Barrier Permeability and Intestinal Transport
by Melis Cokdinleyen, Alberto Valdés, Huseyin Kara, Elena Ibáñez and Alejandro Cifuentes
Pharmaceuticals 2025, 18(5), 629; https://doi.org/10.3390/ph18050629 - 26 Apr 2025
Viewed by 1004
Abstract
Background/Objectives: Alzheimer’s disease (AD) is the most common type of dementia, characterized by complex processes such as neuro-inflammation, oxidative damage, synaptic loss, and neuronal death. Carotenoids are among the potential therapeutic molecules that have attracted attention due to their neuroprotective properties, but their [...] Read more.
Background/Objectives: Alzheimer’s disease (AD) is the most common type of dementia, characterized by complex processes such as neuro-inflammation, oxidative damage, synaptic loss, and neuronal death. Carotenoids are among the potential therapeutic molecules that have attracted attention due to their neuroprotective properties, but their efficacy is limited mainly by their capacity to cross the blood–brain barrier (BBB). Results: The results showed that T. chuii extracts could protect neuronal cells from neurotoxic damage, especially against L-glutamate and H2O2. Moreover, the BBB permeability and the intestinal transport analyses revealed that fucoxanthinol, crocoxanthin, diatoxanthin, neoxanthin, violaxanthin, and prasinoxanthin have diverse permeabilities depending on the incubation time and the cell model used. Fucoxanthinol was the carotenoid with the highest and similar permeability in HBMEC cells (4.41%, 5.13%, and 18.94% at 2, 4, and 24 h, respectively) and Caco-2 cells (7.01%, 8.63%, and 18.36% at the same times), while crocoxanthin, diatoxanthin, and neoxanthin showed different kinetics. Methods: The neuroprotective potential of two extracts obtained from Tetraselmis chuii microalga were evaluated against Aβ1-42-, L-glutamate-, and H2O2-induced toxicities in SH-SY5Y cells. In addition, the BBB permeability and the intestinal transepithelial transport of the main carotenoids present in the extracts were evaluated and compared using two cell culture models, HBMEC and Caco-2 cells. For that aim, the transport of the bioactive molecules across the barriers was evaluated using UHPLC-q-TOF-MS after 2, 4, and 24 h of incubation. Conclusions: These findings indicate that T. chuii is a promising natural source of bioactive compounds to develop functional foods against neurodegenerative diseases. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts)
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17 pages, 2815 KiB  
Article
Clove (Syzygium aromaticum) Pods: Revealing Their Antioxidant Potential via GC-MS Analysis and Computational Insights
by Abdelmuhsin Abdegadir Abdelmuhsin, Abdel Moniem Elhadi Sulieman, Zakaria Ahmed Salih, Meshari Al-Azmi, Naimah Asid Alanaizi, Ahmed Eisa Goniem and Mohammad Jahoor Alam
Pharmaceuticals 2025, 18(4), 504; https://doi.org/10.3390/ph18040504 - 31 Mar 2025
Viewed by 1957
Abstract
Background: Syzygium aromaticum is a tree whose aromatic dried flower buds are known as cloves. When it comes to phenolic chemicals, such as flavonoids, hydroxybenzoic acids, hydroxycinnamic acids, and hydroxyphenyl propane, clove is a major plant source of these substances. Finding out [...] Read more.
Background: Syzygium aromaticum is a tree whose aromatic dried flower buds are known as cloves. When it comes to phenolic chemicals, such as flavonoids, hydroxybenzoic acids, hydroxycinnamic acids, and hydroxyphenyl propane, clove is a major plant source of these substances. Finding out how effective clove buds are as antioxidants was the driving force behind this study’s GC-MS investigation and computational discoveries. Methods: This inquiry into clove pods focused on the chemical composition of clove using the GC-MS technique, as well as its antioxidant qualities and computational modeling. Results: This antioxidant may be more effective in lower doses than ascorbic acid (A.A.), butylate hydroxytoluene (BHT), and β-carotene, with 57.22 ± 0.41 mg QE/g of total phenols and flavonoids and 7.25 ± 0.12 mg GAE/g of clove extract. Phenols destroy free radicals, which boosts antioxidant activity. Flavonoids defend against ROS, which also boosts antioxidant activity. Clove pod GC-MS analysis identified 21 components, of which eugenol accounted for 58.86%. The absence of nitrogen and chlorine molecules emphasizes the composition’s organic nature. Eugenol, the major component of clove oil, is a phenolic molecule that binds strongly to bacterial enzymes such as DNA gyrase and dihydrofolate reductase. Docking experiments have shown that clove chemicals interact with acetylcholinesterase, a crucial enzyme in insect larvae, paralyzing and killing them. Conclusions: This study demonstrates the immense potential of plants in providing novel therapeutic and environmental solutions. We must support further research into nature’s inherent benefits. The extensive knowledge that can be gained from botany can be used to improve health, ecology, and sustainability. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts)
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21 pages, 9529 KiB  
Article
The Effect of Ethanolic Extract of Brazilian Green Propolis and Artepillin C on Cytokine Secretion by Stage IV Glioma Cells Under Hypoxic and Normoxic Conditions
by Małgorzata Kłósek, Anna Kurek-Górecka, Radosław Balwierz, Grażyna Pietsz and Zenon P. Czuba
Pharmaceuticals 2025, 18(3), 389; https://doi.org/10.3390/ph18030389 - 9 Mar 2025
Cited by 1 | Viewed by 2476
Abstract
Background: The majority of gliomas are astrocytic in nature. Gliomas have the lowest survival rate among all tumors of the central nervous system (CNS), characterized by high aggressiveness and poor response to treatment. The tumor microenvironment is a source of cytokines such as [...] Read more.
Background: The majority of gliomas are astrocytic in nature. Gliomas have the lowest survival rate among all tumors of the central nervous system (CNS), characterized by high aggressiveness and poor response to treatment. The tumor microenvironment is a source of cytokines such as IL-6, IFN-γ, VEGF, and PDGF-BB, secreted mainly by tumor and immune cells. These cytokines play a significant role in angiogenesis, invasion, and metastasis formation. In vitro and in vivo studies have shown that Brazilian green propolis, derived from Baccharis dracunculifolia DC and rich in artepillin C, exhibits anti-inflammatory, antimicrobial, chemopreventive, and anticancer activities. Additionally, it can penetrate the blood–brain barrier, demonstrating neuroprotective effects. The aim of the present study was to determine the concentration of selected cytokines produced by astrocytes of the CCF-STTG1 cell line, isolated from the brain of a patient with stage IV glioma (astrocytoma). Methods: The cytotoxicity of the EEP-B was evaluated using the MTT assay. Astrocytes were stimulated with LPS at a final concentration of 200 ng/mL and/or IFN-α at 100 U/mL, followed by incubation with EEP-B (25–50 µg/mL) and artepillin C (25–50 µg/mL) under 2-h hypoxia and normoxia conditions. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine kit. Results: The absence of cytotoxic effects of EEP-B and artepillin C on human astrocytes of the CCF-STTG1 lineage was demonstrated. Stimulation with LPS, IFN-α, and their combination (LPS + IFN-α) significantly increased the secretion of the tested cytokines compared to the control cell line. The most pronounced and statistically significant reduction in cytokine levels, particularly IL-6 and VEGF, was observed following EEP-B treatment at both tested concentrations under both hypoxic and normoxic conditions. Conclusions: Brazilian green propolis may serve as a potential immunomodulator in combination therapies for gliomas of varying malignancy grades. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts)
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17 pages, 3757 KiB  
Article
Phytochemical Composition and Skin-Friendly Activities of the Ethyl Acetate Fraction in Ophioglossum vulgatum Linn., an In Vitro Study
by Sihan Feng, Zhiguang Huang, Yichen Cao, Zixuan Huang, Chen Xu, Yibo Zeng, Yuhang Xu, Lijian Zhu and Bin Ding
Pharmaceuticals 2025, 18(3), 345; https://doi.org/10.3390/ph18030345 - 27 Feb 2025
Viewed by 827
Abstract
Background: Ophioglossum vulgatum Linn. is a medical herb widely distributed in Southwest China. It has been used for the treatment of various diseases, including wounds or dermatitis, since ancient times, but little is known about its pharmacological and pharmaceutical chemistry. Methods: [...] Read more.
Background: Ophioglossum vulgatum Linn. is a medical herb widely distributed in Southwest China. It has been used for the treatment of various diseases, including wounds or dermatitis, since ancient times, but little is known about its pharmacological and pharmaceutical chemistry. Methods: The ethyl acetate fraction of O. vulgatum (OpvE) was prepared with the reflex extraction and fractional extraction method. Its components were detected and identified with the UPLC-Q/TOF-MS system and the SCIEX OS database. The related biological activities and the underlying mechanisms were predicted by computational analysis. HaCaT cells were treated with gradient concentrations of OpvE, and a CCK-8 assay was performed to determine the cell viability. The OpvE-pretreated HaCaT cells were exposed to H2O2 or LPS for antioxidative and anti-inflammatory assessment. DPPH, GSH, SOD, and MDA kits were used to evaluate oxidative stress. A serially diluted microbiota assay and a disc diffusion assay were used to evaluate anti-Staphylococcus aureus activities. The transcription of genes was semi-quantitatively studied by reversed real-time PCR. Protein levels were determined with western blotting. Results: The extract ratio of OpvE was 2.00 ± 0.12% (g/g). A total of 21 ingredients were identified. The computational analysis found that the PI3K/Akt signaling pathway might be a crucial target of OpvE. OpvE (7.5~125 μg/mL) stimulated HaCaT cell proliferation and migration by stimulating the over-expressed collagen type I alpha 1 Chain (COL1A1) and fibronectin 1 (FN1) and upregulating PI3K/AKT/GSK3-β signaling pathway. In the antioxidative assay test, 250 μg/mL OpvE scavenged obvious 97.28% DPPH-released free radicals. Pretreatment of OpvE inhibited H2O2-induced oxidative stress and protected against LPS-induced inflammatory injury by respectively regulating the Nrf2/HO-1/COX2 and TLR4/MYD88 signaling pathways. OpvE also showed anti-S. aureus properties with a MIC of 1.2 mg/mL, and with this concentration, OpvE produced an 8.3 ± 0.16 mm inhibition zone on a bacterial plate. Conclusions: This work highlighted the phytochemical character and some bioactivities, as well as the underline mechanism, which would support the further studies and application of O. vulgatum Linn. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts)
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18 pages, 10235 KiB  
Article
Oxidative Stress, Inflammation, and Altered Lymphocyte E-NTPDase Are Implicated in Acute Dyslipidemia in Rats: Protective Role of Arbutin
by Reem S. Alruhaimi, Omnia E. Hussein, Sulaiman M. Alnasser, Mousa O. Germoush, Meshal Alotaibi, Emad H. M. Hassanein, Mohamed El Mohtadi and Ayman M. Mahmoud
Pharmaceuticals 2024, 17(10), 1343; https://doi.org/10.3390/ph17101343 - 8 Oct 2024
Cited by 2 | Viewed by 1913
Abstract
Background/Objectives: Dyslipidemia is frequently linked to various disorders, and its clinical relevance is now recognized. The role of inflammation and oxidative stress (OS) in dyslipidemia has been acknowledged. This study assessed the potential of arbutin (ARB) to prevent dyslipidemia and its associated OS [...] Read more.
Background/Objectives: Dyslipidemia is frequently linked to various disorders, and its clinical relevance is now recognized. The role of inflammation and oxidative stress (OS) in dyslipidemia has been acknowledged. This study assessed the potential of arbutin (ARB) to prevent dyslipidemia and its associated OS and inflammation in rats with acute hyperlipidemia. Methods: Rats received ARB orally for 14 days and a single intraperitoneal injection of poloxamer-407 on day 15. Results: Poloxamer-407 elevated circulating cholesterol (CHOL), triglycerides (TG), very low-density lipoprotein (vLDL), and LDL, and reduced high-density lipoprotein (HDL)-C and lipoprotein lipase (LPL). ARB ameliorated the circulating lipids and LPL, and suppressed 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in rat liver and in vitro. Fatty acid synthase (FAS) in rat liver and its in vitro activity were suppressed by ARB, which also upregulated the LDL receptor (LDL-R) and ABCA1, and had no effect on ABCG5 and ABCG8 mRNA. ARB ameliorated liver malondialdehyde and nitric oxide and enhanced antioxidants in rats with dyslipidemia. Liver NF-κB p65 and blood inflammatory cytokines were increased in dyslipidemic rats, effects that were reversed by ARB. Moreover, ARB effectively suppressed lymphocyte E-NTPDase and E-ADA activities in dyslipidemic rats. The biochemical findings were supported by in silico data showing the affinity of ARB to bind LDL-R PCSK9 binding domain, HMGCR, FAS, and E-NTPDase. Conclusions: ARB possessed anti-dyslipidemia, anti-inflammatory, and antioxidant effects mediated via the modulation of CHOL and TG synthesis, LPL, lymphocyte E-NTPDase and E-ADA, and cytokine release in rats. Thus, ARB could be an effective agent to attenuate dyslipidemia and its associated OS and inflammation, pending further studies as well as clinical trials. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts)
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Review

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23 pages, 1148 KiB  
Review
Ferulic Acid as an Anti-Inflammatory Agent: Insights into Molecular Mechanisms, Pharmacokinetics and Applications
by Jiaying Liu, Yu Guan, Le Yang, Heng Fang, Hui Sun, Ye Sun, Guangli Yan, Ling Kong and Xijun Wang
Pharmaceuticals 2025, 18(6), 912; https://doi.org/10.3390/ph18060912 - 18 Jun 2025
Viewed by 938
Abstract
Ferulic acid (FA), a hydroxycinnamic acid derivative, is a key bioactive component in traditional medicinal plants including Angelica sinensis and Asafoetida. Accumulating evidence supports its therapeutic efficacy in inflammatory disorders, such as rheumatoid arthritis (RA) and ulcerative colitis (UC). FA exerts anti-inflammatory [...] Read more.
Ferulic acid (FA), a hydroxycinnamic acid derivative, is a key bioactive component in traditional medicinal plants including Angelica sinensis and Asafoetida. Accumulating evidence supports its therapeutic efficacy in inflammatory disorders, such as rheumatoid arthritis (RA) and ulcerative colitis (UC). FA exerts anti-inflammatory effects through (1) the regulation of inflammatory cytokine levels; (2) modulation of signaling pathways such as nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and janus kinase/signal transducer and activator of transcription (JAK/STAT); (3) amelioration of oxidative stress; and (4) regulation of immune cell homeostasis. At the pharmacokinetic level, studies show that FA is rapidly absorbed but exhibits low bioavailability, mainly due to the influence of metabolic pathways and food matrix characteristics. This review systematically summarizes the literature on the anti-inflammatory effects of FA, covering molecular mechanisms, pharmacokinetic characteristics, and application scenarios. Preclinical studies show that FA has low toxicity and good safety, demonstrating potential for development as a novel anti-inflammatory drug. However, its clinical translation is hindered by bottlenecks such as low bioavailability and insufficient human clinical data. Future research should prioritize developing novel drug delivery systems and conducting large-scale clinical trials to facilitate its clinical translation. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Effects of Natural Product Extracts)
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