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A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: 5 May 2025 | Viewed by 13620

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Dr. Rita Kiss

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Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Interests: pharmacology; CV system; neurodegenerative disorders; diabetes mellitus; retinopathy; herbals; antioxidants; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Annamária Pallag

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Faculty of Medicine and Pharmacy, University of Oradea, Piata 1 Decembrie, 410028 Oradea, Romania
Interests: pharmacology; herbals; plant extracts; polyphenols; SIRT1; antioxidants; oxidative stress; apoptosis

Special Issue Information

Dear Colleagues,

Plants have been integral to healing practices since ancient times, and their significance persists in contemporary drug development and modern medicine. According to surveys conducted by the World Health Organization (WHO), a substantial 80% of the global population continues to rely on plants or plant-derived preparations. Within plants and plant extracts, a plethora of beneficial active ingredients exists, offering a wide array of biomedical applications owing to their structural and biological diversity. Remarkably, only a small fraction—roughly 10–15%—of these plant-based compounds have undergone comprehensive chemical examination. This implies a vast reservoir of untapped potential for the medical and pharmaceutical utilization of plants. In the present era, advanced techniques in molecular biology, chemistry, and pharmaceutical technology play crucial roles in uncovering novel therapeutically active biomolecules and in broadening their biomedical applications. We believe that plants and natural compounds represent a significant and unique resource for humanity, particularly from a medicinal standpoint. The ongoing research of plant-based compounds holds the promise of unlocking further breakthroughs in the medical and pharmaceutical field. Considering the significance of plants as an unparalleled resource for medicinal purposes, our Special Issue aims to disseminate research findings that focus on exploring and utilizing newly discovered therapeutically active substances within the scientific community.

Dr. Rita Kiss
Prof. Dr. Annamária Pallag
Guest Editors

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Keywords

herbals
plant extracts
polyphenols
anthocyanins
isolation
characterization
preparation
oxidative stress
apoptosis
inflammation
dermatitis
CNS
new target molecules

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Published Papers (11 papers)

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29 pages, 6571 KiB

Open AccessArticle

Clitoria ternatea L. (Butterfly Pea) Flower Against Endometrial Pain: Integrating Preliminary In Vivo and In Vitro Experimentations Supported by Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Studies

by Najneen Ahmed, Nazifa Tabassum, Parisa Tamannur Rashid, Basrat Jahan Deea, Fahmida Tasnim Richi, Anshuman Chandra, Shilpi Agarwal, Saima Mollick, Kaushik Zaman Dipto, Sadia Afrin Mim and Safaet Alam

Life 2024, 14(11), 1473; https://doi.org/10.3390/life14111473 - 13 Nov 2024

Viewed by 729

Abstract

Clitoria ternatea L. (CT) is a perennial herbaceous plant with deep blue flowers native to tropical Asia. This work explores the endometrial pain (EP) regulation of CT flower through a multifaceted approach. Phytochemical screening unveiled the presence of alkaloids, steroids, flavonoids, glycosides, and tannins in CT flower methanolic extract (ME). In the in vitro membrane stabilizing experiment, the ME demonstrated 91.47% suppression of heat-induced hemolysis. Upon carrageenan-induced paw edema assay conducted on male Swiss albino mice at doses of 200 mg/kg and 400 mg/kg, 65.28% and 81.89% inhibition rates, respectively, of paw edema were reported. For the same doses, upon acetic acid-induced-writhing assay, 75.6% and 76.78% inhibition rates, respectively, were observed. For network pharmacology analyses, a protein–protein interaction network was constructed for 92 overlapping gene targets of CT and EP, followed by GO and KEGG pathway enrichment analyses. Network pharmacology-based investigation identified the anti-EP activity of CT to be mostly regulated by the proteins SRC homology, ESR1, and PI3KR1. Physicochemical, pharmacokinetic, and toxicity property predictions for the compounds with stable ligand–target interactions and a molecular dynamics simulation for the highest interacting complex further validated these findings. This work affirmed the anti-EP role of CT flower against EP, suggesting a probable molecular mechanism involved. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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23 pages, 2602 KiB

Open AccessArticle

Assessing the Optimal Antibacterial Action of Lavandula stoechas L., Thymus zygis L., and Eucalyptus camaldulensis Dehnh Essential Oils

by Farah Aabouch, Saoussan Annemer, Badr Satrani, Ismail Ettaleb, Mohammed Kara, Mohamed Ghanmi, Abdelaaty Abdelaziz Shahat, Ravish Choudhary, Abdellah Farah, Mohamed Ouajdi and Jamila Dahmani

Life 2024, 14(11), 1424; https://doi.org/10.3390/life14111424 - 5 Nov 2024

Viewed by 527

Abstract

The use of combined essential oils (EOs) is a new technique that can improve their preservative effects while minimizing their sensory impact in foods. The aim of this study was to determine the chemical profile of three essential oils (EOs) extracted from Lavandula stoechas L. (Ls), Thymus zygis L. (Tz), and Eucalyptus camaldulensis Dehnh (Ec) and to evaluate their synergistic antibacterial activity for optimal inhibition against Bacillus subtilis, Escherichia coli, and Staphylococcus aureus using an augmented Simplex centroid mixing scheme. The essential oils were extracted by hydrodistillation and analyzed via gas chromatography–mass spectrometry. Anti-bacterial potency was evaluated by disk diffusion. Chemical analysis revealed the main compounds in Lavandula stoechas (Ls) essential oil: camphor (36.15%), followed by fenchone (16.57%) and Z-8-hydroxy linalool (8.28%). The Thymus zygis (Tz) essential oil is dominated by δ-terpineol (27.64%), δ-3-carene (15.7%), and thymol (14.17%). In contrast, the Eucalyptus camaldulensis (Ec) essential oil contains mainly 1,8-cineole (43.61%), γ-terpinene (11.71%), and α-terpineol (10.58%). The optimal mixture is the binary association of 40% E. camaldulensis EO and 60% T. zygis EO, which provides an effective inhibition diameter (ID) of 13.37 mm to inhibit S. aureus. Furthermore, the formulation of 27% and 73% EOs of E. camaldulensis and T. zygis, respectively, corresponds to the mixture required to achieve the optimum inhibition diameter (ID = 11.55 mm) against E. coli. In addition, the mixture of 29% EO of E. camaldulensis and 71% EO of T. zygis is the optimum mixture to inhibit B. subtilis, with an inhibition diameter of 12.31 mm. These findings highlight the potency of antibacterial formulations of these essential oils and suggest that they might be used as substitutes for conventional drugs to prevent the development of bacteria responsible for serious infections and food spoilage. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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16 pages, 2953 KiB

Open AccessArticle

Effects of Drying Methods on the Phytochemical Contents, Antioxidant Properties, and Anti-Diabetic Activity of Nasturtium officinale R.Br. (Betong Watercress) from Southern Thailand

by Praporn Kijkuokool, Irina Stepanov, Sakaewan Ounjaijean, Pimpisid Koonyosying, Kittipan Rerkasem, Hataichanok Chuljerm, Wason Parklak and Kanokwan Kulprachakarn

Life 2024, 14(9), 1204; https://doi.org/10.3390/life14091204 - 23 Sep 2024

Viewed by 1530

Abstract

Nasturtium officinale R.Br. (Betong watercress) contains high levels of secondary metabolites that offer health benefits. However, fresh-cut watercress has a short shelf life. This study aimed to assess the effect of drying methods on the phytochemical contents, antioxidant activity, and anti-diabetic activity of Betong watercress. The watercress was dried using three methods: roasting (R, 50 °C, 40 min); roasting and drying (RD, 40 min roasting at 50 °C and 1 h drying at 80 °C); and blanching, roasting, and drying (BRD, 30 s blanching at 80 °C, 20 min roasting at 50 °C, and 1 h drying at 80 °C). Aqueous extracts from each drying method were analyzed for total phenolic content, total flavonoid content, total glucosinolate content, antioxidant activities (FRAP, DPPH, and ABTS assays), and α-amylase enzyme inhibition. From the results, the R method provided the highest level of total phenolic, total flavonoid, and total glucosionolate content compared to the RD and BRD methods. Similarly, antioxidant activities and α-amylase enzyme inhibition were highest in the R method, followed by the RD and BRD methods. Our results demonstrate that roasting of Betong watercress without the addition of blanching or drying effectively preserves the phytochemical contents, antioxidant activities, and anti-diabetic activity. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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13 pages, 2091 KiB

Open AccessArticle

From Nature to Treatment: The Impact of Pterostilbene on Mitigating Retinal Ischemia–Reperfusion Damage by Reducing Oxidative Stress, Inflammation, and Apoptosis

by Beáta Pelles-Taskó, Réka Szekeres, Barbara Takács, Anna Szilágyi, Dóra Ujvárosy, Mariann Bombicz, Dániel Priksz, Balázs Varga, Rudolf Gesztelyi, Zoltán Szabó, Zoltán Szilvássy and Béla Juhász

Life 2024, 14(9), 1148; https://doi.org/10.3390/life14091148 - 11 Sep 2024

Viewed by 754

Abstract

Retinal ischemia–reperfusion (I/R) injury is a critical pathogenic mechanism in various eye diseases, and an effective therapeutic strategy remains unresolved. Natural derivatives have recently reemerged; therefore, in our present study, we examined the potential therapeutic effects of a stilbenoid that is chemically related to resveratrol. Pterostilbene, recognized for its anti-inflammatory, anti-carcinogenic, anti-diabetic, and neuroprotective properties, counteracts oxidative stress during I/R injury through various mechanisms. This study explored pterostilbene as a retinoprotective agent. Male Sprague Dawley rats underwent retinal I/R injury and one-week reperfusion and were treated with either vehicle or pterostilbene. After this functional electroretinographical (ERG) measurement, Western blot and histological analyses were performed. Pterostilbene treatment significantly improved retinal function, as evidenced by increased b-wave amplitude on ERG. Histological studies showed reduced retinal thinning and preserved the retinal structure in the pterostilbene-treated groups. Moreover, Western blot analysis revealed a decreased expression of glial fibrillary acidic protein (GFAP) and heat shock protein 70 (HSP70), indicating reduced glial activation and cellular stress. Additionally, the expression of pro-apoptotic and inflammatory markers, poly(ADP-ribose) polymerase 1 (PARP1) and nuclear factor kappa B (NFκB) was significantly reduced in the pterostilbene-treated group. These findings suggest that pterostilbene offers protective effects on the retina by diminishing oxidative stress, inflammation, and apoptosis, thus preserving retinal function and structure following I/R injury. This study underscores pterostilbene’s potential as a neuroprotective therapeutic agent for treating retinal ischemic injury and related disorders. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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19 pages, 2230 KiB

Open AccessArticle

Evaluation of the Interaction between Carvacrol and Thymol, Major Compounds of Ptychotis verticillata Essential Oil: Antioxidant, Anti-Inflammatory and Anticancer Activities against Breast Cancer Lines

by Mohamed Taibi, Amine Elbouzidi, Mounir Haddou, Abdellah Baraich, Douaae Ou-Yahia, Reda Bellaouchi, Ramzi A. Mothana, Hanan M. Al-Yousef, Abdeslam Asehraou, Mohamed Addi, Bouchra El Guerrouj and Khalid Chaabane

Life 2024, 14(8), 1037; https://doi.org/10.3390/life14081037 - 20 Aug 2024

Cited by 2 | Viewed by 1194

Abstract

The objective of this study was to evaluate the antioxidant, anti-inflammatory, and anticancer properties of thymol, carvacrol, and their equimolar mixture. Antioxidant activities were assessed using the DPPH, ABTS, and ORAC methods. The thymol/carvacrol mixture exhibited significant synergism, surpassing the individual compounds and ascorbic acid in DPPH (IC₅₀ = 43.82 ± 2.41 µg/mL) and ABTS (IC₅₀ = 23.29 ± 0.71 µg/mL) assays. Anti-inflammatory activity was evaluated by inhibiting the 5-LOX, COX-1, and COX-2 enzymes. The equimolar mixture showed the strongest inhibition of 5-LOX (IC₅₀ = 8.46 ± 0.92 µg/mL) and substantial inhibition of COX-1 (IC₅₀ = 15.23 ± 2.34 µg/mL) and COX-2 (IC50 = 14.53 ± 2.42 µg/mL), indicating a synergistic effect. Anticancer activity was tested on MCF-7, MDA-MB-231, and MDA-MB-436 breast cancer cell lines using the MTT assay. The thymol/carvacrol mixture demonstrated superior cytotoxicity (IC₅₀ = 0.92–1.70 µg/mL) and increased selectivity compared to cisplatin, with high selectivity indices (144.88–267.71). These results underscore the promising therapeutic potential of the thymol/carvacrol combination, particularly for its synergistic antioxidant, anti-inflammatory, and anticancer properties against breast cancer. This study paves the way for developing natural therapies against breast cancer and other conditions associated with oxidative stress and inflammation, leveraging the synergistic effects of natural compounds like thymol and carvacrol. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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12 pages, 2403 KiB

Open AccessArticle

Rosmarinic Acid Potentiates Cytotoxicity of Cisplatin against Colorectal Cancer Cells by Enhancing Apoptotic and Ferroptosis

by Jhen-Yu Huang, Ta-Wen Hsu, Yu-Ru Chen and Shao-Hsuan Kao

Life 2024, 14(8), 1017; https://doi.org/10.3390/life14081017 - 15 Aug 2024

Viewed by 738

Abstract

Rosmarinic acid (RA) has demonstrated anticancer effects on several types of malignancies. However, whether RA promotes the anticancer effect of cisplatin on colorectal cancer cells remains sketchy. This study aimed to explore whether RA potentiates the cytotoxicity of cisplatin against colon cancer cells and the underlying mechanism. Cell viability, cell cycle progression, and apoptosis was evaluated using sulforhodamine B (SRB) assay, flow cytometric analysis, and propidium iodide/Annexin V staining, respectively. Western blotting was utilized to analyze signaling pathways. Our findings showed that RA significantly enhanced the inhibitory effect on cell viability and the induction of apoptosis on the colon cancer cell lines DLD-1 and LoVo. Signaling cascade analysis revealed that the combination of RA and cisplatin jointly induced Bax and caspase activation while downregulating Bcl-2, glutathione peroxidase 4 (GPX4), and SLC7A11 in DLD-1 cells. Moreover, caspase inhibitor and ferroptosis inhibitor significantly reversed the inhibition of cell viability in response to RA combined with cisplatin. Collectively, these findings demonstrate that RA enhances the cytotoxicity of cisplatin against colon cancer cells, attributing to the promotion of apoptosis and ferroptosis. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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17 pages, 4559 KiB

Open AccessArticle

Wound Healing Potential of a Novel Sedum Species: S. album Murales

by Francesca Truzzi, Elettra Frassineti, Camilla Tibaldi, Eros D’Amen and Giovanni Dinelli

Life 2024, 14(8), 958; https://doi.org/10.3390/life14080958 - 30 Jul 2024

Viewed by 777

Abstract

Natural wound healing products are in increased demand. The potential for unexplored Sedum species in wound healing was discovered based on benefits of the genus reported in traditional medicine. The objectives were to screen ten Sedum species for wound healing, to ascertain the optimal harvest period using the five best, and finally to investigate effects of extraction protocols on wound healing using the most promising species. Different protocols were used to extract leaf polyphenol and mucilage content. Wound healing was assessed from L929 fibroblast migration. April was the optimal harvest month for wound healing efficacy, whereas the highest polyphenol content and antioxidant activity were evident in September and November. S. album Murales (ALBU), the best candidate, was then compared with S. telephium (TELE), which is well recognized in skin care. The mucilage-containing aqueous extract of ALBU was shown for the first time to induce the highest fibroblast migration after 24 h, not evident in TELE. Moreover, functional constituents contained within the absolute acetone- and isopropanol-containing polyphenol pools from ALBU induced significantly higher migration compared to TELE. A prototype cream, containing the water- and solvent-extracted bioactive compounds was effective at inducing fibroblast migration at 24 h in ALBU. The potential of ALBU in wound healing was evidenced and warrants further investigation. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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15 pages, 2344 KiB

Open AccessArticle

Piceatannol Upregulates SIRT1 Expression in Skeletal Muscle Cells and in Human Whole Blood: In Vitro Assay and a Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Trial

by Kenta Tanaka, Shinpei Kawakami, Sadao Mori, Takumi Yamaguchi, Eriko Saito, Yuko Setoguchi, Yuko Matsui, Eisaku Nishimura, Shukuko Ebihara and Toshihiro Kawama

Life 2024, 14(5), 589; https://doi.org/10.3390/life14050589 - 5 May 2024

Viewed by 2218

Abstract

Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, is reported to promote fat metabolism. This study investigated whether PIC affects sirtuin 1 (SIRT1) expression and metabolic factors in C2C12 skeletal muscle cells. C2C12 myotubes were stimulated with PIC, and alterations in gene expression, protein levels, mitochondrial DNA content, and fatty acid levels were assessed using real-time PCR, Western blotting, and Nile red staining. Furthermore, we examined changes in SIRT1 expression following the consumption of a test food containing 100 mg PIC for 2 weeks among adults with varying age and body mass index ranges. Both PIC and passion fruit seed extract induced SIRT1 expression in C2C12 myotubes to a greater extent than resveratrol. PIC also increased the expression of genes associated with mitochondrial biogenesis and fatty acid utilization, increased mitochondrial DNA content, and suppressed oleic acid-induced fat accumulation. Moreover, participants who consumed PIC exhibited significantly higher SIRT1 mRNA expression in whole blood compared to those in the placebo group. These findings suggest that PIC induces SIRT1 expression both in vitro and in the human body, which may promote mitochondrial biosynthesis and fat metabolism. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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15 pages, 1364 KiB

Open AccessEditor’s ChoiceArticle

Deciphering the Systemic Impact of Herbal Medicines on Allergic Rhinitis: A Network Pharmacological Approach

by Sa-Yoon Park, Yoon Yeol Lee, Min Hee Kim and Chang-Eop Kim

Life 2024, 14(5), 553; https://doi.org/10.3390/life14050553 - 25 Apr 2024

Cited by 4 | Viewed by 1386

Abstract

Allergic rhinitis (AR) is a systemic allergic disease that has a considerable impact on patients’ quality of life. Current treatments include antihistamines and nasal steroids; however, their long-term use often causes undesirable side effects. In this context, traditional Asian medicine (TAM), with its multi-compound, multi-target herbal medicines (medicinal plants), offers a promising alternative. However, the complexity of these multi-compound traits poses challenges in understanding the overall mechanisms and efficacy of herbal medicines. Here, we demonstrate the efficacy and underlying mechanisms of these multi-compound herbal medicines specifically used for AR at a systemic level. We utilized a modified term frequency–inverse document frequency method to select AR-specific herbs and constructed an herb–compound–target network using reliable databases and computational methods, such as the Quantitative Estimate of Drug-likeness for compound filtering, STITCH database for compound-target interaction prediction (with a high confidence score threshold of 0.7), and DisGeNET and CTD databases for disease-gene association analysis. Through this network, we conducted AR-related targets and pathway analyses, as well as clustering analysis based on target-level information of the herbs. Gene ontology enrichment analysis was conducted using a protein–protein interaction network. Our research identified 14 AR-specific herbs and analyzed whether AR-specific herbs are highly related to previously known AR-related genes and pathways. AR-specific herbs were found to target several genes related to inflammation and AR pathogenesis, such as PTGS2, HRH1, and TBXA2R. Pathway analysis revealed that AR-specific herbs were associated with multiple AR-related pathways, including cytokine signaling, immune response, and allergic inflammation. Additionally, clustering analysis based on target similarity identified three distinct subgroups of AR-specific herbs, corroborated by a protein–protein interaction network. Group 1 herbs were associated with the regulation of inflammatory responses to antigenic stimuli, while Group 2 herbs were related to the detection of chemical stimuli involved in the sensory perception of bitter taste. Group 3 herbs were distinctly associated with antigen processing and presentation and NIK/NF-kappa B signaling. This study decodes the principles of TAM herbal configurations for AR using a network pharmacological approach, providing a holistic understanding of drug effects beyond specific pathways. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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Review

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19 pages, 2073 KiB

Open AccessReview

A Natural Approach to the Prevention and Treatment of Gingivitis and Periodontitis: A Review of Pomegranate’s Bioactive Properties

by Georgiana Ioana Potra Cicalău, Laura Grațiela Vicaș, Gabriela Ciavoi, Timea Claudia Ghitea, Nagy Csaba, Roxana Alexandra Cristea, Florina Miere (Groza) and Mariana Ganea

Life 2024, 14(10), 1298; https://doi.org/10.3390/life14101298 - 13 Oct 2024

Viewed by 1125

Abstract

(1) Background: This systematic review explores the bioactive properties of Punica granatum (pomegranate) and its potential applications in the prevention and treatment of gingivitis, periodontitis, and other oral diseases. (2) Methods: A comprehensive literature search was conducted using PubMed and Google Scholar, focusing on pomegranate and oral diseases. Inclusion criteria included studies evaluating the effects of pomegranate on oral health, while exclusion criteria eliminated non-peer-reviewed and non-English articles. This review aims to assess the efficacy of pomegranate extracts as a natural alternative to synthetic pharmaceuticals in oral health care. A structured search strategy included key terms such as “pomegranate”, “oral health”, “gingivitis”, and “periodontitis”. A total of 125 relevant references were reviewed to identify the most pertinent findings. (3) Results: The results indicate that pomegranate extracts have demonstrated efficacy in reducing plaque, inhibiting harmful oral microorganisms, and promoting overall oral health. Furthermore, clinical studies highlight the potential of pomegranate-based products, such as mouthwashes and gels, as viable alternatives to conventional pharmaceuticals, particularly in resource-limited settings. However, the review also notes the need for further research, particularly in the form of clinical trials, to establish optimal formulations and long-term safety. (4) Conclusions: Pomegranate presents a promising, natural solution for preventing and treating gingivitis and periodontitis. Further studies should focus on long-term effects and clinical efficacy. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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18 pages, 1371 KiB

Open AccessReview

Therapeutic Potential of Pomegranate Extract for Women’s Reproductive Health and Breast Cancer

by Jung Yoon Jang, Donghwan Kim, Eunok Im and Nam Deuk Kim

Life 2024, 14(10), 1264; https://doi.org/10.3390/life14101264 - 3 Oct 2024

Viewed by 1758

Abstract

Pomegranate extract has potential benefits for women’s reproductive health, including fertility enhancement, menstrual cycle regulation, pregnancy support, and polycystic ovary syndrome (PCOS) treatment. It possesses antioxidant properties, reducing oxidative stress and improving fertility. Pomegranate extract may help regulate hormonal imbalances and promote regular menstrual cycles. The extract’s rich nutrient profile supports placental development and fetal growth and may reduce the risk of preterm birth. Additionally, pomegranate extract shows promise in improving insulin sensitivity and reducing inflammation and oxidative damage in PCOS. Some studies suggest its potential anticancer properties, particularly against breast cancer. However, further research, including human clinical trials, is necessary to establish its effectiveness and safety. The current evidence is limited and primarily based on in vitro studies, animal studies, and clinical trials. This review provides a comprehensive summary of the benefits of pomegranate extract for women’s reproductive health and breast cancer, serving as a reference for future research. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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