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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 5685

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Special Issue Editors

Dr. Arik Dahan

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Guest Editor

Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Interests: oral drug absorption; intestinal permeability; drug solubility; drug dissolution; biopharmaceutics classification system (BCS); drug delivery and targeting
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Dr. Ludmila Yarmolinsky

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Guest Editor Assistant

Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Interests: properties of medicinal plants (antiviral, antimicrobial, anti-inflammatory and so on); isolation, purification, and identification of active compounds from medicinal plants

Special Issue Information

Dear Colleagues,

Numerous scientific studies in recent decades have indicated that medicinal plants can serve as a promising source for pharmacologically active phytochemicals, combating various diseases. In recent years, a large number of phytochemicals, including polyphenols (flavonoids, phenolic acids, lignans, tannins, stilbenes, and coumarins), terpenes, carotenoids, saponins, alkaloids, thiophenes, different sugars, fatty oils, resins, phytosterols, proteins, peptides, and many others, have exhibited noteworthy anticancer, antibacterial, anti-inflammatory, and countless other therapeutic actions, with significant potential to make it to the market as drug/drug-like substances. This Special Issue aims to provide verified data on the pharmacological activities of phytochemicals isolated from medicinal plants of the world flora. We welcome submissions of review and research articles describing, but not limited to, significant anti-inflammatory, antidiabetic, neuroprotective, anticancer, antioxidative, antimicrobial, antiviral, and antifungal activities of phytochemicals isolated from medicinal plants. Given that the medical and scientific communities have become increasingly interested in using phytochemicals isolated from medicinal plants for therapeutic purposes, we cordially invite clinicians, pharmacologists, and researchers to submit their scientific work to this Special Issue.

Dr. Arik Dahan
Guest Editor

Dr. Ludmila Yarmolinsky
Guest Editor Assistant

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Keywords

medicinal plant
pharmacological activity
phytochemical
disease
drug
therapeutic
polyphenol
terpene
carotenoid
saponin
alkaloid
thiophene
sugar
fatty oil
resin
phytosterol
protein
peptide
anti-inflammatory
antidiabetic
neuroprotective
anticancer
antioxidative
antimicrobial
antiviral
antifungal

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Published Papers (6 papers)

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Research

18 pages, 2851 KB

Open AccessArticle

Anti-Neuroinflammatory Cannabinoid Acids as a New Therapeutic Approach for Multiple Sclerosis

by Nitsan Sharon, Yvonne Ventura, Nirit Bernstein, Jonathan Gorelick, Shimon Ben-Shabat and Sigal Fleisher-Berkovich

Molecules 2026, 31(7), 1227; https://doi.org/10.3390/molecules31071227 - 7 Apr 2026

Viewed by 535

Abstract

Neuroinflammation is a hallmark of multiple sclerosis (MS). MS is marked by glial cell activation, autoreactive T cells, and the release of pro-inflammatory cytokines and free radicals. Current therapeutic strategies aim to modulate the immune response using disease-modifying therapies, to slow disease progression. The specific aims of this study were: (a) to investigate the effect of cannabinoid acids on the release of glial neuroinflammatory mediators, (b) to examine the effect of intraperitoneally administered cannabinoid acids on symptoms of MS, and (c) to evaluate their effects on microglial and astrocyte activation and CD4⁺ T cell infiltration into the spinal cords of MS mice. Exposure of BV2 microglia to cannabinoid acids attenuated lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase by 40–90% it also reduced the release of nitric oxide and interleukin-17A. Among the cannabinoid acids tested, cannabidiolic acid (CBDA) significantly increased tumor necrosis factor alpha (TNFα) secretion by up to 40% in LPS-stimulated BV2 cells. Intraperitoneal administration of CBDA also resulted in a twofold increase in TNFα secretion in splenocytes isolated from MS mice, compared to untreated MS controls. This study provides evidence that CBDA significantly reduces neurological scores, while both cannabinoid acids attenuate microgliosis, astrogliosis, and CD4+ T cell migration in lumbar spinal cord sections of MS mice. These compounds cross the blood–brain barrier (BBB) and act directly within the central nervous system. The consistent elevation of TNFα in the presence of CBDA across three experimental models suggests a distinctive immunomodulatory role for CBDA, with potential therapeutic implications in MS. Full article

(This article belongs to the Special Issue Back to Nature: Pharmacological Activities of Phytochemicals Isolated from Medicinal Plants)

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18 pages, 2659 KB

Open AccessArticle

Blackened Panax quinquefolius L. Saponins and Their Cytotoxic Effect on HepG2 Cells

by Yuanyuan Tian, Jiaqi Gao, Yongqi Liu and Rui Liu

Molecules 2026, 31(7), 1173; https://doi.org/10.3390/molecules31071173 - 1 Apr 2026

Viewed by 511

Abstract

In the present work, the blackening process of Panax quinquefolius L. (PQ) was systematically investigated at temperatures of 70–90 °C, relative humidities (RHs) of 70–85%, and treatment times of 0–14 days. Ginsenoside compositions and transformation pathways were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography coupled with ion trap time-of-flight tandem mass spectrometry (LC-IT-TOF-MS/MS). The results demonstrated that blackening treatment significantly increased total saponin content from 2.72% to 5.73% after being treated at 80 °C and 70% RH for 12 days, accompanied by the highest conversion efficiencies for newly generated ginsenosides Rk1 (8.89 mg/g) and Rg5 (17.69 mg/g). Furthermore, compared with untreated PQ saponins (PQS), the blackened PQ saponins treated under optimal conditions (BPQS) exhibited superior 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation (ABTS⁺) radical scavenging activities, with IC₅₀ values of 0.2999 mg/mL and 0.2640 mg/mL, respectively, as well as stronger reducing power. Meanwhile, BPQS exhibited higher cytotoxicity toward HepG2 cells and effectively inhibited cell survival and proliferation by promoting the expression of apoptosis-related proteins, including caspase 3 and caspase 9. Our findings indicate that BPQS may be a functional ingredient suitable for use in dietary supplements and disease chemoprevention. Full article

(This article belongs to the Special Issue Back to Nature: Pharmacological Activities of Phytochemicals Isolated from Medicinal Plants)

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21 pages, 3640 KB

Open AccessArticle

Hypoglycemic Effects of Glehniae Radix Polysaccharides in Female db/db Mice via Modulation of the Gut Microbiota-PPAR Signaling Axis

by Haochen Xu, Hanqing Lin, Hetong Lin, Peng Wu, Fang Zhang and Longhe Yang

Molecules 2026, 31(6), 1046; https://doi.org/10.3390/molecules31061046 - 20 Mar 2026

Viewed by 486

Abstract

Glehniae Radix, the dried root of Glehnia littoralis Fr. Schmidt ex Miq. (Apiaceae), exhibits diverse biological activities. However, research on the hypoglycemic effects of Glehniae Radix polysaccharides (GRPs), particularly in vivo studies clarifying their mechanisms of action, remains limited. This study aimed to verify the in vivo hypoglycemic activity of crude GRP in a diabetic model and to elucidate its mechanism. GRP was extracted by water extraction and ethanol precipitation, yielding an extraction rate of 38% and a polysaccharide content of 73.48%. Its hypoglycemic effects and mechanisms were investigated in female B6.BKS(D)-Leprdb/J (db/db) mice following daily administration of GRP at doses of 300 and 600 mg/kg for five consecutive weeks. Following GRP administration, mice in the CH group (600 mg/kg) exhibited a mean reduction in fasting blood glucose levels of approximately 40.7% and an improvement in insulin tolerance test (ITT) outcomes by about 28.4%. Additionally, GRP alleviated damage to the liver, kidney, and colon; decreased hepatic total cholesterol (TC) and triglycerides (TGs) by approximately 40.8% and 24.6%, respectively; and increased colonic Zonula Occludens-1 (ZO-1) expression by an average of 49.5%. Mechanistically, GRP significantly upregulated the expression of peroxisome proliferator-activated receptor-α (PPAR-α) and PPAR-γ in the liver, while also increasing the abundance of beneficial gut bacteria such as Alistipes and suppressing harmful bacteria including Escherichia-Shigella. Furthermore, GRP activated the galactose metabolism pathway and inhibited abnormal enrichment of the steroid biosynthesis pathway, collectively ameliorating glucose metabolic disorders in female db/db mice via the “gut microbiota–PPAR signaling axis”. In light of these results, GRP exerts significant in vivo hypoglycemic effects by modulating gut microbiota balance and activating the PPAR signaling pathway. Full article

(This article belongs to the Special Issue Back to Nature: Pharmacological Activities of Phytochemicals Isolated from Medicinal Plants)

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16 pages, 1963 KB

Open AccessArticle

DES/Extraction and Process Optimization of Callistemon citrinus (Curtis) Skeels Essential Oil

by Xiao-Nan Zhang, Bing-Bing Wang, Jia-Lu Liu, Hong-Zi Lai, Yan Huang, Yi-Yi Peng, Zhi-Wei Liu and Hai-Tang Wang

Molecules 2026, 31(5), 819; https://doi.org/10.3390/molecules31050819 - 28 Feb 2026

Viewed by 360

Abstract

The essential oil of Callistemon citrinus (Curtis) Skeels is a valuable natural product with a complex volatile composition. In this study, an ultrasonic-assisted hydrodistillation process was systematically optimized using a combination of the steepest ascent method and response surface methodology (RSM) to refine key extraction parameters and identify the central point of the experimental design. Heating time, heating power, and ultrasonic treatment time were selected as critical variables influencing extraction efficiency. The optimized conditions were determined to be a heating time of 57 min, a heating power of 563 W, and an ultrasonic treatment time of 23 min, under which an essential oil yield of 0.8 mL/kg (dry weight basis) was achieved. Gas chromatography–mass spectrometry (GC–MS) analysis indicated that pretreatment with different metal ions resulted in pronounced differences in the chemical profiles of the extracted essential oils, particularly in major constituents such as cineole and α-terpineol. Among the tested ions, Sr²⁺ and Ca²⁺ pretreatments were associated with a higher relative abundance of monoterpenoid compounds, which suggests a selective influence of divalent metal ions on the extraction behavior of volatile components. Principal component analysis (PCA) further revealed clear discrimination among the essential oils obtained under different ion pretreatment conditions, confirming the compositional variability induced by ion-assisted extraction. Full article

(This article belongs to the Special Issue Back to Nature: Pharmacological Activities of Phytochemicals Isolated from Medicinal Plants)

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15 pages, 2205 KB

Open AccessArticle

Phytochemical Analysis and In-Vitro Biological Activities of Three Wild Eryngium Species: E. beecheyanum, E. heterophyllum, and E. mexiae

by Mariana Villa-Santiago, Brenda Hildeliza Camacho-Díaz, Argelia López-Bonilla, Hortencia Gabriela Mena-Violante, Jeanette Guadalupe Cárdenas-Valdovinos, Zaida Ochoa-Cruz and María Valentina Angoa-Pérez

Molecules 2025, 30(21), 4250; https://doi.org/10.3390/molecules30214250 - 31 Oct 2025

Viewed by 897

Abstract

The genus Eryngium (Apiaceae Lindley) includes over 250 species distributed worldwide. In Michoacán, Mexico, 22 species have been recorded, among them E. beecheyanum (EB), E. heterophyllum (EH), and E. mexiae (EM), which are commonly used in traditional medicine. However, our understanding of their biology and chemical composition remains limited. This study evaluated the phytochemical profile, as well as the antioxidant and hypoglycemic activities of leaves and roots from these three wild species. Flavonoids, phenolic compounds, and sterols were analyzed using high-performance thin-layer chromatography (HPTLC). Antioxidant activity was assessed in vitro using ABTS·+ and DPPH· assays, while antihyperglycemic activity was determined by α-glucosidase inhibition. Six metabolites were detected across all species, with organ-dependent variation. In the leaves, EB showed a high rutin content (241.3 µg/mL), EM contained catechin (137.3 µg/mL), and EH exhibited β sitosterol (315.9 µg/mL). Both leaves and roots of all species showed notable antioxidant activity. EB leaves exhibited inhibition rates of 69.5% and 85.5% in ABTS•+ and DPPH• assays, respectively (IC₅₀ = 22 and 23.47 µg/mL). EH roots showed higher activity, reaching 89.4% and 78.2% inhibition (IC₅₀ = 21.8 and 20.72 µg/mL). Conversely, EM organs exhibited relatively lower radical scavenging capacities; however, EM leaves showed the highest α-glucosidase inhibition (49.1%). Overall, these results suggest that roots generally possess stronger antioxidant potential than leaves, whereas EM leaves stand out for their enzymatic inhibitory activity. These findings highlight the diverse phytochemical and bioactive profiles of E. beecheyanum, E. heterophyllum, and E. mexiae. Full article

(This article belongs to the Special Issue Back to Nature: Pharmacological Activities of Phytochemicals Isolated from Medicinal Plants)

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15 pages, 3839 KB

Open AccessArticle

Therapeutic Potential of Ficus benjamina: Phytochemical Identification and Investigation of Antimicrobial, Anticancer, Pro-Wound-Healing, and Anti-Inflammatory Properties

by Arik Dahan, Ludmila Yarmolinsky, Arie Budovsky, Boris Khalfin and Shimon Ben-Shabat

Molecules 2025, 30(9), 1961; https://doi.org/10.3390/molecules30091961 - 28 Apr 2025

Cited by 2 | Viewed by 2269

Abstract

Ficus benjamina is a common park tree, with previous reports of some medicinal properties. In this work, we identified and explored phytochemicals from F. benjamina for potential antimicrobial, pro-wound-healing, anti-inflammatory, and effect on cancer cell lines’ proliferation, both experimentally and bioinformatically. Gas chromatography/mass spectrometry (GC/MS) analysis was performed to identify the volatile compounds. The nonvolatile active components of the extract were identified by HPLC and LC-ESI-MS. We found that some drug-resistant microorganisms (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Serratia marcescens, and Salmonella enteritidis) were inhibited by the extract, the 80% fraction, and all the identified flavonoids except quercetin 3-O-rutinoside. Furthermore, the extract and above-mentioned compound also inhibited the growth of biofilm-producing bacterium. The extract and 80% fraction were very potent (p < 0.001) at inducing death of MCF7 and U87 cancer cell cultures and were more effective in that than the chemotherapeutic agent doxorubicin which served as a positive control. Additionally, the extract of F. benjamina, the 80% fraction, and selected phytochemicals had pronounced pro-wound-healing properties. Finally, the extracts, the 80% fraction, caffeic acid, kaempferol 3-O-rutinoside, and kaempferol 3-O-robinobioside significantly inhibited the secretion of pro-inflammatory cytokines, IL-6 and IL-8 (p < 0.001). In conclusion, this comprehensive research revealed convincing and promising indications of significant therapeutic potential of a F. benjamina extract and its active phytochemicals. Full article

(This article belongs to the Special Issue Back to Nature: Pharmacological Activities of Phytochemicals Isolated from Medicinal Plants)

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