Planta Med. [JOURNAL]
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200 papers
Boldine and Laurolitsine Protect against Periodontitis-Associated Bone Loss via RANKL Downregulation.
Castro-Saavedra S, Fuentes-Barros G, Rojas C … +5 more , Pellegrini E, García M, Hernández M, Vernal R, Cassels BK
Planta Med · 2026 Mar · PMID 41839226 · Publisher ↗
Periodontitis is a chronic inflammatory disease driven by dysbiosis of the subgingival microbiota, leading to immune dysregulation and progressive alveolar bone loss. In recent years, immunotherapeutic approaches, partic...
Periodontitis is a chronic inflammatory disease driven by dysbiosis of the subgingival microbiota, leading to immune dysregulation and progressive alveolar bone loss. In recent years, immunotherapeutic approaches, particularly those involving natural products, have gained attention as potential adjuvants to conventional therapy. This study evaluated the effects of four alkaloids, boldine, laurolitsine, laurotetanine, and -methyl-laurotetanine, on alveolar bone loss and local immune regulation in experimental periodontitis.Male and female C57BL/6 mice with ligature-induced periodontitis received daily oral administration of each alkaloid (20 mg/kg) for 10 days. Alveolar bone loss was quantified by micro-computed tomography (micro-CT). Periodontal immune responses were assessed by RT-qPCR analysis of pro-inflammatory cytokines, T-cell-related transcription factors, and bone metabolism mediators (RANKL and OPG). In addition, regulatory T (Treg) cells in cervical lymph nodes were analyzed by flow cytometry.Boldine and laurolitsine significantly reduced alveolar bone loss compared with untreated periodontitis, in parallel with decreased RANKL expression. All four alkaloids significantly reduced IL-6 expression, with laurolitsine additionally suppressing IL-17A expression in periodontal tissues, whereas -methyl-laurotetanine reduced IL-10 expression. No significant changes were observed in CD4, CD4FoxP3, and CD4FoxP3CD25 T-cell frequencies between treated and untreated groups.Oral administration of boldine and laurolitsine attenuates periodontitis-associated alveolar bone loss, likely through differential modulation of cytokine networks and osteoclastogenic signaling. These findings support their potential as host-modulating agents in the management of periodontitis.
An Update on the Therapeutic Potential of Bixin and Norbixin Apocarotenoids.
Gómez-Linton DR, Monroy A, Alavez S … +1 more , Pérez-Flores LJ
Planta Med · 2026 Mar · PMID 41839212 · Publisher ↗
Plants have been a central source of natural resources for humanity with all kinds of uses and applications: food, cosmetics, natural remedies and medicines, dyes, textiles, construction materials, ornamental uses, and t...
Plants have been a central source of natural resources for humanity with all kinds of uses and applications: food, cosmetics, natural remedies and medicines, dyes, textiles, construction materials, ornamental uses, and the extraction of various compounds, including natural pigments. Within pigments, there are four major groups of interest: anthocyanins, chlorophylls, betalains, and carotenoids. Carotenoids are characterized by being formed by relatively long hydrocarbon chains (25 - 50 C), which can end in linear or cyclic structures. In the carotenoid group, bixin and norbixin are two compounds of undeniable relevance as food and cosmetic pigments. However, in recent years, these compounds have been studied to understand other possible effects, mainly in the field of health, yielding promising results. This review features results from studies published in recent years with a focus on possible applications in the field of public health, mainly related to metabolic problems such as sugar and fat metabolism. Additionally, various other health applications are analyzed, and the results are summarized. The main conclusions reached by the authors are also mentioned for a better understanding of the importance of each study. Finally, general conclusions and perspectives are provided in order to continue exploring the possible applications of bixin and norbixin as potential bioactive and functional compounds.
Correction: Phaeosphaeride A Isolated from an Endophytic Paraphoma sp. Alleviates ABCG2-mediated Resistance to Mitoxantrone in Breast Cancer Cells.
Tavakkoli A, Mortazavi H, Iranshahi M … +5 more , Kalalinia F, Jamialahmadi K, Thorson JS, Shaaban KA, Mosaffa F
Planta Med · 2026 Mar · PMID 41819154 · Publisher ↗
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Antioxidant and Cytoprotective Role of Citral-Rich Essential Oils in In Vitro Animal Cell Models.
Barbosa BS, Pereira AF
Planta Med · 2026 Mar · PMID 41819153 · Publisher ↗
Citral-rich essential oils (CEO) exhibit remarkable antioxidant potential. In this review, we discuss chemical and biological aspects of citral and CEO, estimating possible mechanisms of action. To this end, a literature...
Citral-rich essential oils (CEO) exhibit remarkable antioxidant potential. In this review, we discuss chemical and biological aspects of citral and CEO, estimating possible mechanisms of action. To this end, a literature search was carried out in the Scielo, PubMed, and Google Scholar databases, focusing on the antioxidant potential of CEO. Analyzed studies demonstrated the protective capacity of citral and CEO in cells stressed by hydrogen peroxide and excess glucose in the medium. Moreover, citral has antimicrobial, anti-inflammatory, and antimutagenic activity that can be exploited in a cell culture. The antioxidant activity of citral is attributed to the presence of an aldehyde group and multiple unsaturations in its structure, which enable it to scavenge free radicals and convert them into auto-oxidizing epoxides that are rapidly eliminated by the cell. Citral epigenetically modulates DNA, increasing the activity of endogenous antioxidant enzymes, while inhibiting enzymes involved in lipid peroxidation. In parallel, CEO and citral contribute to maintaining DNA integrity through kinase-related signaling pathways. Despite growing evidence of their antioxidant potential, studies investigating the bioactivity of citral and CEOs in animal cell cultures remain limited. Furthermore, research exploring the synergistic activity of citral with other compounds is still scarce, despite their significant scientific relevance. This scenario reinforces the need for further investigations to elucidate their mechanisms of action and to establish reference parameters guiding their application in different cellular and reproductive models .
Toxic Risks of Nightshade Species: A comprehensive review of the documented toxicity of Atropa belladonna, Solanum dulcamara, and Solanum nigrum.
Aćimović M
Planta Med · 2026 Mar · PMID 41819152 · Publisher ↗
The Solanaceae family comprises numerous species of economic and pharmacological importance, including the toxic deadly nightshade (), bittersweet nightshade (), and black nightshade (). These plants are native to Europe...
The Solanaceae family comprises numerous species of economic and pharmacological importance, including the toxic deadly nightshade (), bittersweet nightshade (), and black nightshade (). These plants are native to Europe, North Africa, and Western Asia, and have been used since ancient times in both ritual practices and medicine. contains potent tropane alkaloids (atropine, hyoscyamine, and scopolamine) and is widely utilized in modern pharmacology, although accidental poisonings still occur, often due to confusion with edible plants or the misuse of herbal and homeopathic preparations. In contrast, contains glycoalkaloids such as solanine, solasodine, and -solamarine, while contains solanine, solamargine, and solasonine. Both species have a history of traditional use as narcotics, diuretics, and treatments for skin, rheumatic, and respiratory conditions, as well as for pain, inflammation, fever, and other disorders; however, they also pose significant toxicological risks to humans and animals. Although poisonings from these two species are less common than those caused by , they still occur. A review of the literature identified 41 studies reporting poisoning cases associated with these plants, primarily resulting from berry ingestion. Poisoning typically produces anticholinergic syndrome, underscoring the importance of accurate identification and prompt treatment.
Inter-Laboratory Comparison of Photometric and LC Assay Methods for Hydroxyanthracene Glycosides Determination in Senna Herbal Drugs and Dry Extracts.
Peter S, Schenk A, Höwer-Fritzen H … +4 more , Steuber A, Wolfram E, Wagner B, Steinhoff B
Planta Med · 2026 Mar · PMID 41802773 · Publisher ↗
Herbal preparations of leaves or fruits are commonly used as laxatives. The European Medicines Agency (EMA) sets a daily dose of 10 - 30 mg for the hydroxyanthracene glycosides (HAG) determined by spectrophotometry. A r...
Herbal preparations of leaves or fruits are commonly used as laxatives. The European Medicines Agency (EMA) sets a daily dose of 10 - 30 mg for the hydroxyanthracene glycosides (HAG) determined by spectrophotometry. A recent revision of the European Pharmacopoeia monographs on replaced the photometric assay with HPLC. The new method offers improved reproducibility and specificity but results in lower content, while the dose recommendation in the EMA monograph still refers to the photometric determination.The systematic difference between the photometric and the HPLC method has been studied in a collaborative inter-laboratory trial by seven participating quality control laboratories. The goal was to compare precision and reproducibility and ideally to derive a conversion factor. The HAG determination by spectrophotometry according to the method from Ph. Eur. Edition 8.3. was compared to the HPLC assay according to the new method for leaves or pods (Ph. Eur. Ed. 10.1).The photometric method showed a low inter-laboratory reproducibility of about ± 28% (RSD) but an intra-laboratory precision of around 2%, while the HPLC method showed an inter-laboratory precision of around ± 10% and an intra-laboratory precision of 1.5%.Assay values obtained by HPLC were about 90% of the values of the photometric method, but this relation seems to be sample dependent. Because of its dependency on the raw material, a simple conversion factor between the two methods is not yet satisfying, but an additional method-specific dose recommendation for the EMA monographs is proposed by the authors.
Oleandrin Suppresses the PI3K/AKT Pathway to Inhibit Growth and Induce Apoptosis in T-cell Acute Lymphoblastic Leukemia Cells and Xenograft Mice.
Zhuang H, Jiang X, Li F … +2 more , Sha W, Lu Y
Planta Med · 2026 Mar · PMID 41786305 · Publisher ↗
T-cell acute lymphoblastic leukemia (T-ALL) remains a clinical challenge due to its high relapse rate and limited treatment options. This study aimed to investigate the cytotoxic effects of oleandrin on T-ALL and its und...
T-cell acute lymphoblastic leukemia (T-ALL) remains a clinical challenge due to its high relapse rate and limited treatment options. This study aimed to investigate the cytotoxic effects of oleandrin on T-ALL and its underlying mechanism to explore novel therapeutic strategies. In human T-ALL cell lines, it inhibited cell growth and induced apoptosis in a dose- and time-dependent manner, with half-maximal inhibitory concentration (IC₅₀) values ranging from 16 to 31 nM. In mouse xenograft models, oleandrin reduced tumor burden and prolonged survival without significant toxicity. Integrated mechanistic studies, including network pharmacology, transcriptomics, and Western blot analysis, indicated that the anti-leukemic effects of oleandrin are associated with suppression of the PI3K/AKT signaling pathway, as evidenced by reduced levels of key proteins such as PIK3CA, phosphorylated AKT (p-AKT), phosphorylated GSK3 (p-GSK3), c-Myc, Bcl-2, and Bcl-xL. These findings suggest oleandrin is a promising therapeutic candidate for T-ALL, likely through suppression of the PI3K/AKT pathway.
A Decade of Decline: The Decreasing Use of Positive Controls Threatens the Reliability of In vitro Cancer Research.
van den Berg H, van Niekerk S, Netshimbupfe MH … +1 more , van der Kooy F
Planta Med · 2026 Mar · PMID 41771299 · Publisher ↗
Positive controls are indispensable for validating cancer bioassays and ensuring reproducibility in cancer drug discovery research. However, evidence suggests their inclusion in bioassays during drug discovery is decli...
Positive controls are indispensable for validating cancer bioassays and ensuring reproducibility in cancer drug discovery research. However, evidence suggests their inclusion in bioassays during drug discovery is declining, undermining assay reliability, reproducibility, and scientific integrity. This mini-review analysed 150 peer-reviewed studies published in 2015, 2020, and 2025 (50 from each year) to evaluate trends in positive control usage within cytotoxicity assays targeting cancer cell lines. Results indicate that only 52% (2015) and 54% (2020) of studies included appropriate positive controls; however, this dropped to a worrying 32% in 2025. The omission was most pronounced in natural product research and studies using high-throughput assays, such as MTT. In addition, reporting of dose-response parameters (e.g., IC₅₀) decreased from 26% to only 16% across the decade. These findings highlight a systemic erosion of methodological rigor, likely driven by publication pressure, limited resources, and a lack of standardised protocols. We recommend the mandatory inclusion of validated positive controls, transparent reporting of preparation and storage conditions, and journal-level enforcement of experimental standards. Reinforcing these practices will improve reproducibility, comparability, and ultimately the translatability of preclinical cancer research outcomes.
Mesembryanthemum tortuosum and Zembrin: Mixed Evidence from In vivo Animal and Clinical Studies on their Antidepressant and Anxiolytic Effects.
de Jong M, van Niekerk S, Hamman J … +1 more , van der Kooy F
Planta Med · 2026 Mar · PMID 41771298 · Publisher ↗
is a succulent plant native to southern Africa and was traditionally used to enhance mood. Recent research into 's mood-enhancing effects has culminated in the development of a standardised extract, Zembrin, containing c...
is a succulent plant native to southern Africa and was traditionally used to enhance mood. Recent research into 's mood-enhancing effects has culminated in the development of a standardised extract, Zembrin, containing consistent levels of mesembrine alkaloids considered to be the main bioactive compounds. This review aims to critically investigate published animal and clinical studies using , Zembrin, and mesembrine alkaloids, to evaluate the study designs, formulations, and dosages used, and to assess the results in terms of safety and therapeutic efficacy as an antidepressant and anxiolytic. Four databases, namely PubMed, Scopus, Web of Science, and ScienceDirect, were searched using terms relating to 'clinical trials', '', '', '', 'pre-clinical', 'Sceletium', '', and 'Zembrin'. The search was conducted to identify original research articles published before July 2025. Although published pre-clinical animal and clinical studies on derived products offer valuable insights, such as a favourable safety profile and potential efficacy as an anxiolytic and antidepressant, several limitations have been identified, including small sample sizes and studies conducted in clinically irrelevant populations. A limited number of reported outcomes suggest that Zembrin may have positive effects on anxiety, cognitive function, stress resilience, and mood. However, not all studies showed consistent benefits, and some outcomes were limited to specific measures such as EEG changes or reaction time under cognitive stress. Large-scale clinical trials in relevant populations should be conducted to determine the potential of -derived products as anxiolytics and antidepressants.
Anticandidal and Antibiofilm Activity of the Essential Oils from the Leaves of Citrus limon and Citrus sinensis.
Albuquerque Fernandes MA, Linhares de Aguiar FL, Lima Rodrigues PH … +6 more , Lima Torres Martins MD, Bezerra de Souza E, Parcelli Costa do Vale J, Rodrigues THS, Salles de Brito EH, Fontenelle RODS
Planta Med · 2026 Mar · PMID 41771297 · Publisher ↗
is an opportunistic pathogen whose virulence factors, such as polymorphism and biofilm formation, facilitate infection. Due to rising antifungal resistance, essential oils (EOs) from and are being investigated for thei...
is an opportunistic pathogen whose virulence factors, such as polymorphism and biofilm formation, facilitate infection. Due to rising antifungal resistance, essential oils (EOs) from and are being investigated for their antimicrobial potential. This study analyzes the chemical composition, antifungal activity against in planktonic and biofilm forms, cytotoxicity on human erythrocytes, and pharmacokinetic properties of and essential oils. The essential oils were extracted from the leaves by hydrodistillation, and their composition was analyzed by GC-MS. Antifungal activity was assessed using broth microdilution and time-kill kinetics. Combined effects were assessed using checkerboard assays, while antibiofilm tests were evaluated using polystyrene plate assays and microscopy. Hemolytic activity tests were performed using percentage hemolysis. essential oil had limonene 40.8%, -pinene 16.5%, and citronellal 12.3%, while had limonene 36.7%, -pinene 14.6%, and eucalyptol 10.5% as its main constituents. The MIC was 0.312 - 1.25 mg/mL, with kill kinetics of up to 10 h. It showed additive effects for /fluconazole and synergistic effects for /fluconazole. It exhibited anti-adhesion and anti-polymorphism effects, inhibiting biofilm formation. It also exhibited low cytotoxicity, with an LC of 14 000 µg/mL for and 13 000 µg/mL for . ADMET and BOILED-egg pharmacokinetic predictions indicated safety for systemic use, with caution for topical application of limonene, citronellal, and eucalyptol. Both EOs exhibited strong anti- activity with minimal cytotoxicity. Its additive/synergistic effects with fluconazole highlight its potential as an alternative or adjuvant therapy against infections.
Hormonal Modulation with Withania somnifera: Systematic Review and Meta-Analysis of Randomized-controlled Trials.
Fornalik M, Malkiewicz A, Adamczak D … +3 more , Nawrocki F, Zielinska A, Mondal SA
Planta Med · 2026 Feb · PMID 41740946 · Publisher ↗
Hormonal imbalances, particularly involving the hypothalamic-pituitary-adrenal and gonadal axes, contribute to chronic conditions such as stress-related disorders, infertility, and metabolic dysregulation. Ashwagandha (....
Hormonal imbalances, particularly involving the hypothalamic-pituitary-adrenal and gonadal axes, contribute to chronic conditions such as stress-related disorders, infertility, and metabolic dysregulation. Ashwagandha (.) has been proposed as a potential oral modulator of endocrine function due to its adaptogenic properties. This review aims to systematically evaluate the effects of oral ashwagandha supplementation on circulating hormone levels in adults. Our literature search included MEDLINE, Embase, and ClinicalTrials.gov. The protocol was registered in PROSPERO (CRD42024611576). We included randomized, placebo-controlled trials in adults assessing oral ashwagandha versus placebo that reported changes in hormone levels. Two reviewers independently screened studies, extracted summary data, and assessed risk of bias using the Cochrane tool. Meta-analyses were conducted using a random-effects model to calculate mean differences (MD) or standardized mean differences (SMD), with heterogeneity and publication bias assessed using I² and Egger's test, respectively. Twenty-three trials were included, encompassing 1706 patients. Ashwagandha significantly reduced cortisol (SMD =- 1.18, p < 0.04) and increased serotonin (MD = 31.75 ng/ml, p < 0.01). Subgroup analyses suggested possible dose-response effects based on withanolide content. No effect was found on TSH or T3, but T4 levels increased modestly (MD = 0.61 µg/dL, p = 0.02). Ashwagandha increased testosterone in men (MD = 57.43 ng/dl) but not in women (MD = 5.09 ng/dl), with a significant gender difference. This treatment did not influence E2 levels in either gender. Ashwagandha supplementation appears to modulate key hormonal pathways, particularly cortisol and sex hormones. However, heterogeneity and limited data on some endpoints warrant further standardized trials.
Fabrication and Evaluation of 3D-printed Dittany-infused Patches for Anti-inflammatory Dermatological Applications.
Paloukopoulou C, Chachlioutaki K, Papadimitriou-Tsantarliotou A … +6 more , Koltsakidis S, Tzetzis D, Vizirianakis IS, Vakirlis E, Fatouros DG, Karioti A
Planta Med · 2026 Feb · PMID 41740945 · Publisher ↗
This study aimed to validate the dermatological potential of (dittany) infusion, traditionally recognized for its anti-inflammatory properties. To this end, 3D-printed hydrogel patches incorporating dittany were develop...
This study aimed to validate the dermatological potential of (dittany) infusion, traditionally recognized for its anti-inflammatory properties. To this end, 3D-printed hydrogel patches incorporating dittany were developed and evaluated for biocompatibility, wound-healing, anti-inflammatory activity, and effects on skin barrier. Hydrogel patches were fabricated via extrusion-based 3D printing using aloe vera gel, hydroxypropyl methylcellulose (HPMC), glycerol, and combinations of dittany infusion and panthenol. assays with HaCaT keratinocytes included cytotoxicity testing, scratch-wound healing, and qPCR-based analysis of inflammatory biomarkers. transepidermal water loss (TEWL) measurements were performed to assess skin barrier integrity and hydration after patch application. The traditional use of dittany infusion in skin ailments was confirmed, along with its relatively low cytotoxicity. Three 3D-printed gel types were evaluated , all showing superior performance to the raw plant extract. The optimal formulation contained 2% HPMC, 2% glycerol, 5% panthenol, and 0.06% dittany infusion (w/w% relative to aloe vera gel). At 3.25 mg/mL, this formulation achieved ~ 70% wound closure and significantly reduced IL-6 and TNF- levels, indicating strong anti-inflammatory activity (p < 0.05). Both crude extract and patches show a trend toward reducing pro-inflammatory interleukins while simultaneously upregulating the anti-inflammatory cytokine IL-4. TEWL measurements indicated that none of the patches impaired the skin barrier function, confirming their compatibility with various skin types. This study provides the first scientific evidence that the incorporation of dittany infusion into 3D-printed hydrogels holds promise for safe, effective, plant-based topical therapies.
The Potential of Passiflora Species in the Treatment of Cardiovascular Diseases: Phytochemical, Pharmacological, and Therapeutic Perspectives.
Bareño Ariza LL, Guerrero MF
Planta Med · 2026 Mar · PMID 41702568 · Publisher ↗
Cardiovascular diseases (CVDs) remain a major global health challenge, underscoring the need for novel, accessible, and effective therapeutic strategies. This review critically evaluates the phytochemical composition and...
Cardiovascular diseases (CVDs) remain a major global health challenge, underscoring the need for novel, accessible, and effective therapeutic strategies. This review critically evaluates the phytochemical composition and cardioprotective potential of the species, summarizes the mechanisms of action of their principal bioactive compounds, and identifies key research gaps hindering clinical translation. With over 500 species distributed worldwide, many plants are traditionally used in herbal medicine. Preclinical evidence suggests that compounds such as phenolics, alkaloids, and triterpenoid saponins exert cardioprotective effects through antioxidant and anti-inflammatory activities, vasodilation, blood pressure regulation, endothelial function improvement, and autonomic nervous system modulation. However, these findings are largely based on a limited number of species, often using non-standardized extracts, and lack comprehensive structure-activity relationship (SAR) analyses and clinical validation. Endemic species remain underexplored, despite their potential to yield novel compounds with enhanced bioactivity. This review emphasizes the need for extract standardization, robust pharmacokinetic studies, and the integration of omics technologies and molecular modeling to accelerate compound discovery and development. Overall, species contain promising bioactive molecules with significant and cardioprotective effects. Nonetheless, rigorous and standardized research, including clinical trials, is essential to fully assess their therapeutic value and support their integration into evidence-based cardiovascular care.
Chemical Diversity and Biological Activities of the Artemisia L. Genus Beyond Antimalarial Effects.
Karoutzou O, Skaltsounis LA
Planta Med · 2026 Mar · PMID 41655570 · Publisher ↗
The genus L. constitutes one of the largest and most widely distributed groups within the Asteraceae family, renowned for its pharmacological significance. Used in traditional medicine for over two millennia, species h...
The genus L. constitutes one of the largest and most widely distributed groups within the Asteraceae family, renowned for its pharmacological significance. Used in traditional medicine for over two millennia, species have been employed to treat a broad spectrum of ailments, with modern pharmacological studies increasingly validating these traditional uses. Interest in the genus surged following the groundbreaking discovery of the antimalarial sesquiterpene lactone artemisinin from L. Beyond antimalarial activity, species exhibit diverse pharmacological effects including anti-inflammatory, antiproliferative, cytotoxic, antimicrobial, and antiviral properties, largely attributed to secondary metabolites such as sesquiterpene lactones, furofuran lignans, polyacetylenes, and methylated flavonoids. This present study covers the bioactivities of extracts, essential oils, and isolated compounds from genus reported between 1998 and 2025. Representative compounds from the most characteristic classes of secondary metabolites are linked to biological activities, incorporating and studies, pharmacokinetics, clinical data, and toxicity profiles, while for each compound species-specific origin is reported.
Eupafolin in Nature and Science: Occurrence, Chemistry, Biosynthesis, Analytical Methods, and Potential Multifaceted Applications.
Ojo O, Prinsloo G
Planta Med · 2026 Mar · PMID 41643742 · Publisher ↗
Eupafolin (nepetin) is a bioactive flavonoid with a flavone backbone and hydroxyl groups contributing to its pharmacological properties. It is found in various medicinal plants and has garnered significant attention due...
Eupafolin (nepetin) is a bioactive flavonoid with a flavone backbone and hydroxyl groups contributing to its pharmacological properties. It is found in various medicinal plants and has garnered significant attention due to its biological activities, including anti-inflammatory, anticancer, antioxidant, antidiabetic, antimicrobial, and neuroprotective effects. This review explores eupafolin's natural occurrence, chemical structure, and biosynthetic pathway, highlighting its roles in different scientific domains, including pharmacology, pharmaceutical nanotechnology, and agriculture. Research data on eupafolin were sourced from databases, including Google Scholar, Science Direct, Scopus, and PubMed, up to April 2025, resulting in over 100 electronic references. Eupafolin shows promise in drug development and green nanoparticle synthesis, supporting eco-friendly nanomedicine and material science applications. Beyond the biomedical benefits of this flavone, its antimicrobial and anti-inflammatory properties also indicate potential use in plant protection and stress tolerance enhancement. Despite its pharmacological benefits, studies on eupafolin's direct toxicity and safety are lacking, with toxicity mainly observed in cultured cancer cells, suggesting chemotherapeutic potential. Thus, robust and studies are needed to determine its safety profile for drug development. Overall, this review presents a comprehensive analysis of eupafolin's occurrence, chemistry, derivatives, biosynthesis, and applications, emphasizing its potential in medicine, pharmaceutical nanotechnology, and agriculture.
Phaeosphaeride A Isolated from an Endophytic Paraphoma sp. Alleviates ABCG2-mediated Resistance to Mitoxantrone in Breast Cancer Cells.
Tavakkoli A, Mortazavi H, Iranshahi M … +5 more , Kalalinia F, Jamialahmadi K, Thorson JS, Shaaban KA, Mosaffa F
Planta Med · 2026 Jun · PMID 41638243 · Publisher ↗
ABSTRACT: The efficacy of breast cancer chemotherapies is frequently limited by multidrug resistance (MDR), partly through efflux by ABC transporters, including ABCG2. This study evaluated whether phaeosphaeride A (PPA),...
ABSTRACT: The efficacy of breast cancer chemotherapies is frequently limited by multidrug resistance (MDR), partly through efflux by ABC transporters, including ABCG2. This study evaluated whether phaeosphaeride A (PPA), a fungal metabolite isolated from a sp. endophyte of , can modulate ABCG2-mediated resistance to mitoxantrone (MTX). The endophyte was cultured and extracted with ethyl acetate, and the extract was purified by column chromatography and HPLC to yield PPA, whose structure was confirmed by NMR and MS analyses. Cytotoxicity of MTX, PPA, and their combination was assessed in MCF-7- and ABCG2-overexpressing MCF-7/MX cells. MTX showed marked differential cytotoxicity (IC = 1.6 µM, 95% CI: 1.4 - 1.9 in MCF-7 vs. > 25 µM in MCF-7/MX; p < 0.0001), whereas PPA exhibited comparable activity in both lines (23.2 µM, 95% CI: 18.0 - 30.1 vs. 36.1 µM, 95% CI: 28.7 - 46.0; p = 0.01). Co-treatment with PPA IC significantly reduced MTX IC to 0.4 µM (95% CI: 0.3 - 0.6) in MCF-7 and 1.9 µM (95% CI: 1.2 - 2.7) in MCF-7/MX, restoring MTX sensitivity in resistant cells to near MCF-7 levels. Flow cytometry showed that PPA (IC) increased intracellular MTX accumulation with stronger effects in MCF-7/MX cells (p < 0.0001) than in MCF-7 (p < 0.05). In combination with MTX, PPA (IC) increased Sub-G1 apoptotic populations in both lines. ABSTRACT: These findings demonstrate that PPA is unlikely to be a substrate of ABCG2 but functionally inhibits ABCG2-mediated efflux, contributing to the restoration of MTX sensitivity, although there may be additional mechanisms involved. PPA could be a promising MDR-reversal agent in ABCG2-driven chemotherapy resistance.
Synergistic Neuroprotection by Cannabis sativa and Tilia × viridis: Attenuation of Hippocampal Neurons Glutamate-Induced Oxidative Stress and LPS-Driven Microglial Inflammation.
Saint Martin EM, Barreiro-Arcos ML, Gomez MB … +7 more , Soldavini GC, Marrassini C, Cogoi L, Peralta I, Reinés A, Alonso MR, Anesini C
Planta Med · 2026 Jun · PMID 41628619 · Publisher ↗
ABSTRACT: Throughout history, has been linked to the therapeutic management of epilepsy and × has a tradition of use as a sedative. ABSTRACT: This study aimed to evaluate the protective effect of an ethanolic extract...
ABSTRACT: Throughout history, has been linked to the therapeutic management of epilepsy and × has a tradition of use as a sedative. ABSTRACT: This study aimed to evaluate the protective effect of an ethanolic extract of (CSRD), an aqueous extract of × (TE), and their combination against oxidative stress induced by glutamate in a murine hippocampal neuronal (HT-22) cell line, as well as their anti-inflammatory activity in male Wistar rats' microglial cells stimulated with LPS. A phytochemical analysis was also conducted. Glutamate-induced reactive oxygen species (ROS) were quantified using 2',7'-dichlorodihydrofluorescein diacetate via fluorescence microscopy. Cell viability was assessed using the MTT assay. Distinct microglial cell phenotypes were identified via immunofluorescence. ABSTRACT: Extracts partially reversed glutamate-induced loss of cell viability (52% to 200% for CSRD; 22% to 82% for TE). Their combination produced a greater effect, reversing glutamate-induced toxicity by 133% to 284% and fully restoring cell viability to control levels. Moreover, the combined treatment reduced intracellular ROS levels (52% to 58%). Notably, the combination also exhibited the most pronounced anti-inflammatory effects, significantly reducing the proportion of reactive phenotype 1 cells, while increasing the population of anti-inflammatory phenotype 2 cells and preserving the trophic phenotype 3 subpopulation. In conclusion, this study not only validates the ethnobotanical uses of and × but also reveals a potent synergy when combined. This provides a strong foundation for the development of phytomedicines with translational potential for managing complex pathologies like epilepsy or neuroinflammation associated with neurodegenerative diseases.
Efficacy and Safety of Ivy Leaf Dry Extract EA 575 in Cough Management: An Updated Review of Clinical Evidence.
Trompetter I, Braun S
Planta Med · 2026 Feb · PMID 41576988 · Publisher ↗
EA 575, the ivy leaf dry extract of the herbal medicine Prospan, has been widely used for the management of cough associated with various respiratory conditions. Over the past decade, new evidence has emerged from interv...
EA 575, the ivy leaf dry extract of the herbal medicine Prospan, has been widely used for the management of cough associated with various respiratory conditions. Over the past decade, new evidence has emerged from interventional and non-interventional studies offering a more comprehensive understanding of its efficacy, safety, and tolerability. This review provides an updated synthesis of clinical evidence of EA 575 in pediatric and adult patients with respiratory disease. A total of 27 publications were included, covering 13 interventional trials, 13 non-interventional studies, and 1 meta-analysis. These studies collectively enrolled 102 239 patients, of whom 84 022 received EA 575 treatment. The findings consistently demonstrate that EA 575 improves cough symptoms and lung function, as shown by improvements in the Bronchitis Severity Score, spirometry, and body plethysmography, depending on the parameters that have been assessed. Moreover, the tolerability of EA 575 has been increasingly confirmed through large real-world evidence studies that report a low number of non-serious adverse events. These results reinforce the well-established role of EA 575 in the effective and safe treatment of cough in clinical practice.
Phytochemical Diversity and Pharmacological Potential of Genista Species in Algeria: A Systematic Review.
Bouchliti S, Alallam B, Lim V … +4 more , Djebbar R, Boucelha L, Azizi J, Tan WN
Planta Med · 2026 Jun · PMID 41558514 · Publisher ↗
, a genus in the Fabaceae family mainly found in the Mediterranean, includes 25 species in Algeria where 11 are native. Locally, these species are used medicinally to treat gastrointestinal disorders, hyperglycemia, and...
, a genus in the Fabaceae family mainly found in the Mediterranean, includes 25 species in Algeria where 11 are native. Locally, these species are used medicinally to treat gastrointestinal disorders, hyperglycemia, and respiratory infections and as diuretics. This systematic review investigates the phytochemical diversity and pharmacological potential of the Algerian species. A comprehensive literature search was conducted in ScienceDirect, Scopus, Web of Science, PubMed, and Google Scholar up to December 2024, with no start date restrictions. The inclusion criteria focused on studies involving species collected from Algeria that investigated the identification and/or quantification of specific phytochemical profiles and/or pharmacological activities, using extracts, residues, fractions, or essential oils. Thirty-two studies met the criteria, covering nine species and identifying 132 compounds across major classes such as phenolic acids, flavonoids, terpenoids, alkaloids, saponins, and fatty acids. Total phenolic content (TPC) reached 690.32 mg gallic acid equivalent (GAE)/g, and total flavonoid content (TFC) was up to 318 mg quercetin equivalent (QE)/g. The highest antioxidant activity showed an IC of 3.65 µg/mL. Antibacterial effects were strongest against , with a 19 mm inhibition zone and minimum inhibitory concentration (MIC) values as low as 10 µg/mL. Hepatoprotective effects showed over 80% inhibition, while cytotoxicity had IC values as low as 5 µg/mL. Anti-inflammatory activity reached 96.54%. These findings highlight the diverse pharmacological activities of the genus and its potential for therapeutic applications. However, many bioactivities, such as antidiabetic, antispasmodic, gastroprotective, and immunomodulatory effects, remain underexplored, highlighting the need for further rigorous research.
Comprehensive Investigation of the Metabolism Profile of Norisoboldine in Rats Using UPLC-Q-TOF-MS/MS Method.
Li Y, Liu Y, Lin L … +2 more , Dai Y, Xia Y
Planta Med · 2026 May · PMID 41558513 · Publisher ↗
Linderae Radix, a traditional Chinese medicine known for its anti-inflammatory, antirheumatic, and analgesic effects, contains norisoboldine (NOR) as its primary bioactive component. NOR exhibits significant anti-inflamm...
Linderae Radix, a traditional Chinese medicine known for its anti-inflammatory, antirheumatic, and analgesic effects, contains norisoboldine (NOR) as its primary bioactive component. NOR exhibits significant anti-inflammatory effects in preclinical studies, particularly in rheumatoid arthritis and inflammatory bowel disease. Despite the various pharmacological activity of NOR, its metabolism and biotransformation patterns have yet to be elucidated. This study aimed to systematically elucidate the metabolic pathways of NOR, the excretion patterns of its metabolites, and the primary metabolic enzyme subtypes involved. Biosamples were collected from rats following oral administration of NOR (30 mg/kg). UPLC-Q-TOF-MS/MS was used to identify NOR metabolites in plasma, tissues, and excreta. Differences in the distribution of metabolites across excretion pathways were compared. Chemical inhibition assays and human recombinant enzyme experiments were conducted to determine the key cytochrome P450 (CYP450) enzyme subtypes involved. A total of 14 metabolites were identified, including 8 phase I metabolites and 6 phase II conjugates; the major metabolic reactions were hydrolysis, glucuronidation, sulfation, and dehydrogenation. The glycosylated conjugates (M13 - M15) predominantly underwent renal excretion via urine, whereas the hydrophobic metabolites (M2 - M9) were primarily eliminated through fecal routes due to limited aqueous solubility. The identification of CYP450 enzyme subtypes indicated that CYP3A1/2 and CYP2C11 were the key functional subtypes mediating NOR biotransformation. This study provides the first comprehensive characterization of NOR metabolism, demonstrating that CYP3A1/2 and CYP2C11 catalyze its conversion into 14 metabolites. These findings provide a theoretical basis for the clinical development of NOR and metabolic research on similar compounds.
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