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21 pages, 30578 KB  
Review
Diverse Utilization of Bidens pilosa and Prospects for Sustainable Management
by Li-Li Zhong, Xing-Song Zhou, Bin-Sheng Luo, Ruo-Zhu Lin, Shi Shi and Fei-Fei Li
Diversity 2026, 18(6), 349; https://doi.org/10.3390/d18060349 - 7 Jun 2026
Abstract
Bidens pilosa L. (Asteraceae), a globally invasive weed native to the Americas, is widely distributed across tropical and subtropical regions and is listed as invasive alien species in many countries. Despite its ecological hazards, it possesses a long history of traditional use and [...] Read more.
Bidens pilosa L. (Asteraceae), a globally invasive weed native to the Americas, is widely distributed across tropical and subtropical regions and is listed as invasive alien species in many countries. Despite its ecological hazards, it possesses a long history of traditional use and substantial resource potential that remains incompletely synthesized. This review systematically compiles ethnobotanical records from 15 countries, documenting 60 traditional medicinal indications across 14 disease categories spanning Latin America, Africa, Asia, and Oceania. A structured cross-referencing analysis reveals that 26 (43.33%) of these traditional applications are supported by 17 verified pharmacological mechanisms, mediated by 19 classes of bioactive compounds, principally flavonoids, polyacetylenes, and phenolic acids. Among these, anti-inflammatory, antidiabetic, antitumor, and antimicrobial activities are the most consistently validated. Moreover, this review synthesizes four non-medicinal utilization pathways: dietary use, animal feed, environmental remediation, and industrial raw materials. The resource value of B. pilosa has been independently recognized in the native and introduced ranges alike. Building on this evidence, we propose a “control-through-utilization” framework. To mitigate potential risks in practical exploitation, three targeted strategies are put forward, including timely harvesting, on-site processing and heavy metal safety inspection. This review supports the sustainable management of B. pilosa and offers methodological references for resource exploitation and control of other invasive plants. Full article
(This article belongs to the Special Issue Plant Diversity Discovery and Resource Utilization)
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38 pages, 2860 KB  
Review
Phytochemical-Based Therapeutic Strategies for Sarcopenia: From Molecular Mechanisms to Clinical Translation
by Gengyun Le-Chan, Nicole Q. Amoah, Hailey M. Sofia, Aidan H. Quee, Sunny S. K. Chan and Cindy A. Thomas-Charles
Pharmaceuticals 2026, 19(6), 905; https://doi.org/10.3390/ph19060905 - 7 Jun 2026
Abstract
Sarcopenia is a progressive, age-related musculoskeletal disorder characterized by the loss of skeletal muscle mass, strength, and physical performance, which contributes to frailty, disability, and mortality in older adults. Although resistance exercise and optimized protein intake remain first-line interventions, effective pharmacological therapies are [...] Read more.
Sarcopenia is a progressive, age-related musculoskeletal disorder characterized by the loss of skeletal muscle mass, strength, and physical performance, which contributes to frailty, disability, and mortality in older adults. Although resistance exercise and optimized protein intake remain first-line interventions, effective pharmacological therapies are limited, highlighting the need for novel adjunctive strategies. Increasing interest has focused on phytochemicals, plant-derived bioactive compounds with antioxidant, anti-inflammatory, and metabolic regulatory properties that may target multiple mechanisms underlying muscle aging. This review summarizes the molecular and translational potential of phytochemicals in sarcopenia management. Experimental and emerging clinical evidence indicates that flavonoids, polyphenols, alkaloids, and terpenoids modulate key pathways involved in sarcopenia pathogenesis, including PI3K/Akt/mTOR-mediated anabolic signaling, AMPK–SIRT3–PGC-1α-dependent mitochondrial biogenesis, NF-κB-driven inflammation, oxidative stress responses, autophagy, and satellite cell function. Through these pleiotropic effects, phytochemicals may attenuate the anabolic resistance, mitochondrial dysfunction, chronic inflammation, and impaired muscle regeneration associated with aging. Despite promising mechanistic evidence, clinical translation remains limited by poor bioavailability, variability in formulation and dosing, a lack of long-term randomized trials, and inconsistent functional outcome measures. Current evidence suggests that phytochemicals are most effective when integrated with resistance exercise and nutritional support rather than used as stand-alone therapies. Overall, phytochemicals represent promising complementary candidates for sarcopenia prevention and management. Future studies should prioritize standardized formulations, biomarker-guided approaches, and rigorously designed clinical trials focused on clinically meaningful functional outcomes to establish their efficacy, safety, and translational relevance in aging populations. Full article
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21 pages, 6345 KB  
Article
Drying-Induced Changes in Metabolite Profiles and Antioxidant Activity of Cordyceps militaris: Insights from Integrated Metabolomics and Network Pharmacology
by Xiaodan Wu, Weidi Fu, Wen Zhang, Hao Yu and Jianshuang Zhang
Foods 2026, 15(12), 2061; https://doi.org/10.3390/foods15122061 - 7 Jun 2026
Abstract
Cordyceps militaris, a medicinal and edible mushroom, is renowned for its bioactive constituents and health-promoting effects. This study investigated the effects of vacuum freeze drying (VF), vacuum drying (VD), oven drying (OV), and sun drying (SU) on the metabolite profiles and antioxidant [...] Read more.
Cordyceps militaris, a medicinal and edible mushroom, is renowned for its bioactive constituents and health-promoting effects. This study investigated the effects of vacuum freeze drying (VF), vacuum drying (VD), oven drying (OV), and sun drying (SU) on the metabolite profiles and antioxidant activities of C. militaris. VF showed the highest levels of total phenolics, total carotenoids, cordycepin, and N6-(2-hydroxyethyl)-adenosine, whereas VD better preserved total flavonoids. VF- and VD-treated samples also exhibited stronger antioxidant capacities than those processed by OV and SU in 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS•+), hydroxyl radical (•OH), and ferric reducing antioxidant power (FRAP) assays. Metabolomics analysis identified 193 significantly altered metabolites after drying treatments. VF, VD, and SU increased carbohydrates, vitamins, and phenolic acids, while leading to reductions in amino acids, nucleotides, and fatty acids. KEGG analysis revealed that drying significantly affected pathways related to purine and pyrimidine metabolism, amino acid biosynthesis, and phenylpropanoid biosynthesis. Network pharmacology further identified 8 key compounds potentially associated with antioxidant effects through interactions with 37 core targets. These findings highlight the importance of selecting appropriate drying methods to preserve the bioactive compounds and functional quality of C. militaris. Full article
(This article belongs to the Section Foodomics)
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19 pages, 4436 KB  
Article
Curcumin Induces Pyroptosis-Associated Molecular Changes in Osteosarcoma Cells Correlating with the ROS/NLRP3/CASPASE-1/GSDMD Axis with Concomitant PI3K/AKT Suppression and Apoptosis Activation
by Keqing Yuan, Xingyu Zhao, Jiayi Guo, Yue Lu, Yufei Cui, Wei Zhang and Wenhe Zhu
Nutrients 2026, 18(11), 1831; https://doi.org/10.3390/nu18111831 - 5 Jun 2026
Viewed by 79
Abstract
Curcumin, a natural polyphenolic compound derived from turmeric, exhibits broad-spectrum anticancer activities, but its ability to induce pyroptosis in osteosarcoma remains unknown. Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, and novel therapeutic strategies are urgently needed to [...] Read more.
Curcumin, a natural polyphenolic compound derived from turmeric, exhibits broad-spectrum anticancer activities, but its ability to induce pyroptosis in osteosarcoma remains unknown. Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, and novel therapeutic strategies are urgently needed to overcome osteosarcoma chemoresistance. Aim: This study aimed to investigate whether curcumin induces pyroptosis-associated molecular changes in human osteosarcoma cells and to explore the underlying molecular mechanisms, focusing on the ROS/NLRP3/CASPASE-1/GSDMD axis and the PI3K/AKT signaling pathway. Methods: Human osteosarcoma U2OS and MG63 cells were treated with curcumin (20–40 μmol·L−1 for 24 h). Cell viability was assessed by CCK-8 assay. Pyroptotic morphology was observed by scanning electron microscopy. Lactate dehydrogenase (LDH) release was measured colorimetrically, and IL-1β/IL-18 secretion was quantified by ELISA. Mitochondrial membrane potential (ΔΨm) and intracellular reactive oxygen species (ROS) levels were analyzed by flow cytometry. Protein expression levels of NLRP3, cleaved CASPASE-1, GSDMD-N, PI3K, AKT, p-AKT, Bax, Bcl-2 and cleaved CASPASE-3 were detected by Western blotting. Pharmacological validation was performed using the pan-caspase inhibitor Z-VAD-FMK. Results: Curcumin significantly inhibited the proliferation of U2OS and MG63 cells in a dose- and time-dependent manner. Scanning electron microscopy revealed characteristic pyroptotic features including cell swelling, membrane pore formation, and rupture. Curcumin treatment markedly increased LDH release and elevated IL-1β/IL-18 secretion. Mechanistically, curcumin induced mitochondrial membrane depolarization and ROS accumulation, upregulated NLRP3, cleaved CASPASE-1, and GSDMD-N expression, and concomitantly reduced PI3K/AKT pathway activity. Additionally, curcumin upregulated pro-apoptotic Bax, downregulated anti-apoptotic Bcl-2, and activated cleaved CASPASE-3. The pan-caspase inhibitor Z-VAD-FMK partially reversed curcumin-induced cytotoxicity, confirming that caspase-dependent apoptosis contributes to the overall anticancer effect. Conclusions: This study provides evidence that curcumin induces both apoptosis and pyroptosis-associated molecular changes in human osteosarcoma cells. The pyroptotic effect involves the ROS/NLRP3/CASPASE-1/GSDMD axis, accompanied by PI3K/AKT suppression, while caspase-dependent apoptosis also plays an important role. These findings uncover a previously unreported mechanism of curcumin’s anti-osteosarcoma activity and suggest that targeting multiple cell death pathways may represent a promising strategy to overcome apoptosis resistance in osteosarcoma. Full article
(This article belongs to the Special Issue Botanicals and Nutritional Approaches in Metabolic Disorders)
24 pages, 5915 KB  
Article
Study of Artemisia ordosica Krasch. Against Allergic Rhinitis Based on the P815 Mast Cell Degranulation Model, Network Pharmacology, Molecular Docking, and Molecular Dynamics
by Mengmeng Wang, Jingming Zou, Qi Zhang, Xianxiang Bai, Si Wu, Yawei Hu, Xiaoyan Han, Na Han and Bin Xiao
Int. J. Mol. Sci. 2026, 27(11), 5122; https://doi.org/10.3390/ijms27115122 - 5 Jun 2026
Viewed by 61
Abstract
Allergic rhinitis (AR) is one of the most prevalent allergic disorders worldwide. Current pharmacological treatments are often limited by suboptimal efficacy and notable adverse effects. Herbal medicines, with their multi-component and multi-target therapeutic characteristics, have attracted increasing attention. Artemisia ordosica Krasch. (AOK), a [...] Read more.
Allergic rhinitis (AR) is one of the most prevalent allergic disorders worldwide. Current pharmacological treatments are often limited by suboptimal efficacy and notable adverse effects. Herbal medicines, with their multi-component and multi-target therapeutic characteristics, have attracted increasing attention. Artemisia ordosica Krasch. (AOK), a traditional Chinese/Mongolian medicine has demonstrated immunomodulatory, antioxidant, and anti-inflammatory activities. The anti-AR potential of AOK extract fractions was evaluated using in vitro mast cell degranulation inhibition assays, network pharmacology analysis, molecular docking, and molecular dynamics simulations to elucidate underlying pharmacological mechanisms. The P815 mast cell model induced by compound 48/80 was employed to assess the inhibitory activity and cytotoxicity of different extract fractions. Among the tested fractions, the ethyl acetate fraction exhibited the most potent inhibitory effect on mast cell degranulation without significant cytotoxicity. Network pharmacology analysis identified 254 potential AR-related targets of AOK, with Signal Transducer and Activator of Transcription 3(STAT3), Src protein(SRC), Tumor protein 53(TP53), AKT Serine/Threonine Kinase 1(AKT1), Heat Shock Protein 90 Alpha Family Class A Member 1(HSP90AA1), Estrogen Receptor 1(ESR1), and Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA) identified as key hub proteins. Gene Ontology and KEGG pathway enrichment analyses indicated that AOK primarily modulated inflammatory and oxidative stress-related processes through the lipid and atherosclerosis, hypoxia-inducible factor-1, and AGE-RAGE signaling pathways. Molecular docking and dynamics simulations demonstrated strong binding affinities and stable interactions between major active constituents, particularly hydroxygenkwanin, and key targets such as SRC. The ethyl acetate fraction of AOK extract exhibited significant mast cell degranulation inhibitory activity, likely mediated via a synergistic multi-component, multi-target mechanism involving regulation of inflammatory and immune-related signaling pathways. These findings provide a pharmacological basis for the potential application of AOK in AR treatment. Full article
(This article belongs to the Section Molecular Pharmacology)
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15 pages, 646 KB  
Article
Sustainable Use of Natural Resources and Traditional Medicine in Tropical Countries: Uncovering the Main Antioxidant Compounds and Antihypertensive Potential of the Diospyros comorensis Leaves as Health-Promoting Food Application for Local Population
by Ahmed Ali, Dario Donno, Zoarilala Rinah Razafindrakoto, Nantenaina Tombozara, Azali Ahamada-Himidi, Mamy Julien Randrianirina, Giovanni Gamba, Jean François Rajaonarison, Gabriele Loris Beccaro and David Ramanitrahasimbola
Plants 2026, 15(11), 1757; https://doi.org/10.3390/plants15111757 - 5 Jun 2026
Viewed by 485
Abstract
Diospyros comorensis Hiern is a medicinal plant traditionally utilized in the management of cardiovascular disorders. Despite its common use, the pharmacological properties and phytochemical composition remain unexplored. This study aimed to evaluate the vasorelaxant, diuretic, and antioxidant activities, as well as toxicity and [...] Read more.
Diospyros comorensis Hiern is a medicinal plant traditionally utilized in the management of cardiovascular disorders. Despite its common use, the pharmacological properties and phytochemical composition remain unexplored. This study aimed to evaluate the vasorelaxant, diuretic, and antioxidant activities, as well as toxicity and phytochemical profiling, of a methanol–water extract of D. comorensis leaves (MDCR) and a decoction of D. comorensis leaf (DDCR) extract. The main phytochemicals were quantified using High-Performance Liquid Chromatography (HPLC). Antioxidant capacity was assessed using DPPH and FRAP assays. The vasorelaxant effect was evaluated in vitro on phenylephrine-precontracted aortic rings. Diuretic activity was determined by measuring Wistar rats’ urine output and electrolyte levels (Na+, Cl, and K+). Toxicity was assessed using Swiss mice. The extracts showed a total phenolic content (TPC) of 29,693.02 ± 3493.75 mg GAE/100 g DW (Folin–Ciocalteu method), which was markedly higher than the total phenolics quantified by HPLC (3743.12 ± 457.32 mg/100 g DW, representing 76.38% of the total bioactive fraction). Among the quantified constituents, ellagic acid (56.36%) was the main compound. Both extracts exhibited marked antioxidant capacity along with significant vasorelaxant effects on phenylephrine-precontracted rat aorta rings, with EC50 values of 3.83 ± 0.81 µg/mL for MDCR and 4.87 ± 0.79 µg/mL for DDCR. Acute toxicity was not observed with either extract. The identified compounds may be involved in the observed antioxidant and pharmacological effects. These results show experimental evidence useful to support the traditional use of D. comorensis leaves in managing high blood pressure and highlight the antihypertensive potential of this Comorian endemic species. Further studies are necessary to characterize the biological mechanisms involved and relative bioactive substances. Reporting the pharmacological activities of D. comorensis may contribute to the sustainable use of natural resources in the Comoros Islands and Madagascar. Full article
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29 pages, 2228 KB  
Review
Phosphoproteomics and Multi-Omics for Oleanolic Acid Target Deconvolution: From Phosphorylation Signatures to Mechanistic Validation
by Andrzej Günther and Barbara Bednarczyk-Cwynar
Kinases Phosphatases 2026, 4(2), 14; https://doi.org/10.3390/kinasesphosphatases4020014 - 5 Jun 2026
Viewed by 153
Abstract
Oleanolic acid (OA) is a pentacyclic triterpenoid with broad biological activity, but its primary molecular points of engagement remain incompletely resolved. Most available studies describe OA through selected pathway markers, particularly within PI3K/AKT/mTOR, AMPK/mTOR, MAPK, NF-κB, and Nrf2 signaling, without clearly distinguishing direct [...] Read more.
Oleanolic acid (OA) is a pentacyclic triterpenoid with broad biological activity, but its primary molecular points of engagement remain incompletely resolved. Most available studies describe OA through selected pathway markers, particularly within PI3K/AKT/mTOR, AMPK/mTOR, MAPK, NF-κB, and Nrf2 signaling, without clearly distinguishing direct target engagement from downstream adaptive responses. This limits mechanistic interpretation and weakens translational prioritization. This review focuses specifically on phosphoproteomics-centered and multi-omics-assisted target deconvolution of OA rather than providing a comprehensive catalog of all reported biological effects of OA. We examine why phosphoproteomics is particularly informative for capturing early signaling events, how it can be integrated with total proteomics, transcriptomics, metabolomics, and chemoproteomic approaches, and why orthogonal target-engagement methods remain essential for stronger causal inference. We also organize the current signaling evidence for OA and its derivatives, distinguishing pathway association, kinase/phosphatase activity inference, target prioritization, and direct target validation. The strongest mechanistic support for the parent compound currently concerns AMPK/mTOR-linked regulation of autophagy and apoptosis, whereas evidence for several other pathways remains more heterogeneous, derivative-dependent, or marker-based. Finally, we propose a stepwise workflow for OA target deconvolution based on time-resolved phosphoproteomics, informative phosphosite subsets, multi-omics integration, kinase/phosphatase activity inference, and experimental target validation. This framework may help move OA research from descriptive pathway pharmacology toward mechanism-based target prioritization and more rational derivative development. Full article
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47 pages, 16002 KB  
Article
Integrated Chemical Profiling, Serum Pharmacochemistry, and Network Pharmacology to Elucidate the Anti-Hyperlipidemic Effects of Rosa laxa Retz. Fruits from Different Geographical Origins
by Yuan He, Qianqian Feng, Wenhui Zhao and Li Tian
Metabolites 2026, 16(6), 392; https://doi.org/10.3390/metabo16060392 - 4 Jun 2026
Viewed by 91
Abstract
Background: The fruits of Rosa laxa Retz. (FRL) is a traditional medicinal and edible fruit widely used in Xinjiang for its potential health benefits. Its chemical variations across geographical origins remain poorly understood, as do the molecular mechanisms underlying its anti-hyperlipidemic effects. This [...] Read more.
Background: The fruits of Rosa laxa Retz. (FRL) is a traditional medicinal and edible fruit widely used in Xinjiang for its potential health benefits. Its chemical variations across geographical origins remain poorly understood, as do the molecular mechanisms underlying its anti-hyperlipidemic effects. This study aimed to characterize the chemical profile of FRL extract (FRLE) from different origins, identify its bioactive constituents and metabolites in vivo, and evaluate its efficacy and potential mechanisms against HLP. Methods: UPLC-QTOF-MS was employed for qualitative and quantitative profiling, combined with PCA to differentiate samples from five origins. An HLP mouse model was established to evaluate the pharmacodynamic effects, while acute and sub-chronic toxicity tests assessed safety. Serum pharmacochemistry was used to track absorbed constituents and metabolites. Finally, network pharmacology, molecular docking, and Western blot were integrated to elucidate the underlying mechanisms. Results: A total of 60 compounds were identified in FRLE, with 20 key components quantified via the TOF-MRM mode. PCA indicated that the Yamalike Mountain samples possessed the most diverse chemical profile and the highest response of active markers. Pharmacodynamic results showed that FRLE (extraction yield 24.19%) significantly improved TC, LDL-C, and corrected abnormal HDL-C levels in HLP mice, while H&E staining confirmed the alleviation of hepatic steatosis. Safety evaluations revealed no significant acute or cumulative toxicity at the maximum feasible dose of 16.6 g/kg. In rat plasma, 15 prototypes and 14 metabolites were identified. FRLE acted on the “Lipid and Atherosclerosis” pathway by modulating key targets, including NFE2L2, CYP1A1, NOS3, and MAPK1. Conclusions: Our findings demonstrate that FRLE is a safe and effective candidate for the management of hyperlipidemia. This study establishes a link between the material basis and biological mechanisms of FRL, thereby providing a scientific foundation for its further resource development and clinical application. Full article
(This article belongs to the Section Plant Metabolism)
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25 pages, 3731 KB  
Article
Protective Effects of Momordica charantia Extract on Dexamethasone-Induced Sarcopenic Changes in C2C12 Cells: Integrated Network Pharmacology and Experimental Validation
by Jung Eun Park, Kang Sub Kim, Mina Jeong, Hee Woon Ann, Rajath Ramachandran, Il-Ho Park, Ki Hyun Kim, Ki Sung Kang and Dae-Woon Eom
Pharmaceuticals 2026, 19(6), 893; https://doi.org/10.3390/ph19060893 - 4 Jun 2026
Viewed by 133
Abstract
Background/Objectives: Sarcopenia is characterized by progressive skeletal muscle loss and impaired myogenic differentiation and is closely associated with inflammation and metabolic dysfunction. Methods: This study investigated the protective effects of Momordica charantia extract against dexamethasone-induced sarcopenia and explored the underlying mechanisms [...] Read more.
Background/Objectives: Sarcopenia is characterized by progressive skeletal muscle loss and impaired myogenic differentiation and is closely associated with inflammation and metabolic dysfunction. Methods: This study investigated the protective effects of Momordica charantia extract against dexamethasone-induced sarcopenia and explored the underlying mechanisms using network pharmacology, C2C12 cell-based assays, Western blotting, and molecular docking. Network pharmacology analysis identified quercetin, ascorbic acid, and tocopherol as major active compounds associated with targets related to inflammation, extracellular remodeling, and metabolic dysfunction. Results: M. charantia extract (MCE) did not markedly reduce cell viability at concentrations up to 100 μg/mL and improved dexamethasone-induced morphological impairment of myotubes. The extract reduced MAFbx, MMP-2, and MMP-9 expression while restoring phosphorylated p38, MyoD, and myogenin expression, indicating suppression of atrophy- and remodeling-related responses, together with the recovery of myogenic signaling. Among the major identified compounds, all attenuated dexamethasone-induced myotube atrophy and quercetin showed the most pronounced morphological recovery. Molecular docking analysis targeting p38α showed the highest binding affinity for α-tocopherol, followed by quercetin and ascorbic acid, supporting potential interactions between the major compounds and p38 MAPK-related signaling. Conclusions: Collectively, these findings suggest that M. charantia attenuates sarcopenic changes by promoting myogenic differentiation and modulating the p38 MAPK-associated pathways. Full article
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26 pages, 2617 KB  
Review
Green Extraction of Bioactive Compounds from Marine Macroalgae: Chemistry, Pharmacological Activities, and Biotechnological Applications
by Yongjing Guan, Yuxin Guo, Luoxuan Lin, Lizhu Zhang, Weichao Chen and Chao Zhao
Mar. Drugs 2026, 24(6), 198; https://doi.org/10.3390/md24060198 - 4 Jun 2026
Viewed by 133
Abstract
Marine macroalgae are widely distributed renewable resources that offer substantial economic and environmental benefits. This review comprehensively examines seaweeds from the phyla Chlorophyta, Heterokontophyta, and Rhodophyta, highlighting key advances and persistent challenges. Global seaweed production is highly concentrated: Asia accounts for 97% of [...] Read more.
Marine macroalgae are widely distributed renewable resources that offer substantial economic and environmental benefits. This review comprehensively examines seaweeds from the phyla Chlorophyta, Heterokontophyta, and Rhodophyta, highlighting key advances and persistent challenges. Global seaweed production is highly concentrated: Asia accounts for 97% of the total, with China as the dominant producer. These seaweeds synthesize a diverse array of bioactive compounds, including sulfated polysaccharides, phlorotannins, terpenoids, proteins, peptides, polyunsaturated fatty acids, and pigments. Notably, brown algae represent the richest source of both phlorotannins and polyunsaturated fatty acids. To recover these valuable compounds efficiently, a range of advanced green extraction techniques have been developed, such as enzyme-assisted, microwave-assisted, ultrasound-assisted, and supercritical fluid extraction, along with natural deep eutectic solvents. These methods consistently outperform conventional approaches in terms of yield, extraction time, and environmental sustainability. The isolated compounds exhibit a broad spectrum of validated pharmacological activities, including immunomodulatory, anti-inflammatory, anti-diabetic, neuroprotective, antitumor, and antiviral effects. Consequently, they have found diverse applications in functional foods, biomedicine, cosmetics, agriculture, aquaculture, and environmental protection. Despite this promise, critical challenges remain in elucidating structure–activity relationships, developing scalable and sustainable extraction protocols, and advancing clinical translation. Future research should prioritize the discovery of novel marine bioactives, the enzymatic production of oligosaccharides, efficient purification of algal proteins and peptides, and the scaling-up of industrial processes to fully realize the pharmaceutical and biotechnological potential of marine macroalgae. Full article
(This article belongs to the Special Issue Green Extraction of High-Value Compounds in Marine Algae)
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27 pages, 2535 KB  
Systematic Review
Validating the Effectiveness of Forest Therapy Programs for Middle-Aged Korean Women: A Systematic Review and Meta-Analytic Approach
by Young-Ho Lee, Gyeong-Min Min and Pyeong-Sik Yeon
Healthcare 2026, 14(11), 1569; https://doi.org/10.3390/healthcare14111569 - 3 Jun 2026
Viewed by 226
Abstract
Background/Objectives: Middle-aged Korean women (aged 40–65 years) face compounded physiological and psychosocial health burdens, yet controlled evidence for non-pharmacological interventions in this population remains limited. This systematic review and meta-analysis aimed to quantify the effects of forest therapy on health-related outcomes in middle-aged [...] Read more.
Background/Objectives: Middle-aged Korean women (aged 40–65 years) face compounded physiological and psychosocial health burdens, yet controlled evidence for non-pharmacological interventions in this population remains limited. This systematic review and meta-analysis aimed to quantify the effects of forest therapy on health-related outcomes in middle-aged Korean women and to identify program characteristics associated with differential therapeutic effects. Methods: Ten databases were searched for controlled studies published from January 2000 to February 2025 following PRISMA 2020 and PICOTS-SD criteria; only controlled studies conducted in Korea were included in the meta-analysis. Of 9563 records screened, 24 controlled Korean studies (RCT, n = 13; NRCT, n = 11; k = 128 effect sizes) met inclusion criteria. A three-level random-effects model with robust variance estimation (RVE) was used as the primary analysis. Results: The primary three-level RVE model, applied to 24 controlled Korean studies, yielded a pooled Hedges’ g = 0.596 (95% CI: 0.432–0.760); a supplementary standard random-effects model yielded g = 0.542 (95% CI: 0.420–0.664). Substantial heterogeneity and potential publication bias were observed; overall evidence certainty was rated Low (GRADE). Conclusions: These findings provide preliminary, low-certainty evidence (overall GRADE: Low) that forest therapy may benefit middle-aged Korean women. They do not justify broad clinical or policy adoption at present. High-quality, independently conducted international RCTs and standardized trials outside Korea are required to confirm and generalize these findings. Full article
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19 pages, 7212 KB  
Article
Structure-Based Identification of Allosteric Glucocerebrosidase Stabilizers from Xylia xylocarpa (Roxb.) Taub. for Parkinson’s Disease Using LC-MS Profiling and Computational Analysis
by Irshad Ahammed Ebrahim Thaivalappil, Aswin Mohan, Anuroopa G. Nadh, Rajesh Raju and Mohammed Gulzar Ahmed
Plants 2026, 15(11), 1731; https://doi.org/10.3390/plants15111731 - 3 Jun 2026
Viewed by 150
Abstract
Parkinson’s disease is strongly linked to lysosomal dysfunction, particularly reduced activity of glucocerebrosidase (GCase) encoded by the GBA1 gene. Stabilizing GCase using small-molecule modulators represents a promising therapeutic strategy. In this study, phytochemicals from Xylia xylocarpa (Roxb.) Taub., a medicinal plant with reported [...] Read more.
Parkinson’s disease is strongly linked to lysosomal dysfunction, particularly reduced activity of glucocerebrosidase (GCase) encoded by the GBA1 gene. Stabilizing GCase using small-molecule modulators represents a promising therapeutic strategy. In this study, phytochemicals from Xylia xylocarpa (Roxb.) Taub., a medicinal plant with reported neuroprotective potential, were profiled using LC-QTOF-MS and evaluated as GCase stabilizers through an integrated computational approach. LC-MS analysis in positive and negative modes tentatively identified 19 metabolites, of which 13 low-molecular-weight compounds (<500 Da) were selected for molecular docking against human GCase. Docking revealed six compounds with higher predicted binding affinity than the reference activator Pyrrolopyrazine. Pharmacokinetic screening based on Lipinski’s rule of five and ADMET predictions identified Senbusine A as a viable lead candidate. It exhibited favorable binding interactions, forming stabilizing contacts within a non-catalytic inter-monomer interface associated with structural modulation of GCase. PASS analysis suggested a high probability of neuroactive properties. Molecular dynamics simulations (200 ns) confirmed stable binding and reduced conformational fluctuations compared to apo and control systems. Overall, computational predictions identify Senbusine A as a potential pharmacological chaperone-like stabilizer of GCase, exhibiting a favorable pharmacological profile and warranting further experimental validation. Full article
(This article belongs to the Special Issue Applications of Omics and Bioinformatics in Medicinal Plants)
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61 pages, 2605 KB  
Review
Herbal Neurotherapeutics for Cognitive Disorders: Integrative Mechanisms Linking Neurotransmitter Systems, Neurodegeneration, and the Gut-Brain Axis
by Muntajin Rahman, Khadija Akter, Amama Rani, Moon Nyeo Park and Bonglee Kim
Nutrients 2026, 18(11), 1796; https://doi.org/10.3390/nu18111796 - 2 Jun 2026
Viewed by 558
Abstract
Cognitive disorders, including Alzheimer’s disease, Parkinson’s disease, schizophrenia, depression, and vascular dementia, are associated with dysregulation of neurotransmitter systems, including acetylcholine, dopamine, serotonin, glutamate, and γ-aminobutyric acid (GABA). These disorders are increasingly recognized as multifactorial conditions involving oxidative stress, neuroinflammation, mitochondrial dysfunction, synaptic [...] Read more.
Cognitive disorders, including Alzheimer’s disease, Parkinson’s disease, schizophrenia, depression, and vascular dementia, are associated with dysregulation of neurotransmitter systems, including acetylcholine, dopamine, serotonin, glutamate, and γ-aminobutyric acid (GABA). These disorders are increasingly recognized as multifactorial conditions involving oxidative stress, neuroinflammation, mitochondrial dysfunction, synaptic impairment, blood–brain barrier disruption, metabolic imbalance, and gut–brain axis dysregulation. Current pharmacological therapies may provide symptomatic relief; however, their clinical benefits are often limited and associated with adverse effects. Herbal medicines have gained increasing attention as potential complementary approaches for cognitive support and neuroprotection. Preclinical evidence and emerging clinical studies suggest that herbal bioactive compounds may exert neuroprotective effects through antioxidants, anti-inflammatory, and neurotransmitter-modulating mechanisms. Medicinal herbs such as Bacopa monnieri, Withania somnifera, Ginkgo biloba, Glycyrrhiza glabra, Moringa oleifera, and ginseng have shown potential cognitive benefits in experimental models and selected human studies. Advanced delivery systems, including nanoparticles and phytosomes, may further improve the bioavailability and brain-targeting efficiency of herbal compounds. However, current clinical evidence remains heterogeneous and limited by insufficient standardization, small sample sizes, and short study durations. Further large-scale clinical studies and standardized safety assessments are essential before herbal neurotherapeutics can be widely applied in cognitive and neurological disorders. Full article
(This article belongs to the Special Issue Dietary Factors and Interventions for Cognitive Neuroscience)
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15 pages, 3827 KB  
Article
Patterns of Biflavonoid Accumulation in Ginkgo (Ginkgo biloba L.) Leaves from 90 Trees and Their Variation with Age, Gender, and Location
by Dunja Šamec, Barbara Medvedec, Iva Jurčević Šangut and Ana Jurinjak Tušek
Plants 2026, 15(11), 1724; https://doi.org/10.3390/plants15111724 - 2 Jun 2026
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Abstract
Biflavonoids are dimeric flavonoids recognized for their diverse biological activities and significant pharmacological potential, with ginkgo (Ginkgo biloba L.) serving as a primary natural source. This study presents a comprehensive spatiotemporal characterization of the biflavonoid profile across a diverse population of 90 [...] Read more.
Biflavonoids are dimeric flavonoids recognized for their diverse biological activities and significant pharmacological potential, with ginkgo (Ginkgo biloba L.) serving as a primary natural source. This study presents a comprehensive spatiotemporal characterization of the biflavonoid profile across a diverse population of 90 trees. High-resolution chromatographic analysis quantified five major biflavonoids, revealing a consistent hierarchical abundance: sciadopitysin > isoginkgetin > ginkgetin > bilobetin > amentoflavone. Notably, sciadopitysin emerged as the predominant constituent (1532.89 ± 544.13 µg/g dw). To decode the complex drivers of metabolite accumulation, we integrated Principal Component Analysis (PCA) with Piecewise Linear Regression (PLR). PCA confirmed a robust chemical structure, explaining 71.5% of the total variance, where Factor 1 represents a general biflavonoid gradient and Factor 2 captures localized environmental influences. The PLR models (R2 = 0.75–0.83) identified tree age as a primary negative regulator, showing a significant decline in total biflavonoids as trees mature beyond the 30-year reproductive threshold. While sexual dimorphism and location exhibited compound-specific nonlinear effects, younger trees (10–30 years) demonstrated the highest biosynthetic plasticity and potency. These findings establish a predictive framework for optimizing the pharmaceutical harvest of ginkgo leaves, highlighting that age-related physiological shifts, rather than gender or broad geography, are the critical determinants of biflavonoids yield. Full article
(This article belongs to the Section Phytochemistry)
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21 pages, 16735 KB  
Article
Sources of Polyphenols with Potential α-Glucosidase-Inhibitory Activities from Thai Local Edible Plants: In Vitro and Network Pharmacology Approaches
by Ploenthip Puthongking, Juthamat Ratha, Pimolwan Siriparu, Muhammad Subhan, Panyada Panyatip, Ployvadee Sripadung, Tanit Padumanonda, Sarin Tadtong, Vuanghao Lim and Bunleu Sungthong
Plants 2026, 15(11), 1721; https://doi.org/10.3390/plants15111721 - 2 Jun 2026
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Abstract
Plant polyphenols possess various biological activities such as antioxidant and antidiabetic activities. Based on the high plant biodiversity in Thailand, selected edible plants were therefore investigated to explore how dietary polyphenols and α-glucosidase-inhibitory activity can contribute to significant control and prevention of type [...] Read more.
Plant polyphenols possess various biological activities such as antioxidant and antidiabetic activities. Based on the high plant biodiversity in Thailand, selected edible plants were therefore investigated to explore how dietary polyphenols and α-glucosidase-inhibitory activity can contribute to significant control and prevention of type 2 diabetes mellitus (T2DM). Network pharmacology of antidiabetic activity was employed to predict the underlying antidiabetic mechanisms of the phytochemicals identified in the 15 selected edible Thai plants. The results showed that wild guava (Careya arborea Roxb.; CaA) leaf extract presented the highest total phenolic content (TPC). CaA exhibited the highest antioxidant activities in all the assays as a function of its TPC. Moreover, CaA showed the highest inhibitory effect on α-glucosidase activity in the test, with an IC50 of 0.13 µg/mL, being approximately 1600 times more potent than the standard α-glucosidase-inhibitory drug acarbose. Phenolic profile analysis revealed that the CaA leaf extract consisted of gallic acid, caffeic acid, sinapic acid, rutin, and quercetin. The phytochemical contents of CaA strongly contributed to its antioxidant and α-glucosidase-inhibitory activity. In addition to other phytochemicals, the highest contents of the indolamine compounds tryptophan and melatonin were found in malabar spinach (Basella alba L.; BA) and water clover (Marsilea crenata C. Presl; MaC), at 2213.05 and 99.17 ng/g DW, respectively. Network pharmacology on antidiabetic activity exhibited the most relevant pathway involved in the insulin resistance and AGE-RAGE signaling pathways that caused glucose and glycogen synthesis in skeletal muscle, increasing hepatic gluconeogenesis, and reduced glycogen synthesis in the liver. The implication of these findings is that these Thai edible plants have the potential to combat diabetes by inhibiting the function of α-glucosidase. Full article
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