Phyllanthus lawii and P. scabrifolius are underexplored medicinal species within the genus Phyllanthus, renowned for phenolic-rich metabolites with diverse pharmacological activities. This study aimed to provide a comprehensive metabolite overview and chemotaxonomic insight into these taxa using LC-HRMS based untargeted metabolomics. Crude extracts from leaves, stems and roots of both species were profiled by LC-HRMS in negative ion mode, and metabolites were tentatively identified by combining accurate mass measurements with fragmentation patterns. This analysis resulted in the tentative annotation of 51 metabolites, including gallic acid derivatives, ellagitannins, bergenin/norbergenin and their galloyl/coumaroyl esters, flavan 3 ols and multiple quercetin/myricetin glycosides along with other metabolites. Distinct species and tissue specific distribution patterns were observed emerging as potential chemical markers for both species. These findings underscore the potential of untargeted metabolomics for structural hypothesis generation, species authentication. Collectively, this work provides first untargeted metabolomic overview of P. lawii and P. scabrifolius and substantially expands the catalog of tentatively identified metabolites known from these species. Beyond structural discovery, the set of putative chemical markers and the tissue specific metabolite patterns generated here offer a robust basis for species authentication, quality control, and provides a rational starting point for future bioactivity guided metabolomics.
Abstract Centella asiatica (L.) (Gotu Kola) is a medicinal herb traditionally used in Asia for cognitive enhancement, wound healing, and systemic disorders. This systematic review appraises preclinical and clinical evidence on its cardiovascular and neurological effects. Following PRISMA 2020, we searched PubMed, ScienceDirect, Scopus, Embase, and ClinicalTrials.gov (to June 2026) for studies of whole-plant extracts or bioactive compounds (asiatic acid, asiaticoside, madecassoside, madecassic acid, caffeoylquinic acids) in vitro, in animals, or in humans, excluding dermatological studies, reviews, and articles lacking methods. Sixty-two studies met criteria: 54 preclinical and eight clinical trials, assessed using SYRCLE, an in vitro checklist, and Cochrane RoB 2. Preclinically, C. asiatica modulated ischemia-reperfusion injury, reduced doxorubicin-induced cardiotoxicity, improved cognitive deficits in Alzheimer’s and Parkinson’s models, and showed antidepressant-like effects, via Nrf2/HO-1 antioxidant activation and NF-κB/MAPK anti-inflammatory suppression. Clinical evidence was mixed: Gotu Kola matched or exceeded folic acid for poststroke vascular cognitive impairment, and three trials of a standardized triterpenic fraction (TTFCA) improved microcirculation in venous hypertensive and diabetic microangiopathy; however, a type 2 diabetes trial found no significant effect on glycated hemoglobin, glucose, or LDL cholesterol, a mild cognitive impairment trial found no added benefit over exercise alone, and a Phase 1 safety trial is ongoing. C. asiatica shows preclinical promise as a multitarget cardiovascular and neurological agent, but clinical evidence remains limited and inconsistent, compounded by an 800-fold preclinical dosing range, variable treatment durations, and geographic concentration (47% from one country). Larger, standardized, multiregion trials targeting these outcomes are needed before therapeutic claims are warranted.
Abstract The urgent need for effective Alzheimer’s disease (AD) therapies has spurred the search for novel bioactive compounds within the vast chemical space of microbial natural products. Here, we integrated nontargeted metabolomics with network pharmacology to explore the neuroprotective potential of Streptomyces flavusporus HC307. Systematic profiling of the HC307 metabolome revealed nearly 3000 features. Subsequent statistical screening and database matching narrowed the focus to 34 potential anti-AD candidates, facilitating the targeted isolation of the bioactive cyclodipeptide, cyclo(Gly-L-Pro) (307-1). Network pharmacology analysis predicted that cyclo(Gly-L-Pro) may modulate a network of 86 AD-related targets, with EGFR, CTSB, GSK3B, PARP1, and SIRT1 serving as core nodes. Molecular docking showed favorable binding affinities, particularly toward GSK3B and PARP1 (−6.6 kcal mol−1 for both), suggesting a multifaceted mechanism spanning tau protein regulation, anti-inflammation, and oxidative stress mitigation. This study establishes S. flavusporus HC307 as a promising source of neuroactive leads and elucidates the multitarget profile of cyclo(Gly-L-Pro), providing a basis for its further development as an anti-AD lead.
Abstract Idesia polycarpa, a dioecious tree distributed across East Asia, is known for its pharmacologically relevant secondary metabolites. In this study, a comprehensive phytochemical investigation was conducted to characterize and quantify the major polyphenolic metabolites in different plant tissues. Leaves and stems from female and male plants, together with unripe and ripe fruits from female trees, were analyzed using liquid chromatography coupled with diode-array detection and quadrupole time-of-flight mass spectrometry (LC-DAD-QToF-MS). Four major polyphenolic compounds (idesin, chlorogenic acid, idescarpin, and apigenin 7-O-glucuronide) were identified and quantified. Idescarpin was the predominant compound in all tissues, with the highest concentration in ripe fruits (122.9 mg/g), followed by unripe fruits (105.0 mg/g) and female leaves (99.1 mg/g). Idesin was also enriched in fruits, reaching 16.3 mg/g in ripe fruits. In contrast, chlorogenic acid and apigenin 7-O-glucuronide were mainly detected at 4.6 and 5.8 mg/g, respectively, in female leaves. Comparisons between male and female plants indicated moderate differences, although organ type and developmental stage had a greater influence on metabolite accumulation. This study provides a detailed quantitative profile of major polyphenolic metabolites in I. polycarpa and highlights pronounced tissue- and developmental-stage-dependent variation, contributing to a better understanding of the chemical diversity of this species.
Abstract The genus Iberis is mainly distributed in the Mediterranean basin, with Europe representing the primary center of diversity, while a limited number of species occur in Northwest Africa and Southwest to Central Asia. The genus is represented by 10 taxa in Türkiye, including four endemic taxa: Iberis carica, Iberis halophila, Iberis gypsicola, and Iberis saxatilis subsp. magnesiana. Previous studies emphasized morphology and phylogeny, whereas comprehensive metabolomic and phytochemical analyses of the genus remain limited. In this study, plant materials from prior morphological and molecular analyses underwent LC-MS-based untargeted metabolomic profiling to provide complementary chemotaxonomic evidence and evaluate how closely metabolomic patterns align with other taxonomic datasets. A total of 149 LC–MS features were putatively annotated. Primary metabolites showed high conservation across taxa, whereas secondary metabolites displayed significant interspecific variation. Multivariate analyses revealed clear clustering patterns largely consistent with molecular phylogenies and morphological data. I. sempervirens, I. saxatilis, and I. odorata formed distinct groups, and the I. simplex species complex structure was reflected in metabolite-based clustering. Furthermore, the enrichment of pathways like riboflavin and tryptophan metabolism highlights the interplay between core primary metabolism and specialized secondary metabolite diversification across the investigated taxa. Metabolite profiling of Turkish Iberis taxa, combined with morphological, anatomical, and phylogenetic data, provides a valuable complementary approach for exploring chemotaxonomic relationships and chemical evolution. The findings highlight the genus as a promising bioactive source and support integrating metabolomics with other taxonomic datasets to improve chemotaxonomic interpretations within Iberis.
