Hypercholesterolemia is increasingly recognized as a multifactorial metabolic disorder characterized by dysregulated cholesterol homeostasis and chronic inflammation, both of which accelerate atherosclerosis and cardiovascular disease. MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators linking sterol regulatory element-binding proteins (SREBPs) and nuclear factor-kappa B (NF-κB), thereby integrating lipid metabolism with inflammatory signaling. Herbal phytochemicals possess promising hypolipidemic and anti-inflammatory activities; however, their clinical application is limited by poor bioavailability, rapid metabolism, and inadequate tissue targeting. Nanoparticle-based delivery systems have been developed to overcome these limitations by enhancing stability, cellular uptake, and targeted intracellular delivery. This review summarizes current evidence regarding the regulatory effects of herbal nanoparticles on miRNA-mediated modulation of the SREBP-NF-κB signaling pathway in hypercholesterolemia. A systematic literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2010 and May 2026. Available evidence demonstrates that nanoformulated phytochemicals improve bioavailability and effectively regulate key miRNAs, including miR-33a/b, miR-122, miR-155, miR-21, and miR-146a. These molecular changes suppress SREBP-mediated cholesterol synthesis, enhance cholesterol efflux, attenuate NF-κB-driven inflammatory responses, and restore lipid homeostasis. Collectively, herbal nanoparticles act as both efficient drug delivery platforms and molecular modulators of the miRNA-SREBP-NF-κB regulatory axis. Despite encouraging preclinical findings, clinical translation remains constrained by challenges related to formulation standardization, scalable manufacturing, long-term safety, and regulatory approval. Future studies should prioritize mechanistic investigations, standardized nanoparticle formulations, and well-designed clinical trials to validate miRNA-targeted herbal nanomedicine as a precision therapeutic strategy for hypercholesterolemia and associated cardiovascular disorders.
Five undescribed cyclopiazonic acid indole alkaloids (CPAs), penibrasdines A - E (1-5), and eleven known analogues were isolated from the fungus Penicillium brasilianum. Their structures and configurations were elucidated based on HRESIMS, 1D and 2D NMR spectroscopic data, ECD calculations, and single-crystal X-ray diffraction. Penibrasdine A (1) bearing a rigid and sterically congested hexacyclic indole-tetrahydrofuran scaffold, is the epimer of penicillamine A. Bioactivity evaluation indicated that all isolated compounds showed no effective antibacterial activity against the tested bacterial strains.
Phytochemical investigation of the whole plant of Euphorbia antiquorum L. led to the isolation of sixteen diterpenoids, including five new compounds, euphiquorins A-E (1, 5-8), together with eleven known analogues (2-4, 9-16). The structures of the new compounds were elucidated by comprehensive spectroscopic analyses and quantum chemical calculations. Compound 1 possesses an unprecedented 5/6/6/5 fused tetracyclic ent-abietane-derived framework featuring oxidative A-ring cleavage, carbon contraction, and intramolecular cyclization. Compounds 5-8 represent new ingol-type diterpenoids with diverse oxygenated substitution patterns. The known compounds were identified as three ent-abietane diterpenoids (2-4), six ingol diterpenoids (9-14), and two ent-atisane diterpenoids (15-16) by comparison of their spectroscopic data with those reported in the literature. A plausible biogenetic pathway for compounds 1-4 was proposed. Selected compounds were evaluated for their cytotoxic activities against MCF-7 and MCF-7/DOX cells, and none of the tested compounds exhibited significant cytotoxicity at a concentration of 30 μM.
A pair of amide enantiomers, (+)-magenamide B [(+)-1] and (-)-magenamide B [(-)-1], and six undescribed alkaloids, magenamides CF (2-5), along with 2-nonyl-3,5-dioctylpyridine (6) and 3-decyl-2-nonyl-5-octylpyridine (7), together with 19 known compounds (8-26) were isolated from the stems of Piper magen (Piperaceae). The chemical structures of all the new compounds were elucidated using NMR and MS data. Magenamide C and 5,6-dihydro-1-[(2E)-3-(4-methoxyphenyl)-1-oxo-2-propen-1-yl]-2(1H)-pyridinone (15) strongly inhibited NO production, with IC50 values of 30.09 μM and 3.16 μM, respectively (positive control: L-NMMA, IC50 = 42.24 μM). Moreover, corydalisin C (24) showed DPPH radical scavenging activity, with an IC50 value of 26.10 μM (positive control: Trolox, IC50 = 21.38 μM). Compound 15 and magenamide A demonstrated protective effects against corticosterone-induced neuronal injury at a concentration of 2 μM (P < 0.001). 1-(m-Methoxycinnamoyl)pyrrolidine (16) exhibited BACE1 inhibitory activity, with an IC50 value of 8.73 μM (positive control: LY2886721, IC50 = 31.80 nM).
Background Phyllanthus emblica L. (PE) is a traditional medicinal and edible plant with cardiovascular protective potential, but its bioactive compounds and molecular targets are unclear. This study aimed to identify the core in vivo bioactive compounds and elucidate their mechanisms in attenuating lipid deposition and endothelial inflammation via the Hippo-YAP signal pathway. Methods UPLC-Q-Exactive-MS was utilized to profile constituents in PE extract, medicated rat serum, and zebrafish tissues. An in vitro ox-LDL-induced HUVEC model and an in vivo high-cholesterol diet induced zebrafish model were established to analyze the efficacy and mechanism of the drug and its bioactive compounds. Molecular docking, Drug Affinity Responsive Target Stability (DARTS), Cellular Thermal Shift Assay (CETSA), and Surface Plasmon Resonance (SPR) were employed to verify direct drug-target interactions. Results 128 compounds were identified in extract, and 14 and 8 absorbed constituents in serum and tissues, respectively. Intersection analysis and functional screening pinpointed corilagin and ethyl gallate as primary bioactives. They directly bound YAP with high affinity, enhancing its thermal and proteolytic stability, facilitating phosphorylation and cytoplasmic sequestration, and preventing nuclear translocation and pro-inflammatory gene transcription. In vivo, PE extract and compounds significantly reduced vascular lipid plaques, TC/TG/LDL-C, and inflammatory markers Conclusions PE protects against endothelial injury and lipid deposition through corilagin and ethyl gallate, which directly bind YAP, enforcing cytoplasmic retention and shutting down inflammation, offering a natural YAP-targeted strategy for cardiovascular protection.
BACKGROUND:Tiliacora triandra is a medicinal plant with promising cosmetic applications owing to its rich phytochemical composition. This study aims to investigate the microwave-assisted extraction (MAE) of phenolic compounds from T. triandra leaves using conventional and polyol-based green solvents, evaluate the bioactivity of the selected extracts, characterize their phytochemical profiles, and assess their potential for cosmetic formulations. METHODS:Seven solvents, including water, ethanol, and five polyols, were evaluated. Extraction conditions were investigated based on the total phenolic content (TPC), and the best-performing conditions within the investigated range were selected. The selected extracts were further assessed for antioxidant activity, mushroom tyrosinase inhibition, metabolite profiling by LC-QTOF-MS/MS, cellular anti-melanogenic and anti-tyrosinase activities, and formulation stability. RESULTS:Among the tested solvents, 1,2-hexanediol (HDO) achieved the highest extraction efficiency. The best-performing conditions within the investigated range were 60% solvent concentration, a 1:30 g/mL solid-to-liquid ratio, 90 °C, and 10 min extraction time. MAE with HDO produced higher TPC, antioxidant activity, and tyrosinase inhibition than ethanol and conventional extraction. LC-QTOF-MS/MS identified 12 metabolites, including phenolic acids, flavonoids, alkaloids, terpenes, and ubiquinones. The extracts exhibited concentration-dependent anti-melanogenic and anti-tyrosinase activities in B16F10 cells. Gel-based serum formulations containing 1% and 3% extract showed acceptable physicochemical stability during storage. CONCLUSIONS:MAE using HDO is an efficient, eco-friendly strategy for producing bioactive-rich T. triandra extracts with promising antioxidant and skin-lightening properties for cosmetic applications.
Leishmaniasis remains a major neglected tropical disease for which current treatments are limited by toxicity, variable efficacy, and high cost. Natural products continue to represent an important source of new antiparasitic agents. In this study, a dereplication/bioactivity-guided approach was employed to investigate the antileishmanial constituents of Melaleuca viminalis leaves. The MeOH extract was partitioned into hexane, CH2Cl2, and EtOAc phases and their activities were evaluated against promastigote forms of Leishmania amazonensis. The CH2Cl2 phase showed the highest activity (EC50 = 36 ± 7 μg/mL) and was subjected to a bioactivity-guided fractionation combined with UHPLC-ESI-HRMS/MS dereplication and molecular networking (GNPS2). This approach revealed the presence of several metabolites, including the triterpenes 3-hydroxy-11-ursene-28,13-olide, betulinic acid, and uvaol, the fatty acid erucamide, and several phloroglucinol derivatives. Further purification led to the isolation of the previously undescribed phloroglucinol derivative 3,6-dihydroxy-1-isobutyryl-4-methoxy-3-methylcyclohexa-1,5-dien-2-one, named callistenone Q, whose structure was elucidated using HR-ESI-MS, NMR, IR, and ECD analysis. Evaluation of antileishmanial activity showed that callistenone Q exhibited potent activity against intracellular amastigote forms of L. amazonensis (EC50 = 5.4 ± 0.6 μg/mL), comparable to the reference drug miltefosine (EC50 = 7.6 ± 0.9 μg/mL), while displaying no cytotoxicity toward macrophages (CC50 > 100 μg/mL), resulting in a selectivity index (SI) higher than 18.5. These findings highlight M. viminalis as a promising source of bioactive phloroglucinols, with callistenone Q emerging as a potential scaffold for the development of new antileishmanial agents.
An LC/MS guided phytochemical investigation of the pericarps of Alpinia zerumbet yielded five new kavalactone derivatives (1, 4, 5, 21, and 22) along with some known compounds. These comprised two new kavalactone-monoterpene conjugates possessing tricyclic α-pyrone or bicyclic α-pyrone scaffolds and three new hydroxylated kavalactones. Their structures were elucidated by comprehensive spectroscopic analyses (HRESIMS and 1D/2D NMR) and TD-DFT ECD calculations. Moreover, the absolute configuration of the previously described zerumin E4 (18) was revised. Plausible biosynthetic pathways are proposed to rationalize the oxidative derivatization of kavalactone scaffolds and the limited diastereomeric outcomes observed in the kavalactone-monoterpene conjugates. The present findings expand the current knowledge of chemical diversity of the pericarps and provide insights into the phytochemical basis underlying the medicinal use of A. zerumbet fruits.
Exolide A (1), a novel ent-18-norbeyerane diterpenoid possessing a hexacarbocyclic framework, 7/5/6/6/5/3 along with four known terpenoids (2-5) were isolated from the chloroform extract of the stems of Excoecaria agallocha. The structure of 1 was elucidated by comprehensive spectroscopic data analysis (IR, HRESIMS, 1H, 13C NMR, DEPT, HSQC, HMBC, 1H-1H COSY, 1H-1H NOESY), chemical methods, and biogenetic considerations. Compound 2 exhibited a potent α-glucosidase inhibitory activity (IC50 0.11 μg/mL) compared to acarbose (IC50 1.44 μg/mL).
Phytochemical investigation of the roots of Sophora flavescens afforded nineteen piscidic acid and isoflavone derivatives, including seven undescribed compounds (1-7) and four compounds (9-12) reported here for the first time as natural products. Comprehensive analysis of 1D and 2D NMR data, aided by GIAO NMR/DP4+ analyses, induced circular dichroism (ICD) spectra, calculated electronic circular dichroism (ECD) spectra, and X-ray diffraction analysis, enabled their structural elucidation. Structurally, compounds 1-4 were characterized as unusual heterodimers of furfural with either a piscidic acid or an isoflavone derivative, linked via a methylene group; compounds 5-7 were unusual heterodimers of an isoflavone glucoside with a piscidic acid derivative. Additionally, the absolute configurations of the known piscidic acid analogs, ethyl 2-(4-hydroxybenzyl)tartrate (16) and monobutyl 2-(4-hydroxybenzyl)tartrate (19), were established for the first time, based on a comparison of their NMR data, optical rotation values, and ECD spectra with those of compound 15. All isolates were tested for in vitro hepatoprotective activity at 10 μM using ethanol induced AML-12 cells, with compounds 1-9, 14, 16, and 17 demonstrating more significant efficacy. The hepatoprotective effect of piscidic acid (14) was further evaluated in the acute alcohol-induced liver injury (AALI) model rats. The results revealed that its administration significantly reduced levels of ALT, AST, and T-CHO while enhancing SOD activity, thus representing the validation of its hepatoprotective activity. Mechanistically, 14 alleviates AALI via the MAPK signaling pathway, as evidenced by the downregulation of p-JNK and p-ERK protein expression.
From the endophytic fungus Diaporthe phaseolorum associated with Polygonatum cyrtonema Hua, nine carboxamides were isolated, comprising five new compounds, phaseolorines A-E (1-3a, 4a, 6), along with four known compounds (3b, 5, 7, 8). Compounds 1-3 feature a rare 3-imidazolinozone structural unit, previously reported only once in metabolites of the fungus Xylariaceae sp. BSNB-0294. Compound 4a, a new phenylalanine derivative, was identified as the biosynthetic precursor to compounds 1-3. The structures of all isolates were unequivocally established through comprehensive 1D and 2D NMR, HR-ESI-MS, quantum chemical calculations, crystal X-ray diffraction, and chemical synthesis. When evaluated for anti-inflammatory activity in an LPS-induced RAW 264.7 macrophage model, compound 7 exhibited potent inhibition of NO production, with an IC50 value of 5.76 ± 0.76 μM.
Phytochemical investigations on the root bark of Morus alba (Sang-Bai-Pi) let to isolate twenty-five constituents (1-25), including two new flavonoids, (2S)-5,7,2',4'-tetrahydroxy-5'-C-β-D-glucopyranosylflavanone-7-O-glucoside (1) and cyclomethoxymoruol (2), and one new coumarin, esculetin 7-O-β-d-xylopyranosyl-(1 → 6)-β-D-glucopyranoside (3). The structures of these compounds were elucidated through a comprehensive approach involving HRESIMS, NMR, UV, CD, and TDDFT-ECD calculation methods. Biological studies revealed that compounds 3 and 18 exhibited significant tyrosinase inhibition, with IC50 values of 0.51 ± 0.01 μM and 5.12 ± 0.09 μM, respectively. In comparison, the positive control, phenethyl resorcinol (377), demonstrated stronger inhibitory activity with an IC50 value of 0.16 ± 0.01 μM. Furthermore, compounds 3, 8, 13, 17, 19, 22 and 23 showed notable protection against UVA-induced apoptosis in human dermal fibroblast-alpha (HDF-α) cells. Notably, the protective effects of 3 and 22 at a lower concentration of 10 μM surpassed the positive control, vitamin C (100 μM). Of particular interest, the new compound 3 possesses both tyrosinase inhibitory and anti-UV damage effects, suggesting potential applications in cosmetics and related industries.
The genus Sedum (Crassulaceae), together with several taxa historically treated under Sedum, has long been used in traditional medicine and is increasingly investigated as a source of bioactive natural products. Yet its medicinal potential remains difficult to evaluate because the literature is fragmented by taxonomic revisions, species-specific reports, incomplete chemical standardisation, and heterogeneous bioassays. This review critically synthesises evidence published from 1950 to May 2026 on medicinally relevant Sedum taxa, integrating traditional-use records, accepted nomenclature, phytochemical diversity, analytical characterisation, pharmacological activity, and translational limitations. Searches of PubMed, Scopus, Web of Science, Google Scholar, and CNKI were combined with taxonomic verification using Plants of the World Online. Reported constituents include flavonoids, megastigmanes, non-flavonoid phenolics, sterols, triterpenoids, nitrogen-containing compounds, and other metabolites. Flavonol glycosides dominate the flavonoid profile, whereas gallotannins, megastigmane glycosides, δ-amyrone, tricin derivatives, and pectic polysaccharides emerge as recurrent chemical or bioactivity-linked markers. Pharmacological evidence most consistently supports anticancer, antioxidant, anti-inflammatory, antibacterial and antimicrobial activities. However, most findings remain preclinical and are limited by inadequate botanical authentication, weak extract standardisation, incomplete quantitative fingerprints, non-comparable assays, sparse pharmacokinetic data, limited toxicity assessment, and absence of clinical validation. Future research should move from broad activity screening toward authenticated taxa, chemically defined preparations, mechanism-validated targets, and safety-informed translational development.
A phytochemical investigation on the twigs and leaves of Excoecaria agallocha led to the discovery of eight undescribed diterpenoids, along with 21 known analogues. Their structures were elucidated based on comprehensive HRESIMS, HREIMS, and NMR spectroscopic analyses. The cytotoxicity of some isolates was tested against human lung cancer cells (A549) and human promyelocytic leukemia cells (HL-60). Compounds 2 and 4 showed moderate cytotoxic effect against HL-60 with IC50 values of 7.60 ± 2.67 μM and 12.64 ± 0.13 μM, respectively. However, other tested compounds displayed little or weak inhibitory effects against A549 and HL-60 with inhibition rate less than 50% at the concentration of 20 μM.
Dianella ensifolia (L.) DC. is a medicinal plant traditionally used externally for the treatment of skin infections, abscesses, lymphadenitis, traumatic swelling, and wounds. To characterize its chemical constituents and identify potential anti-inflammatory compounds, a systematic phytochemical investigation of the roots of D. ensifolia was conducted. Seventeen flavans were isolated and characterized, including two undescribed tetracyclic flavans, diaensifols A and B (1 and 2), which were resolved into two pairs of enantiomers, (+)-1/(-)-1 and (+)-2/(-)-2, five undescribed flavans (3-7), and ten known analogues (8-17). Their structures were elucidated by extensive spectroscopic analyses, experimental and calculated ECD analyses, and single-crystal X-ray diffraction. Acute toxicity screening in zebrafish larvae showed that the four enantiomers, (+)-1, (-)-1, (+)-2, and (-)-2, maintained near-complete larval survival at concentrations below 40 μM. In a CuSO4-induced acute inflammation model using Tg (mpo: EGFP) zebrafish larvae, the enantiomers of 1 and 2 reduced neutrophil recruitment to the lateral line region. The enantiomers of 1 showed inhibitory effects at 20-40 μM, whereas those of 2 showed moderate inhibition mainly at 40 μM. These findings expand the structural diversity of flavans from D. ensifolia and identify tetracyclic flavan enantiomers as candidate anti-inflammatory constituents that may contribute to the traditional external use of this plant for inflammation-associated conditions.
Seven previously undescribed compounds (1-7), including two norsesquiterpenes (1 and 3), one cadinane-type sesquiterpene (2), one flavonoid (4), and three xanthones (5-7), along with 17 known analogs (8-24), were isolated from the ethyl acetate extract from the fruits of Hypericum ascyron L. Four pairs of enantiomers (4a/4b, 5a/5b, 6a/6b and 7a/7b) were resolved from naturally scalemic mixtures by chiral HPLC. Their full structures were unambiguously established through comprehensive spectroscopic analyses, including 1D and 2D NMR, HR-ESI-MS, electronic circular dichroism (ECD) calculations, and DP4+ probability. Notably, 13 isolated compounds (1, 2, and 8-18) of them belong to five types of sesquiterpenes. The NO inhibitory activities of the isolated compounds were preliminarily evaluated in LPS-stimulated RAW264.7 cells. Compounds 3, 15, 18, 22, and 24 demonstrated moderate NO inhibitory effects, and compound 22 exhibited the strongest NO inhibitory effect among the tested compounds, with an IC50 value of 32.00 ± 1.54 μM, suggesting that it may warrant further investigation.
Indole diketopiperazine (IDKP) alkaloids are widely recognized as an important class of rigid three-dimensional scaffolds in microbial secondary metabolism and possess a broad spectrum of biological properties with therapeutic potential. For the past over half-century, great achievements had been made in discovery, biosynthetic characterization, and pharmacological investigation of novel IDKPs from the genus Aspergillus. However, despite the increasing number of reported compounds and growing understanding of their biosynthetic pathways, a systematic overview specifically focusing on Aspergillus-derived IDKPs remains lacking. Herein, we provide a comprehensive overview of Aspergillus-derived IDKPs (1-444), integrating their occurrence, structural diversity, biosynthetic logic, and biological activities. Beyond summarizing the reported metabolites, this review emphasizes the unique capacity of Aspergillus species to generate structurally diverse IDKPs and highlights the potential of genome mining and biosynthetic gene cluster (BGC) analysis for uncovering previously unexplored IDKP biosynthetic pathways. Current challenges and future perspectives associated with expanding the chemical diversity and therapeutic potential of Aspergillus-derived IDKPs are also discussed.
