Microalgae’s adaptability and resilience to Earth’s diverse environments have evolved these photosynthetic microorganisms into a biotechnological source of industrially relevant physiological functions and biometabolites. Despite this, microalgae-based industries only exploit a handful of species. This lack of biodiversity hinders the expansion of the microalgal industry. Microalgal bioprospecting, searching for novel biological algal resources with new properties, remains a low throughput and time-consuming endeavour due to inefficient workflows that rely on non-selective sampling, monoalgal culture status and outdated, non-standardized characterization techniques. This review will highlight the importance of microalgal bioprospecting and critically explore commonly employed methodologies. We will also explore current advances driving the next generation of smart algal bioprospecting focusing on novel workflows and transdisciplinary methodologies with the potential to enable high-throughput microalgal biodiscoveries. Images adapted from (Addicted04 in Wikipedia File: Australia on the globe (Australia centered).svg. 2014.; Jin et al. in ACS Appl Bio Mater 4:5080–5089, 2021; Kim et al. in Microchim Acta 189:88, 2022; Tony et al. in Lab on a Chip 15, 19:3810–3810; Thermo Fisher Scientific INC. in CTS Rotea Brochure).

The integration of phytochemistry into forensic science has emerged as a groundbreaking frontier, providing unprecedented insights into nature's secrets through the precise application of phytochemical fingerprinting of phytotoxins as a cutting-edge approach. This study explores the dynamic intersection of phytochemistry and forensic science, highlighting how the unique phytochemical profiles of toxic plants and their secondary metabolites, serve as distinctive markers for forensic investigations. By utilizing advanced techniques such as Ultra-High-Performance Liquid Chromatography (UHPLC) and High-Resolution Mass Spectrometry (HRMS), the detection and quantification of plant-derived are made more accurate in forensic contexts. Real-world case studies are presented to demonstrate the critical role of plant toxins in forensic outcomes and legal proceedings. The challenges, potential, and future prospects of integrating phytochemical fingerprinting of plant toxins into forensic science were discussed. This review aims to illuminate phytochemical fingerprinting of plant toxins as a promising tool to enhance the precision and depth of forensic analyses, offering new insights into the complex stories embedded in plant toxins.

In the twenty-first century, we have witnessed multiple coronavirus pandemics. Despite declining SARS-CoV-2 cases, continued research remains vital. We report the discovery of sydowiol B, a natural product, as a dual inhibitor of SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro). Sydowiol B interacts with the nano-channel at the Mpro dimer interface and the PLpro active site. Molecular dynamics simulations suggest that sydowiol B inhibits Mpro by limiting active site expansion rather than inducing collapse. Furthermore, sydowiol B binding may amplify the fluctuation of two loops coordinating with the structural Zn²⁺ in PLpro, displacing Zn²⁺ from the zinc finger domain to the S2 helix. Sydowiol B and its analogue, violaceol I, exhibit broad-spectrum antiviral activity against homologous coronaviruses. Given the conservation of Mpro and PLpro, sydowiol B and violaceol I are promising leads for designing and developing anti-coronavirus therapies.

Angelica L. has attracted global interest for its traditional medicinal uses and commercial values. However, few studies have focused on the metabolomic differences among the Angelica species. In this study, widely targeted metabolomics based on gas chromatography-tandem mass spectrometry was employed to analyze the metabolomes of four Angelica species (Angelica sinensis (Oliv.) Diels (A. sinensis), Angelica biserrata (R.H.Shan & Yuan) C.Q.Yuan & R.H.Shan (A. biserrata), Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. (A. dahurica) and Angelica keiskei Koidz. (A. keiskei)). A total of 698 volatile metabolites were identified and classified into fifteen different categories. The metabolomic analysis indicated that 7-hydroxycoumarin and Z-ligustilide accumulated at significantly higher levels in A. sinensis, whereas bornyl acetate showed the opposite pattern. Furthermore, a high correspondence between the dendrogram of metabolite contents and phylogenetic positions of the four species. This study provides a comprehensive biochemical map for the exploitation, application and development of the Angelica species as medicinal plants or health-related dietary supplements.

Fifteen novel carbazole alkaloids, euchrestifolines A–O (1–15), were obtained from Murraya euchrestifolia. Their structures were elucidated by spectroscopic analysis, Mosher’s ester, calculated ECD, and transition metal complex ECD methods. Notably, euchrestifolines A–C (1–3) are the first naturally occurring pyrrolidone carbazoles to be identified, while euchrestifolines D–F (4–6) represent rare carbazole alkaloids containing a phenylpropanyl moiety; euchrestifoline G (7) features a unique benzopyranocarbazole skeleton. More importantly, these compounds exhibited significant anti-ferroptotic activity, along with inhibitory effects of nitric oxide (NO) production and notable cytotoxicity. This study marks the first disclosure of carbazole's inhibitory effects against ferroptosis, and the EC₅₀ values of some carbazoles ranging from 0.04 to 1 μM, substantially lower than the positive control, ferrostatin-1. In sum, this research not only enhances our understanding of carbazole alkaloids but also opens new avenues for the discovery of ferroptosis-related leading compounds.

A chemical investigation of Streptomyces sp. GZWMJZ-662, an endophytic actinomycete isolated from Houttuynia cordata Thunb., has yielded eleven bohemamine dimers (1-11). Notably, the newly identified dibohemamines I–O (1-7) have not been previously reported. Their structures were elucidated through detailed spectroscopic analysis, encompassing high-resolution electrospray ionization mass, nuclear magnetic resonance, infrared radiation, ultraviolet–visible, and electronic circular dichroism spectroscopy. Dibohemamine I (1) exhibited selective cytotoxic effects against the cancer cell lines 786-O and GBC-SD among the 18 cell lines evaluated, with the half-inhibitory concentration values of 3.24±0.20 and 7.36±0.41 μM, respectively.

Chemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules. Prepared through direct derivatization of natural extracts, they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs. Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent, and their α-glucosidase inhibition properties were compared. For the most bioactive mixture, a chemically modified propolis extract, enzyme inhibition increased 22 times due to the reaction sequence. Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin. The inhibitor results from the action of the two reagents used on four common functional groups present in natural products (carbonyl, phenol, aromatic carbon, and a double bond). The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one, as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material, all within a complex mixture of natural products. Overall, these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.

The Plectranthinae clade, which includes genera such as Plectranthus, Ocimum, and Aeollanthus, is well known for its diverse array of diterpenoids. While numerous studies have deepened the understanding of diterpene diversity across the clade, Aeollanthus species remain underexplored, with only two studies focusing on their diterpene profiles. The NMR-based chemical profiling of the EtOAc leaf extract of the rocky and succulent species Aeollanthus buchnerianus Briq. reveals a range of diterpenes with isopimarane and abietane skeletons including several previously unreported analogues. Interestingly, the isolated compounds provided insights into the breakdown patterns of both diterpene classes by examining the product ions in their MS2 spectra. These data offer valuable information for evaluating the taxonomic position of this species in relation to other species within the clade.

The euglenatides are a family of hybrid polyketide-nonribosomal peptides produced by the unicellular algae Euglena gracilis. These compounds have antiproliferative activity against fungal pathogens and mammalian cancer cell lines. Analysis of E. gracilis extracts revealed that the algae produce not only the euglenatides, but also a corresponding family of analogs that have the same molecular weights as the euglenatides, but are lacking the characteristic triene chromophore. In comparison to the euglenatides, the activity of these analogs is greatly reduced in a mammalian cytotoxicity assay, indicating that the triene is critical to the biological activity of the euglenatides.

Teucrifarides A–D (1–4), four previously unreported neo-clerodane-type diterpenoids, combined with sixteen known analogs (5–20), were purified from Teucrium quadrifarium. The absolute forma of compounds 1–4 were determined via spectroscopic and ECD calculation methods, together with X-ray crystallography experiments. Among them, compound 1 possessed a 5,20-epoxy ring featuring a unique cage-like 12-oxatricyclo [5.3.2.0^1,6]undecane skeleton. Meanwhile, 2 incorporated a 6,20-epoxy ring with a novel 12-oxatricyclo [6.2.2.0^2,7]undecane skeleton. Compounds 1 and 12 exhibited significant inhibitory effects against HT-22 cells ferroptosis induced by RSL3, with EC₅₀ values of 11.8±1.0 μM, and 4.52±1.24 μM, respectively. Moreover, ROS accumulation in HT22 cells treated with compound 1 was also observed.

Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications, particularly in oncology. This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023. With a focus on recent research findings, the review explores the rich biodiversity of marine organisms, including sponges, corals, algae, and microorganisms, which have yielded numerous compounds exhibiting promising anticancer properties. Emphasizing the multifaceted mechanisms of action, the review discusses the molecular targets and pathways targeted by these compounds, such as cell cycle regulation, apoptosis induction, angiogenesis inhibition, and modulation of signaling pathways. Additionally, the review highlights the innovative strategies employed in the isolation, structural elucidation, and chemical modification of marine natural products to enhance their potency, selectivity, and pharmacological properties. Furthermore, it addresses the challenges and opportunities associated with the development of marine-derived anticancer drugs, including issues related to supply, sustainability, synthesis, and clinical translation. Finally, the review underscores the immense potential of marine natural products as a valuable reservoir of novel anticancer agents and advocates for continued exploration and exploitation of the marine environment to address the unmet medical needs in cancer therapy

Ganoderma polysaccharides (GPs), derived from various species of the Ganoderma genus, exhibit diverse bioactivities, including immune modulation, anti-tumor effects, and gut microbiota regulation. These properties position GPs as dual-purpose agents for medicinal and functional food development. This review comprehensively explores the structural complexity of six key GPs and their specific mechanisms of action, such as TLR signaling in immune modulation, apoptosis pathways in anti-tumor activity, and their prebiotic effects on gut microbiota. Additionally, the structure-activity relationships (SARs) of GPs are highlighted to elucidate their biological efficacy. Advances in green extraction techniques, including ultrasonic-assisted and enzymatic methods, are discussed for their roles in enhancing yield and aligning with sustainable production principles. Furthermore, the review addresses biotechnological innovations in polysaccharide biosynthesis, improving production efficiency and making large-scale production feasible. These insights, combined with ongoing research into their bioactivity, provide a solid foundation for developing health-promoting functional food products that incorporate GPs. Furthermore, future research directions are suggested to optimize biosynthesis pathways and fully harness the health benefits of these polysaccharides.

The rapid emergence of drug-resistant microbial pathogens has posed challenges to global health in the twenty-first century. This development has significantly made most antibiotics ineffective in the treatment of infections they cause, resulting in increasing treatment costs and annual death rates. To address the challenge posed by these pathogens, we explore the potential of secondary metabolites from Aspergillus species as a source of new and effective therapeutic agents to treat drug-resistant infections. Terpenoids, a distinct group of natural products, are extensively distributed in plants and fungi, and have been attributed with significant antibacterial, anticancer, and antiviral activities. In this review, we present an overview of Aspergillus species, and review the novel terpenoids isolated from them from 2019 to April 2024, highlighting anti-infective activity against members of the ESKAPE pathogens. We further focus on the strategies through which the structural framework of these new terpenoids could be modified and/or optimized to feed a pipeline of new lead compounds targeting microbial pathogens. Overall, this review provides insight into the therapeutic applications of terpenoids sourced from Aspergillus species and the potential for the discovery of new compounds from these fungi to combat antimicrobial resistance.

Anchusa italica Retz. (AIR), a traditional herbal remedy, is commonly applied in managing heart and brain disorders. However, its specific function and mechanism in acute cerebral ischemia-reperfusion injury (CIRI) are not fully understood. This research focused on the interventional effects and potential mechanisms of AIR extract (AIRE) in a rat model of CIRI. The model was established using the filament occlusion method, which involved blocking the middle cerebral artery for 1.5 h and then removing the filament to restore blood flow. Transcriptomic and metabolomic analyses were conducted to explore the molecular pathways and metabolites affected by AIRE. ATP level was measured using an ATP assay kit. Additionally, RT-qPCR and western blot tests were conducted to evaluate the influence of AIRE on the Wnt signaling pathway and mitochondrial function. Transcriptomic and metabolomic analyses indicated that AIRE regulated the Wnt signaling pathway in CIRI and modulated metabolites associated with mitochondrial energy metabolism, such as citrate and succinate. ATP assay result demonstrated that AIRE enhanced ATP production in CIRI. Further, RT-qPCR and western blot analyses revealed that AIRE activated the Wnt/β-catenin signaling pathway and corrected mitochondrial dysfunction. These results proposed that AIRE mitigated mitochondrial energy metabolism deficits in CIRI via the Wnt/β-catenin pathway. By restoring the balance of mitochondrial function and energy metabolism, AIRE might offer a potentially therapeutic strategy for addressing CIRI.

Natural products are the important sources in cardiovascular drug development. In this study, twenty-nine buthutin derivatives were designed, synthesized, and evaluated for their NHE-1 inhibition and protective effects on cardiomyocyte injury. The structure of the newly synthesized compounds had been confirmed by ¹H-NMR, ¹³C-NMR, and HR-ESI-MS spectra. Among all target compounds at 1 μM, compounds 9d, 9f, 9k, 9m, and 9n, with a protection ratio exceeding 30%, exerted stronger protective effects on H9c2 cardiomyocyte than positive control dexrazoxane and buthutin A. Meanwhile, compounds 9k, 9m, and 9o showed the significant NHE-1 inhibitory activities on H9c2 cardiomyocyte, all with a dpHi/min value less than 0.23. What is more, compounds 9k, 9m, 9o and buthutin A all exhibited the specificity on NHE-1 inhibition. Molecular modelling studies suggested the ability of compounds 9m and 9o to establish interactions with three hydrogen bonds to Asp267 and Glu346 of NHE-1, but also the ability with much lower CDOCKER energies than positive control cariporide and buthutin A. The structure-activity relationship (SAR) studies suggested that the presences of amide group, four-carbon linker, and para hydroxyl benzene ring were advantageous pharmacophores for above two pharmacological actions. This research would open new avenues for developing amide-guanidine-based cardioprotective agents.

Pseudomonas aeruginosa-induced bacterial keratitis is one of the most sight-threatening corneal infections associated with intense ocular inflammatory reactions that may lead to vision loss. Hence, this study investigated the efficacy of three nanocomposite chitosan-coated penetration enhancer vesicles (PEVs) to augment the ocular delivery of saponin(s), α-hederin (PEVI), hederacoside C (PEVII), or both (PEVIII) for treatment of Pseudomonas keratitis and its induced inflammatory response. The three formulations were prepared using the ethanol injection method and comprehensively characterized. In vitro, the antibacterial activity of the three formulations against P. aeruginosa was evaluated using agar well-diffusion method, pyocyanin production inhibition, and swarming and twitching motility inhibition assays. The therapeutic effect of the three formulations has been investigated in P. aeruginosa keratitis by gross lesion monitoring, determination of bacterial bioburden, biochemical markers, histopathological examination, and scoring after 7 days of topical treatment. Data revealed that PEVI, PEVII, and PEVIII nanocomposites showed particle size in the nanometer range, high entrapment efficiency, good stability, and sustained release of the saponins throughout 24 h. Among them, PEVIII exhibited notably strong in vitro antipseudomonal activity. Additionally, animals treated topically with PEVIII showed an appreciable gross lesion reduction, corneal tissue improvement, and formidable bacterial load reduction compared with untreated and gentamicin sulfate eye (GENTAWISE^®) ointment-treated groups. Moreover, PEVIII treatment showed the most significant reduction in TNF-α, NF-κB, ROS levels, and OPRL virulence gene expression while enhancing PI3K/Akt activation. Therefore, this study offers PEVIII as a promising treatment for P. aeruginosa keratitis.

The basidiomycetes Stereum hirsutum and Boreostereum vibrans are two fungi of the same genus. In this study, chemical investigation on the co-cultures of the two congeneric fungi led to the isolation of eleven new vibralactone derivatives, hirsutavibrins A-K (1-11). The structures of 1-11 were elucidated by extensive NMR and HRESIMS spectroscopic analysis, and computational methods. Hirsutavibrins A (1) and B (2) showed weak cytotoxicity against the human lung cancer cell line A549. Hirsutavibrin D (4) showed moderate anti-nitric oxide activity in murine monocytic RAW 264.7 macrophages. This work not only expands the members of vibralactone derivatives with variable configurations but also opens a new avenue for fungal co-culturing study between congeneric fungi.

Five novel emestrin-type epipolythiodioxopiperazines (ETPs), prenylemestrins C-G (1-5), along with two known ETPs, prenylemestrin A (6) and prenylemestrin B (7), were obtained from Aspergillus nidulans. Their structures were characterized by spectroscopic data, X-ray crystallographic data, ECD comparisons and calculations. Prenylemestrins C-G (1 - 5) represent a rare class of ETPs, characterized by a 2,5-dithia-7,9-diazabicyclo[4.2.2]decane-8,10-dione core involving a hemiterpene moiety. Notably, compound 6 exhibited moderate cytotoxicity, inducing G2/M cell cycle arrest and apoptosis of L1210 cells by regulating the PI3K/AKT signaling pathway and mitochondrial apoptotic mechanisms.

Phytochemical study of the n-BuOH extract of Ilex asprella resulted in the discovery of ten new pentacyclic triterpenoid glycosides, comprising nine ursane-type glycosides (1-9) and one oleanane-type glycoside (10), along with seven known compounds (11-17). Compound 1 is the first reported 19,22-epoxy ursane triterpenoid glycoside, whereas 4 and 5 are rare examples of ursane triterpenoid glycosides containing a 28,19-lactone group. The structural characterization of these compounds was achieved using spectroscopic and chemical techniques, as well as single-crystal X-ray analysis. Compounds 7, 12, 15, and 17 exhibited moderate cytotoxic activities against H1975 and HCC827 cancer cells.

Natural product pseudolaric acid A (PAA), the main bioactive component from Traditional Chinese Medicine Pseudolarix cortex (“tujingpi”), is a promising anticancer agent. However, its potential molecular targets are not clear and this hinders its development. In this study, chemical proteomics approaches including activity-based protein profiling (ABPP) and drug affinity responsive target stability (DARTS) technology, followed by quantitative proteomics, were combined to reveal the target of PAA. Target validation was performed by NMR techniques and surface plasmon resonance. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) was identified and further confirmed to be the target of PAA. The direct interaction and binding mode between MTHFD1L and PAA were elaborated. PAA induced the accumulation of the reactive oxygen species (ROS) which mediates the antitumor effect. Transcriptome and network pharmacology analysis reveals the effects of PAA on the gene expressions of the associated pathways. Taken together, our findings proposed a new target that could be used for structure-based rational design and modifications of PAA.

Natural products play a crucial role in new drug development, but their druggability is often limited by uncertain molecular targets and insufficient research on mechanisms of action. In this study, we developed a new RPL19-TRAP^KI-seq method, combining CRISPR/Cas9 and TRAP technologies, to investigate these mechanisms. We identified and validated seven ribosomal large subunit surface proteins suitable for TRAP, selecting RPL19 for its high enrichment. We successfully established a stable cell line expressing EGFP-RPL19 using CRISPR knock-in and verified its efficiency and specificity in enriching ribosomes and translating mRNA. Integrated with next-generation sequencing, this method allows precise detection of translating mRNA. We validated RPL19-TRAP^KI-seq by investigating rapamycin, an mTOR inhibitor, yielding results consistent with previous reports. This optimized TRAP technology provides an accurate representation of translating mRNA, closely reflecting protein expression levels. Furthermore, we investigated SBF-1, a 23-oxa-analog of natural saponin OSW-1 with significant anti-tumor activity but an unclear mechanism. Using RPL19-TRAP^KI-seq, we found that SBF-1 exerts its cytotoxic effects on tumor cells by disturbing cellular oxidative phosphorylation. In conclusion, our method has been proven to be a promising tool that can reveal the mechanisms of small molecules with greater accuracy, setting the stage for future exploration of small molecules and advancing the fields of pharmacology and therapeutic development.

Natural products obtained from medicinal and aromatic plants are increasingly recognized as promising anticancer agents due to their structural richness, including terpene and flavonoid molecules, which induce apoptosis and modulate gene expression. These compounds offer an alternative to conventional treatments, often costly, which face challenges such as multidrug resistance. This review aims to provide a promising alternative approach to effectively control cancer by consolidating significant findings in identifying natural products and anticancer agent development from medicinal and aromatic plants. It synthesizes the findings of a comprehensive search of academic databases, such as PubMed and Springer, prioritizing articles published in recognized peer-reviewed journals that address the bioprospecting of medicinal and aromatic plants as anticancer agents. The review addresses the anticancer activities of plant extracts and essential oils, which were selected for their relevance to chemoprevention and chemotherapy. Compounds successfully used in cancer therapy include Docetaxel (an antimitotic agent), Etoposide VP-16 (an antimitotic agent and topoisomerase II inhibitor), Topotecan (a topoisomerase I inhibitor), Thymoquinone (a Reactive Oxygen Species-ROS inducer), and Phenethyl isothiocyanate (with multiple mechanisms). The review highlights natural products such as Hinokitiol, Mahanine, Hesperetin, Borneol, Carvacrol, Eugenol, Epigallocatechin gallate, and Capsaicin for their demonstrated efficacy against multiple cancer types, including breast, cervical, gastric, colorectal, pancreatic, lung, prostate, and skin cancer. Finally, it highlights the need for continued bioprospecting studies to identify novel natural products that can be successfully used in modern chemoprevention and chemotherapy.

Sesquiterpenoids represent a structurally diverse class of natural products widely recognized for their ecological significance and pharmacological potential, including antimicrobial, anti-inflammatory, and anticancer properties. As part of our efforts to explore bioactive secondary metabolites from phytopathogenic fungi, we conducted a molecular networking-based analysis of Bipolaris sorokiniana isolate BS11134, which was fermented on a rice medium. This analysis led to the identification of three new seco-sativene-type sesquiterpenoids (1-3) and seven known analogues (4-10), with the NMR data of compound 4 being reported for the first time. The structures of these compounds were elucidated using HR-ESI-MS and extensive spectroscopic data analysis. Notably, compound 9 significantly inhibited nitrous oxide expression in lipopolysaccharide (LPS)-treated RAW264.7 cells in vitro (inhibition rate: 84.7±1.7% at 10 μM), while compound 1 (10 μM) showed a weak inhibitory effect (inhibition rate=28.0±2.4%). Additionally, we proposed a biosynthetic pathway for these compounds. This study not only expands the chemical space of the helminthoporene class of molecules but also underscores the untapped potential of phytopathogenic fungi as promising sources of structurally unique and biologically active natural products.

A series of structurally diverse polyketides (1-3), sesterterpenoids (24 and 25), and alkaloids (26-34) were isolated from the fermentation of a plant-derived fungus Penicillium canescens L1 on solid rice medium. Among these secondary metabolites, penicanesols A-G (1-7) were new structures, which were elucidated by NMR, HR-ESI-MS, ECD calculation, and X-ray diffraction. Penicanesol A (1) represented a rare dimer derived from phthalan derivatives, characterized by a 5/6/6/6/5 heteropentacyclic core. The bioassay on the NCI-H1975 cell model showed that two compounds had good cytotoxic activities, and the most significant activate compound 13 had an IC₅₀ value of 4.24±0.13 μM, more than the positive control drug (12.99±0.13 μM).

Mosquitoes (Diptera: Culicidae) are vectors of various pathogens of public health concern and replacing conventional insecticides remains a challenge. In this regard, natural products represent valuable sources of potential insecticidal compounds, thus increasingly attracting research interest. Commiphora myrrha (T.Nees) Engl. (Burseraceae) is a medicinal plant whose oleo-gum resin is used in food, cosmetics, fragrances, and pharmaceuticals. Herein, the larvicidal potential of its essential oil (EO) was assessed on four mosquito species (Aedes albopictus Skuse, Aedes aegypti L., Anopheles gambiae Giles and Anopheles stephensi Liston), with LC₅₀ values ranging from 4.42 to 16.80 μg/mL. The bio-guided EO fractionation identified furanosesquiterpenes as the main larvicidal compounds. A GC-MS-driven untargeted metabolomic analysis revealed 32 affected metabolic pathways in treated larvae. The EO non-target toxicity on Daphnia magna Straus (LC₅₀ = 4.51 μL/L) and its cytotoxicity on a human kidney cell line (HEK293) (IC₅₀ of 14.38 μg/mL) were also assessed. This study shows the potential of plant products as innovative insecticidal agents and lays the groundwork for the possible exploitation of C. myrrha EO in sustainable approaches for mosquito management.

Two new cytochalasans, xylariaides A (1) and B (2), were isolated and identified from a soil fungus Xylaria sp. Y01. Their structures were unambiguously determined by extensive spectroscopic methods including high resolution electrospray ionization mass spectrometry, ultraviolet radiation, infrared spectroscopy, and 1D/2D NMR, as well as in-depth quantum chemical calculations of gauge-including atomic orbital (GIAO) ¹³C NMR chemical shifts, electronic circular dichroism (ECD), and spin-spin coupling constants. The unprecedented core structure with a 5/6/5/3 fused tetracyclic ring system further enriches the scaffold types of cytochalasans.

Three pairs of enantiomeric phthalide dimers, including two new ones, angesicolides A (1) and B (2), and a new phthalide monomer (3), were obtained from the rhizomes of Angelica sinensis. Their structures were established through spectroscopic methods, quantum calculations, and chiral HPLC analysis. Compounds 1 and 2 were [2+2] and [4+2] cycloadducts of phthalide monomers, and their hypothetical biogenetic origin was proposed. Compounds 2, (+)-2, (-)-2, 4, (+)-4, and (-)-4 exhibited significant inhibitory activity against NO production with IC₅₀ values range from 1.23 to 5.55 μM.

Purpose This study aimed to investigate the potential of corylin, a bioactive compound isolated from the aerial part of Pueraria lobata, as a novel skin-whitening agent. Specifically, the research sought to evaluate its effects on melanin synthesis, understand its underlying mechanisms, and validate its efficacy in mitigating hyperpigmentation.
Methods Bioactive compound was isolated from Pueraria lobata through a systematic fractionation process involving activated carbon pigment removal, sequential solvent extraction, and resin-based chromatography. It was shown to inhibit melanin synthesis by targeting tyrosinase activation and modulating key signaling pathways. Its efficacy in reducing melanin production was validated through cellular assays and a UVB-stimulated 3D human skin model, highlighting its potential as a skin-whitening agent.
Results Through fractionation, the bioactive compound was identified as corylin, which reduced melanin content and tyrosinase activity without cytotoxicity, modulated signaling pathways to downregulate MITF and melanogenic enzymes, and inhibited α-glucosidase, disrupted glycosylation. In a UVB-stimulated 3D skin model, it effectively decreased melanin production, confirming its potential to mitigate hyperpigmentation.
Conclusion Corylin is a promising candidate for skin-whitening applications, effectively mitigating hyperpigmentation by targeting multiple stages of melanin synthesis, including enzymatic activity and regulatory pathways. Further clinical studies are needed to confirm its safety and therapeutic potential for dermatological use.

Salt-inducible kinase 1 (SIK1) participates in various physiological processes, yet its involvement in regulating skeletal muscle glucose uptake remains unclear. Previously, we showed that phanginin A, a natural compound isolated from Caesalpinia sappan Linn, activated SIK1 to suppress gluconeogenesis in hepatocytes. Here, we aimed to elucidate the effects of SIK1 on skeletal muscle glucose uptake by using phanginin A. The C2C12 myotubes were incubated with phanginin A and then glucose uptake, mRNA levels, membrane GLUT4 content, phosphorylation levels of proteins in SIK1/HDACs and Akt/AS160 signaling pathways were determined. Phanginin A significantly promoted glucose uptake, while the pan-SIK inhibitor or knocking down SIK1 expression abolished the promotion. Further exploration showed that phanginin A enhanced GLUT4 mRNA levels by increasing histone deacetylase (HDAC) 4/5 phosphorylation and MEF2a mRNA and protein level, and knocking down SIK1 blocked these effects. Additionally, phanginin A induced HDAC7 phosphorylation, upregulated the junction plakoglobin (JUP) expression and Akt/AS160 phosphorylation. Knocking down JUP or SIK1 both attenuated the phanginin A-induced Akt/AS160 signaling and glucose uptake, suggesting that activation of SIK1 by phanginin A inactivated HDAC7 to increase JUP expression and Akt/AS160 phosphorylation, led to upregulation of GLUT4 translocation and glucose uptake. In vivo study showed that phanginin A increased phosphorylation levels of SIK1, HDAC4/5/7, Akt/AS160, and gene expression of MEF2a, GLUT4 and JUP, accompanied by elevated membrane GLUT4 and glycogen content in gastrocnemius muscle of C57BL/6 J mice, indicating enhanced glucose utilization. These findings reveal a novel mechanism that SIK1 activation by phanginin A stimulates skeletal muscle glucose uptake through phosphorylating HADC4/5/7 and the subsequent enhancement of GLUT4 expression and translocation.

Antimicrobial resistance is one of the most pressing global health challenges, as many pathogens are rapidly evolving to evade existing treatments. Despite this urgent need for new solutions, natural plant-derived compounds remain relatively underexplored in the development of antimicrobial drugs. This report highlights an innovative approach to discovering potent antimicrobial agents through bioguided fractionation of numerous plant species from the rich Argentinean flora. By systematically screening 60 species (over 177 extracts) for antimicrobial activity against representative strains of gram-positive and gram-negative bacteria, we identified promising bioactive compounds within the Asteraceae family—particularly sesquiterpene lactones from the Xanthium genus. Building on this basis, we synthesized semi-synthetic derivatives by chemically modifying plant sub-extracts, focusing on structures incorporating heteroatoms and/or heterocycles containing oxygen and nitrogen (important for the bioavailability and bioactivity that they are capable of providing). These modifications were evaluated for their potential to enhance antimicrobial efficacy against bacteria and Candida species, including resistant strains. Our findings suggest that tailoring natural metabolites from Xanthium and related Asteraceae species can significantly improve their antimicrobial properties. This strategy offers a promising pathway for the development of novel therapeutic agents to combat bacterial and fungal infections in an era of rising drug resistance.

Otteacumienes G–K (1–5), five pairs of enantiomeric diarylheptanoids, along with one undescribed diarylheptanoid glycoside and one new lignan, were isolated from Ottelia acuminata var. acuminata. Compounds 1–5 were identified as five pairs of enantiomers and their structural configurations were determined through a combination of spectroscopic analysis, X-ray crystallography, and ECD calculation. Notably, compound 6 was the first diarylheptanoid glycoside isolated from this aquatic species, and its absolute configuration was unequivocally established through semi-synthesis. Biological evaluation demonstrated that compound 1 exhibited α-glucosidase inhibitory activity, with an inhibition ratio of 38.97% (acarbose as the positive control, inhibition ratio = 13.52%).

In this work, six pairs of undescribed enantiomeric prenylated flavonoids, ( ±)-epimesatines J–O (1a/1b–6a/6b), were isolated from the aerial parts of Epimedium sagittatum Maxim. Their structures and absolute configurations were determined based on spectroscopic data, quantum chemical calculations of electronic circular dichroism (ECD) and ¹³C NMR, as well as ECD experiments induced by Mo₂(OAc)₄ and Rh₂(OCOCF₃)₄. The cytotoxicity assay revealed that compounds 1a/1b, 2a/2b, and 4a/4b–6a/6b demonstrated significant inhibitory effects on the viability of human breast cancer cells MCF-7 while exhibiting no obvious toxicity towards human breast epithelial cells MCF-10A. Additionally, these compounds were found to decrease the expression of sphingosine kinase 1 (Sphk1) in MCF-7 cells. Notably, compounds 4a and 5b exhibited IC₅₀ values of 7.45 and 8.97 μM, respectively, in MCF-7 cells.

Two new together with 32 known compounds were isolated from the leaves of Lycium barbarum. Their structures were elucidated using 1D and 2D NMR, HRESIMS, and ECD spectroscopic techniques. Compounds 1–34 were evaluated for their anti-rheumatoid arthritis activities in a lipopolysaccharide (LPS)-induced MH7A cells inflammatory model. As a result, compounds 1–3, 6, 8, 10, 14, 17–19, 29 and 31 inhibited the activity of lactate dehydrogenase (LDH) and nitric oxide (NO) at concentrations 20 μM. Among them, compound 1 showed the best effectiveness, with inhibition rates of 46.7% for NO and 32.8% for LDH.

Natural products (NPs) are invaluable resources for drug discovery, characterized by their intricate scaffolds and diverse bioactivities. AI drug discovery & design (AIDD) has emerged as a transformative approach for the rational structural modification of NPs. This review examines a variety of molecular generation models since 2020, focusing on their potential applications in two primary scenarios of NPs structure modification: modifications when the target is identified and when it remains unidentified. Most of the molecular generative models discussed herein are open-source, and their applicability across different domains and technical feasibility have been evaluated. This evaluation was accomplished by integrating a limited number of research cases and successful practices observed in the molecular optimization of synthetic compounds. Furthermore, the challenges and prospects of employing molecular generation modeling for the structural modification of NPs are discussed.

The use of natural products as antibiotic adjuvants to enhance efficacy and mitigate resistance is increasingly recognized as a promising strategy. This study explored five novel synergistic antimicrobial combinations (SACs) of carvacrol (CARV) and three already identified SACs of thymol (THY) with chloramphenicol, gentamicin, and streptomycin against Staphylococcus aureus and Acinetobacter baumannii, critical WHO-listed pathogens, and investigated their mechanisms of action and resistance-prevention capabilities. Despite being isomers, CARV and THY exhibited distinct synergistic effects and fractional inhibitory concentration index (FICI) values depending on the antibiotic and bacterial species. The SACs significantly reduced the required antibiotic dose by 4- to 16-fold, with FICI values ranging from 0.25 to 0.5. Growth kinetics revealed that SACs completely inhibited planktonic bacterial growth, outperforming antibiotics alone. Additionally, the SACs demonstrated efficacy in both inhibiting and eradicating biofilms of S. aureus and A. baumannii. Resistance development studies highlighted that neither THY nor CARV induced resistance in these pathogens. Moreover, SACs combining aminoglycosides with THY reduced the emergence of resistance in A. baumannii by up to 32-fold. In S. aureus, THY mitigated gentamicin resistance by 16-fold. CARV exhibited similar, albeit slightly less potent, effects.
Mechanistic investigations revealed that THY and CARV exert antimicrobial action by multiple mechanisms, including bacterial membrane depolarization and disruption, efflux pump inhibition, disrupting ATP metabolism and mitigating oxidative stress induced by antibiotics. These findings highlight the potential of SACs to enhance antibiotic efficacy while preventing resistance, positioning them as strong candidates for innovative antimicrobial therapies against multidrug-resistant pathogens.

Four previously undescribed polyprenylated acylphloroglucinols, hyperisenins A–D (1–4), along with two known analogues (5 and 6), were obtained from the aerial part of Hypericum seniawinii Maxim. Compounds 1 and 2 were two highly degraded polyprenylated acylphloroglucinols with a cyclohexanone-monocyclic skeleton, while compound 3 was the first example of O-prenylated acylphloroglucinols with a 6/6/6 ring system. Their structures were identified by analyzing NMR, HRESIMS data, and quantum chemical calculations. The biosynthetic pathway of 1 and 2 might originate from bicyclic polyprenylated acylphloroglucinols via a series of complex retro-Claisen, keto-enol tautomerism, and intramolecular cyclization. The bioassay results showed that 4 exhibited quorum sensing inhibitory activity against Pseudomonas aeruginosa, which could decrease the activation of the rhl system, and significantly reduce rhamnolipid levels at a concentration of 100 μM, and the mechanism might be the ability to bind 4 to lasR and pqsR.

Our continuous study of the fruits of Garcinia xanthochymus and Garcinia subelliptica led to the isolation and structural characterization of six new polyprenylated acylphloroglucinols, xanthochymusones N and O (1 and 2), (–)-garciyunnanin L (3), and garsubelones C–E (4–6), together with two known analogues. Their structures were elucidated by interpretation of NMR and MS spectroscopic data. It was found that the Grossman-Jacobs rule is no longer applicable to determination of the C-7 configuration of compounds 1–3, as they possess a complex 6/6/6/6/6 fused ring system. The inhibitory activities of all the compounds against two human hepatocellular carcinoma cell lines Huh-7 and HepG2 were evaluated, and compound 1 exhibited moderate cytotoxic activities against HepG2 cells with IC₅₀ value 7.3 μM. Furthermore, the previous assignments of some polyprenylated acylphloroglucinols have been proved to be incorrect in this study, and analysis of NMR data enabled the structural revision of seven analogues: hyperselancins A and B, garcinielliptones F and G, garxanthochins A and B, and 13,14-didehydroxygarcicowin C. The revised structures of garcinielliptone F and garxanthochin A were shown to have the same structures of garsubelone B and xanthochymusone K, respectively, and the revised structures of other five compounds have not been reported.

The activation of conventional (α) and novel (δ) protein kinase C (PKC) isoforms promotes lysosomal biogenesis, a critical process for clearance of pathogenic protein aggregates including β-amyloid (Aβ) and phosphorylated Tau (p-Tau) in neurodegenerative disorders. Notably, PKC activators HEP14/15, characterized by 20-methyl moiety, fail to establish classical C1B domain pharmacophore interactions, suggesting a non-canonical activation mechanism. In this study, structural diversification of 20-deoxyingenol through esterification and acetonide protection yielded 18 new derivatives (2–19). Systematic screening revealed their lysosome-promoting activities, with structure–activity relationship analysis identifying compounds 4 and 18 as superior autophagy inducers. At 20 μM, these derivatives enhanced autophagic flux by 2.45-fold and 2.31-fold versus vehicle control. Moreover, compounds 4 and 18 exhibited a dose-dependent increase in lysosome numbers, promoted TFEB nuclear translocation, and enhanced lysosome-mediated lipid droplet clearance. Western blot analysis further revealed that compounds 4/18 upregulated proteins associated with the autophagy-lysosome system, suggesting their potential as promising autophagy inducers. Mechanistically, molecular docking simulations indicated thier high-affinity binding to PKCδ, which may explain their autophagy-enhancing properties.

Qingfei Paidu decoction (QFPDD) has been extensively used in clinical treatments during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic. SARS-CoV-2 primarily invades host cells via its spike (S) protein binding to the angiotensin-converting enzyme 2 (ACE2) on the cell membrane, mediating viral-host membrane fusion. Blocking viral entry is a crucial step in preventing infection, with the interaction between the S receptor binding domain (S-RBD) and ACE2 being a key antiviral target. Given that SARS-CoV-2 predominantly affects the respiratory system and approximately 25% of patients suffering from corona virus disease 2019 (COVID-19) with gastrointestinal symptoms, we are committed to identifying more active ingredients in QFPDD that target the respiratory and gastrointestinal tracts of COVID-19 patients. Among medicinal plants, ephedra and liquorice derived from QFPDD, along with two other Chinese herbs, Platycodon grandiflorum and Radix Rhei Et Rhizome (rhubarb), have garnered our interest. These herbs have historically been used in traditional Chinese medicine (TCM) for treating infectious diseases with respiratory and digestive symptoms. Here, we established a library containing all components of the four individual herbs gathered from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and performed structure-based virtual screening to identify potential ACE2/S-RBD inhibitors. Subsequently, we selected 10 ingredients from the top 30 candidates and evaluated their activities using a pseudovirus neutralization assay. Delphinidin and deapio platycodin D (DPD) showed significant antiviral potential with half-maximal inhibitory concentration (IC₅₀) values of 45.35 μM and 1.38 μM, respectively. Furthermore, delphinidin also inhibited the 3-chymotrypsin-like protease (3CL^pro), indicating its dual-viral target inhibitory potential. Notably, DPD effectively suppressed HCoV-229E replication in BEL-7402 cells. This study not only provides a strategy for rapid identifying antiviral agents from TCM in anticipation of future pandemics but also offers theoretical and experimental evidence to support for the clinical use of QFPDD.

Two concise and efficient synthetic routes were developed for the synthesis of three 1,7-diarylheptanoids (1–3) containing a 1,4-pentadiene unit, which were originally isolated from Ottelia acuminata var. acuminata. The first approach focused on the construction of linear diarylheptanoids 1 and 3 featuring a (1E,4E)-pentadiene moiety, via a Suzuki coupling reaction. The second strategy enabled the synthesis of sixteen-membered macrocyclic ether 2 with a (1Z,4E)-pentadiene unit. The challenging macrocyclization was successfully accomplished through an Ullmann coupling. Notably, the formation of the Z-olefin within the macrocyclic framework was promoted by the inherent ring strain of diarylether-type heptane system, which preferentially stabilizes this particular configuration.