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.

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.

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

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.

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.

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.

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.

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.

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.