Tuberculosis (TB) is a leading infectious disease killer and one of the major causes of deaths worldwide. Although TB is a curable and preventable disease, in 2023, approximately 10.8 million people fell ill with TB and there were an estimated 1.25 million of deaths worldwide. Despite some research progress for new drug candidates, drug repurposing, and new regimens, there is still an urgent need for the new medicins to treat TB, especially due to the growing cases of multidrug and extensively drug-resistant (MDR/XDR) strains. Drug resistance is a challenging obstacle to TB care and prevention globally, making TB harder and longer to treat, often with poorer outcomes for patients. The Actinomycetota encompass Gram-positive bacteria that produce a milieu of bioactive metabolites, including antibiotics, antiproliferative drugs, immunosuppressive agents, and other important medical molecules. Actinomycetota have a special place in the therapeutic arsenal to fight TB, as rifamycins, aminoglycosides, and cycloserine are derived from Streptomyces species, one of the most important genera in this phylum. Furthermore, hundreds of antimycobacterial metabolites have been isolated from Actinomycetota and can serve as effective drugs or useful agents for the discovery of new lead compounds to combat TB. The present review covers more than 171 isolated substances as potential antimycobacterial agents discovered between the years 1972 to 2024. Among the most potent compounds, with MIC in the submicromolar range, steffimycins, ilamycins/rufomycins, nosiheptide, actinomycins, lassomycin and boromycin are the most promising compounds. These compounds represent highly promising candidates for development of new antitubercular drugs. Additionally, some of these substances also demonstrated activity against resistant Mycobacterium tuberculosis (Mtb) strains, which is particularly relevant given the difficulty of treating MDR and XDR strains. Thus, actinobacteria have played and continue to play an important role in fight TB, remaining a promising source of antibiotic metabolites. Their unique metabolic diversity enables the production of metabolites with innovative mechanisms of action, making them a strategic reservoir for discovering therapies against untreatable forms of the disease.

Modern pharmacology has found that both Realgar and Coptis chinensis can induce apoptosis in tumor cells, and traditional Chinese medicine theory suggests the possibility of combining the two, however, the specific mechanisms involved have not been elucidated. This study investigated the therapeutic mechanism of the Realgar-Coptis chinensis drug pair (RCCD) against hepatocellular carcinoma (HCC) by identifying its key active compounds and targets. Through integrated LC-MS analysis, transcriptomics, network pharmacology, and bioinformatics, we identified the mechanism of action, key bioactive compounds, and core targets. Molecular docking, molecular dynamics simulations, and microscale thermophoresis (MST) validated the binding affinity between key compounds and core targets. TIMER2.0 database was used to analyze the relationship between the core targets and HCC. H22 tumor xenograft mouse model and immunohistochemistry and pathology analyses were performed to validate the antitumor efficacy of the active compounds. RCCD has a high degree of selectivity of lipid metabolism pathway, 4-Methylumbelliferone (4-MU) was the key active compound with strong binding activity to the core target fatty acid synthase (FAS), and 4-MU down-regulated the expression of FASN in tumor tissues and induced apoptosis in HCC cells. In addition, as a hyaluronan synthase (HAS2/3) inhibitor, 4-MU interfered with the HA-dependent tumor microenvironment and fibrosis process by inhibiting HAS2/3. Thus, 4-MU may inhibit tumor progression by inhibiting FAS and HAS2/3. 4-MU extracted from RCCD exerts anti-HCC effects by modulating the activities of FAS and HAS2/3, thereby reprogramming lipid metabolism and regulating hyaluronan synthesis.

Background Depression promotes breast cancer progression. Given the lack of specific targets for depression-associated breast cancer, there are currently no therapeutic drugs for this type of breast cancer.
Methods Transcriptomic analysis was conducted to identify and functionally annotate genes with differential expression in breast cancer patients exhibiting depressive symptoms. Subsequently, Mendelian randomization was employed to investigate the causal associations between these pivotal genes and breast cancer, thereby validating their potential roles as therapeutic targets. Furthermore, molecular docking techniques were utilized to screen for candidate compounds that may exert therapeutic effects on depression-associated breast cancer. The efficacy of the selected compounds was further assessed using both in vitro cellular experiments and in vivo animal models.
Results We identified IL-8 as a key gene involved in depression-mediated breast cancer progression using transcriptomics. Mendelian randomized analysis suggested that high IL-8 expression promoted breast cancer progression. Further studies demonstrated that IL-8 mediated the breast cancer-promoting effect of depression through the receptor CXCR2. Evidence from both in vitro and in vivo experiments indicates that senkyunolide H may exert its therapeutic effect by regulating CXCR2, thereby counteracting the protumor effects associated with depression in breast cancer.
Conclusion Depression activates CXCR2-mediated breast cancer cell proliferation through IL-8, and senkyunolide H regulates CXCR2 and inhibits its ability to block the cancer-promoting effects of depression, ultimately inhibiting the growth of breast cancer in the context of depression.

Two pairs of undescribed alkaloid enantiomers, (+)-/(-)-ormohenins A (1) and B (2), were isolated from the seeds of Ormosia henryi Prain, along with four undescribed alkaloids (3, 4, 7 and 8) and seven known ones (5, 6, 9-13). Compounds 1-6 belong to the ormosanine-type alkaloids, compounds 7, 9, and 11 are of the lupinine-type, compounds 8 and 10 are classified as anagyrine-type alkaloids, 12 and 13 are cytisine-type alkaloids. The chemical structures of 1-13 were elucidated through comprehensive NMR and MS data analyses. Furthermore, the racemates (±)-1 and (±)-2 were successfully resolved into their respective optically pure enantiomers using a chiral HPLC system. The absolute configurations of compounds 1-3 were determined using single-crystal X-ray diffraction and corroborated by DFT calculations of specific rotations. The absolute configurations of 4, 7, and 8 were assigned by the experimental electronic circular dichroism (ECD) with those predicted using TDDFT calculations. Compound 12 exhibited significant acetylcholinesterase (AChE) inhibitory activity with the IC₅₀ value of 6.581 ± 1.203 μM. The neuroprotective effects of these compounds against Aβ_25-35 induced cell damage in PC12 cells were investigated, and compounds 3, 9, and 12 exhibited significant neuroprotective effects against Aβ_25-35 induced PC12 cell damage, with the EC₅₀ values of 7.99-15.49 μM, respectively.

Polysaccharides are the primary active constituents of Polygonatum kingianum Coll. et Hemsl. However, the comprehensive characterization of P. kingianum polysaccharides (PKP) remains scarce, impeding investigations into the structure-activity relationship. In this study, a novel polysaccharide, PKP1, was purified using Cellulose DE-52 and Sephadex G-50 column chromatography, and its complete structure was elucidated through monosaccharide composition analysis, methylation analysis, as well as 1D and 2D NMR analysis. The results revealed that PKP1 primarily comprised Fru and Glc, exhibiting a molecular weight of 5.3 × 10³ Da and a polymer dispersity index of 1.20. The completed structure of PKP1 consisted of β-D-Fruf-(2 → , → 1,2)-β-D-Fruf-(6 → , → 1)-β-D-Fruf-(2 → and → 1)-α-D-Glcp-(6 → as the main chain sugar residues, with β-D-Fruf-(2 → and → 2)-β-D-Fruf-(6 → serving as the side chains sugar residues. The detailed structure of PKP1 suggested it is a novel Fru-dominated neutral polysaccharide. Biological assays indicated that PKP1 significantly reduced the levels of NO, IL-6, and TNF-α in RAW264.7 macrophages, while also exerting regulatory effects on the gut microbiota structure and its metabolites in vitro. Our findings enriched the understanding of the structural characteristics of P. kingianum polysaccharides and laid a solid foundation for considering P. kingianum as a potential functional food supplement.

Propolis, consisting of plant-derived materials, wax, and bee secretions, is abundant in bioactive constituents like flavonoids, phenolic compounds, and terpenes, which enhance its various biological functions. These encompass antioxidant, anti-inflammatory, antibacterial, anticancer, antidiabetic, and immunomodulatory properties. Propolis has demonstrated effectiveness in the prevention and treatment of multiple illnesses, including cardiovascular disease, atherosclerosis, infections, diabetes, wound healing, and burns. Its extensive health benefits endorse its application in medications, nutritional supplements, and cosmetics, where it is acknowledged as a safe and efficacious natural product. Propolis, whether utilized in its raw state, as extracts, or in conjunction with other products, exhibits considerable promise in alternative medicine and nutritional health. Propolis extracts are crucial to examine as a key component in health and wellness, offering prospective applications in disease prevention and therapeutic support Further research is necessary to clarify its molecular mechanisms, examine potential allergic reactions, and determine ideal dosages for various ages. This article provides a comprehensive comparative examination of various propolis types, emphasizing their distinct phytochemical contents and varying biological effects concurrently. It integrates results from both in vitro and in vivo investigations, enhancing the comprehension of health applications and mechanisms of action, grounded comparisons in pertinent prior studies.

Five new heterodimers, chalasoergodimers A-E (1-5), and three known heterodimers (6-8), along with four chaetoglobosin monomers (9-12), were isolated from a marine-derived Chaetomium sp. fungus. The structures of new compounds 1-5 were elucidated by HRESIMS, NMR, chemical calculated ¹³C NMR and ECD methods. Among them, compound 1 was derived from C-2' substitution of chaetoglobosin Fex (9) with ergosta-4,6,8(14),22-tetraen-3β-ol, representing a new dimerization mode among chaetoglobosin-ergosterol derivative hybrids. Compound 2 featured substitution at NH-1' and constituted the first example of this dimeric type bearing an R-configuration at C-3''. Compounds 3-5 were formed via a Diels-Alder cycloaddition between chaetoglobosins and 14-dehydroergosterol. Furthermore, it was revealed that compound 9-12 exhibited the significant cytotoxic activity against the human non-small cell lung cancer cell (A549), with compound?12 showing the most potent effect at an IC₅₀ of 5.14 μM.

Nidulin is a secondary metabolite of the depsidone family produced by Aspergillus spp., and has shown promises in pharmacological applications. This study aimed to investigate the effect of nidulin on glucose metabolism in skeletal muscle, the primary site of physiological glucose disposal, and its underlying mechanisms. Using a 2-[³H]-deoxy-glucose (2-DG) uptake assay, nidulin stimulated 2-DG in L6 myotubes in a dose- and time-dependent manner. This effect of nidulin was additive to insulin and metformin, and remained effective under palmitic acid-induced insulin resistance. At the molecular level, nidulin upregulated the mRNA expression and promoted membrane translocation of glucose transporters, GLUT4 and GLUT1. Although nidulin activated AMPK and p38 signaling, pharmacological inhibition of this pathway had minimal effect on nidulin-enhanced 2-DG uptake activity. Notably, nidulin activated key insulin signaling proteins, including IRS1, AKT, and p44/42, and its effect was attenuated by an AKT inhibitor. This study further compared the upstream mechanism of nidulin with that of insulin. While nidulin did not directly activate the insulin receptor β-subunit, it modulated redox homeostasis and intracellular calcium, evidenced by increased cytosolic H₂O₂ and Ca²⁺ levels. The 2-DG uptake-enhancing effect of nidulin and its activation of AKT were suppressed by either an antioxidant or calcium chelator treatment. These findings position nidulin as a promising insulin-sensitizing agent, offering mechanistic insights and therapeutic potential for improving glucose homeostasis in type 2 diabetes.

Bioactive compounds from food-compatible medicinal herbs have shown promise as preventive agents against age-related neurodegenerative conditions, particularly Alzheimer's disease (AD). The present work aimed to find Lobetyolin as a new suppressor of Aβ aggregation and its interventions on abnormal metabolism in AD. Aβ-expressing Caenorhabditis elegans (strain CL4176) and wild-type worms were employed to evaluate paralysis onset, lifespan, cerebral Aβ deposition, and intracellular reactive oxygen species (ROS) after Lobetyolin administration. Untargeted ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) metabolomics coupled with RNA-seq transcriptomics was carried out to profile systemic metabolic and gene-expression changes. Differential metabolites and transcripts were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and pathway-impact analyses; hub targets were prioritized by integrating enrichment scores with in-silico docking. Lobetyolin (12.5-50 μM) markedly protected C. elegans from Aβ-driven toxicity and oxidative stress. In CL2006 worms, β-amyloid deposits fell by 54.8 ± 9.4%, while paralysis in CL4176 was delayed by 20.9 ± 4.5%. Lifespan increased by up to 18.2% in CL4176 and 25.0% in wild-type N2 worms. Concomitantly, intracellular ROS declined maximally by 28.1 ± 8.9% (N2) and 22.4 ± 3.8% (CL4176). Integrative metabolomic-transcriptomic analyses, validated by RT-qPCR, revealed selective remodeling of glutathione metabolism: gst-38 expression was suppressed, whereas gst-1 was elevated. Lobetyolin confers neuroprotective and geroprotective benefits in vivo, primarily through reprogramming glutathione-centered redox metabolism and selectively modulating glutathione-S-transferases (GST) isoforms. These findings position Lobetyolin as a promising dietary lead compound for AD prevention and healthy aging interventions.

Strophioglandins A-C (1-3), three highly rearranged norditerpenoids featuring an unusual tricyclo[6.4.1.0^4,13]tridecane core, were isolated from Strophioblachia glandulosa var. cordifolia. Integrated spectroscopic analyses, X-ray crystallography, and ECD calculations synergistically determined their molecular architectures. Remarkably, all compounds manifested potent anti-inflammatory effects in LPS-activated RAW264.7 cells with IC₅₀ values ranging from 7.83 ± 1.11 to 15.09 ± 1.21 μM. Mechanism study revealed that strophioglandin A (1), the most potent compound, could suppress the expression of multiple inflammatory factors by inhibiting the P38 and Erk1/2 MAPK signaling pathways.

Syngnathoides biaculeatus, a potential functional food from marine sources, was found to enhance nonspecific immunity, but its functional ingredients have rarely been reported. Therefore, this study focused on the preparation and physicochemical properties of its water-soluble natural ingredients with their immunomodulatory activities and potential mechanisms. Firstly, we optimized the extraction method of glycoproteins from S. biaculeatus and prepared the crude glycoprotein SYB, from which the fraction glycoprotein SYB-1 was further purified. The carbohydrates of SYB-1 were 8.46% comprising mannose, glucose, and galactose, with an average molecular weight of 9.423 kDa. Amino acid analysis demonstrated that its major amino acids are glycine, glutamic acid, aspartic acid, and proline, with a total amino acid content of 88.81%. Furthermore, SYB-1 could significantly increase the cell viability of macrophages, and promote the release of NO, TNF-α, and IL-6. Metabolomics revealed that it was associated with arachidonic acid metabolism. The CYP450 enzyme family members and PTGS2 may be key targets for the regulatory role. These results suggested that the glycoprotein of S. biaculeatus may be an attractive functional food supplement from natural sources for immunocompromised populations.

Parkinson's disease (PD), the second most common neurodegenerative disorder globally, arises from selective dopaminergic neuron degeneration. While current therapies address symptoms, disease-modifying agents remain an unmet need. Herein, we investigated Nicotiana tabacum L. (Solanaceae), a plant linked epidemiologically to reduced PD risk, as a source of multi-target neuroprotective compounds. From ultra-low nicotine (< 0.04%) tobacco leaves, we isolated 22 molecules, including a novel 21-norsesterterpenoid (Nicotiazanorpenoid A) and eight previously unreported compounds. Systematic evaluation revealed three synergistic neuroprotective mechanisms: (1) Antioxidant activity: Scopoletin (3) and isoferulic acid (6) showed significant radical scavenging capacity (ABTS assay; IC₅₀ = 27.74, and 18.13 μM, respectively); (2) Neuronal protection: cis-11,14,17-Eicosatrienoic acid methyl ester (14) enhanced survival (93.94% vs. control) in 6-OHDA-induced PC12 cells, surpassing rasagiline (88.36% at equivalent concentrations); (3) MAO-B inhibition: five compounds displayed selective inhibition, with scopoletin (3) exhibiting highest potency (K_i = 20.7 μM). Notably, plant prostaglandins (10/11) were identified as competitive MAO-B inhibitors first time through molecular docking and 100-ns MD simulations, revealing stable binding at the FAD site (ΔG = - 10.42, and- 9.75 kcal/mol, respectively).

An undescribed phenylpropanoid dimer featuring a rare cyclobutane ring was isolated from the rhizomes of Kaempferia galanga L., a medicinal plant traditionally used in Southeast Asia for its anti-inflammatory and therapeutic properties. Kaemphenolide (1), along with five known constituents, was obtained by separations of methanolic extract using chromatography. The presence of a cyclobutane ring within the phenylpropanoid scaffold represents an unusual structural motif among natural products and underscores the chemical uniqueness of this molecule. To evaluate its biological relevance, 1 was tested for its ability to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The compound exhibited anti-inflammatory activity, with an IC₅₀ value of 23.1 ± 6.40 μM.

The resurgence of interest in traditional herbal remedies stems from an increasing appreciation for their complex phytochemical profiles and potential for synergistic therapeutic effects. However, the therapeutic potential of plant extracts is often limited by poor absorption and potential toxicity related to conventional delivery methods. This review explores the application of nanocarrier-mediated delivery systems, such as nanoparticles (NPs), liposomes, and nanoemulsions, to address these challenges. These biocompatible carriers offer enhanced stability and targeted delivery of herbal compounds, improving their efficacy and reducing unwanted side effects. By enabling precise distribution, nanotechnology optimizes the potency of herbal medicine across diverse applications, including regenerative medicine, wound healing, anticancer, and infection treatment. This review provides a systematic description of successful applications of nano-delivery technologies, nanoparticles, liposomes, nanoemulsions, and hybrid carriers, for the targeted delivery of some well-characterized herbal bioactives (curcumin, allicin, berberine, resveratrol etc.) and the enhanced therapeutic performance of herbal bioactives across a variety of preclinical models.