Liver disease is a serious threat to human health, so its prevention and treatment have been the focus of medical research. In the past few years, natural products have proved to be promising and valuable in the treatment of liver diseases. The bioactive substance paeonol, extracted from the root bark of peony (Paeonia lactiflora) of the buttercup family, is a promising drug candidate because of its low toxicity and multifaceted pharmacological properties. This review comprehensively explored the therapeutic potential of paeonol in different liver pathologies as well as the regulatory mechanisms. Despite its promising potential, the poor solubility and rapid metabolism of paeonol hindered its clinical translation. To improve bioavailability and liver targeting, we highlighted the potential of paeonol as a next-generation therapy for liver diseases by integrating preclinical evidence and technological advances, while exploring key avenues for future research, such as metabolic regulation and smart nanocarrier design.

PurposeTriple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, remains clinically challenging due to the lack of effective targeted therapies. This investigation revealed the anti-TNBC potential of Trichoderma viride ethyl acetate extract (TVEAE) from the endophytic fungus Trichoderma viride isolated from Coreopsis basalis.
MethodsPharmacological validation of TVEAE's anti-TNBC efficacy was conducted through in vitro and in vivo pharmacological models. The cell death mechanisms were systematically investigated using Hoechst staining, reactive oxygen species (ROS) detection, and lipid peroxidation assays. Potential therapeutic targets and signaling pathways were identified by integrating network pharmacology, transcriptomics, and weighted gene co-expression network analysis (WGCNA). Furthermore, this study validated key tumor-related proteins involved in tumor progression and cell death pathways via Western blotting. Finally, chemical constituents were characterized through molecular network coupled with Global Natural Products Social Molecular Networking (GNPS) analysis.
ResultsBoth in vitro and in vivo models established TVEAE's significant anti-TNBC efficacy. Mechanistic interrogation established TVEAE-mediated ferroptosis induction via selective modulation of leukocyte transendothelial migration (TEM) signaling cascades. Integrative analysis combining transcriptomics, WGCNA, and network pharmacology identified IL-6/TNF-α/HSP90AA1 as core therapeutic targets regulating TEM pathway dynamics. GNPS-assisted molecular networking uncovered six structurally novel anti-TNBC metabolites, including N-lauryldiethanolamine, erucamide, and Gliotoxin.
ConclusionThis study provides the first evidence of TVEAE's anti-TNBC activity through multi-target engagement along the leukocyte TEM signaling axis, effectively triggering ferroptosis. The mechanistic elucidation advances TNBC therapeutic development, offering a multi-dimensional targeting strategy against this recalcitrant malignancy.

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.

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.

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.

Natural product tanshinone I exhibits weak potency and poor drug-like properties, which have restricted its clinical development as an anticancer agent. Herein, twenty novel tanshinone I-pyridinium salt derivatives and a pyridinium salt precursor were designed and synthesized, and their antitumor activities were evaluated. Among these tanshinone I-pyridinium salts, compound a4, bearing a 4-bromobenzoylmethyl substituent at the N-1 position of the pyridine ring, showed the most potent cytotoxicity against breast cancer (MDA-MB-231), hepatocellular carcinoma (HepG2), and prostate cancer (22RV1) cell lines, with IC₅₀ values of 1.40-1.63 μM. Preliminary mechanistic studies suggest that a4 targets PI3Kα with the IC₅₀ of 9.24 ± 0.20 μM and exerts effective inhibition of the phosphorylation of key PI3K/Akt/mTOR signaling proteins. Besides, a4 significantly downregulates the expression of the immune checkpoint protein PD-L1, indicating its potential to activate tumor immunity. These findings demonstrate that tanshinone I-pyridinium salt derivative a4 is a novel PI3Kα inhibitor, providing a solid foundation for further development of antitumor agents.

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.

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 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.

Three new ent-kaurane diterpenoids, silvaticusins A-C (1-3), along with a new ent-kaurane dimer silvaticusin D (4) were isolated from the aerial parts of Isodon silvaticus. The structures of these new compounds were established mainly by comprehensive analysis of their NMR and MS data. The absolute configuration of compounds 1 and 4 were determined using a single-crystal X-ray diffraction and computational methods, respectively. Compounds 2 and 3 were found to exhibit remarkable cytotoxic effects against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, and SW-480), with IC₅₀ values spanning from 1.27±0.08 to 7.52±0.33 μM.

N-Hydroxyapiosporamide (N-hydap), a marine product derived from a sponge-associated fungus, has shown promising inhibitory effects on small cell lung cancer (SCLC). However, there is limited understanding of its metabolic pathways and characteristics. This study explored the in vitro metabolic profiles of N-hydap in human recombinant cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs), as well as human/rat/mice microsomes, and also the pharmacokinetic properties by HPLC-MS/MS. Additionally, the cocktail probe method was used to investigate the potential to create drug-drug interactions (DDIs). N-Hydap was metabolically unstable in various microsomes after 1 h, with about 50% and 70% of it being eliminated by CYPs and UGTs, respectively. UGT1A3 was the main enzyme involved in glucuronidation (over 80%), making glucuronide the primary metabolite. Despite low bioavailability (0.024%), N-hydap exhibited a higher distribution in the lungs (26.26%), accounting for its efficacy against SCLC. Administering N-hydap to mice at normal doses via gavage did not result in significant toxicity. Furthermore, N-hydap was found to affect the catalytic activity of drug metabolic enzymes (DMEs), particularly increasing the activity of UGT1A3, suggesting potential for DDIs. Understanding the metabolic pathways and properties of N-hydap should improve our knowledge of its drug efficacy, toxicity, and potential for DDIs.

Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed.

Three previously undescribed compounds, cordycicadione (1), cordycicadin F (2), and 7-hydroxybassiatin (3), were isolated from the cultures of Cordyceps cicadae JXCH1, an entomopathogenic fungus. Their structures and relative configurations were elucidated primarily by NMR spectroscopic analysis. The absolute configurations of 1 and 2 were determined by ECD calculations. Single-crystal X-ray diffraction method was adopted to determine the absolute configuration of 3. Compound 2 is a polycyclic polyketide with an unusual enol ether moiety and a spiro ring. The compounds obtained in this study were subjected to screening their inhibition against the proliferation of the human lung cancer cell line A549 and the production of nitric oxide in murine macrophages RAW264.7.

DNA topoisomerases are essential nuclear enzymes in correcting topological DNA errors and maintaining DNA integrity. Topoisomerase inhibitors are a significant class of cancer chemotherapeutics with a definite curative effect. Natural products are a rich source of lead compounds for drug discovery, including anti-tumor drugs. In this study, we found that narciclasine (NCS), an amaryllidaceae alkaloid, is a novel inhibitor of topoisomerase I (topo I). Our data demonstrated that NCS inhibited topo I activity and reversed its unwinding effect on p-HOT DNA substrate. However, it had no obvious effect on topo II activity. The molecular mechanism of NCS inhibited topo I showed that NCS did not stabilize topo-DNA covalent complexes in cells, indicating that NCS is not a topo I poison. A blind docking result showed that NCS could bind to topo I, suggesting that NCS might be a topo I suppressor. Additionally, NCS exhibited a potent anti-proliferation effect in various cancer cells. NCS arrested the cell cycle at G₂/M phase and induced cell apoptosis. Our study reveals the antitumor mechanisms of NCS and provides a good foundation for the development of anti-cancer drugs based on topo I inhibition.