Search Results (96)

In order to investigate bioactive natural products derived from the endophytic fungus Penicillium ochrochloron SWUKD4.1850, a comprehensive study focusing on secondary metabolites was conducted. This research led to the isolation of twenty distinct compounds, including a novel nortriterpenoid (compound 20), alongside nineteen compounds that had been previously characterized (compounds 1–19). The chemical structures of these compounds were elucidated using spectroscopic techniques and nuclear magnetic resonance (NMR) analyses. Compounds 1–17 were isolated for the first time as metabolites of P. ochrochloron. Except for compounds 1–14, significant structural similarity was discerned between the metabolites of the endophytic fungus and those of the host plant. Compound 20 is noted as the inaugural instance of a naturally occurring 27-nor-3,4-secocycloartane schinortriterpenoid, while compound 17 was identified in fungi for the first time. An antifungal assay showed that compound 10 displayed a broader antifungal spectrum and a stronger inhibitory effect towards four important plant pathogens, at inhibitory rates of 74.9 to 85.3%. The in vitro radical scavenging activities of compounds 1, 3, 8, 15, and 16 showed higher antioxidant activity than vitamin C. Moreover, a cytotoxic assay revealed that compound 20 had moderate cytotoxicity against the HL-60, SMMC-7721, and MCF-7 cell lines (IC₅₀ 6.5–17.8 μM). Collectively, these findings indicate that P. ochrochloron has abundant secondary metabolite synthesis ability in microbial metabolism and that these metabolites have good biological activity and have the potential to enhance plant disease resistance. Full article

As a major global health challenge, hepatocellular carcinoma (HCC) still faces substantial limitations in its treatment options. This study investigates the anti-HCC potential of ACY-1215, a selective Histone deacetylase 6 (HDAC6) inhibitor, and its mechanism targeting p53 regulation. In vitro studies conducted with HepG2 and SMMC-7721 cells revealed that ACY-1215 markedly inhibited HCC cell proliferation, migratory capacity, and invasive potential, as evidenced by CCK-8, colony formation, and Transwell assays. Furthermore, ACY-1215 induced caspase-dependent apoptosis. Mechanistically, ACY-1215 enhanced p53 acetylation by disrupting HDAC6-p53 interaction, thereby stabilizing p53 protein levels. Concurrently, it inhibited Murine Double Minute 2 (MDM2)-mediated ubiquitination, blocking proteasomal degradation and prolonging p53 half-life. This dual modulation restored p53 transcriptional activity, leading to the upregulation of downstream effector molecules associated with cell cycle regulation and apoptosis. Collectively, our findings reveal that ACY-1215 exerts potent anti-HCC effects through coordinated regulation of p53 acetylation and ubiquitination, offering a novel dual-targeting strategy for HCC therapy. Full article

Benzophenone UV absorbers (BPs), a widely used family of organic UV absorbers (UVAs), have attracted considerable attention for their effects on organisms in recent years. Previous research has been unable to illuminate the intricate situation of BP pollution. To address this knowledge gap, we devised a BAPG-chain model that surpasses existing approaches based on biochemical detection, antioxidant defense systems, proteins, and genes to investigate the biological mechanisms of benzophenone-1 (BP-1) and benzophenone-3 (BP-3) within human hepatoma SMMC-7721 cells as model organisms. The BAPG-chain model links the cellular model, molecular level, macroscopic scale, and microscopic phenomena by adopting a global assessment mindset. Our findings indicate that BPs induce apoptosis via the excessive production of reactive oxygen species (ROS), mitochondrial and nuclear damage, and disruption of the antioxidant stress system. Notably, BPs induce apoptosis via alterations in the expression of genes and proteins associated with apoptosis in the mitochondria. Our experimental evidence sheds light on the biological effects of BPs and highlights the need for further research in this area. Full article

Background: Liver cancer, specifically hepatocellular carcinoma (LIHC), ranks as the second most common cause of cancer-related fatalities globally. Moreover, the occurrence rate of LIHC is steadily increasing. A recently identified gene, SPSB2, has been implicated in cell signaling, impacting the development and progression of non-small cell lung cancer. Nevertheless, studies on the role of SPSB2 in the pathogenesis of LIHC are lacking. Methods: Using the TCGA, GTEx, and GEO databases, we obtained differentially expressed genes that affect the prognosis of patients with LIHC. We utilized the Kruskal–Wallis test, along with univariate and multivariate COX regression analyses, to determine the correlation between SPSB2 and patient clinical indicators. Potential biological functions of SPSB2 in LIHC were explored by enrichment analysis, ssGSEA, and Spearman correlation analysis. Finally, LIHC cell lines Huh7 and SMMC-7721 were used to validate the biological function of SPSB2. Results: The results showed LIHC patients with higher SPSB2 expression had a poorer prognosis, and SPSB2 expression was significantly correlated with LIHC patients’ Histologic grade, Pathologic T stage, Prothrombin time, Pathologic stage, BMI, weight, adjacent hepatic tissue inflammation, AFP level, and OS event (p < 0.05). SPSB2 shows notable enrichment in pathways linked to tumorigenesis and the immune system. Moreover, its expression is strongly connected to immune cells and immune checkpoints. Knockdown of SPSB2 expression in Huh7 cells and SMMC-7721 cells inhibits SPSB2’s biological functions, including proliferation, invasion, metastasis, and other phenotypes. Conclusions: SPSB2 plays a crucial role in the development of LIHC. It is related to the immune response and unfavorable outcomes. SPSB2 may function as a clinical biomarker for prognosis. Full article

In this experiment, the excellent coordination ability of sulfur-containing ligands was utilized. Diphenylacetyl disulfide and 3,3′-diaminodiphenyl sulfone were selected as ligands, and Cu(NO₃)₂·3H₂O, Ni(NO₃)₂·6H₂O and ZnCl₂ were reacted under one-pot conditions to synthesize three mononuclear complexes: [C₄H₁₈CuO₁₂S₂](I), [C₁₂H₁₈N₄NiO₁₁S](II) and [C₂₄H₂₄Cl₂N₄O₄S₂Zn](III). Complex (I) belongs to the orthorhombic crystal system with space group Pbca, while complexes (II) and (III) belong to the monoclinic crystal system with space groups P21/n and P2/n. The crystal structure of the complex was determined using X-ray diffraction (XRD). The structure of the complex was analyzed using infrared Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–Vis), nuclear magnetic resonance (NMR), and electrospray mass spectrometry (ESI-MS), and the thermal stability and composition of the complex were detected via thermogravimetry (TGA). In terms of application, the biological activity of complexes (I)–(III) in human cancer cell lines (lung cancer A549, liver cancer SMMC-7721, breast cancer MDA-MB-231, and colon cancer SW480) was tested using the MTS method. The results showed that complex (II) had a good inhibitory effect on breast cancer MDA-MB-231. Full article

Objective: To explore the influence of NRAS-AS on the proliferation, apoptosis, cell cycle, migration, and invasion ability of HCC cells, as well as its underlying mechanisms. Methods: A double-stranded cDNA library for liver cancer cells was constructed, and identified NRAS-AS through High-throughput sequencing, bioinformatics, chain-specific fluorescent quantitative PCR, and RACE. NRAS-AS′s effects on HepG2 and SMMC-7721 cells and gene expression were evaluated. Additionally, the study analyzed the influence of NRAS-AS overexpression on tumor formation in nude mice. Immunohistochemistry and Western blotting were used to detect NRAS protein levels in clinical samples. RT-qPCR examined NRAS-AS and NRAS gene expression in HCC and adjacent tissues. Results: NRAS-AS overexpression suppresses HCC cell proliferation and invasion, induces cell cycle alterations in HepG2 and SMMC-7721 cells, and enhances apoptosis. NRAS-AS interference promoted liver cancer invasion, inhibited apoptosis, and influences the cell cycle. Nude mice overexpressing NRAS-AS showed smaller tumors. NRAS-AS expression in liver cancer patients correlated with clinical factors. RT-qPCR revealed an inverse correlation between NRAS-AS and NRAS gene expression in liver cancer and adjacent tissues. IHC analysis revealed reduced NRAS protein expression in HepG2 and SMMC-7721 cells following NRAS-AS overexpression. The impact of AZA treatment on antisense NRAS-AS and sense NRAS gene expression in liver cancer cells was observed, and antisense. Conclusion: Reduced NRAS-AS expression is frequently observed in HCC and is inversely related to NRAS gene expression, suggesting a role in HCC pathogenesis through NRAS regulation. Targeting antisense RNA NRAS-AS could hold promise as a therapeutic target and diagnostic biomarker for HCC. Full article

Many naturally occurring chemical metabolites with significant cytotoxic activities have been isolated from medicinal plants and have become the leading hotspot of anti-cancer research in recent years. Hyptis rhomboidea Mart. et Gal is used as a folk medicine in South China to treat or assist in the treatment of liver disease, ulcers, and edema. But its chemical constituents have not been fully investigated yet. This study aimed to assess the cytotoxicity of H. rhomboidea, which was chemically characterized by chromatography–mass spectrometry methods. The results showed that the 95% ethanol extract of H. rhomboidea has marked inhibitory effects on five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480), with IC₅₀ values ranging from 15.8 to 40.0 μg/mL. A total of 64 compounds were identified by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatograph–mass spectroscopy (GC-MS) analysis of H. rhomboidea crude extract. Among them, kaempferol, quercetin, rosmarinic acid, squalene, and campesterol were found to be abundant and might be the major metabolites involved to its bioactivity. The cytotoxic characterization and metabolite profiling of H. rhomboidea displayed in this research provides scientific evidence to support its use as medicinal properties. Full article

Isoamyl 4-methoxycinnamate (IMC) is widely used in various fields because of its exceptional UV-filter properties. However, due to its cytotoxicity and anti-microbial degradability, the potential eco-environmental toxicity of IMC has become a focus of attention. In this study, we propose a host–guest supramolecule approach to enhance the functionality of IMC, resulting in a more environmentally friendly and high-performance materials. Sulfobutyl-β-cyclodextrin sodium salt (SBE-β-CD) was used as the host molecule. IMC-SBE-β-CD supramolecular substances were prepared through the “saturated solution method”, and their properties and biosecurity were evaluated. Meanwhile, we conducted the AOS tree evaluation system that surpasses existing evaluation approaches based on apoptosis, oxidative stress system, and signaling pathways to investigate the toxicological mechanisms of IMC-SBE-β-CD within human hepatoma SMMC-7721 cells as model organisms. The AOS tree evaluation system aims to offer the comprehensive analysis of the cytotoxic effects of IMC-SBE-β-CD. Our findings showed that IMC-SBE-β-CD had an encapsulation rate of 84.45% and optimal stability at 30 °C. Further, IMC-SBE-β-CD promoted cell growth and reproduction without compromising the integrity of mitochondria and nucleus or disrupting oxidative stress and apoptosis-related pathways. Compared to IMC, IMC-SBE-β-CD is biologically safe and has improved water solubility with the UV absorption property maintained. Our study provides the foundation for the encapsulation of hydrophobic, low-toxicity organic compounds using cyclodextrins and offers valuable insights for future research in this field. Full article

Deep eutectic solvents (DESs) are novel solvents with physicochemical properties similar to those of ionic liquids, and they have attracted extensive attention for the extraction of bioactive compounds from different plant materials in the context of green chemistry and sustainable development. In this study, seven DESs with different polarities were explored as green extraction solvents for cembratrien-diols (CBT-diols) from waste tobacco flowers. The best solvent, DES-3 (choline chloride: lactic acid (1:3)), which outperformed conventional solvents (methanol, ethanol, and ethyl acetate), was selected and further optimized for microwave-assisted DES extraction using the response surface methodology. The maximum yield of CBT-diols (6.23 ± 0.15 mg/g) was achieved using a microwave power of 425 W, microwave time of 32 min, solid/liquid ratio of 20 mg/mL, and microwave temperature of 40 °C. Additionally, the isolated CBT-diols exhibited strong antimicrobial activity against Salmonella, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa and antitumor activity in the human liver cancer HepG2 and SMMC-7721 cell lines. This study highlights the feasibility of recovering CBT-diols from tobacco flower waste using DESs and provides opportunities for potential waste management using green technologies. Full article

Plants that possess a diverse range of bioactive compounds are essential for maintaining human health and survival. The diversity of bioactive compounds with distinct therapeutic potential contributes to their role in health systems, in addition to their function as a source of nutrients. Studies on the genetic makeup and composition of bioactive compounds have revealed them to be rich in steroidal alkaloids, saponins, terpenes, flavonoids, and phenolics. The Solanaceae family, having a rich abundance of bioactive compounds with varying degrees of pharmacological activities, holds significant promise in the management of different diseases. Investigation into Solanum species has revealed them to exhibit a wide range of pharmacological properties, including antioxidant, hepatoprotective, cardioprotective, nephroprotective, anti-inflammatory, and anti-ulcerogenic effects. Phytochemical analysis of isolated compounds such as diosgenin, solamargine, solanine, apigenin, and lupeol has shown them to be cytotoxic in different cancer cell lines, including liver cancer (HepG2, Hep3B, SMMC-772), lung cancer (A549, H441, H520), human breast cancer (HBL-100), and prostate cancer (PC3). Since analysis of their phytochemical constituents has shown them to have a notable effect on several signaling pathways, a great deal of attention has been paid to identifying the biological targets and cellular mechanisms involved therein. Considering the promising aspects of bioactive constituents of different Solanum members, the main emphasis was on finding and reporting notable cultivars, their phytochemical contents, and their pharmacological properties. This review offers mechanistic insights into the bioactive ingredients intended to treat different ailments with the least harmful effects for potential applications in the advancement of medical research. Full article

Background: Astragaloside IV (AS-IV) is a pivotal contributor to anti-tumour effects and has garnered extensive attention in research. Tumour cell immune suppression is closely related to the increase in Programmed Death-Ligand 1 (PD-L1). Hepatocellular carcinoma (HCC) is a malignant tumour originating from hepatic epithelial tissue, and the role of AS-IV in regulating PD-L1 in anti-HCC activity remains unclear. Methods: Various concentrations of AS-IV were administered to both human liver immortalised cells (THEL2) and HCC (Huh-7 and SMMC-7721), and cell growth was assessed using the CCK-8 assay. HCC levels and cell apoptosis were examined using flow cytometry. Mice were orally administered AS-IV at different concentrations to study its effects on HCC in vivo. Immunohistochemistry was employed to evaluate PD-L1 levels. Western blotting was employed to determine PD-L1 and CNDP1 protein levels. We carried out a qRT-PCR to quantify the levels of miR-135b-3p and CNDP1. Finally, a dual-luciferase reporter assay was employed to validate the direct interaction between miR-135b-3p and the 3′UTR of CNDP1. Results: AS-IV exhibited a dose-dependent inhibition of proliferation in Huh-7 and SMMC-7721 while inhibiting PD-L1 expression induced by interferon-γ (IFN-γ), thus attenuating PD-L1-mediated immune suppression. MiR-135b-5p showed significant amplification in HCC tissues and cells. AS-IV mitigated PD-L1-mediated immune suppression through miR-135b-5p. MiR-135b-5p targeted CNDP1, and AS-IV mitigated PD-L1-induced immunosuppression by modulating the miR-135b-5p/CNDP1 pathway. Conclusion: AS-IV decreases cell surface PD-L1 levels and alleviates PD-L1-associated immune suppression via the miR-135b-5p/CNDP1 pathway. AS-IV may be a novel component for treating HCC. Full article

Euphorbia stracheyi Boiss was used for hemostasis, analgesia, and muscular regeneration in traditional Chinese medicine. To study the chemical constituents of E. stracheyi, the ethyl acetate part of the methanol extract of the whole plant was separated by silica gel, sephadex LH-20 column chromatography, and semi-preparative HPLC. The isolation led to the characterization of a new lathyrane type diterpenoid, euphostrachenol A (1), as well as eleven known compounds (2–11), including a lathyrane, three ingenane-type and two abietane-type diterpenoids, two ionones, and two flavonoids. The structures of these compounds were established using 1D- and 2D-NMR experiments, mass spectrometry, and X-ray crystallographic experiments. The MTT method was used to determine the cytotoxic activity of five cancer cell lines (Leukemia HL-60, lung cancer A-549, liver cancer SMMC-7721, breast cancer MCF-7, and colon cancer SW480) on the isolated compounds. However, only compound 4 showed moderate cytotoxicity against these cell lines, with IC₅₀ values ranging from 10.28 to 29.70 μM, while the others were inactive. Our chemical investigation also confirmed the absence of jatrophane-type diterpenoids in the species, which may be related to its special habitat. Full article

Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), one of the most prevalent malignant tumors worldwide that poses a significant threat to human health. The multifunctional regulator known as Hepatitis B virus X-protein (HBx) interacts with host factors, modulating gene transcription and signaling pathways and contributing to hepatocellular carcinogenesis. The p90 ribosomal S6 kinase 2 (RSK2) is a member of the 90 kDa ribosomal S6 kinase family involved in various intracellular processes and cancer pathogenesis. At present, the role and mechanism of RSK2 in the development of HBx-induced HCC are not yet clear. In this study, we found that HBx upregulates the expression of RSK2 in HBV-HCC tissues, HepG2, and SMMC-7721 cells. We further observed that reducing the expression of RSK2 inhibited HCC cell proliferation. In HCC cell lines with stable HBx expression, RSK2 knockdown impaired the ability of HBx to promote cell proliferation. The extracellularly regulated protein kinases (ERK) 1/2 signaling pathway, rather than the p38 signaling pathway, mediated HBx-induced upregulation of RSK2 expression. Additionally, RSK2 and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were highly expressed and positively correlated in HBV-HCC tissues and associated with tumor size. This study showed that HBx upregulates the expression of RSK2 and CREB by activating the ERK1/2 signaling pathway, promoting the proliferation of HCC cells. Furthermore, we identified RSK2 and CREB as potential prognostic markers for HCC patients. Full article

One new dibenzyltyrolactone lignan dysoslignan A (1), three new arylnaphthalide lignans dysoslignan B–C (2–4), along with fourteen known metabolites (5–18), were isolated from the roots and rhizomes of Dysosma versipellis. Their structures and stereochemistry were determined from analysis of NMR spectroscopic and circular dichroism (CD) data. Compound 2 represents the first report of naturally occurring arylnaphthalide lignan triglycoside. The cytotoxic activities of all isolated compounds were evaluated against A-549 and SMMC-7721 cell lines. Compounds 7–10 and 14–16 were more toxic than cisplatin in two tumor cell lines. This investigation clarifies the potential effective substance basis of D. versipellis in tumor treatment. Full article

Many unique chemical metabolites with significant antitumor activities have been isolated from Garcinia species and have become a leading hotspot of antitumor research in recent years. The aim of this study was to identify bioactive compounds from different plant parts (leaf, branch, stem bark, fruit, and seed) of G. xanthochymus through combining LC-MS-based metabolomics with cytotoxicity assays. As a result, 70% methanol seed extract exerted significant cytotoxic effects on five human cancer cell types (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480). LC-MS-based metabolomics analysis was used, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), in order to identify 12 potential markers from seed extract that may relate to bioactivity. LC-MS guidance isolated the markers to obtain three compounds and identified new isopentenyl phloroglucinols (1–3, named garxanthochin A–C), using spectroscopic methods. Among them, garxanthochin B (2) demonstrated moderate inhibitory activities against five human cancer cell types, with IC₅₀ values of 14.71~24.43 μM. These findings indicate that G. xanthochymus seed has significant cytotoxic activity against cancer cells and garxanthochin B has potential applications in the development of antitumor-led natural compounds. Full article