Fully bio-based and intrinsically flame retardant unsaturated polyester cross-linked with isosorbide-based diluents.

Unsaturated polyester resins (UPR) are composed of prepolymers and styrene diluents, while the former are produced by co-polycondensation between diol, unsaturated diacid and saturated diacid. In this work, bio-based UPR prepolymers were synthesized from bio-based oxalic acid, itaconic acid, and ethylene glycol, which were then diluted with bio-based isosorbide methacrylate (MI). Meanwhile, the phenylphosphonate were introduced into the molecular chains of prepolymers to achieve intrinsic flame retardancy of bio-based UPR. The potential of the reactive MI diluents as substitutes of volatile styrene, was also assessed through the volatility test, curing kinetics and gel contents analysis. For UPR materials with styrene diluents, the UPR materials can achieve UL-94 V0 level and the 28% of limiting oxygen index (LOI) with 2.63 wt% of phosphorus contents. By contrast, the UPR materials with MI diluents can reach UL-94 V0 level with only 2.14 wt% of phosphorus contents. As the phosphorus contents were further increased to 2.63 wt%, UPR materials can achieve highest 29%, while the peak of heat release rate (PHRR) and total heat release (THR) were decreased by 68.01% and 48.62%, respectively. The Flame Retardancy Index (FRI) was also used to comprehensively evaluate the flame retardant performance of UPR composites. Compared with neat UPR, the composites with MI diluents and phosphorus containing structures increased from 1.00 to 6.46. The mechanism for improved flame retardancy was analyzed from gaseous and condensed phase. Additionally, the tensile strengths of bio-based UPR materials with styrene and MI diluents were studied. This work provides an effective method to prepared high-performance and fully bio-based UPR materials with improved flame retardant properties and safety application of reactive diluents.

Cobalt-doped hollow polydopamine for oxygen generation and GSH consumption enhanced chemo-PTT combined cancer therapy.

Nanotechnology has revolutionized the field of therapeutics by introducing a plethora of nanomaterials capable of enhancing traditional drug efficacy or paving the way for innovative treatment methods. Within this domain, we propose a novel Cobalt-doped hollow polydopamine nanosphere system. This system, incorporating Doxorubicin loading and hyaluronic acid (HA) surface coating (CoHPDA@DOX-HA), is designed for combined tumor therapy. The overarching aim is to diminish the administration dosage, mitigate the cytotoxic side effects of chemotherapy drugs, augment chemosensitivity within neoplastic tissues, and attain superior results in tumor treatment via combined therapeutic strategies. The targeted molecule, hyaluronic acid (HA), amplifies the biocompatibility of CoHPDA@DOX-HA throughout circulation and fosters endocytosis of the nanoparticle system within cancer cells. This nanosphere system possesses pH sensitivity properties, allowing for a meticulous drug release within the acidic microenvironment of tumor cells. Concurrently, Polydopamine (PDA) facilitates proficient photothermal therapy upon exposure to 808 nm laser irradiation. This process further amplifies the Glutathione (GSH) depletion, and when coupled with the oxygen production capabilities of the Cobalt-doped hollow PDA, significantly enhances the chemo-photothermal therapeutic efficiency. Findings from the treatment of tumor-bearing mice substantiate that even at dosages equivalent to a singular DOX administration, the CoHPDA@DOX-HA can provide efficacious synergistic therapy. Therefore, it is anticipated that multifunctional nanomaterials with Photoacoustic Tomography (PAT) imaging capabilities, targeted delivery, and a controlled collaborative therapeutic framework may serve as promising alternatives for accurate diagnostics and efficacious treatment strategies.

Yolk-shell shaped Au-Bi2S3heterostructure nanoparticles for controlled drug release and combined tumor therapy.

To fabricate a novel stimuli-responsive system enabling controlled drug release and synergistic therapy, yolk-shell shaped bismuth sulfide modified with Au nanoparticles (Au-Bi2S3) was prepared. The Au-Bi2S3nanomaterial with heterojunction structure exhibited excellent photothermal conversion efficiency and considerable free radicals yield under laser irradiation. The drug delivery capacity was confirmed by co-loading Berberine hydrochloride (BBR) and a phase change material 1-tetradecanol (PCM), which could be responsible for NIR light induced thermal controlled drug release.In vitroinvestigation demonstrated that Au-Bi2S3has cell selectivity, and with the assistance of the properties of Au-Bi2S3, the loaded drug could give full play to their cancer cell inhibition ability. Our work highlights the great potential of this nanoplatform which could deliver and control Berberine hydrochloride release as well as realize the synergistic anti-tumor strategy of photothermal therapy, photodynamic therapy and chemotherapy for tumor therapy.

Concomitant Medication Use With Xiyanping Injection and the Risk of Suspected Allergic Reactions: A Nested Case-Control Study Based on China's National Medical Insurance Database.

Introduction: Xiyanping injection (XYP), a type of Traditional Chinese Medicine, is widely used and often applied in combination with other medications in treating bronchitis, tonsillitis, and bacillary dysentery in China. In recent years, an elevated risk of allergic reactions has been observed following XYP, but whether concomitant medication use contributes to this risk is still unknown. Objective: This study aims to investigate the association between the concomitant use of XYP and the 25 most frequently co-applied medications with suspected allergic reactions for China's patients receiving XYP. Methods: A nested case-control study was conducted using the sampling data from 2015 China's Urban Employees Basic Medical Insurance and Urban Residents Basic Medical Insurance database. Four anti-allergic marker drugs were used to evaluate suspected allergic reactions. Univariate analyses and multivariable conditional logistic regression were conducted, and results were reported as odds ratios (ORs) with a 95% confidence interval (CI). Sensitivity analyses were performed on the expanded sample by including those prescribed with anti-allergic marker drugs on the same day as XYP and then stopped XYP on the next day. Results: Out of 57,612 participants with XYP prescription, we obtained 949 matched case-control pairs. Multivariable conditional logistic regression revealed that seven concomitant medications including gentamicin [OR = 4.29; 95% CI (2.52, 7.30)], cefoperazone-sulbactam [OR = 4.26; 95% CI (1.40, 13.01)], lidocaine [OR = 2.76; 95% CI (1.79, 4.25)], aminophylline [OR = 1.73; 95% CI (1.05, 2.85)], ribavirin [OR = 1.54; 95% CI (1.13, 2.10)], potassium chloride [OR = 1.45; 95% CI (1.10, 1.91)], and vitamin C [OR = 1.32; 95% CI (1.03, 1.70)] were associated with increased risk, while cefathiamidine [OR = 0.29; 95% CI (0.16, 0.51)] was associated with reduced risk. Sensitivity analysis on 2,438 matched pairs revealed similar findings. Conclusion: Increased risks for suspected allergic reactions were found for the concomitant use of XYP with seven medications. Our data suggest that gentamicin, cefoperazone-sulbactam, lidocaine, and ribavirin should be applied with precautions for patients receiving XYP, and further studies on drug interactions and allergy mechanisms are warranted.

Comparative Proteomic Analysis Revealed the Mechanism of Tea Tree Oil Targeting Lipid Metabolism and Antioxidant System to Protect Hepatopancreatic Health in Macrobrachium rosenbergii.

Tea tree oil (TTO) is a pure natural plant essential oil. The studies evaluated the hepatopancreas lipid metabolism and antioxidant efficacy of Macrobrachium rosenbergii fed with 0 (CT group) and 100 mg/kg TTO (TT group) by label-free quantification proteomic analysis. Compared to the CT group, the TT group improved growth performance and increased the survival rate after stress. Dietary TTO also decreased hemolymph AST and ALT activities and decreased hepatopancreatic vacuolation. At the same time, hepatopancreas lipids droplets and hemolymph lipids (TG, TC, LDL-C) were decreased, and the peroxidation products content (MDA, LPO, 4-HNE) was also decreased. In addition, the levels of hepatopancreas antioxidant enzymes (T-AOC, CAT, and SOD) were increased in the TT group. With proteomic analysis, a total of 151 differentially expressed proteins (DEPs) (99 up-regulated and 52 down-regulated) were identified in the hepatopancreas. Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction analysis showed that the 16 DEPs have interactions, which are mainly involved in the pathways related to lipid metabolism (fatty acid biosynthesis, fatty acid metabolism, glycerophospholipid metabolism) and redox reaction (cytochrome P450 enzyme systems). Furthermore, the mRNA expression of 15 proteins followed the proteomic analysis with qRT-PCR validation. Pearson correlation analysis showed that fatty acids and glycerophospholipid metabolism-related proteins were highly correlated to peroxide content, glycerophospholipid metabolism, and cytochrome P450 system-related proteins (CYP1A1, GSTT1, GPX4) were highly correlated to AST and ALT. Additionally, GPX4 is closely related to peroxide content and antioxidant enzyme activity. Our results revealed that TTO plays a protective role in the hepatopancreas targeting the critical enzymes and antioxidant reactions in lipid metabolism. Provides a new perspective to elucidate the action path of TTO in protecting invertebrate hepatopancreas, highlights the influence of lipid metabolism on hepatopancreas health and the interaction between lipid metabolism and antioxidant system in the regulation of TTO.

Covalent grafting diazotized black phosphorus with ferrocene oligomer towards smoke suppression and toxicity reduction.

In comparison with the thermal hazard of polymers, noxious smoke and gas produced by the combustion of polymers make the environment self-purification a huge challenge. As a new type of a highly effective flame retardant, black phosphorus (BP) can effectively decrease the thermal hazard of polymers, but its performances in smoke suppression and toxicity reduction are unsatisfactory. In this article, a method of covalently grafting diazotized BP with a ferrocene oligomer was applied to promote the smoke suppression and toxicity reduction efficiency of BP. In our work, the BP-NH nanomaterials with a mass of amino groups on the surface were acquired by diazotizing the BP. Then, the BP-Fe was obtained by covalently grafting the ferrocene chloride salt and nitrogen-containing heterocycles on the surface of BP. The smoke production rate (SPR) and total smoke production (TSP) values of the epoxy resin (EP) decreased by 49.8% and 52.5% with the addition of 2 wt% BP-Fe, respectively. In comparison with previous studies, this work was far more effective than the previous work in smoke suppression and flame retardant. The release of toxic gases (CO and HCN) and volatile organic compounds in the EP was also effectively inhibited at the same time. In addition, the storage modulus and tensile strength of nanocomposites increased by 35.1% and 27.2% with the addition of 1 wt% BP-Fe. This work also provides a new idea on how to simultaneously strengthen the toxic smoke suppression, mechanical properties, and flame retardant of polymer materials.

Exploration on structural rules of highly efficient flame retardant unsaturated polyester resins.

Owing to the lack of research on structure-activity relationship and interaction mechanism between unsaturated polyester resins (UPR) and flame retardants, it has been a big challenge to prepare high-efficiency flame retardants for UPR in industry. In this research, to explore structural rules of high-efficiency flame retardants, several polymeric flame retardants were synthesized with varied main-chain, side-chain, phosphorus valence states and contents of flame retardant elements. The thermal stabilities of flame retardants and UPR composites were firstly assessed. It has been found the interaction existed between flame retardants and UPR, through transesterification reaction and ß scission pathway in polyester and polystyrene chains. With only 15 wt% of PCH3-S, UPR composites can reach V0 rating in UL-94. The PHRR and THR values can be maximumly decreased by 71.66 % and 77.67 %, with 20 wt% of PB-S. It has been found flame retardants with sulfone group and + 3 valence state of phosphorus in molecular backbone can release SO2 and phosphorus containing compounds in gaseous phase, which diluted fuel fragments and catalyzed H⋅ and HO⋅ radical removal. The mechanism for improved flame retardancy of UPR composites with various polymeric flame retardants were discussed in detail. Some general rules for highly efficient flame retardant UPR can be summarized: First, gaseous phase flame retardant mechanism plays the major role in improvement of flame retardant performance of UPR composites; Second, the combination of + 3 valence state of phosphorus structures, higher phosphorus contents and sulfone groups effectively improves the flame retardant efficiency of flame retardants.

Hindered phenolic antioxidant passivation of black phosphorus affords air stability and free radical quenching.

As an antioxidant, hindered phenol scavenges free radicals. Due to the oxidative degradation of black phosphorus (BP) in the presence of water and oxygen, free radical quenching of hindered phenol antioxidants can solve this issue and improve the environmental stability and flame retardant efficiency of BP. Herein, hydroxyl-modified BP (BP-OH) with active groups on the surface was obtained by hydroxylation, and then the hindered phenol antioxidant was grafted onto the surface of BP-OH through an isophorone diisocyanate bridging covalent reaction to obtain hindered phenol-modified BP (BP-HPL). The fire hazard of thermoplastic polyurethane (TPU) can be significantly reduced by introducing BP-HPL into TPU. Adding 2 wt% BP-HPL can reduce the heat release rate and total heat release values of TPU by 49.9% and 49.0%, respectively. In addition, the reductions in smoke volume and carbon monoxide production were also significant. Compared with BP-OH, the environmental stability of BP-HPL is significantly improved. This work provides a reference for the application of BP in the field of fire safety and simultaneously achieves the improvement of the environmental stability and flame retardant performance of BP.

New insights into molecular mechanisms of "Cold or Hot" nature of food: When East meets West.

Traditional Chinese medicines are largely adopted in China and have a key importance in the world medical system. Cold-hot nature is the important characteristics of food and Chinese Materia Medica in the traditional Chinese medicine, relating to food functions in the organism. As compared to the studies on the cold and hot nature in Chinese medicine, the research studies carried out to establish the association between cold-hot nature and food are insufficient. Intending to investigate the criteria to discriminate the cold-hot nature of food and Chinese medicine scientifically, this review collected the cold-hot nature-related literature in recent 20 years in several popular databases such as PubMed, Google Scholar, and Science Direct. This review explored that the cold and hot natures are not only linked to the chemical components such as water, carbohydrates, lipids, and amino acids, but also correlated to the biological effects, comprising of energy metabolism, inflammation response, oxidation reaction, immune response, and cell growth and proliferation. Besides, this review further put forward the possibility that cold-hot nature of food and Chinese medicine exert different biological effects on the inflammatory response via regulating the signaling pathways viz. NF-κB and MAPK. More extensive studies are needed to consider the overall connections between both the biological effects and chemical components and how food processing affects the cold-hot nature of the food.

Dehydrocostus Lactone Attenuates the Senescence of Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration via Inhibition of STING-TBK1/NF-κB and MAPK Signaling.

The progression of intervertebral disc degeneration (IDD) is multifactorial with the senescence of nucleus pulposus (NP) cells and closely related to inflammation in NP cells. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone isolated from medicinal plants that has anti-inflammatory properties. Thus, DHE may have a therapeutic effect on the progression of IDD. In this study, NP cells were used to determine the appropriate concentration of DHE in vitro. The role of DHE in tumor necrosis factor-α (TNF-α)-induced activation of inflammatory signaling pathways and cellular senescence, together with anabolism and catabolism of extracellular matrix (ECM) in NP cells, was examined in vitro. The therapeutic effect of DHE in vivo was determined using a spinal instability model of IDD in mice. The TNF-α-induced ECM degradation and the senescence of NP cells were partially attenuated by DHE. Mechanistically, DHE inhibited the activation of NF-κB and MAPK inflammatory signaling pathways and ameliorated the senescence of NP cells caused by the activation of STING-TBK1/NF-κB signaling induced by TNF-α. Furthermore, a spinal instability model in mice demonstrated that DHE treatment could ameliorate progression of IDD. Together, our findings indicate that DHE can alleviate IDD changes and has a potential therapeutic function for the treatment of IDD.

Autophagy-based unconventional secretion of HMGB1 by keratinocytes plays a pivotal role in psoriatic skin inflammation.

The precise mechanism through which macroautophagy/autophagy affects psoriasis is poorly understood. Here, we found that keratinocyte (KC) autophagy, which was positively correlated with psoriatic severity in patients and mouse models and could be inhibited by mitogen-activated protein kinase (MAPK) family inactivation. The impairment of autophagic flux alleviated psoriasisform inflammation. We also found that an autophagy-based unconventional secretory pathway (autosecretion) dependent on ATG5 (autophagy related 5) and GORASP2 (golgi reassembly stacking protein 2) promoted psoriasiform KC inflammation. Moreover, the alarmin HMGB1 (high mobility group box 1) was more effective than other autosecretory proteins in regulating psoriasiform cutaneous inflammation. HMGB1 neutralization in autophagy-efficient KCs eliminated the differences in psoriasiform inflammation between Krt14+/+-Atg5f/f KCs and Krt14Cre/+-atg5f/f KCs, and conversely, recombinant HMGB1 almost completely restored psoriasiform inflammation in Krt14Cre/+-atg5f/f KCs in vivo. These results suggest that HMGB1-associated autosecretion plays a pivotal role in cutaneous inflammation. Finally, we demonstrated that Krt14Cre/+-hmgb1f/f mice displayed attenuated psoriatic inflammation due to the essential crosstalk between KC-specific HMGB1-associated autosecretion and γδT cells. Thus, this study uncovered a novel autophagy mechanism in psoriasis pathogenesis, and the findings imply the clinical significance of investigating and treating psoriasis.Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AGER: advanced glycosylation end-product specific receptor; Anti-HMGB1: anti-HMGB1 neutralizing antibody; Anti-IL18: anti-IL18 neutralizing antibody; Anti-IL1B: anti-IL1B neutralizing antibody; ATG5: autophagy related 5; BAF: bafilomycin A1; BECN1: beclin 1; CASP1: caspase 1; CCL: C-C motif chemokine ligand; CsA: cyclosporine A; ctrl shRNA: lentivirus harboring shRNA against control; CXCL: C-X-C motif chemokine ligand; DCs: dendritic cells; DMEM: dulbecco's modified Eagle's medium; ELISA: enzyme-linked immunosorbent assay; EM: electron microscopy; FBS: fetal bovine serum; GORASP2 shRNA: lentivirus harboring shRNA against GORASP2; GORASP2/GRASP55: golgi reassembly stacking protein 2; GR1: a composite epitope between LY6 (lymphocyte antigen 6 complex) locus C1 and LY6 locus G6D antigens; H&E: hematoxylin and eosin; HMGB1: high mobility group box 1; HMGB1 shRNA: lentivirus harboring shRNA against HMGB1; IFNG/IFN-γ: interferon gamma; IL17A: interleukin 17A; IL18: interleukin 18; IL1A/IL-1α: interleukin 1 alpha; IL1B/IL-1ß: interleukin 1 beta; IL22/IL-22: interleukin 22; IL23A: interleukin 23 subunit alpha; IL23R: interleukin 23 receptor; IMQ: imiquimod; ITGAM/CD11B: integrin subunit alpha M; ITGAX/CD11C: integrin subunit alpha X; IVL: involucrin; KC: keratinocyte; KD: knockdown; KO: knockout; Krt14+/+-Atg5f/f mice: mice bearing an Atg5 flox allele, in which exon 3 of the Atg5 gene is flanked by two loxP sites; Krt14+/+-Hmgb1f/f: mice bearing an Hmgb1 flox allele, in which exon 2 to 4 of the Hmgb1 gene is flanked by two loxP sites; Krt14Cre/+-atg5f/f mice: keratinocyte-specific atg5 knockout mice generated by mating Atg5-floxed mice with mice expressing Cre recombinase under the control of the promoter of Krt4; Krt14Cre/+-hmgb1f/f mice: keratinocyte-specific hmgb1 knockout mice generated by mating Hmgb1-floxed mice with mice expressing Cre recombinase under the control of the promoter of Krt14; Krt14-Vegfa mice: mice expressing 164-amino acid Vegfa splice variant recombinase under the control of promoter of Krt14; LAMP1: lysosomal associated membrane protein 1; LDH: lactate dehydrogenase; LORICRIN: loricrin cornified envelope precursor protein; M5: TNF, IL1A, IL17A, IL22 and OSM in combination; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MKI67: marker of proliferation Ki-67; MTT: thiazolyl blue tetrazolium bromide; NFKB/NF-κB: nuclear factor kappa B; NHEKs: primary normal human epidermal keratinocytes; NS: not significant; OSM: oncostatin M; PASI: psoriasis area and severity index; PtdIns3K: class III phosphatidylinositol 3-kinase; qRT-PCR: quantitative RT-PCR; RELA/p65: RELA proto-oncogene, NF-kB subunit; rHMGB1: recombinant HMGB1; rIL18: recombinant interleukin 18; rIL1B: recombinant interleukin 1 beta; S100A: S100 calcium binding protein A; SQSTM1/p62: sequestosome 1; T17: IL17A-producing T; TCR: T-cell receptor; tcrd KO mice: tcrd (T cell receptor delta chain) knockout mice, which show deficient receptor expression in all adult lymphoid and epithelial organs; TLR: toll-like receptor; TNF/TNF-α: tumor necrosis factor; WOR: wortmannin; WT: wild-type; γδT17 cells: IL17A-producing γδ T cells.

Extrasynaptic NMDA Receptors on Rod Pathway Amacrine Cells: Molecular Composition, Activation, and Signaling.

In the rod pathway of the mammalian retina, axon terminals of glutamatergic rod bipolar cells are presynaptic to AII and A17 amacrine cells in the inner plexiform layer. Recent evidence suggests that both amacrines express NMDA receptors, raising questions concerning molecular composition, localization, activation, and function of these receptors. Using dual patch-clamp recording from synaptically connected rod bipolar and AII or A17 amacrine cells in retinal slices from female rats, we found no evidence that NMDA receptors contribute to postsynaptic currents evoked in either amacrine. Instead, NMDA receptors on both amacrine cells were activated by ambient glutamate, and blocking glutamate uptake increased their level of activation. NMDA receptor activation also increased the frequency of GABAergic postsynaptic currents in rod bipolar cells, suggesting that NMDA receptors can drive release of GABA from A17 amacrines. A striking dichotomy was revealed by pharmacological and immunolabeling experiments, which found GluN2B-containing NMDA receptors on AII amacrines and GluN2A-containing NMDA receptors on A17 amacrines. Immunolabeling also revealed a clustered organization of NMDA receptors on both amacrines and a close spatial association between GluN2B subunits and connexin 36 on AII amacrines, suggesting that NMDA receptor modulation of gap junction coupling between these cells involves the GluN2B subunit. Using multiphoton Ca2+ imaging, we verified that activation of NMDA receptors evoked an increase of intracellular Ca2+ in dendrites of both amacrines. Our results suggest that AII and A17 amacrines express clustered, extrasynaptic NMDA receptors, with different and complementary subunits that are likely to contribute differentially to signal processing and plasticity.SIGNIFICANCE STATEMENT Glutamate is the most important excitatory neurotransmitter in the CNS, but not all glutamate receptors transmit fast excitatory signals at synapses. NMDA-type glutamate receptors act as voltage- and ligand-gated ion channels, with functional properties determined by their specific subunit composition. These receptors can be found at both synaptic and extrasynaptic sites on neurons, but the role of extrasynaptic NMDA receptors is unclear. Here, we demonstrate that retinal AII and A17 amacrine cells, postsynaptic partners at rod bipolar dyad synapses, express extrasynaptic (but not synaptic) NMDA receptors, with different and complementary GluN2 subunits. The localization of GluN2A-containing receptors to A17s and GluN2B-containing receptors to AIIs suggests a mechanism for differential modulation of excitability and signaling in this retinal microcircuit.

Magnetic double-network hydrogels for tissue hyperthermia and drug release.

Magnetic-field driven soft materials have found extensive applications in fields such as soft robotics, shape morphing and biomedicine. Compared to magnetoactive elastomers (MAEs), magnetic hydrogels have shown significant advantages for in vivo applications, because of their better biocompatibility, as well as their soft and wet nature. However, the poor mechanical properties and ion sensitivity of conventional magnetic hydrogels will severely limit their applications especially under physiological conditions. Double network hydrogels are tough and stable, but do not respond to environmental stimuli. Here magnetic double network (M-DN) hydrogels have been developed with outstanding mechanical performances and ion-resistant stability. M-DN hydrogels show a high modulus of ∼0.4 MPa and a high toughness of ∼1500 J m-2. The volume, magnetic and mechanical properties of M-DN hydrogels show negligible deterioration in ionic solutions. M-DN hydrogels exhibit magnetic responsiveness and have been used for tissue hyperthermia and drug release by magnetic induction heating. The induction heating behavior of M-DN hydrogels can be tuned to meet the clinical requirements, by changing the magnetic field strength or the composition of magnetic hydrogels. M-DN hydrogels may be inspiring to the development of responsive DN hydrogels and expand their more potential applications in load-bearing biomedical engineering.

Pennogenyl saponins induce cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Pennogenyl saponins, the characterized components of Rhizoma Paridis, have been reported to have anticancer activity through induction of apoptosis or anti-metastasis in cultured cells or animal models. The aim of the study was to evaluate the anticancer properties of four pennogenyl saponins (PS1-PS4) on a panel of human cancer and normal cell lines, and explore the potential mechanisms underlying the selective anticancer effects of the steroidal saponins in cancer cells. MATERIALS AND METHODS: Differences in the anticancer activity of pennogenyl saponins were examined by MTT assay in human cancer cell lines (HepG2 hepatocellular carcinoma cells, UACC-257 melanoma cells, MCF-7 breast and PC-3 prostate cancer cells) and normal human cell lines (L-02 liver cells and HEK293 kidney cells). Flow cytometry analysis, JC-1 staining and western blot analysis were applied to detect the effects of anticancer pennogenyl saponins on apoptosis, cell cycle, and expression and/or activation of main effectors involved in the potential signaling pathways. RESULTS: Among the tested four saponins, only PS1 and PS2 selectively inhibited cell growth in HepG2, MCF-7 and PC-3 cells. Moreover, PS1 and PS2 could significantly induce apoptosis and cell cycle G2/M arrest in HepG2 cells, which were at least associated with activation of mitochondrial caspase-dependent and -independent apoptotic cascades, inhibition of cyclin-dependent kinase 1 and PI3K/Akt signaling pathway, and modulation of mitogen-activated protein kinases. CONCLUSIONS: PS1 and PS2 had potent and selective anticancer activity to breast, liver and prostate cancer cells. Furthermore, the anticancer effects of PS1 and PS2 were associated with induction of apoptosis and blockage of cell cycle progression through multiple targets in HepG2 cells. These findings suggest that PS1 and PS2 can be considered as potential agents for the treatment of some cancers such as hepatoma.