Biflavonoids from Selaginella doederleinii as Potential Antitumor Agents for Intervention of Non-Small Cell Lung Cancer.
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ABSTRACT:
SUBMITTER: Kang F
PROVIDER: S-EPMC8434134 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Amentoflavone, robustaflavone, 2″,3″-dihydro-3',3‴-biapigenin, 3',3‴-binaringenin, and delicaflavone are five major hydrophobic components in the total biflavonoids extract from Selaginella doederleinii (TBESD) that display favorable anticancer properties. The purpose of this study was to develop a new oral delivery formulation to improve the solubilities, dissolution rates, and oral bioavailabilities of the main ingredients in TBESD by the solid dispersion technique. Solid dispersions of TBESD with various hydrophilic polymers were prepared, and different technologies were applied to select the suitable carrier and method. TBESD amorphous solid dispersion (TBESD-ASD) with polyvinylpyrrolidone K-30 was successfully prepared by the solvent evaporation method. The physicochemical properties of TBESD-ASD were investigated by scanning electron microscopy, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. As a result, TBESD was found to be molecularly dispersed in the amorphous carrier. The solubilities and dissolution rates of all five ingredients in the TBESD-ASD were significantly increased (nearly 100% release), compared with raw TBESD. Meanwhile, TBESD-ASD showed good preservation stability for 3 months under accelerated conditions of 40 °C and 75% relative humidity. A subsequent pharmacokinetic study in rats revealed that Cmax and AUC0-t of all five components were significantly increased by the solid dispersion preparation. An in vivo study clearly revealed that compared to raw TBESD, a significant reduction in tumor size and microvascular density occurred after oral administration of TBESD-ASD to xenograft-bearing tumor mice. Collectively, the developed TBESD-ASD with the improved solubility, dissolution rates and oral bio-availabilities of the main ingredients could be a promising chemotherapeutic agent for cancer treatment.
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Project description:Selaginella doederleinii Hieron has been traditionally used as a folk antitumor herbal medicine in China. In this paper, the phytochemical components of the total biflavonoids extract from S. doederleinii were studied by using high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF MS/MS) in negative ion mode, and their in vitro and in vivo anticancer effects were evaluated. Four types of biflavonoids from S. doederleinii, including IC3'-IIC8'', IC3'-IIC6'', IC3'-IIC3''', and C-O linked biflavonoids were examined originally using QTOF MS/MS. The fragmentation behavior of IC3'-IIC3''' linked biflavonoids was reported for the first time. A total of twenty biflavonoids were identified or tentatively characterized and eight biflavonoids were found from S. doederleinii for the first time. Furthermore, the 3-(4,5-Dimethyl-2-thizolyl)-2,5-diphenyltertazolium bromide (MTT) assay and xenograft model of mouse lewis lung cancer(LLC) in male C57BL/6 mice revealed favorable anticancer properties of the total biflavonoids extracts from S. doederleinii. The results of this work could provide useful knowledge for the identification of biflavonoids in herbal samples and further insights into the chemopreventive function of this plant.
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Project description:The antitumor activities of ethyl acetate extracts from Selaginella doederleinii Hieron (SD extracts) in vitro and in vivo and its possible mechanism were investigated. HPLC method was developed for chemical analysis. SD extracts were submitted to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay on different cells, flow cytometry, and RT-PCR analysis using HepG2 cell and antitumor activity in vivo using H-22 xenograft tumor mice. Six biflavonoids from SD extracts were submitted to molecular docking assay. The results showed that SD extracts had considerable antitumor activity in vitro and in vivo without obvious toxicity on normal cells and could induce cell apoptosis. The mechanisms of tumorigenesis and cell apoptosis induced by SD extracts may be associated with decreasing the ratio of bcl-2 and bax mRNA level, activating caspase-3, suppressing survivin, and decreasing the gene expression of COX-2, 5-LOX, FLAP, and 12-LOX mRNA. The main active component in SD extracts is biflavonoids and some exhibited strong interactions with COX-2, 5-LOX, 12-LOX, and 15-LOX. These results offering evidence of possible mechanisms of SD extracts suppress cell proliferation and promote apoptosis and provide the molecular theoretical basis of clinical application of S. doederleinii for cancer therapy.
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Project description:Selaginella tamariscina, a traditional Chinese medicine, contains a variety of bioactive components, among which biflavonoids are the main active ingredients and have antioxidant, antitumor, and anti-inflammatory properties. In this study, ultrasonic-assisted ionic liquid extraction (UAILE) is used for the first time to extract two main biflavonoids (amentoflavone (AME) and hinokiflavone (HIN)) from S. tamariscina. A high-performance liquid chromatography method is used for the simultaneous determination of AME and HIN in S. tamariscina. Then, three novel ILs are synthesized for the first time by a one-step method using benzoxazole and three acids or acid salts as raw materials, and the structures of the synthesized ILs are characterized by elemental analysis, infrared spectroscopy, and NMR spectroscopy, as well as the thermal stability of the ILs is evaluated by thermogravimetric analysis. After screening the extraction effects of three benzoxazole ILs, three pyridine ILs, and three imidazole ILs, it is found that [Bpy]BF4 is the best and therefore selected as the extractant. The optimal extraction process is explored in terms of the yields of AME and HIN from S. tamariscina by a single-factor experiments and response surface analysis. Under the optimal level of each influencing factor (IL concentration of 0.15 mol/L, solid-liquid ratio of 1:12 g/mL, ultrasonic power of 280 W, ultrasonic time of 30 min, and three extraction cycles), the extraction rates of AME and HIN from S. tamariscina are 13.51 and 6.74 mg/g, respectively. Moreover, the recovery experiment of [Bpy]BF4 on the extraction of biflavonoids shows that the recovered IL can repeatedly extract targets six times and the extraction rate is about 90%, which indicates that the IL can be effectively reused. UAILE can effectively and selectively extract AME and HIN, laying the foundation for the application of S. tamariscina.
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Project description:Metagenomics can be used to identify potential biocontrol agents for invasive species and was used here to identify candidate species for biocontrol of an invasive club moss in New Zealand. Profiles were obtained for Selaginella kraussiana collected from nine geographically disjunct locations in Northern New Zealand. These profiles were distinct from those obtained for the exotic club moss Selaginella moellendorffii and the native club mosses Lycopodium deuterodensum and Lycopodium volubile also collected in Northern New Zealand. Fungi and bacteria implicated elsewhere in causing plant disease were identified on plants of Selaginella that exhibited signs of necrosis. Most notably, high densities of sequence reads from Xanthomonas translucens and Pseudomonas syringae were associated with some populations of Selaginella but not Lycopodium. Since these bacteria are already in use as biocontrol agents elsewhere, further investigation into their potential as biocontrol of Selaginella in New Zealand is suggested.
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Project description:Selaginella doederleinii (SD) is a perennial medicinal herb widely distributed in China. In this study, the volatile components of SD from two regions (24 batches), namely Zhejiang and Guizhou, were determined by combining headspace solid phase microextraction and gas chromatography-mass spectrometry (HS-SPME/GC-MS). After investigating different influence factors, the optimal conditions for extraction were as follows: The sample amount of 1 g, the polydimethylsiloxane-divinylbenzene (PDMS-DVB) fiber of 65 µm, the extraction time of 20 min, and the extraction temperature of 100 °C. Based on the above optimum conditions, 58 volatiles compounds, including 20 terpenes, 11 alkanes, 3 alcohols, 6 ketones, 3 esters, 11 aldehydes, 1 ether, 1 aromatic, 1 phenol, and 1 furan, were found and identified in SD. Furthermore, hierarchical cluster analysis and principal component analysis were successfully applied to distinguish the chemical constituents of SD from two regions. Additionally, anethol, zingerone, 2,4-di-tert-butylphenol, ledene, hexyl hexanoate, α-cadinol, phytone, hinesol, decanal, octadecene, cedren, 7-tetradecene, copaene, β-humulene, 2-butyl-2-octenal, tetradecane, cedrol, calacorene, 6-dodecanone, β-caryophyllene, 4-oxoisophorone, γ-nonanolactone, 2-pentylfuran, 1,2-epoxyhexadecane, carvacrol, n-pentadecane, diisobutyl phthalate, farnesene, n-heptadecane, linalool, 1-octen-3-ol, phytane, and β-asarone were selected as the potential markers for discriminating SD from 24 habitats in Zhejiang and Guizhou by partial least squares discrimination analysis (PLS-DA). This study revealed the differences in the components of SD from different regions, which could provide a reference for the future quality evaluation.
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Project description:Constitutively activated STAT3 plays a critical role in non-small cell lung carcinoma (NSCLC) progression by mediating proliferation and survival. STAT3 activation in normal cells is transient, making it an attractive target for NSCLC therapy. The therapeutic potential of blocking STAT3 in NSCLC was assessed utilizing a decoy approach by ligating a double-stranded 15-mer oligonucleotide that corresponds to the STAT3 response element of STAT3-target genes, to produce a cyclic STAT3 decoy (CS3D). The decoy was evaluated using NSCLC cells containing either wild-type EGFR (201T) or mutant EGFR with an additional EGFRi resistance mutation (H1975). These cells are resistant to EGFR inhibitors and require an alternate therapeutic approach. CS3D activity was compared with an inactive cyclic control oligonucleotide (CS3M) that differs by a single base pair, rendering it unable to bind to STAT3 protein. Transfection of 0.3 ?mol/L of CS3D caused a 50% inhibition in proliferation in 201T and H1975 cells, relative to CS3M, and a 2-fold increase in apoptotic cells. Toxicity was minimal in normal cells. CS3D treatment caused a significant reduction of mRNA and protein expression of the STAT3 target gene c-Myc and inhibited colony formation by 70%. The active decoy decreased the nuclear pool of STAT3 compared with the mutant. In a xenograft model, treatments with CS3D (5 mg/kg) caused a potent 96.5% and 81.7% reduction in tumor growth in 201T (P < 0.007) and H1975 models (P < 0.0001), respectively, and reduced c-Myc and p-STAT3 proteins. Targeting STAT3 with the cyclic decoy could be an effective therapeutic strategy for NSCLC. Mol Cancer Ther; 17(9); 1917-26. ©2018 AACR.
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