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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-4-29)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-4-29)
    Abstract: Selaginella doederleinii Hieron is a traditional Chinese medicinal herb widely used to treat different cancers. Previously, we showed that the total bioflavonoid extract of S. doederleinii (TBESD) exhibits anti-carcinogenic activities both in vitro and in vivo . However, the plasma protein binding and pharmacokinetics parameters of TBESD remain unclear. To investigate plasma protein binding, tissue distribution, and excretion of TBESD, rats were administered a single dose of TBESD (600 mg/kg) intragastrically and tissue distribution and excretion of TBESD components were determined by rapid high-performance liquid chromatography and tandem mass spectrometry. TBESD binding to human serum albumin (HSA) was assessed by fluorescence spectroscopy. TBESD components amentoflavone, delicaflavone, robustaflavone, 2″,3″-dihydro-3′,3‴-biapigenin, and 3′,3‴-binaringenin were rapidly absorbed and distributed in various tissues, mostly in the lungs, kidneys, and ovaries, without long-term accumulation. The excretion of bioflavonoids occurred mostly via the intestinal tract and constituted 30% of the administered dose up to 48 h. Spectral analysis indicated that TBESD had a dynamic quenching effect on HSA by binding to one HSA site through hydrophobic interactions and hydrogen bond formation. This is the first comprehensive report on the tissue distribution, excretion, and plasma protein binding of TBESD. This study provides important information on TBESD pharmacokinetics necessary for its further development into a therapeutic form for clinical applications.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 2
    In: Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2022 ( 2022-8-8), p. 1-16
    Abstract: Our previous studies have shown that delicaflavone (DLL), a biocomponent extracted from Selaginella doederleinii Hieron, has antitumor activity. However, the role of DLL in the antitumor immune response is unknown. In this study, we tested the potential roles of DLL in antitumor immune response. An animal tumor model with Lewis lung cancer cell line (3LL) in C57BL/6 mice was established to determine whether DLL induced the tumor-bearing host’s antitumor immune response. m6A-MeRIP-qPCR, western blot, and flow cytometry were performed to explore the underlying mechanisms. DLL inhibited the proliferation of 3LL lung cancer cells in vitro and in vivo and induced tumor cell oxidative stress. DLL significantly inhibited tumor growth in immunocompetent mice compared with nude mice. DLL treatment significantly increased Th1 cytokine production and CD8+ T cell infiltration into tumor tissues in tumor-bearing mice. DLL-mediated antitumor immune effects were reversed by overexpression of the N6-methyladenosine (m6A) transferase Mettl3/Mettl14. Mechanistically, DLL upregulated the expression of Stat1 and Irf1 and the secretion of cytokines by inhibiting Mettl3 and Mettl14 in lung cancer cells. In conclusion, DLL inhibited lung cancer cell growth by suppressing Mettl3/Mettl14 to activate antitumor immunity. These findings provided an opportunity to enhance lung cancer immunotherapy.
    Type of Medium: Online Resource
    ISSN: 1942-0994 , 1942-0900
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2455981-7
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  • 3
    In: British Journal of Pharmacology, Wiley, Vol. 178, No. 6 ( 2021-03), p. 1388-1406
    Abstract: Here, we review the molecular mechanism and pharmacokinetics of flavonoids in the treatment of resistant EGF receptor (EGFR)‐mutated non‐small‐cell lung cancer (NSCLC) and particularly the possible mechanism(s) of delicaflavone, a biflavonoid extracted from S elaginella doederleinii Hieron . EGFR TK inhibitors (EGFR‐TKI) are ubiquitously used in the treatment of NSCLC bearing EGFR mutations. However, patients treated with EGFR‐TKI inevitably and continuously develop resistance. In laboratory studies, flavonoids, as potential adjuvants for cancer chemotherapy, exhibited anti‐cancer properties such as inhibition of chemoresistance by interference with ABC transporters‐induced drug efflux, curbing of c‐MET amplification, or reversal of T790M mutation‐mediated resistance. The current review aims at summarizing the association between the anti‐cancer potentials of flavonoids and their possible regulatory roles in certain types of mutation that could trigger EGFR‐TKI resistance in NSCLC. Potential practical applications of these phytochemicals, as well as the relevant pharmacokinetics, are also discussed.
    Type of Medium: Online Resource
    ISSN: 0007-1188 , 1476-5381
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2029728-2
    SSG: 15,3
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