Tylophorine reduces protein biosynthesis and rapidly decreases cyclin D1, inhibiting vascular smooth muscle cell proliferation in vitro and in organ culture

Joa, Helge; Blažević, Tina; Grojer, Christoph S.; Zeller, Iris; Heiss, Elke H.; Atanasov, Atanas G.; Feldler, Ines; Gruzdaitis, Päivi; Czaloun, Christa; Proksch, Peter; Meßner, Barbara; Bernhard, David; Dirsch, Verena M.

doi:10.1016/j.phymed.2019.152938

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…16 Additionally, numerous studies have demonstrated that targeting CCND1 is useful for treating neointimal formation. 9,17,18 The Wnt genes were first characterized in 1978 in mutant wingless Drosophila melanogaster. 19 Since then, the Wnt family has been implicated in a myriad of physiological processes, including cell proliferation, differentiation, and migration.…”

Section: Discussionmentioning

confidence: 99%

Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis

Wen

et al. 2022

Journal of Cardiovascular Pharmacology

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:Angioplasty often fails due to the abnormal proliferation of vascular smooth muscle cells (VSMCs). Success rates of angioplasty may increase following the administration of an agent that effectively ameliorates aberrant vascular remodeling. Icariside II (ICS-II) is a natural flavonol glycoside extract from the Chinese herbal medicine Epimedii that possesses several medicinal qualities that are beneficial in humans. Nevertheless, the role of ICS-II in addressing aberrant vascular remodeling have yet to be clarified. The current investigation studies the molecular effects of ICS-Ⅱ on balloon-inflicted neointimal hyperplasia in rats in vivo and on platelet-derived growth factor–induced vascular proliferation in primary rat aortic smooth muscle cells (VSMCs) in vitro. ICS-II was found to be as effective as rapamycin, the positive control used in this study. ICS-II inhibited neointimal formation in injured rat carotid arteries and notably reduced the expression of Wnt7b. ICS-Ⅱ significantly counteracted platelet-derived growth factor–induced VSMCs proliferation. Cell cycle analysis showed that ICS-II triggered cell cycle arrest during the G1/S transition. Western blot analysis further indicated that this cell cycle arrest was likely through Wnt7b suppression that led to CCND1 inhibition. In conclusion, our findings demonstrate that ICS-II possesses significant antiproliferative qualities that counteracts aberrant vascular neointimal hyperplasia. This phenomenon most likely occurs due to the suppression of the Wnt7b/CCND1 axis.

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Section: Discussionmentioning

confidence: 99%

Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis

Wen

et al. 2022

Journal of Cardiovascular Pharmacology

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“…Tylophorine ( 1 ) potently inhibited the PDGF-BB-induced proliferation of rat aortic vascular smooth muscle cells (VSMCs) in a concentration-dependent manner with an IC 50 of 0.13 µM, by arresting cells in G1 phase of the cell cycle as well as migration in activated VSMCs. It could decrease de novo protein synthesis, result in downregulation of cyclin D1 and prevent neointimal thickening in human saphenous vein organ culture (Joa et al 2019 ). Anti-angiogenic results indicated tylophorine ( 1 ) and antofine ( 2 ) could be used as promising lead compounds for further studies towards the treatment of vasculo-proliferative disorders, such as restenosis.…”

Section: Antiviral Activitymentioning

confidence: 99%

Possible pharmaceutical applications can be developed from naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids

Jia

Zhao

et al. 2020

Phytochem Rev

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Naturally occurring phenanthroindolizidine and phenanthroquinolizidine alkaloids (PIAs and PQAs) are two small groups of herbal metabolites sharing a similar pentacyclic structure with a highly oxygenated phenanthrene moiety fused with a saturated or an unsaturated N -heterocycle (indolizidine/quinolizidine moieties). Natural PIAs and PQAs only could be obtained from finite plant families (such as Asclepiadaceae, Lauraceae and Urticaceae families, etc.). Up to date, more than one hundred natural PIAs, while only nine natural PQAs had been described. PIA and PQA analogues have been applied to the development of potent anticancer agents all along because of their excellent cytotoxic activity. However, in the last two decades, other great biological properties, such as anti-inflammatory and antiviral activities were revealed successively by different pharmacological assays. Especially because of their potent antiviral activity against coronavirus (TGEV, SARS CoV and MHV) and tobacco mosaic virus, PIA and PQA analogues have attracted much pharmaceutical attention again, some of them have been used to present interesting targets for total or semi synthesis, and structure–activity relationship (SAR) study for the development of antiviral agents. In this review, natural PIA and PQA analogues obtained in the last two decades with their herbal origins, key spectroscopic characteristics for structural identification, biological activity with possible SARs and application prospects were systematically summarized. We hope this paper can stimulate further investigations on PIA and PQA analogues as an important source for potential drug discovery.

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“…The properties and bioactivities of tylophorine has been well investigated (Table 1). Tylophorine possesses antiproliferative action in cancer cells; it rapidly diminishes cyclin D1, reduces protein biosynthesis and prevents vascular smooth muscle cell proliferation in vitro (Joa et al 2019). Apoptosis could be mediated by unique application of tylophorine or tylophorine plus doxorubicin in T47D breast cancer cells; this happened because it regulated the expression of genes of caspases 3 and 9 (Pratama et al 2018).…”

Section: Bioactive Properties and Application Of Tylophorinementioning

confidence: 99%