Background: Novel bioactive plant secondary metabolites, including flavonoids, offer a spectrum of
chemo-protective responses against a range of human tumor models. However, the clinical translation of these
promising anti-cancer agents has been hindered largely by their poor solubility, rapid metabolism, or a combination
of both, ultimately resulting in poor bioavailability upon oral administration.
Objective: To circumvent the challenges associated with herbal drug development and for effective integration
into clinical setting, nano-engineering is one of the emerging pragmatic strategies which has promise to deliver
therapeutic concentrations of bio-actives upon oral administration.
Method: We assessed the nano-encapsulated flavonoid-rich fraction isolated from a traditional Indian herb
Selaginella bryopteris (Sanjeevani) (NP.SB). Both in vitro and in vivo studies were performed to evidence the
epigenetic protection mechanisms of NP.SB through a mitochondrial-targeted pre-clinical validation strategy.
Results: The mito-protective activity of NP.SB revealed a dose-dependent effect when tested in GC-1 spg
(mouse spermatogonial epithelial) and B/CMBA.Ov (mouse ovarian epithelial) following exposure to Nsuccinimidyl
N-methylcarbamate, a potential human carcinogen. Smaller size, rapid internalization, faster mobility
and site specific delivery conferred significant cancer protection in cultured cells. Notably, this encapsulated
flavonoid supplementation; prevented emergence of neoplastic daughter clones from senescent mother
phenotypes in pro-oxidant treated GC-1 spg and B/CMBA.Ov cells by selective abrogation of mitochondrial
oxidative stress-induced aberrant epigenetic modifications. In vivo studies using a diethylnitrosamine and 2-
acetylaminofluorene mouse model demonstrated that NP.SB has a significant inhibitory effect on tumor growth
which clearly substantiated our in vitro findings.
Conclusion: Anti-carcinogenic property in conjunction with low toxicity of NP.SB, underscores the translational
significance of dietary flavonoids as cancer-protective agents for preferential application in clinical