Abstract
Background and Purpose: The Bazhen decoction is one of the most
extensively used Traditional Chinese medicine (TCM) prescriptions for
anti-aging. However, due to the complicity of the components, the
pharmacological mechanism of Bazhen decoction is still limited.Experimental approach: We applied RNA sequencing and
transcriptome analysis to get the full view of the signaling pathways
regulated by Bazhen decoction in the wild type cell background. By using
the progeroid cells derived from Werner syndrome mice, we applied
Western blot, Immunofluorescence, flow cytometry and telomere FISH to
verify the transcriptome data. Key Results: The transcriptome
profile revealed that Bazhen decoction might systematically regulate
multiple anti-aging pathways, including stem cell regulation, protein
homeostasis, cardiovascular function, neuronal function,
anti-inflammation, anti-DNA damage induced stress, DNA helicase activity
and telomere lengthening. We found that multiple DNA helicases and
telomere regulating proteins were up-regulated by Bazhen decoction,
which promoted the resolving of G-quadruplex (G4) structure, and
facilitated DNA replication and telomere elongation. These improvements
also endowed the cellular resistance to DNA damages induced by
replication stress. Together these data suggest that Bazhen decoction
facilitate G4 resolving and telomere maintenance, which might contribute
to the longevity sustaining properties revealed by transcriptome
profile. Conclusions & Implications: Our data revealed a new
strategy for recovering the pharmacological signature pathways for TCM,
which could help the clinical precision medicine of TCM. By applying
transcriptome in TCM-treated normal cell, we tried out a systematic
analysis for dissecting the molecular mechanism of complicated TCM
prescription in the normal genetic background.