Integrated Omics Reveals the Orchestrating Role of Calycosin in Danggui Buxue Tang, a Herbal Formula Containing Angelicae Sinensis Radix and Astragali Radix, in Inducing Osteoblastic Differentiation and Proliferation.

Tin Yan Wong,Henry H N Lam,Karl W K Tsim,Tina T X Dong,Kenneth K L Kwan,Anna X D Yu

doi:10.3389/fphar.2021.670947

Tin Yan Wong, Henry H N Lam + Show 4 more

Open Access

https://doi.org/10.3389/fphar.2021.670947

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Abstract

Systems biology unravels the black box of signaling pathway of cells; but which has not been extensively applied to reveal the mechanistic synergy of a herbal formula. The therapeutic efficacies of a herbal formula having multi-target, multi-function and multi-pathway are the niches of traditional Chinese medicine (TCM). Here, we reported an integrated omics approach, coupled with the knockout of an active compound, to measure the regulation of cellular signaling, as to reveal the landscape in cultured rat osteoblasts having synergistic pharmacological efficacy of Danggui Buxue Tang (DBT), a Chinese herbal formula containing Angelicae Sinensis Radix and Astragali Radix. The changes in signaling pathways responsible for energy metabolism, RNA metabolism and protein metabolism showed distinct features between DBT and calycosin-depleted DBT. Here, our results show that calycosin within DBT can orchestrate the osteoblastic functions and signaling pathways of the entire herbal formula. This finding reveals the harmony of herbal medicine in pharmacological functions, as well as the design of drug/herbal medicine formulation. The integration of systems biology can provide novel and essential insights into the synergistic property of a herbal formula, which is a key in modernizing TCM.

Highlights

The metaphor of “butterfly effect” is based on chaos theory and encapsulates the concept to suggest a small change at any one point in a complex system resulting in dominant effects happening elsewhere (Dodd, 2011)
The herbal extracts at different conditions were prepared by optimized methods (Song et al, 2004), and which were chemically standardized by HPLC
In cultured osteoblasts, applied Danggui Buxue Tang (DBT) was able to enhance in the collagen density significantly, at least ∼7-fold, as indicated by dark red clusters of collagens evenly distributed throughout the stimulated region (Figure 1C)

Summary

Introduction

The metaphor of “butterfly effect” is based on chaos theory and encapsulates the concept to suggest a small change at any one point in a complex system resulting in dominant effects happening elsewhere (Dodd, 2011). Mongholicus (Bunge) Hsiao] at the ratio of 1:5 (Dong et al, 2006; Zheng et al, 2010), recorded in “Neiwaishang Bianhuo Lun” by Li Dongyuan in Jin dynasty (about AD 1247) This ancient herbal formula was suggested to be consumed by patients suffering from “Blood” and “Qi” deficiency syndromes DBT is suggested to be taken every day as a remedy for menopause, i.e., recovery bone fracture in aged women (Gao et al, 2007; Lin et al, 2017) This TCM formula has been used for over 800 years; the mechanism of its pharmacological efficacy is still not known. The correlation between active chemicals within an herbal decoction and the detailed underlying mechanisms have not been elucidated, and which hinders the acceptance of TCM by the general public

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