Understanding the Mechanistic Contribution of Herbal Extracts in Compound Kushen Injection with Transcriptome Analysis

Abstract

Running title: Identification of herbal compatibility mechanisms with transcriptome data AbstractHerbal compatibility is the knowledge of which herbs to combine in traditional Chinese medicine (TCM) formulations. The lack of understanding of herbal compatibility is one of the key problems for the application and popularization of TCM in western society. Because of the chemical complexity of herbal medicines, it is simpler to begin to conduct compatibility research based on herbs rather than component plant secondary metabolites. We have used transcriptome analysis to explore the effects and interactions of two plant extracts (Kushen and Baituling) combined in Compound Kushen Injection (CKI). Based on shared chemical compounds and in vitro cytotoxicity comparisons, we found that both the major compounds in CKI, and the cytotoxicity effects of CKI were mainly derived from the extract of Kushen ( Sophorae flavescentis ). We generated and analyzed transcriptome data from MDA-MB-231 cells treated with single-herb extracts or CKI and results showed that Kushen contributed to the perturbation of the majority of cytotoxicity/cancer related pathways in CKI such as cell cycle and DNA replication. We also found that Baituling ( Heterosmilax yunnanensis Gagnep ) could not only enhance the cytotoxic effects of Kushen in CKI, but also activate immune-related pathways. Our analyses predicted that IL-1 gene expression was upregulated by Baituling in CKI and we confirmed that IL-1 protein expression was increased using an ELISA assay. Altogether, these findings help to explain the rationale for combining Kushen and Baituling in CKI, and transcriptome analysis using single herb extracts is an effective method for understanding herbal compatibility in TCM.

Study on the mechanisms of compound Kushen injection for the treatment of gastric cancer based on network pharmacology

“…Kushen has a long history of being used for the treatment of solid tumors, inflammation and other diseases, such as gynecological diseases [10]. Studies have found that Baituling can not only enhance the cytotoxicity of Kushen in CKI, but also activate immune-related pathways [11]. CKI mainly contains various anticancer ingredients such as matrine and oxymatrine, which can inhibit tumor cell growth, induce the apoptosis of cancer cells, and resist cancer cell metastasis, and is unsusceptible to multidrug resistance and protective against overactive immune responses in the body [12].…”

Understanding the Mechanistic Contribution of Herbal Extracts in Compound Kushen Injection With Transcriptome Analysis

“…This manuscript has been released as a BioRxiv pre-print (MS ID #BIORXIV/2019/592964) at: https://www.biorixiv.org/content/10.1101/59294v1 (33).…”

Quantitative profiling of comprehensive composition in compound herbal injections: An NMR approach applied on Shenmai injection

“…As a mixture of oligomers, the compound peaks of P80 are highly overlapped in 1 H NMR spectroscopy and the corresponding numbers of protons are difficult to determine. 26 Therefore, the external standard curve was applied to quantify P80.…”

“…Given that most of the components in CHIs are proton-containing organics, some researchers have proposed the potential of the proton nuclear magnetic resonance ( 1 H NMR) method for the comprehensive composition characterisation of CHIs. 5,6 As an untargeted approach, 1 H NMR spectroscopy provides access to detect all proton-bearing compounds irrespective of their chemical characteristics, with the advantage of non-destructive sample preparation, informative spectral patterns, simple operation, and high-throughput acquisition. 11 Thus, 1 H NMR is widely used in metabolic profiling of complex mixtures, such as biological samples, 12,13 foods, [14][15][16] herbal medicine, 11,17 and environmental samples.…”

“…5,6 As an untargeted approach, 1 H NMR spectroscopy provides access to detect all proton-bearing compounds irrespective of their chemical characteristics, with the advantage of non-destructive sample preparation, informative spectral patterns, simple operation, and high-throughput acquisition. 11 Thus, 1 H NMR is widely used in metabolic profiling of complex mixtures, such as biological samples, 12,13 foods, [14][15][16] herbal medicine, 11,17 and environmental samples. 18 1 H NMR has quantitative ability with high accuracy and reproducibility.…”