An Integrative Serum Pharmacology-Based Approach to Study the Anti-Tumor Activity of B. paniculatum Aqueous Bulb Extract on the Human Hepatocellular Carcinoma Cell Line BEL-7404

Abstract

The herb Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae family), also known as Tu-Bei-Mu (TBM) in Chinese, has shown curative effects to treat several types of cancer as an adjunctive therapy. Thereby we intend to find its effect on the human hepatocellular carcinoma (HCC) and to understand the pharmacological mechanism behind it. In this study, an integrative serum pharmacology-based approach linking serum pharmacology and bioinformatics prediction was employed. Firstly, we used the serum taken introgastrically from the rats dministered by TBM aqueous bulb extract to culture the HCC cell line BEL-7404 and detect its anti-tumor effects. Secondly, the TBM putative targets were predicted using the ETCM database and known therapeutic targets of NPC were collected from the OMIM database. Then, a TBM-HCC putative targets network was constructed using the DAVID and STRING databases. Thirdly, key gene targets were obtained based on topological analysis and pathway enrichment analysis. The expression of 4 representative key targets were validated by Western blotting. As a result, 36 TBM targets and 26 known therapeutic targets of HCC were identified. These key targets were found to be frequently involved in 13 KEGG pathways and 4 biological processes. The expression of four representative key targets: TP53, CASP3, BCL2 and BAX further supports the suppression of TBM on HCC. In general, our study shows the curative effects of TBM against HCC. By using this integrative approach, we may find novel potential therapeutic targets to suppress HCC using TBM as an adjunctive therapy. And it could also help us understand the mechanism of HCC treatments in response to TBM.

Mechanism Investigation of Wuwei Shexiang Pills on Gouty Arthritis via Network Pharmacology, Molecule Docking, and Pharmacological Verification

“…It has been well-recognized that serum-containing drugs after treatment in experimental animals contain not only the drug prototype but also the metabolites, which mimic the actual composition of TCM entering into circulation [23]. Although WSP-containing-serum was applied to explore the pharmacological mechanism of WSP on gouty inflammation, the active components of WSP-containingserum were not clarified in the present study.…”

“…To verify the prediction of network pharmacology, serum pharmacology is commonly combined to explore the specific mechanisms of TCM by applying drug-containing serum in vitro. Pieces of literature combined network pharmacology with serum pharmacology have been successfully reported [22][23][24].…”

Identification of Key Pathways and Targets of Kai Xin San in The Treatment of Alzheimer's Disease Based On a Network Pharmacology Approach and Experimental Validation

“…When Tau is hyperphosphorylated, the axonal transport of neurons will be hindered, leading to neuronal dysfunction and death [42]. Moreover, the accumulation of Aβ occurs in the early stage of AD, which plays a key role in the progression of AD [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]. All these strongly suggest that the hyperphosphorylation of Tau plays an essential role in promoting the pathogenesis of AD.…”

“…The chemical ingredients of KXS were collected from the Encyclopedia of Traditional Chinese Medicine (ETCM, updated on 2018 Oct 26, doi:10.1093/nar/gky987, http://www.nrc.ac.cn:9090/ETCM/index.php) database, which includes comprehensive and standardized information for the ingredients and target of TCM [31]. The active constituents of KXS are retained according to ADME in pharmacokinetic including absorption, distribution, metabolism as well as excretion.…”

Identification of the Main Active Components and Mechanism of Wang Bi Tablet in Treating Rheumatoid Arthritis Based on Integrative Pharmacology

“…Integrative pharmacology, first proposed in 2014 (Xu and Yang 2014), is an interdisciplinary science that comprehensively explores the interactions between multiple constituents of TCM and the body at multiple levels, such as molecules, cells, tissues, organs, and animals (Wang et al, 2018). Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine (TCMIP v2.0, http://www.tcmip.cn/), which is composed of five databases (Xu et al, 2019) and seven functional modules (Xu et al, 2017), could assist the identification of chemical constituents and the elucidation of the molecular mechanisms of TCM (Mao et al, 2019;Feng et al, 2020;Ma et al, 2020). In the Database of TCM ingredients, we have introduced a characteristic parameter, namely "quantitative estimate of drug-likeness" (QED) to evaluate the druggability of our herbal components.…”