Exploring the Pharmacological Mechanism of the Herb Pair “HuangLian-GanJiang” against Colorectal Cancer Based on Network Pharmacology

Abstract

Since the herb pair Huang Lian-Gan Jiang (HL-GJ) was put forward as conventional compatibility for cold-heat regulation in the middle energizer in the theory of Traditional Chinese Medicine (TCM), their therapeutic effects were observed on the prevention and treatment of intestinal inflammation and tumors including colorectal cancer (CRC). However, the active compounds, crucial targets, and related pathways of HL-GJ against CRC remained unclear. The purpose of this research was to establish a comprehensive and systemic approach that could identify the active compounds, excavate crucial targets, and reveal anti-CRC mechanisms of HL-GJ against CRC based on network pharmacology. We used methods including chemical compound screening based on absorption, distribution, metabolism, and excretion (ADME), compound target prediction, CRC target collection, network construction and analysis, Gene Ontology (GO), and pathway analysis. In this study, eight main active compounds of HL-GJ were identified, including Gingerenone C, Isogingerenone B, 5,8-dihydroxy-2-(2-phenylethyl) Chromone, 2,3,4-trihydroxy-benzenepropanoic acid, 3,4-dihydroxyphenylethyl Alcohol Glucoside, 3-carboxy-4-hydroxy-phenoxy Glucoside, Moupinamide, and Obaculactone. HRAS, KRAS, PIK3CA, PDE5A, PPARG, TGFBR1, and TGFBR2 were identified as crucial targets of HL-GJ against CRC. There were mainly 500 biological processes and 70 molecular functions regulated during HL-GJ against CRC (P < 0.001). There were mainly 162 signaling pathways contributing to therapeutic effects (P < 0.001), the top 10 of which included DAP12 signaling, signaling by PDGF, signaling by EGFR, NGF signaling via TRKA from the plasma membrane, signaling by NGF, downstream signal transduction, DAP12 interactions, signaling by VEGF, signaling by FGFR3, and signaling by FGFR4. The study established a comprehensive and systematic paradigm to understand the pharmacological mechanisms of multiherb compatibility such as an herb pair, which might accelerate the development and modernization of TCM.

Therapeutic Effect and Mechanism of Bushen-Jianpi-Jiedu Decoction Combined with Chemotherapeutic Drugs on Postoperative Colorectal Cancer

“…The treatment of cancer under the holistic or systemic view of TCM has the characteristics of overall regulation with multi-molecular, multi-targets, multi-function, and multi-pathways, which is consistent with the principle of systems biology and network pharmacology. It has been widely applied in effective mechanisms of TCM treatments ( Zhang et al, 2013 ; Cai et al, 2018 ; Wu et al, 2019a ) and also applied in the research of Chinese herbal formulae on CRC treatment ( Liu et al, 2018b ; Gong et al, 2019 ). This study further investigated the effective mechanisms of BSJPJDD by transcriptomics, proteomics, network pharmacology analysis, and experimental verification.…”

Predictive Study of the Active Ingredients and Potential Targets of Codonopsis pilosula for the Treatment of Osteosarcoma via Network Pharmacology

“…Therefore, we selected the candidate compounds based on OB and DL properties. As suggested by the TCMSP database, OB ≥ 30% and DL ≥ 0.18 were used as the screening criteria, and the compounds whose OB ≥ 30% and DL ≥ 0.18 were selected for subsequent experiments [ 25 ]. We searched the oral bioavailability of all the compounds of Dangshen on PubMed.…”

Network pharmacological systems study of Huang‑Lian‑Tang in the treatment of glioblastoma multiforme

“…Studies have also suggested that one of the major components of HLT, Huanglian, has a valuable effect in the treatment of Alzheimer's disease and brain injury (12,13). Furthermore, Huanglian has also been effective in treating certain types of cancer (14)(15)(16)(17).…”