Network Pharmacology-Based Strategy to Investigate the Anti-Breast Cancer Mechanisms of Spatholobus suberectus Dunn

Abstract

Spatholobus suberectus Dunn (SSD) possesses potential antitumor activity; however, the mechanism underlying its anti-proliferative effect on breast cancer is unclear. In this study, we explored potential SSD targets for breast cancer treatment through a network pharmacology approach. First, by integrating multiple databases, a total of 16 potential bioactive compounds and 252 targets were screened. Differentially expressed genes (DEGs) were screened by analyzing breast cancer gene chip data from The Cancer Genome Atlas and Gene Expression Omnibus databases. By overlapping drug targets and DEGs, 33 common targets were found; their functions were further analyzed with Gene Ontology and KEGG analysis. A network of 16 compounds and 33 common targets was constructed, from which 10 hub targets were identified using CytoHubba. Based on the KEGG result and network analysis, the 33 common targets were mainly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway and PPARγ was identified as the potential target of SSD. Moreover, the 10 hub targets were correlated with prognosis and immune infiltration in breast cancer via bioinformatic analysis. Finally, molecular docking and experiments in vitro further verified the targeting ability and anti-breast cancer activity of SSD. SSD is promising in the treatment of breast cancer; PPARγ may be its potential therapeutic target.

Ethnopharmacology, Phytochemistry, and Pharmacological Activities of Spatholobus suberectus Vine Stem

“…Jiang's group designed a virtual screening to predict potential 5-LOX inhibitors from S suberectus stems by Autodock and comparative molecular field analysis. The study suggested that liquiritigenin (49), catechin (65), butin (53), and gallocatechin (64) were the most potential candidates for inhibiting 5-LOX activity. 41 Recent studies provided important evidence for the antiinflammatory effects of S suberectus stems, which is ethnopharmacologically relevant to traditional medicine.…”

“…39 Another study focused on the effects of liquiritigenin ( 49), which is one of the major isoflavones from S suberectus, in atopic dermatitis. Liquiritigenin (49) was shown to block T-cell activation by reducing IL-2 production and CD69 expression via the NF-κB and MAPK pathways. In vivo experiments on dinitrochlorobenzene-exposed atopic dermatitis in mice also indicated the benefits of oral treatment with liquiritigenin (1 mg/mL, 5 times × 4 weeks), such as reduction of ear dermis and epidermis thickness, downregulation of IgE level, and recovery of tissue structure, when compared to the untreated group.…”

“…The authors also confirmed that the plant extract showed cytotoxicity by increasing PPARγ activation and decreasing the expression of PI3K and AKT phosphorylation in both BT-549 and MCF-7 cell lines, which matched the prediction from network pharmacology screening. 49 By employing the same technique, Xie et al 50 predicted that S suberectus extract could prevent lung cancer metastasis by targeting several pathways, including oxidative stress, AGE-RAGE signaling, and microRNAs in cancer. However, the authors did not report any experimental results within the work.…”

“…The study results also showed the correlation between the phloem ring number of the stem and flavonoid content, which provided scientific evidence for appearance-based quality evaluation of Spatholobi Caulis in traditional Chinese medicine. 21 As for flavonoid components, liquiritigenin (49), genistein (20), isoliquiritigenin (59), and 7-hydroxyflavanone (51) were identified as major constituents of S suberectus stems from Daegu market (Korea). Their contents were determined as 0.654, 0.166, 0.665, and 0.193% (d.w.), respectively, by a validated HPLC quantification method.…”

1-Methoxyerythrabyssin II Induces Autophagy in Leukemia Cells via PI3K/Akt/mTOR Pathways

“…Based on network pharmacology, Zeng et al [11] explored the molecular mechanism of salidroside sensitization by using doxorubicin in the treatment of cervical cancer. Our previous research using network pharmacological analysis also revealed that PPARγ is a potential therapeutic target of Spatholobus suberectus Dunn [12]. Thus, network pharmacology may be able to uncover the intricate mechanisms underlying the antiproliferative activities of MET due to its propensity to investigate the pharmacological mechanisms of natural products.…”