Abstract
Herb pair Scleromitrion diffusum (Willd.) R. J. Wang (HD) and Scutellaria barbata D. Don (SB) has been most frequently used for cancer treatment in traditional Chinese medicine. This study aimed to explore the in vitro and in vivo antitumor effects of HD-SB extract and to elucidate the underlying compatibility mechanisms. HD, SB, and HD-SB extracts were prepared, and the components were detected by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method. The in vitro antitumor effects of various concentrations of these extract were detected on several tumor cell lines using MTS assay. The in vivo antitumor effects were evaluated in Panc28 cells–bearing nude mice model. The compatibility mechanisms of herb pair HD-SB were evaluated based on the systems pharmacology strategy and then validated by cellular experiments. HD-SB extract was demonstrated to inhibit the proliferation of the cancer cell lines dose dependently by MTS assay. In vivo antitumor effects of HD-SB were much more potent than either of the two single herbs in Panc28 xenograft mice model. A total 29 active ingredients involved in antitumor effects were selected from HD and SB, and the “herb–composition–target–disease” network was constructed. Then, 58 cancer-related targets and 66 KEGG pathways were identified, and PTGS2-, HSP90-, EGFR-, MMP2-, PPARγ-, and GSTP-mediated pathways were predicted to be the antitumor mechanisms of HD-SB. The cellular experiments showed that HD-SB significantly induced cancer cell apoptosis, decreased p-EGFR, HSP90 and bcl-2 expressions, and increased PPARγ, bax, cleaved caspase 3, cleaved PARP, p-AKT, and p-PI3K expressions compared with HD or SB treatment. Our study showed that HD-SB inhibited tumor growth both in vitro and in vivo, which might be related with apoptosis induction via the EGFR/PPARγ/PI3K/AKT pathway.
Highlights
Despite the wide use of herb formulas in China and other countries, its modernization faced many obstacles due to its multiherb prescription and complexity
HD-Scutellaria barbata D. Don (SB) combination has long been used as a classic herb pair for cancer treatment, and clinical practices show that HD-SB combination exhibits better therapeutic effects than the two single individuals (Yeh et al, 2014)
Herb pair HD-SB was the core couplet in traditional Chinese medicine (TCM) commonly used for anti-inflammation and anticancer treatments (Pan et al, 2016; Yang et al, 2018)
Summary
Despite the wide use of herb formulas in China and other countries, its modernization faced many obstacles due to its multiherb prescription and complexity. The most basic composition units of multiherb formulas, are a centralized representative of Chinese herbal compatibility. Because of their simplicity and the basic characteristics of complex formulas, herb pairs are thought to play key roles in the investigation of herb compatibility (Wang et al, 2012; Zhou et al, 2019). In the clinical practices of traditional Chinese medicine (TCM), herb pair Scleromitrion diffusum (Willd.) R. J. Wang ( named Hedyotis diffusa Willd., HD, Baihuasheshecao in Chinese) and Scutellaria barbata D. Don (SB, Banzhilian in Chinese) is frequently used in numerous classic formulas such as Erbanerbai Tang, Zhongliuhefang, Fuzhenghuadu Tang, Yupengqianbailian Heji, and so on (Pan et al, 2016; Yang et al, 2018)
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