Determination and mechanism of Xiao-Ai Jie-Du decoction against diffuse large B-cell lymphoma: In silico and In vitro studies

Abstract

Ethnopharmacological relevance: Xiao-Ai Jie-Du decoction (XAJDD) has been used in clinical practice to treat diffuse large B-cell lymphoma (DLBCL); its prescriptions vary based on the pathogenesis of patients.

Aim of the study: We aimed to determine the core formula of XAJDD and investigate its mechanism of action against DLBCL.

Materials and methods: Apriori data mining of 187 clinical cases (including 421 Traditional Chinese Medicines, TCMs) was conducted to retrieve the core formula of XAJDD. Comprehensive in silico modeling was used to identify potential active components and corresponding targets. The potential targets of 16 compounds were identified based on network pharmacology using in silico modeling. Thereafter, experimental determination of the active compounds and their mechanism of action in treating DLBCL was performed using different assays (including CCK-8, Annexin V-FITC/PI double-staining, Western blot, and flow cytometry assays).

Results: The core formula of XAJDD included six herbs: Astragalus mongholicus Bunge (Huangqi, family: Fabaceae), Scutellaria barbata D. Don (Banzhilian, family: Lamiaceae), Prunella vulgaris L. (Xiakucao, family: Lamiaceae), Smilax glabra Roxb. (Tufuling, family Smilacaceae) and Fritillaria thunbergii Miq. (Dabei, family: Liliaceae), and Curcuma zanthorrhiza Roxb. (Ezhu, family: Zingiberaceae); Databases including 62 druggable compounds and 38 DLBCL-related structural targets were constructed; ∼0.3 million data points produced by computational modeling based on potential compounds and targets six components from XAJDD, including astibin, folic acid, baicalin, kaempferol, quercetin, and luteolin, significantly inhibited DLBCL cell proliferation, induced apoptosis, and suppressed the expression of key oncogenes.

Conclusion: This study provides an integrated strategy for determining the core formula of XAJDD and reveals the molecular mechanisms underlying the treatment of DLBCL, which were consistent with the principle of "monarch (Jun), minister (Chen), adjunctive (Zuo), and guide (Shi)", confirming that XAJDD may serve as a promising natural therapeutic agent against DLBCL.

Keywords: Diffuse large B-cell lymphoma; Mechanism; Molecular modeling; Pharmacology; Xiao-Ai Jie-Du decoction.