Composition and Bioactivity of a Modified Huang-Lian-Jie-Du Decoction

Background. Epidermal growth factor receptor inhibitors (EGFRIs) and tyrosine kinase inhibitors (TKIs) are key drugs in targeted cancer therapy. However, they may cause skin toxicity. We previously prepared a modified Huang-Lian-Jie-Du (mHLJD) decoction cream using 10 herbs, which effectively alleviated EGFRI/TKI-induced skin toxicity. In the present study, we identified the reference markers of the mHLJD decoction and investigated the anti-inflammatory and antibacterial effects of the mHLJD decoction extract. Methods. We performed high-performance liquid chromatography (HPLC) to determine the composition of the mHLJD decoction. Human epidermoid A431 cells were treated with tumor necrosis factor (TNF)-alpha to induce inflammation; then, the effects of the mHLJD decoction extract on the cytokine expression were determined using a cytokine array and by performing real-time quantitative polymerase chain reaction (qPCR). The antibacterial effects of the extract were examined using disk diffusion and microdilution assays. Results. HPLC results revealed that the mHLJD decoction primarily consisted of geniposide, berberine chloride, baicalin, coptisine, and palmatine. TNF-alpha treatment increased the expression of certain cytokines, including IL-1 beta, IL-8, M-CSF, and TGF-beta 2; however, pretreatment with the mHLJD decoction extract reduced their expression. The qPCR results demonstrated a decreased mRNA expression of IL-8, M-CSF, and TGF-beta 2. The antibacterial assay revealed that the extract exerted inhibitory effects on Staphylococcus aureus, forming an inhibition zone at the minimum inhibitory concentrations of 3.125 and 6.25 mg/mL; however, the extract exerted no effects on Escherichia coli and Pseudomonas aeruginosa. Conclusions. We developed an HPLC method to quantify the reference markers of the mHLJD decoction. The bioactivity analysis provided the potential mechanisms underlying the effects of the mHLJD decoction on EGFRI/TKI-induced skin toxicity.

Automated summary

The study found that the modified Huang-Lian-Jie-Du (mHLJD) decoction effectively alleviated skin toxicity caused by epidermal growth factor receptor inhibitors (EGFRIs) and tyrosine kinase inhibitors (TKIs). The mHLJD decoction primarily consisted of geniposide, berberine chloride, baicalin, coptisine, and palmatine. The extract of the mHLJD decoction showed anti-inflammatory effects by reducing cytokine expression, and exhibited antibacterial effects against Staphylococcus aureus.