Sequential grade evaluation method exploration of Exocarpium Citri Grandis (Huajuhong) decoction pieces based on “network prediction → grading quantization → efficacy validation"

Exocarpium Citri Grandis (Huajuhong) is an authentic Chinese materia medica with excellent curative effects on relieving cough and reducing phlegm, which has been reputed as “Southern Ginseng” in China for a long history. Aim of the study: To establish a sequential grade evaluation method with strong operability and controllable quality for Huajuhong decoction pieces. (1) Indicators of ingredients and bio-effects were predicted by network pharmacology, and the potential pharmacodynamic ingredients and key targets were analyzed integrating screening results and literatures. (2) 45 batches of Huajuhong decoction pieces from different producing areas were collected and graded by original plant, planting place, and harvesting time. The chemical indicators determination of Huajuhong decoction pieces was conducted by Ultra Performance Liquid Chromatography (UPLC). (3) 112 rats with idiopathic pulmonary fibrosis (IPF) model were used to evaluated the efficacy within graded groups. (1) There are 22 key targets corresponding to 20 potential ingredients related to immunity and inflammation pathways for Huajuhong. Naringin and rhoifolin were chosen as the chemical indicators, and IL-6, IL-8, MCP-1, MIP-1α, TNF-α, TGF-β1 were selected as bio-indicators for different grades of Huajuhong decoction pieces. (2) The contents of the naringin and rhoifolin can reflect the quality of different grades of Huajuhong decoction pieces. (3) The efficacy of different grades of Huajuhong decoction pieces can delay the progression of IPF in varying degrees via the selected bio-indicators’ pathways. This sequential grading evaluation method is an attempt to apply systems pharmacology which integrates network pharmacology, quantitative chemical and experiments on animals to the classification of TCM decoction pieces. Combining the concepts of traditional theory and modern technology to explain the complex grading mechanism of TCM decoction pieces is worth popularizing and applying.