Synergism and Rules from Combination of Baicalin, Jasminoidin and Desoxycholic acid in Refined Qing Kai Ling for Treat Ischemic Stroke Mice Model

Abstract

Refined Qing-Kai-Ling (QKL), a modified Chinese medicine, consists of three main ingredients (Baicalin, Jasminoidin and Desoxycholic acid), plays a synergistic effect on the treatment of the acute stage of ischemic stroke. However, the rules of the combination and synergism are still unknown. Based on the ischemic stroke mice model, all different kinds of combination of Baicalin, Jasminoidin, and Desoxycholic acid were investigated by the methods of neurological examination, microarray, and genomics analysis. As a result, it confirmed that the combination of three drugs offered a better therapeutical effect on ischemic stroke than monotherapy of each drug. Additionally, we used Ingenuity pathway Analysis (IPA) and principal component analysis (PCA) to extract the dominant information of expression changes in 373 ischemia-related genes. The results suggested that 5 principal components (PC1-5) could account for more than 95% energy in the gene data. Moreover, 3 clusters (PC1, PC2+PC5, and PC3+PC4) were addressed with cluster analysis. Furthermore, we matched PCs on the drug-target networks, the findings demonstrated that Baicalin related with PC1 that played the leading role in the combination; Jasminoidin related with PC2+PC5 that played a compensatory role; while Desoxycholic acid had the least performance alone which could relate with PC3+PC4 that played a compatible role. These manifestations were accorded with the principle of herbal formulae of Traditional Chinese Medicine (TCM), emperor-minister-adjuvant-courier. In conclusion, we firstly provided scientific evidence to the classic theory of TCM formulae, an initiating holistic viewpoint of combination therapy of TCM. This study also illustrated that PCA might be an applicable method to analyze the complicated data of drug combination.

Qingkailing Suppresses the Activation of BV2 Microglial Cells by Inhibiting Hypoxia/Reoxygenation‐Induced Inflammatory Responses

“…QKL injection has been widely used clinically to treat the acute phase of cerebrovascular disease and has displayed excellent efficacy in improving neurological function [ 10 , 11 ]. We and other investigators demonstrated that QKL injection can improve neurological function, decrease the expression of adhesion molecules, inhibit inflammatory responses, and partially restore BBB function in a rat model of brain ischemia/reperfusion injury [ 12 – 15 ].…”

Synergistic Use of Geniposide and Ginsenoside Rg1 Balance Microglial TNF-αand TGF-β1 following Oxygen-Glucose DeprivationIn Vitro: A Genome-Wide Survey

“…Ginsenoside Rg1 is one of the most active and abundant steroid saponins, with antiapoptotic [ 25 ] and neuroprotective [ 26 ] effects. Stroke is more complex than initially anticipated because it is often caused by multiple molecular abnormalities, rather than being the result of a single effect [ 27 ]. Consequently, multicomponent treatments interact with multiple targets simultaneously and are considered as a rational and efficient form of therapy for complex diseases [ 28 , 29 ].…”

A Network-Based Systematic Study for the Mechanism of the Treatment of Zhengs Related to Cough Variant Asthma

“…Herbs with high conditional probability are more related to the feature Zhengs. However, as TCM pays attention to the rules of composition, it is not suitable to consider each herb separately without consideration of their combination rules [ 29 – 31 ]. Apriori's algorithm [ 32 ] was used here to find out core formulas, and the minimum support was set at 0.4.…”