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Danshen-Chuanxiongqin Injection (DCI) is a commonly used traditional Chinese medicine for the treatment of cerebral ischemic stroke in China. However, its underlying mechanisms remain completely understood. The current study was designed to explore the protective mechanisms of DCI against cerebral ischemic stroke through integrating whole-transcriptome sequencing coupled with network pharmacology analysis. First, using a mouse model of cerebral ischemic stroke by transient middle cerebral artery occlusion (tMCAO), we found that DCI (4.10 mL·kg-1) significantly alleviated cerebral ischemic infarction, neurological deficits, and the pathological injury of hippocampal and cortical neurons in mice. Next, the whole-transcriptome sequencing was performed on brain tissues. The cerebral ischemia disease (CID) network was constructed by integrating transcriptome sequencing data and cerebrovascular disease-related genes. The results showed CID network was imbalanced due to tMCAO, but a recovery regulation was observed after DCI treatment. Pathway analysis of the key genes with recovery efficiency showed that the neuroinflammation signaling pathway was highly enriched, while the TLR2/TLR4-MyD88-NF-κB pathway was predicted to be affected. Consistently, the in vivo validation experiments confirmed that DCI exhibited protective effects against cerebral ischemic stroke by inhibiting neuroinflammation via the TLR2/TLR4-MyD88-NF-κB pathway. More interestingly, DCI markedly suppressed the neutrophils infiltrated into the brain parenchyma via the choroid plexus route and showed anti-neuroinflammation effects. In conclusion, our results provide dependable evidence that inhibiting neuroinflammation via the TLR2/TLR4-MyD88-NF-κB pathway is the main mechanism of DCI against cerebral ischemic stroke in mice.

AIM To verify the applicability of a new theory for chemomic release kinetics of traditional Chinese medicines using the release characteristics of Yinqiaojiedu tablets. METHODS The methodological studies of the preparation of chemomic standard spectrum, linearity, precision and stability tests of the chemomes of Yinqiaojiedu tablets were processed by UV spectrophotometry and Kalman filter methods. The chemomic release profiles of Yinqiaojiedu tablets and powders were determined. RESULT The methodology studies indicated that there was a good linearity of chemomic concentration of Yinqiaojiedu tablets within the range 0.112 to 1.120 mg total herbs / mL ( r = 0.999 7). The values of RSD tested at three chemomic levels were 0.05 %, 0.07 % and 0.31 % respectively. The chemomic solutions were stable for 24 h at concentrations of 0.278, 0.556, and 1.120 mg total herb / mL. CONCLUSION The chemomic release profiles demonstrated multi-component release kinetics illustrated using a simple visualization approach. The new theory of chemomic release kinetics may advantageously provide a quantitative description for the release of the active agents from traditional Chinese medicines from a conventional dosage form or drug delivery system.

AIM To establish a novel theory for the release/dissolution kinetics of the traditional Chinese medicines (TCMs) with the aim of the multi-component chemome. METHODS The theory and method for the release/dissolution kinetics of the TCMs were established on the basis of the overall spectrum of the chemome of the TCMs. The released chemomic levels of TCMs were processed by Kalman filter method with stochastic simulation data as an illustration of the methodology feasibility. RESULTS Methodology study indicated that Kalman filter method was validated with good linearity, reproducibility, stability in calculation of the chemomic concentrations for the evaluation of the multi-component TCM release profile. CONCLUSION Kalman filter method is feasible for the evaluation of chemomic multi-component release/dissolution kinetics of TCMs, which is in line with the holistic theories of traditional Chinese medicine with illustrative visualization to simplify the massive results. The new theory shows methodological significance in optimal design of multi-component drug delivery systems of TCMs. A further study may be required to clarify the significance of the new method to pharmacokinetics and pharmacodynamics of TCM.