network-pharmacology-prediction-metabolomics-validation-mechanism

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia

Hyperlipidemia has become a leading risk factor for cardiovascular diseases and liver injury worldwide. Fructus Phyllanthi (FP) is an effective drug ...

Chengdu University of Traditional Chinese Medicine

Key Laboratory of Traditional Chinese Medicine Regimen and Health of Sichuan Province

 species are the main source of Rhizoma Coptidis (RC) drugs, which have always been used to treat Alzheimer's disease in the clinical experience of ancient China. However, many species of this genus have been largely underutilized until now. With this fact, this research has been designed to investigate for the first time the anti-acetylcholinesterase (AChE) property of different extracts for RC drugs from four  species (, ,  and ) and to quantify the main alkaloids. Petroleum ether, ethyl acetate and n-butanol fractions of RC drugs were sequentially collected using an accelerated solvent extraction technique. Spectrum-effect relationship and molecular docking were applied to analyse the relationships between alkaloids and AChE inhibitory activity. The N-butanol extract was proven to be the main active fraction, and  may be the best source of RC drugs for Alzheimer's disease treatment, with significantly lower IC 20, IC 50 and IC 80 values for AChE inhibition. The UPLC/QqQ-MS quantitative analysis showed that the accumulations of 10 alkaloids in RC drugs from different sources greatly varied. Three data processing methods (Random forest, Boruta and Pearson correlation) comprehensively analysed the spectrum-effect relationship and revealed that columbamine, berberine and palmatine were the most important AChE inhibitors that could be used as quality markers to select RC drugs for Alzheimer's disease treatment. In addition, the dominant compounds were successfully docked against AChE to verify the binding affinity and interactions with the active site. The present study can contribute to the reasonable development and utilization of RC drugs from different sources, especially to provide certain evidence for their application in the treatment of Alzheimer's disease.

Characterization of the anti-AChE potential and alkaloids in Rhizoma Coptidis from different  species combined with spectrum-effect relationship and molecular docking.

Initially described as an ancient and highly conserved catabolic biofunction, autophagy plays a significant role in disease pathogenesis and progression. As the bioactive ingredient of , tanshinone has recently shown profound effects in alleviating and treating various diseases by regulating autophagy. However, compared to the remarkable achievements in the known pharmacological effects of this traditional Chinese medicine, there is a lack of a concise and comprehensive review deciphering the mechanism by which tanshinone regulates autophagy for medicinal research. In this context, we concisely review the advances of tanshinone in regulating autophagy for medicinal research, including human cancer, the nervous system, and cardiovascular diseases. The pharmacological effects of tanshinone targeting autophagy involve the regulation of autophagy-related proteins, such as Beclin-1, LC3-II, P62, ULK1, Bax, ATG3, ATG5, ATG7, ATG9, and ATG12; the regulation of the PI3K/Akt/mTOR, MEK/ERK/mTOR, Beclin-1-related, and AMPK-related signaling pathways; the accumulation of reactive oxygen species (ROS); and the activation of AMPK. Notably, we found that tanshinone played a dual role in human cancers in an autophagic manner, which may provide a new avenue for potential clinical application. In brief, these findings on autophagic tanshinone and its derivatives provide a new clue for expediting medicinal research related to tanshinone compounds and autophagy.

Kaidi Nie

School of Health Preservation and Rehabilitation,
State Administration of Traditional Chinese Medicine Key Laboratory of Traditional Chinese Medicine,
Regimen and Health,
State Administration of Traditional Chinese Medicine Key Laboratory of Traditional Chinese Medicine, Regimen and Health

Chengdu University of Traditional Chinese Medicine

Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia