Systems Pharmacology Dissection of Multi-Scale Mechanisms of Action for Herbal Medicines in Stroke Treatment and Prevention

<div><p>Annually, tens of millions of first-ever strokes occur in the world; however, currently there is lack of effective and widely applicable pharmacological treatments for stroke patients. Herbal medicines, characterized as multi-constituent, multi-target and multi-effect, have been acknowledged with conspicuous effects in treating stroke, and attract extensive interest of researchers although the mechanism of action is yet unclear. In this work, we introduce an innovative systems-pharmacology method that combines pharmacokinetic prescreening, target fishing and network analysis to decipher the mechanisms of action of 10 herbal medicines like <i>Salvia miltiorrhizae</i>, <i>Ginkgo biloba</i> and <i>Ephedrae herba</i> which are efficient in stroke treatment and prevention. Our systematic analysis results display that, in these anti-stroke herbal medicines, 168 out of 1285 constituents with the favorable pharmacokinetic profiles might be implicated in stroke therapy, and the systematic use of these compounds probably acts through multiple mechanisms to synergistically benefit patients with stroke, which can roughly be classified as preventing ischemic inflammatory response, scavenging free radicals and inhibiting neuronal apoptosis against ischemic cerebral damage, as well as exhibiting lipid-lowering, anti-diabetic, anti-thrombotic and antiplatelet effects to decrease recurrent strokes. Relying on systems biology-based analysis, we speculate that herbal medicines, being characterized as the classical combination therapies, might be not only engaged in multiple mechanisms of action to synergistically improve the stroke outcomes, but also might be participated in reducing the risk factors for recurrent strokes.</p></div

Representative active constituents of anti-stroke herbs and their corresponding ADME parameters (Part 2).

<p>The sign * represents the molecule after deglycosylation.</p

Statistics and association analysis between herbs and stroke.

<p>Statistics and association analysis between herbs and stroke.</p

The stroke-related targets of herbs and their corresponding diseases (Part 1).

<p>The stroke-related targets of herbs and their corresponding diseases (Part 1).</p

Compound-target network of anti-stroke herbs.

<p>Node size is proportional to its degree.</p

Inhibiting the Corrosion-Promotion Activity of Graphene

Though an excellent protection material, graphene possesses an unpleasant adverse side effect, which refers to the phenomenon that graphene can aggravate metal corrosion. This effect potentially impedes its applications in metal protection. This work aims to demonstrate a facile graphene encapsulation strategy to effectively inhibit the corrosion-promotion activity of graphene. We encapsulated reduced graphene oxide (rGO) with (3-aminopropyl)­triethoxysilane (APTES). The composite of encapsulated rGO (rGO@APTES) has a flake-like structure with high aspect-ratio. Embedding appropriate amounts of rGO@APTES in polyvinyl butyral coating effectively enhances the barrier properties of the coating by suppressing the penetration of aggressive species. Besides, scratch tests further reveal that the corrosion-promotion activity of the graphene incorporated into the coating is completely inhibited. The strategy of graphene encapsulation can be extended to develop new graphene-based materials with superior physical and chemical properties for the protection of metal components

Systematic Investigation of <i>Ginkgo Biloba</i> Leaves for Treating Cardio-cerebrovascular Diseases in an Animal Model

Globally, cardio-cerebrovascular diseases (CCVDs) are the leading cause of death, and thus the development of novel strategies for preventing and treating such diseases is in urgent need. Traditional Chinese medicine (TCM), used for thousands of years in Asia and other regions, has been proven effective in certain disorders. As a long-time medicinal herb in TCM, <i>Ginkgo biloba</i> leaves (GBLs), have been widely used to treat various diseases including CCVDs. However, the underlying molecular mechanisms of medicinal herbs in treating these diseases are still unclear. Presently, by incorporating pharmacokinetic prescreening, target fishing, and network analysis, an innovative systems-pharmacology platform was introduced to systematically decipher the pharmacological mechanism of action of GBLs for the treatment of CCVDs. The results show that GBLs exhibit a protective effect on CCVDs probably through regulating multiple pathways and hitting on multiple targets involved in several biological pathways. Our work successfully explains the mechanism of efficiency of GBLs for treating CCVDs and, meanwhile, demonstrates that GDJ, an injection generated from GBLs, could be used as a preventive or therapeutic agent in cerebral ischemia. The approach developed in this work offers a new paradigm for systematically understanding the action mechanisms of herb medicine, which will promote the development and application of TCM