Procyanidins Boost the Neuroprotective Effect of Minocycline for Intracerebral Haemorrhage

Abstract

Poor prognosis is often expected after the treatment of intracerebral haemorrhage (ICH) when the approach lacks effective neuroprotective interventions. Minocycline (Mino) is a promising clinical neuroprotective candidate for acute ICH therapy that mainly inhibits activation of microglia/macrophages. However, to address iron neurotoxicity, ferroptosis, and oxidative stress‐induced multiple neuroinjury mechanisms, the neuroprotective effect of minocycline still urgently needs to be enhanced. To address this issue, procyanidins (PACs), typical natural polyphenols, is used to improve the neuroprotective effect of Mino by constructing PACs‐Mino nanoparticles (NPs) using 3‐aminophenylboronic acid as the crosslinker. The yielding NPs possessed improved antioxidant and iron‐removing capacities in vitro. More importantly, PACs‐Mino NPs exerted excellent therapeutic effects on ICH, showing improved neuroprotective activity and resulting in neurobehavioral recovery, in an in vitro cellular model and an in vivo ICH rat model. This study can provide a general strategy that uses natural polyphenols to boost the performance of drugs for ICH treatment, and the results may be further extended to other injuries of the central nervous system, such as brain injury and spinal cord injury.

Polyphenolic oligomer-derived multienzyme activity for the treatment of ischemic Stroke through ROS scavenging and blood–brain barrier restoration

“…33,34 Herein, polyphenols have potential antioxidant capacity based on phenol hydroxyl and activation of cellular antioxidant pathway according to previous ref. 35. To regulate ROS, the in vitro ROS scavenging capacity was evaluated, including O 2 ˙ − , H 2 O 2 , ˙OH, and ABTS˙ + .…”

Modified ZIF-8 Nanoparticles for Targeted Metabolic Treatment of Acute Spinal Cord Injury

“…With the development of Chinese Medicine, a plethora of food plant materials and Chinese traditional medicines have been applied to various diseases. , However, the clinical use and targeting efficiency of these medicines are still limited because of their poor dispersion and stability, poor water solubility and high toxic side effects in vivo. , Increasing evidence show that the nanoplatforms have been recently designed as potential carriers of medicine as nanoplatforms exhibit great potentials over natural enzymes, which are more economical and stable, long-term durable, and versatile. − Nanoplatforms may internalize in different tissues/cells, attributed to cellular endocytosis, contributing to an excellent targeting effect. With the premature release of intracellularly loaded medicine during circulation, the lower accumulation of effective drug concentrations in specific tissues is an urgent problem.…”

Robust and Multifunctional Nanoparticles Assembled from Natural Polyphenols and Metformin for Efficient Spinal Cord Regeneration

“…Natural polyphenols are a class of compounds from a wide range of sources with good biocompatibility, ROS scavenging, and anti-inflammatory properties. The presence of rich phenolic groups can form covalent and noncovalent interactions with many other molecules to develop multifunctional nanosystems with anti-inflammatory, antioxidant, photothermal, metal chelation, antibacterial, and other functions. ,− In this work, we strived to design and fabricate a sequence of robust and multifunctional NPs assembled from natural polyphenols (such as epigallocatechin gallate (EGCG), dihydromyricetin (DHM), and baicalein) and Met via a one-pot reaction. Afterward, in vitro cell experiments and in vivo SCI rat model treatment confirmed the promising biological activities of the resulting NPs.…”

“…Recently, great progress has also been made in activating endogenous neural stem cells (NSCs) to repair the structure and function of SCI in animal models via bioactive drugs, polymer scaffolds, and molecules. − For example, in addition to its therapeutic effect on diabetes, metformin (Met) has been demonstrated to efficiently induce endogenous NSCs to proliferate and repair damaged structures in animal models of brain injury and stroke. − In addition to supporting NSCs transplantation, polymer scaffolds can also support local release of bioactive molecules, induce endogenous NSCs proliferation and differentiation, and then enhance function repair. , More importantly, it was also found that the strategies to expand the limited regeneration by activating the proliferation of endogenous NSCs or transplanting exogenous stem cells are also affected by the harsh microenvironment at the injury sites, which could reduce stem cell survival and lead to the stem cells differentiating into astrocytes instead of neurons and oligodendrocytes. ,− Therefore, the integrated therapy strategy via improving the harsh microenvironment as well as promoting endogenous NSCs to repair the structure of SCI using robust biomaterials is considered to be one of the most promising therapeutic strategies for SCI repair. , Functional nanomaterials are an emerging and highly promising option for integrated therapy strategies, by combining different biologically active drugs into nanoparticles (NPs) or other nanoscale devices through covalent or noncovalent combinations . It is worth noting that for the central nervous system (CNS) injury diseases, including SCI, brain injury, and cerebral hemorrhage, due to the dysfunction of the integrity of the blood–brain/spinal barrier and the increase of vascular permeability, as well as the formation of excessive ROS and the acidic microenvironment at the injury site, nanoscale components have been confirmed to be significantly enriched at the injury site. − In addition, in terms of drug delivery, functional nanomaterials also have the following advantages. First, nanomaterials could solve the problems of poor water solubility and prohibit the active molecules from fast clearance to prolong the action duration .…”