Ischemic stroke (IS) is one of the most fatal diseases. Neuroimmunity, inflammation, and oxidative stress play important roles in various complex mechanisms of IS. In particular, the early proinflammatory response resulting from the overactivation of resident microglia and the infiltration of circulating monocytes and macrophages in the brain after cerebral ischemia leads to secondary brain injury. Microglia are innate immune cells in the brain that constantly monitor the brain microenvironment under normal conditions. Once ischemia occurs, microglia are activated to produce dual effects of neurotoxicity and neuroprotection, and the balance of the two effects determines the fate of damaged neurons. The activation of microglia is defined as the classical activation (M1 type) or alternative activation (M2 type). M1 type microglia secrete pro-inflammatory cytokines and neurotoxic mediators to exacerbate neuronal damage, while M2 type microglia promote a repairing anti-inflammatory response. Fine regulation of M1/M2 microglial activation to minimize damage and maximize protection has important therapeutic value. This review focuses on the interaction between M1/M2 microglia and other immune cells involved in the regulation of IS phenotypic characteristics, and the mechanism of natural plant components regulating microglia after IS, providing novel candidate drugs for regulating microglial balance and IS drug development.

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Introduction Recently, Nrf2/HO-1 has received extensive attention as the main regulatory pathway of intracellular defense against oxidative stress and is considered an ideal target for alleviating endothelial cell (EC) injury. Objectives This paper aimed to summarized the natural monomers/extracts that potentially exert protective effects against oxidative stress in ECs. Methods A literature search was carried out regarding our topic with the keywords of "atherosclerosis" or "Nrf2/HO-1" or "vascular endothelial cells" or "oxidative stress" or "Herbal medicine" or "natural products" or "natural extracts" or "natural compounds" or "traditional Chinese medicines" based on classic books of herbal medicine and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, GoogleScholar, BaiduScholar, and others. Then, we analyzed the possible molecular mechanisms for different types of natural compounds in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. In addition, perspectives for possible future studies are discussed. Results These agents with protective effects against oxidative stress in ECs mainly include phenylpropanoids, flavonoids, terpenoids, and alkaloids. Most of these agents alleviate cell apoptosis in ECs due to oxidative stress, and the mechanisms are related to Nrf2/HO-1 signaling activation. However, despite continued progress in research on various aspects of natural agents exerting protective effects against EC injury by activating Nrf2/HO-1 signaling, the development of new drugs for the treatment of atherosclerosis (AS) and other CVDs based on these agents will require more detailed preclinical and clinical studies. Conclusion Our present paper provides updated information of natural agents with protective activities on ECs against oxidative stress by activating Nrf2/HO-1. We hope this review will provide some directions for the further development of novel candidate drugs from natural agents for the treatment of AS and other CVDs.

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Although moderate concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are crucial for various physiological processes within the human body, their overproduction leads to oxidative stress, defined as the imbalance between the production and accumulation of ROS and the ability of the body to neutralize and eliminate them. In the brain, oxidative stress exhibits significant effects, due to its increased metabolical activity and limited cellular regeneration. Thus, oxidative stress is a major factor in the progressive loss of neurons structures and functions, leading to the development of severe neurodegenerative disorders. In this context, recent years have witnessed tremendous advancements in the field of antioxidant therapies, with a special emphasis for neuroprotection. The aim of this paper is to provide an overview of the oxidative stress and antioxidant defense mechanisms and to present the most recent studies on antioxidant therapies for neuroprotection.

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Prunus mume Sieb. et Zucc., P . armeniaca L., and P . salicina L. are economically important fruit trees in temperate regions. These species are taxonomically perplexing because of shared interspecific morphological traits and variation, which are mainly attributed to hybridization. The chloroplast is cytoplasmically inherited and often used for evolutionary studies. We sequenced the complete chloroplast genomes of P. mume, P. armeniaca , and P. salicina using Illumina sequencing followed by de novo assembly. The three chloroplast genomes exhibit a typical quadripartite structure with conserved genome arrangement, structure, and moderate divergence. The lengths of the genomes are 157,815, 157,797, and 157,916 bp, respectively. The length of the large single-copy region (LSC) region is 86,113, 86,283, and 86,122 bp, and the length of the SSC region is 18,916, 18,734, and 19,028 bp; the IR region is 26,393, 26,390, and 26,383 bp, respectively. Each of the three chloroplast genomes encodes 133 genes, including 94 protein-coding, 31 tRNA, and eight rRNA genes. Differential gene analysis for the three species revealed that trnY-ATA is a unique gene in P. armeniaca ; in contrast, the gene trnI-TAT is only present in P. mume and P. salicina , though the position of the gene in these chloroplast genomes differs. Further comparative analysis of the complete chloroplast genome sequences revealed that the ORF genes and the sequences of linked regions rps16 and atpA , atpH and atpI , trnc-GCA and psbD , ycf3 and atpB , and rpL32 and ndhD are significantly different and may be used as molecular markers in taxonomic studies. Phylogenetic evolution analysis of the three species suggests that P. mume has a closer genetic relationship to P. armeniaca than to P. salicina .

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Asiatic acid (AA) is a naturally occurring aglycone of ursane type pentacyclic triterpenoids. It is abundantly present in many edible and medicinal plants including Centella asiatica that is a reputed herb in many traditional medicine formulations for wound healing and neuropsychiatric diseases. AA possesses numerous pharmacological activities such as antioxidant and anti-inflammatory and regulates apoptosis that attributes its therapeutic effects in numerous diseases. AA showed potent antihypertensive, nootropic, neuroprotective, cardioprotective, antimicrobial, and antitumor activities in preclinical studies. In various in vitro and in vivo studies, AA found to affect many enzymes, receptors, growth factors, transcription factors, apoptotic proteins, and cell signaling cascades. This review aims to represent the available reports on therapeutic potential and the underlying pharmacological and molecular mechanisms of AA. The review also also discusses the challenges and prospects on the pharmaceutical development of AA such as pharmacokinetics, physicochemical properties, analysis and structural modifications, and drug delivery. AA showed favorable pharmacokinetics and found bioavailable following oral or interaperitoneal administration. The studies demonstrate the polypharmacological properties, therapeutic potential and molecular mechanisms of AA in numerous diseases. Taken together the evidences from available studies, AA appears one of the important multitargeted polypharmacological agents of natural origin for further pharmaceutical development and clinical application. Provided the favorable pharmacokinetics, safety, and efficacy, AA can be a promising agent or adjuvant along with currently used modern medicines with a pharmacological basis of its use in therapeutics.

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