Objectives: Overproduction of reactive species, notably reactive oxygen (ROS) and nitrogen (RNS) species, along with the failure of balancing effects of endogenous antioxidant defenses result in destruction of cellular structures, lipids, proteins, and genetic material, which lead to oxidative stress. Oxidative stress-induced neuronal apoptosis plays a pivotal role in pathogenesis of neurodegeneration. Antioxidants represent one of the medical choice strategies for protecting against this unbalanced oxidation-antioxidation status. Recently, natural compounds with neuroprotective potential that can scavenge free radicals and protect cells from oxidative damage have received extensive attention. Methods: In this review, we summarized the detailed research progress on the medicinal plants-derived natural compounds with potential anti-oxidation effects and their molecular mechanisms on modulating the neurotoxin (6-OHDA, H₂O₂, glutamate, Aβ)-induced oxidative stress and cell apoptosis. Results: The natural compounds that efficacious in modulating reactive species production and mitochondrial function include flavonoids, glucosides, alkaloids, polyphenols, lignans, coumarins, terpenoids, quinones and others. They decreased the neurotoxin-induced oxidative damage and apoptosis by (1) decreasing ROS/RNS generation, lipid peroxidation, caspase-3 and caspase-9 activities, LDH release, the ratio of Bax/Bcl-2, Ca²⁺ influx and cytochrome c release, (2) elevating MMP, and (3) restoring endogenous antioxidant enzymatic activities (CAT, GSH-Px, GSR, SOD). And they exerted neuroprotective effects against cell damages and apoptosis by modulating the oxidative cascades of different signaling pathways (Nrf2/HO-1, NF-κB, MAPKs, PI3K/Akt, GSK-3β) and preventing mitochondria-dependent apoptosis pathways. Discussion: The present work reviews the role of oxidative stress in neurodegeneration, highlighting the potential anti-oxidation effects of natural compounds as a promising approach to develop innovative neuroprotective strategy. GRAPHICAL ABSTRACT

Alzheimer’s disease is a neurodegenerative disease that affects a large proportion of older adult people and is characterized by memory loss, progressive cognitive impairment, and various behavioral disturbances. Although the pathological mechanisms underlying Alzheimer’s disease are complex and remain unclear, previous research has identified two widely accepted pathological characteristics: extracellular neuritic plaques containing amyloid beta peptide, and intracellular neurofibrillary tangles containing tau. Furthermore, research has revealed the significant role played by neuroinflammation over recent years. The inflammatory microenvironment mainly consists of microglia, astrocytes, the complement system, chemokines, cytokines, and reactive oxygen intermediates; collectively, these factors can promote the pathological process and aggravate the severity of Alzheimer’s disease. Therefore, the development of new drugs that can target neuroinflammation will be a significant step forward for the treatment of Alzheimer’s disease. Flavonoids are plant-derived secondary metabolites that possess various bioactivities. Previous research found that multiple natural flavonoids could exert satisfactory treatment effects on the neuroinflammation associated with Alzheimer’s disease. In this review, we describe the pathogenesis and neuroinflammatory processes of Alzheimer’s disease, and summarize the effects and mechanisms of 13 natural flavonoids (apigenin, luteolin, naringenin, quercetin, morin, kaempferol, fisetin, isoquercitrin, astragalin, rutin, icariin, mangiferin, and anthocyanin) derived from plants or medicinal herbs on neuroinflammation in Alzheimer’s disease. As an important resource for the development of novel compounds for the treatment of critical diseases, it is essential that we focus on the exploitation of natural products. In particular, it is vital that we investigate the effects of flavonoids on the neuroinflammation associated with Alzheimer’s disease in greater detail.

Baicalin is a natural active ingredient isolated from Scutellariae Radix that can cross the blood-brain barrier and exhibits neuroprotective effects on multiple central nervous system diseases. However, the mechanism behind the neuroprotective effects remains unclear. In this study, rat models of spinal cord injury were established using a modified Allen's impact method and then treated with intraperitoneal injection of Baicalin. The results revealed that Baicalin greatly increased the Basso, Beattie, Bresnahan Locomotor Rating Scale score, reduced blood-spinal cord barrier permeability, decreased the expression of Bax, Caspase-3, and nuclear factor κB, increased the expression of Bcl-2, and reduced neuronal apoptosis and pathological spinal cord injury. SH-SY5Y cell models of excitotoxicity were established by application of 10 mM glutamate for 12 hours and then treated with 40 μM Baicalin for 48 hours to investigate the mechanism of action of Baicalin. The results showed that Baicalin reversed tight junction protein expression tendencies (occludin and ZO-1) and apoptosis-related protein expression (Bax, Bcl-2, Caspase-3, and nuclear factor-κB), and also led to up-regulation of PI3K and Akt phosphorylation. These effects on Bax, Bcl-2, and Caspase-3 were blocked by pretreatment with the PI3K inhibitor LY294002. These findings suggest that Baicalin can inhibit blood-spinal cord barrier permeability after spinal cord injury and reduce neuronal apoptosis, possibly by activating the PI3K/Akt signaling pathway. This study was approved by Animal Ethics Committee of Xi’an Jiaotong University on March 6, 2014.

Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer‐reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master’s dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti‐inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment.

Salvia miltiorrhizaBunge (Lamiaceae), one of the most commonly used traditional Chinese herbs, is widely used for the treatment of cardiovascular disease, cerebrovascular disease, Alzheimer’s disease, and Parkinson’s disease in clinical practice. Salvianolic acid B (Sal B, C₃₆H₃₀O₁₆,FW=718.62) is the main water-soluble active ingredient ofSalvia miltiorrhizaBunge, which performs prophylactic and therapeutic activities against neurodegenerative diseases. So far, numerous studies have proved that multiple factors and mechanisms are involved in the pathological process of neurodegenerative diseases, including amyloidβ(Aβ) aggregation and fibril formation, hyperphosphorylation of tau protein, neuroinflammation, oxidative-stress damage, mitochondrial dysfunction, and neuron apoptosis. This study is aimed at reviewing experimental studies and describing the possible mechanisms of Sal B on neurodegenerative diseases.