Abstract
Cerebral ischemia-reperfusion is a complicated pathological process. The injury and cascade reactions caused by cerebral ischemia and reperfusion are characterized by high mortality, high recurrence, and high disability. However, only a limited number of antithrombotic drugs, such as recombinant tissue plasminogen activator (r-TPA), aspirin, and heparin, are currently available for ischemic stroke, and its safety concerns is inevitable which associated with reperfusion injury and hemorrhage. Therefore, it is necessary to further explore and examine some potential neuroprotective agents with treatment for cerebral ischemia and reperfusion injury to reduce safety concerns caused by antithrombotic drugs in ischemic stroke. Ginseng Rg1 (G-Rg1) is a saponin composed of natural active ingredients and derived from the roots or stems of Panax notoginseng and ginseng in traditional Chinese medicine. Its pharmacological effects exert remarkable neurotrophic and neuroprotective effects in the central nervous system. To explore and summarize the protective effects and mechanisms of ginsenoside Rg1 against cerebral ischemia and reperfusion injury, we conducted this review, in which we searched the PubMed database to obtain and organize studies concerning the pharmacological effects and mechanisms of ginsenoside Rg1 against cerebral ischemia and reperfusion injury. This study provides a valuable reference and clues for the development of new agents to combat ischemic stroke. Our summarized review and analysis show that the pharmacological effects of and mechanisms underlying ginsenoside Rg1 activity against cerebral ischemia and reperfusion injury mainly involve 4 sets of mechanisms: anti-oxidant activity and associated apoptosis via the Akt, Nrf2/HO-1, PPARγ/HO-1, extracellular regulated protein kinases (ERK), p38, and c-Jun N-terminal kinase (JNK) pathways (or mitochondrial apoptosis pathway) and the caspase-3/ROCK1/MLC pathway; anti-inflammatory and immune stimulatory-related activities that involve apoptosis or necrosis via MAPK pathways (the JNK1/2 + ERK1/2 and PPARγ/HO-1 pathways), endoplasmic reticulum stress (ERS), high mobility group protein1 (HMGB1)-induced TLR2/4/9 and receptor for advanced glycation end products (RAGE) pathways, and the activation of NF-κB; neurological cell cycle, proliferation, differentiation, and regeneration via the MAPK pathways (JNK1/2 + ERK1/2, PI3K-Akt/mTOR, PKB/Akt and HIF-1α/VEGF pathways); and energy metabolism and the regulation of cellular ATP levels, the blood-brain barrier and other effects via N-methyl-D-aspartic acid (NMDA) receptors, ERS, and AMP/AMPK-GLUT pathways. Collectively, these mechanisms result in significant neuroprotective effects against cerebral ischemic injury. These findings will be valuable in that they should further promote the development of candidate drugs and provide more information to support the application of previous findings in stroke clinical trials.
Highlights
Stroke is one of the leading causes of death worldwide
The hazards associated with ischemic stroke are mainly caused by cerebral ischemia and reperfusion injury (CI/RI), which is a pathological condition characterized by an initial restriction of blood supply to an organ followed by the subsequent restoration of perfusion and concomitant reoxygenation [2,3]
The damage and cascade of reactions caused by ischemia and reperfusion in brain tissues are related to decreased blood flow, ischemic-induced energy metabolism disorder, oxidative stress, inflammatory stress, cytokine damage, excitatory toxicity by glutamate, intracellular calcium overload, nitric oxide (NO) synthesis, and many other factors [2,3,4,5,6,7,100], even including some genetic disease as a possible complication, such as Fabry disease [100,101]
Summary
Stroke is one of the leading causes of death worldwide. Nearly 6 million people die from stroke each year, and it is estimated that the lifetime risk for stroke is 8% to 10%. While various candidate drugs have failed to treat cerebral ischemia, those studies have prompted series of suggestions that could improve the likelihood of successful translation Among these is that if a systematic review and analysis of preclinical studies of alternative active ingredients the main bioactive compounds responsible for the pharmaceutical actions of ginseng, which show was to be carried out, it would likely promote candidate drug development and provide more little toxicity, and some evidence has shown that its pharmacological effects are remarkable in information from the previous literature that could be used as a bridge into clinical trials of stroke. Rg1” and “Ischemia” as search terms to obtain the literature concerning animal experiments in latest 10 years
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