Schisandra chinensis Stem Ameliorates 3-Nitropropionic Acid-Induced Striatal Toxicity via Activation of the Nrf2 Pathway and Inhibition of the MAPKs and NF-κB Pathways

The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.

Schisandra chinensis (Turcz.) Bail. is often referred to as an example of a medicinal plant with use in modern Chinese medicine. However, Schisandra chinensis first gained recognition as an adaptogen in the official medicine of the USSR in the early 1960s, principally as a result of the large number of pharmacological and clinical studies carried out by Russian scientists in the preceding two decades. Schizandra has now secured an established position within the medicine of Russia/USSR as evidenced by the inclusion of the drug in recent editions of the National Pharmacopoeia of the USSR and in the State Register of Drugs. Pharmacological studies on animals have shown that Schizandra increases physical working capacity and affords a stress-protective effect against a broad spectrum of harmful factors including heat shock, skin burn, cooling, frostbite, immobilisation, swimming under load in an atmosphere with decreased air pressure, aseptic inflammation, irradiation, and heavy metal intoxication. The phytoadaptogen exerts an effect on the central nervous, sympathetic, endocrine, immune, respiratory, cardiovascular, gastrointestinal systems, on the development of experimental atherosclerosis, on blood sugar and acid-base balance, and on uterus myotonic activity. Studies on isolated organs, tissues, cells and enzymes have revealed that Schizandra preparations exhibit strong antioxidant activities and affect smooth muscles, arachidonic acid release, biosynthesis of leukotriene B(4) in leukocytes, platelet activating factor activity, carbohydrate-phosphorus metabolism, the formation of heat shock protein and polyamines, tissue respiration and oxygen consumption, and the tolerance of an organism to oxygen intoxication. In healthy subjects, Schizandra increases endurance and accuracy of movement, mental performance and working capacity, and generates alterations in the basal levels of nitric oxide and cortisol in blood and saliva with subsequent effects on the blood cells, vessels and CNS. Numerous clinical trials have demonstrated the efficiency of Schizandra in asthenia, neuralgic and psychiatric (neurosis, psychogenic depression, astheno-depressive states, schizophrenia and alcoholism) disorders, in impaired visual function, hypotension and cardiotonic disorders, in epidemic waves of influenza, in chronic sinusitis, otitis, neuritis and otosclerosis, in pneumonia, radioprotection of the fetoplacental system of pregnant women, allergic dermatitis, acute gastrointestinal diseases, gastric hyper- and hypo-secretion, chronic gastritis, stomach and duodenal ulcers, wound healing and trophic ulcers. This review describes the considerable diversity of pharmacological effects of Schisandra chinensis reported in numerous studies carried out in the former USSR and which have been confirmed over more than 40 years of use of the plant as an official medicinal remedy. Such knowledge can be applied in the expansion of the use of Schizandra in the pharmacotherapy of European and other countries as well as for the further discovery of new drugs based on the lignans that constitute the main secondary metabolites of this plant.

A wide variety of acute and chronic neurodegenerative diseases, including ischemic/traumatic brain injury, Alzheimer's disease, and Parkinson's disease, share common characteristics such as oxidative stress, misfolded proteins, excitotoxicity, inflammation, and neuronal loss. As no drugs are available to prevent the progression of these neurological disorders, intervention strategies using phytochemicals have been proposed as an alternative form of treatment. Among phytochemicals, isothiocyanate sulforaphane, derived from the hydrolysis of the glucosinolate glucoraphanin mainly present in Brassica vegetables, has demonstrated neuroprotective effects in several in vitro and in vivo studies. In particular, evidence suggests that sulforaphane beneficial effects could be mainly ascribed to its peculiar ability to activate the Nrf2/ARE pathway. Therefore, sulforaphane appears to be a promising compound with neuroprotective properties that may play an important role in preventing neurodegeneration.