title: Aralia elata var. mandshurica (Rupr. & Maxim.) J.Wen: An overview of pharmacological studies.
abstract: OBJECTIVE
  Aralia elata var. mandshurica (Rupr. & Maxim.) J.Wen syn. A. mandshurica Rupr. & Maxim is evaluated for its medicinal application. The aim of this study is to analyze pharmacological studies on A. elata var. mandshurica published until December 2015.
  
  
  METHODS
  The information regarding the chemistry, safety, effectiveness, and pharmacological and clinical effects of A. elata was systematically collected from the scientific literature through library catalogs; online services such as E-library.ru, Medline/PubMed, Scopus, Web of Science, and Google Scholar.
  
  
  RESULTS
  A. elata is often considered an example of a medicinal plant used in Chinese, Korean, and Japanese traditional medicine. However, the contemporary applications of Aralia in officinal medicine result primarily from a large number of pharmacological and clinical investigations carried out in the former USSR in the mid-20th century. Since the 1950s, medicinal preparations from radices of A. elata and radices of A. mandshurica have secured an established position within Russian/USSR medicine as evidenced by the inclusion of the drug in recent editions of the National Pharmacopoeia of the USSR and in the Register of Medicinal Preparations of Russia. Pharmacological studies on animals have shown that Aralia increases physical working capacity and affords a stress-protective effect against a broad spectrum of harmful factors including cold stress, immobilization, UV irradiation, and low air pressure. The phytoadaptogen exerts an effect on the central nervous, reproductive, immune, respiratory, and gastrointestinal systems; the metabolic syndrome including hypolipidemic and antidiabetic effects; and blood coagulation. Together with general properties of adaptogens, Aralia has its own specificity, which manifests in cardioprotective and antiarrhythmic activities. Studies on isolated organs, cells, and enzymes have revealed that Aralia preparations exhibit antioxidant activities and enhance sarcoplasmic reticulum Ca2+-ATPase activity, inhibit endoplasmic reticulum stress-associated apoptosis markers (GRP78, CHOP, Caspase-12, and JNK), and increase phosphorylation of STAT3 and Bcl2/Bax ratio; they also show cytotoxic activities against some tumor cell lines; affect NF-κB and PPARs activities; and regulate biosynthesis of pro-inflammatory cytokines and inflammation-related protein expression, tissue respiration, and oxygen consumption. In healthy subjects, Aralia increases mental performance, working capacity, and endurance of movement. Numerous clinical trials have shown the efficiency of Aralia preparations in patients with traumatic brain injury (accompanied with asthenic syndrome and neurotic reactions, depression, neurasthenia, and psychasthenia), neurological diseases (accompanied with astheno-depressive and astheno-hypochondriasis syndromes), myasthenia syndrome (accompanied with chronic post-influenza arachnoiditis), and arterial hypotension. Aralia tincture and "Saparal" are useful as antiviral remedies. Radioprotective properties of Aralia have been reported in pregnant women. Synergistic antiobesity effect was reported for the combination of A. mandshurica and Engelhardtia chrysolepis extracts and antidiabetic effect for the combination of Aralia and glipizide. Promising stress-relieving effects of Aralia are reported for professionals whose work requires a high level of attention. Its proposed ability to moderate stress-induced damage and dysfunction in the cardiovascular tissue might make Aralia the adaptogen of choice among patients with higher risk for cardiovascular diseases. Because Aralia extract administration appears to affect plasma glucose level and hepatic lipid accumulation and ameliorate hyperinsulinemia, it might also provide benefits and be the adaptogen of choice for patients with obesity and diabetes.
  
  
  CONCLUSIONS
  This review describes the considerable diversity of pharmacological effects of A. elata reported in numerous studies carried out in the former USSR and other countries, which have been confirmed over >47 years of use of the plant as an official medicinal remedy. The knowledge discussed in this review can be applied to the expansion of the use of this high-value plant in the pharmacotherapy of European and other countries and for the further discovery of new drugs based on the secondary metabolites of this plant. Modern approaches in mechanisms of action, including a study of gene expression profiling, suggest the most up-to-date challenges for the future research of Aralia.
authors.affiliation: Saint-Petersburg Institute of Pharmacy, Leningrad region, Vsevolozhsky district, 188663, Kuzmolovo P 245, Russia. Electronic address: spb.pharmacy@gmail.com.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Shikov
authors.affiliation: Saint-Petersburg Institute of Pharmacy, Leningrad region, Vsevolozhsky district, 188663, Kuzmolovo P 245, Russia.
authors.forename: Olga N
authors.initials: ON
authors.lastname: Pozharitskaya
authors.affiliation: Saint-Petersburg Institute of Pharmacy, Leningrad region, Vsevolozhsky district, 188663, Kuzmolovo P 245, Russia.
authors.forename: Valery G
authors.initials: VG
authors.lastname: Makarov
mesh_terms: D000818:Animals; D027983:Aralia / Q000737:chemistry*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D010936:Plant Extracts; C057659:saparal
keywords: Adaptogen; Aralia; Clinical data; Pharmacology; Toxicity