|Inflammation. 2010 Apr;33(2):126-36. |
|Schisantherin A exhibits anti-inflammatory properties by down-regulating NF-kappaB and MAPK signaling pathways in lipopolysaccharide-treated RAW 264.7 cells.[Pubmed: 20238486 ]|
|Schisantherin A, a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent under the name of Wuweizi in Chinese traditional medicine. |
METHODS AND RESULTS:
In the present study, we carry out a screening program to identify the anti-inflammatory potentials of Schisantherin A. We found that Schisantherin A reduced lipopolysaccharide (LPS (1 mg/L))-induced levels of TNF-alpha, IL-6, NO, and PGE2 (p<0.01 or p<0.05), and also reduced levels of iNOS and COX-2 in RAW 264.7 macrophages in a concentration-dependent manner. We further investigated signal transduction mechanisms to determine how Schisantherin A affects. RAW264.7 cells were pretreated with 0.5, 2.5, or 25 mg/L of Schisantherin A 1 h prior to treatment with 1 mg/L of LPS. Thirty minutes later, cells were harvested and mitogen activated protein kinases (MAPKs) activation and I kappaB alpha was measured by Western blot. Alternatively, cells were fixed and nuclear factor-kappaB (NF-kappaB) activation was measured using immunocytochemical analysis. Signal transduction studies showed that Schisantherin A significantly inhibited extracellular signal-regulated kinase (ERK), p38, and c-jun NH2-terminal kinase (JNK) phosphorylation protein expression. Schisantherin A also inhibited p65-NF-kappaB translocation into the nucleus by I kappaB alpha degradation. By using specific inhibitors of ERK, JNK and p38, we found that Schisantherin A may inhibit TNF-alpha mostly through ERK pathway.
Therefore, Schisantherin A may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kappaB and MAPKs signaling in RAW264.7 cells.
|Fitoterapia. 2012 Dec;83(8):1415-9. |
|Strong inhibition of deoxyschizandrin and schisantherin A toward UDP-glucuronosyltransferase (UGT) 1A3 indicating UGT inhibition-based herb–drug interaction.[Pubmed: 23339253]|
|Deoxyschizandrin and Schisantherin A are major bioactive lignans isolated from Fructusschisandrae which has been widely used as a tonic in traditional Chinese medicine for manyyears. Inhibition of UDP-glucuronosyltransferases (UGTs) by herbal components might be animportant reason for clinical herb–drug interaction. The aim of the present study is toinvestigate the inhibitory effect of deoxyschizandrin and Schisantherin A on major UGTisoforms. |
METHODS AND RESULTS:
Recombinant UGT isoforms were used as enzyme source, and a nonspecific substrate4-methylumbelliferone (4-MU) was utilized as substrate. The results showed that 100 μM ofdeoxyschizandrin and Schisantherin A exhibited strong inhibition on UGT1A3, and negligibleinhibition on other tested UGT isoforms. Furthermore, deoxyschizandrin and Schisantherin Awere demonstrated to inhibit UGT1A3 in a concentration-dependent manner, with IC50 valueof 10.8±0.4 μM and 12.5±0.5 μM, respectively. Dixon and Lineweaver–Burk plots showedthat inhibition of UGT1A3 by deoxyschizandrin was best fit to competitive inhibition type, andinhibition kinetic parameter (Ki) was calculated to be 0.48 μM. Inhibition of UGT1A3 bySchisantherin A gave the best fit for types of noncompetitive inhibition, and the results showedKi to be 11.3 μM.
All these experimental data suggested that herb–drug interaction might occurwhen deoxyschizandrin or Schisantherin A containing herbs were co-administered with drugswhich mainly undergo UGT1A3-mediated metabolism. However, given that many in vivofactors could influence the in vitro–in vivo extrapolation (IVIVE), these in vitro inhibitoryparameters should be considered with caution.
|J Ethnopharmacol. 2015 Apr 29. pii: S0378-8741(15)00306-2. |
|Schisantherin A protects against 6-OHDA-induced dopaminergic neuron damage in zebrafish and cytotoxicity in SH-SY5Y cells through the ROS/NO and AKT/GSK3β pathways.[Pubmed: 25934514]|
|The fruit of Schisandra chinensis (Turcz.) Baill, has been traditionally used in management of liver diseases and ageing associated neurodegeneration. The bioactive compound from this medicinal plant would be valuable for its potential use in prevention and treatment of Parkinson׳s disease. The overall objective of the present study was to understand the neuroprotective effect of Schisantherin A, a dibenzocyclooctadiene lignan from the fruit of S. chinensis (Turcz.) Baill, and to elucidate its underlying mechanism of action. |
METHODS AND RESULTS:
This study investigated the protective effect of Schisantherin A against selective dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA)-induced neural damage in human neuroblastoma SH-SY5Y cells and zebrafish models. Oxidative stress and related signaling pathways underlying the neuroprotective effect were determined by multiple biochemical assays and Western blot. Pretreatment with Schisantherin A offered neuroprotection against 6-OHDA-induced SH-SY5Y cytotoxicity. Moreover, Schisantherin A could prevent 6-OHDA-stimulated dopaminergic neuron loss in zebrafish. Our mechanistic study showed that Schisantherin A can regulate intracellular ROS accumulation, and inhibit NO overproduction by down-regulating the over-expression of iNOS in 6-OHDA treated SH-SY5Y cells. Schisantherin A also protects against 6-OHDA-mediated activation of MAPKs, PI3K/Akt and GSK3β.
These findings demonstrate that Schisantherin A may have potential therapeutic value for neurodegenerative diseases associated with abnormal oxidative stress such as Parkinson׳s disease.
|Physiol Behav. 2014 Jun 10;132:10-6. |
|Schisantherin A recovers Aβ-induced neurodegeneration with cognitive decline in mice.[Pubmed: 24813830]|
|Schisantherin A (STA) is a main bioactive lignan isolated from Schisandra chinensis (Turcz.) Baill., which has been widely used as a tonic in traditional Chinese medicine for many years. Lots of studies have reported that STA exhibited anti-inflammatory and antioxidant effects.|
METHODS AND RESULTS:
This paper was designed to investigate the effects of STA on cognitive function and neurodegeneration in the mouse control of Alzheimer's disease (AD) induced by Aβ1-42. It was found that successive intracerebroventricular (ICV) administration of STA (0.01 and 0.1mg/kg) for 5days significantly attenuated Aβ1-42-induced learning and memory impairment as measured by the Y-maze test, shuttle-box test and Morris water maze test. Furthermore, STA at a dose of 0.1mg/kg restored the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as the levels of Aβ1-42, malondialdehyde (MDA) and glutathione (GSH) to some extent in the hippocampus and cerebral cortex. It also noticeably improved the histopathological changes in the hippocampus.
The results suggested that STA might protect against cognitive deficits, oxidative stress and neurodegeneration induced by Aβ1-42, and serve as a potential agent in treatment of AD.