1
|
Schisandrin B inhibits the proliferation and invasion of glioma cells by regulating the HOTAIR-micoRNA-125a-mTOR pathway. Neuroreport 2018; 28:93-100. [PMID: 27977512 DOI: 10.1097/wnr.0000000000000717] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Glioma is one of the most common malignant central nervous system tumors in humans. Schisandrin B (Sch B) has been confirmed to cause the proliferation and invasion of glioma cells. In the present study, the potential mechanism underlying the antitumor effect of Sch B on glioma cells was investigated. The glioma cell lines, U251 and U87, were exposed to Sch B, and the cell viability, apoptosis, migration, and invasion were determined using the MTT assay, flow cytometry, and transwell assay, respectively. Then, the effects of HOTAIR and miR-125a on tumor biology and the mammalian target of rapamycin (mTOR) protein expression in cell lines exposed to Sch B were investigated. The results showed that Sch B decreased HOTAIR expression and increased miR-125a-5p expression. HOTAIR overexpression decreased miR-125a expression and increased mTOR expression in cells with the treatment of Sch B. The miR-125a inhibitor reversed the effects of HOTAIR downregulation on cell proliferation and migration. On co-incubation with rapamycin, a specific mTOR inhibitor, the cell viability, migration, and invasion were decreased and cell apoptosis was increased in two cell lines exposed to Sch B after the treatment of pcDNA-HOTAIR. In conclusion, Sch B played an inhibitory role in the proliferation and invasion of glioma cells by regulating the HOTAIR-micoRNA-125a-mTOR pathway.
Collapse
|
2
|
Cen J, Guo H, Hong C, Lv J, Yang Y, Wang T, Fang D, Luo W, Wang C. Development of tacrine-bifendate conjugates with improved cholinesterase inhibitory and pro-cognitive efficacy and reduced hepatotoxicity. Eur J Med Chem 2018; 144:128-136. [DOI: 10.1016/j.ejmech.2017.12.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 11/29/2017] [Accepted: 12/02/2017] [Indexed: 12/23/2022]
|
3
|
Sowndhararajan K, Deepa P, Kim M, Park SJ, Kim S. An overview of neuroprotective and cognitive enhancement properties of lignans from Schisandra chinensis. Biomed Pharmacother 2017; 97:958-968. [PMID: 29136774 DOI: 10.1016/j.biopha.2017.10.145] [Citation(s) in RCA: 107] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Revised: 10/23/2017] [Accepted: 10/24/2017] [Indexed: 01/17/2023] Open
Abstract
Schisandra chinensis fruits have been traditionally used for thousands of years in Korea, China and Japan to treat various ailments. The fruits contain a variety of bioactive metabolites, especially lignan components have been reported to have various biological activities and have potential in the treatment of numerous neurodegenerative diseases. The lignans from S. chinensis are mainly grouped under dibenzocyclooctadiene lignans. Previous studies have reported that the crude extracts and the isolated pure lignan components effectively protect the neuronal cell damage and significantly enhance the cognitive performances. The experimental findings support the extracts and lignan components from S. chinensis can be used as new therapeutic agents to treat various neurodegenerative diseases. In the current review, we highlight the lignans from S. chinensis as promising resources for the development of natural and effective agents for neuroprotective and cognitive enhancement effects. The lignan extracts and individual compounds from S. chinensis were summarized in relation to their neuroprotective and cognitive enhancement activities.
Collapse
Affiliation(s)
- Kandhasamy Sowndhararajan
- School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Gangwon-do, Republic of Korea
| | - Ponnuvel Deepa
- School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Gangwon-do, Republic of Korea
| | - Minju Kim
- School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Gangwon-do, Republic of Korea
| | - Se Jin Park
- School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Gangwon-do, Republic of Korea
| | - Songmun Kim
- School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon 24341, Gangwon-do, Republic of Korea.
| |
Collapse
|
4
|
Gao Z, Zhang J, Li L, Shen L, Li Q, Zou Y, Du X, Zhao Z. Heat shock proteins 27 and 70 contribute to the protection of Schisandrin B against d-galactosamine-induced liver injury in mice. Can J Physiol Pharmacol 2016; 94:373-378. [PMID: 26666831 DOI: 10.1139/cjpp-2015-0419] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Schisandrin B is a hepatoprotective component isolated from a traditional Chinese herb, Schisandra chinensis (Turcz.) Baill. This study determined the effect of Schisandrin B on d-galactosamine -induced liver injury and the role of heat shock proteins 27 and 70 against liver injury in mice. Acute liver injury was induced by intraperitoneal injection of d-galactosamine to mice, and Schisandrin B was given orally. The protein and gene expression of heat shock proteins 27 and 70 were detected by western blot and real-time quantitative polymerase chain reaction, respectively. Liver tissues were subjected to histological evaluation, and the activities of alanine aminotransferase and aspartate aminotransferase in the serum were measured. Pretreatment of Schisandrin B significantly attenuated d-galactosamine-induced liver injury in mice. This result was evidenced by improved alteration of histopathological hepatic necrosis and reduced alanine aminotransferase and aspartate aminotransferase activities in the serum. The hepatoprotective effect was accompanied with overexpression of heat shock proteins 27 and 70 both at the protein and mRNA levels. However, the aforementioned actions of Schisandrin B were all markedly suppressed by the heat shock protein inhibitor quercetin. Heat shock proteins 27 and 70 were involved in the protective effect of Schisandrin B against d-galactosamine-induced liver injury in mice.
Collapse
Affiliation(s)
- Zhiying Gao
- a Polygenic Disease Institute, Qiqihar Medical University, 333 Bukui Street, Jianhua District, Qiqihar 161006, P. R. China
| | - Jishun Zhang
- b Department of Gastroenterology and Hepatology, Beijing Chaoyang Hospital, Capital Medical University, 5 Jingyuan Road, Shijingshan District, Beijing 100043, P. R. China
| | - Libo Li
- c Department of Pharmacology, Qiqihar Medical University, 333 Bukui Street, Jianhua District, Qiqihar 161006, P. R. China
| | - Longqing Shen
- d School of Basic Medicine, Qiqihar Medical University, 333 Bukui Street, Jianhua District, Qiqihar 161006, P. R. China
| | - Qingyi Li
- c Department of Pharmacology, Qiqihar Medical University, 333 Bukui Street, Jianhua District, Qiqihar 161006, P. R. China
| | - Yu Zou
- c Department of Pharmacology, Qiqihar Medical University, 333 Bukui Street, Jianhua District, Qiqihar 161006, P. R. China
| | - Xiaohui Du
- c Department of Pharmacology, Qiqihar Medical University, 333 Bukui Street, Jianhua District, Qiqihar 161006, P. R. China
| | - Zhibo Zhao
- d School of Basic Medicine, Qiqihar Medical University, 333 Bukui Street, Jianhua District, Qiqihar 161006, P. R. China
| |
Collapse
|
5
|
Li L, Zhang T, Zhou L, Zhou L, Xing G, Chen Y, Xin Y. Schisandrin B attenuates acetaminophen-induced hepatic injury through heat-shock protein 27 and 70 in mice. J Gastroenterol Hepatol 2014; 29:640-7. [PMID: 24219791 DOI: 10.1111/jgh.12425] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/24/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Schisandrin B is an active component isolated from Schisandra chinensis (TurcZ.) Baill. that is widely used as an antihepatotoxic agent. Schisandrin B has significant hepatoprotective effect against chemical and immunological liver injury. This study aimed to investigate the effect of Schisandrin B on the expression of 27- and 70-kDa heat-shock protein (HSP) and its role in protection against acetaminophen-induced liver injury in mice. METHODS After the mice were pretreated, Western blot and real-time quantitative polymerase chain reaction were used to detect the protein and gene expression of HSP27 and HSP70, respectively; the liver tissues were subjected to histological evaluation, and alanine aminotransferase and aspartate aminotransferase activities in the serum were measured. RESULTS Oral administration of Schisandrin B increased the expression of HSP27 and HSP70 in a time- and dose-dependent manner. The inducing effect of Schisandrin B on HSP27 and HSP70 was also confirmed by real-time quantitative polymerase chain reaction. In the acetaminophen-induced liver injury mouse model, the prior oral administration of Schisandrin B (200 mg/kg) three times in 24 h markedly alleviated liver injury as indicated by the amelioration of histopathological hepatic necrosis and the reduction of alanine aminotransferase and aspartate aminotransferase activities in the serum. However, the earlier actions of Schisandrin B were all suppressed significantly by Quercetin, a known HSP inhibitor. CONCLUSION The hepatic cytoprotective action of Schisandrin B against acetaminophen-induced liver injury is mediated, at least in part, by the induction of HSP27 and HSP70 in mice.
Collapse
Affiliation(s)
- Libo Li
- Department of Pharmacology, Qiqihar Medical University, Qiqihar, China
| | | | | | | | | | | | | |
Collapse
|
6
|
Kim HJ, Oh MS, Hong J, Jang YP. Quantitative analysis of major dibenzocyclooctane lignans in Schisandrae fructus by online TLC-DART-MS. PHYTOCHEMICAL ANALYSIS : PCA 2011; 22:258-262. [PMID: 20981871 DOI: 10.1002/pca.1273] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2010] [Revised: 08/10/2010] [Accepted: 08/10/2010] [Indexed: 05/30/2023]
Abstract
INTRODUCTION Direct analysis in real time (DART) ion source is a powerful ionising technique for the quick and easy detection of various organic molecules without any sample preparation steps, but the lack of quantitation capacity limits its extensive use in the field of phytochemical analysis. OBJECTIVE To improvise a new system which utilize DART-MS as a hyphenated detector for quantitation. METHODOLOGY A total extract of Schisandra chinensis fruit was analyzed on a TLC plate and three major lignan compounds were quantitated by three different methods of UV densitometry, TLC-DART-MS and HPLC-UV to compare the efficiency of each method. To introduce the TLC plate into the DART ion source at a constant velocity, a syringe pump was employed. The DART-MS total ion current chromatogram was recorded for the entire TLC plate. The concentration of each lignan compound was calculated from the calibration curve established with standard compound. RESULTS Gomisin A, gomisin N and schisandrin were well separated on a silica-coated TLC plate and the specific ion current chromatograms were successfully acquired from the TLC-DART-MS system. The TLC-DART-MS system for the quantitation of natural products showed better linearity and specificity than TLC densitometry, and consumed less time and solvent than conventional HPLC method. CONCLUSION A hyphenated system for the quantitation of phytochemicals from crude herbal drugs was successfully established. This system was shown to have a powerful analytical capacity for the prompt and efficient quantitation of natural products from crude drugs.
Collapse
Affiliation(s)
- Hye Jin Kim
- Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea
| | | | | | | |
Collapse
|
7
|
Pan SY, Guo BF, Zhang Y, Yu Q, Yu ZL, Dong H, Ye Y, Han YF, Ko KM. Tacrine Treatment at High Dose Suppresses the Recognition Memory in Juvenile and Adult Mice with Attention to Hepatotoxicity. Basic Clin Pharmacol Toxicol 2011; 108:421-7. [DOI: 10.1111/j.1742-7843.2011.00677.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
|
8
|
Panossian A, Wikman G. Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress-Protective Activity. Pharmaceuticals (Basel) 2010; 3:188-224. [PMID: 27713248 PMCID: PMC3991026 DOI: 10.3390/ph3010188] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2009] [Revised: 01/11/2010] [Accepted: 01/16/2010] [Indexed: 12/17/2022] Open
Abstract
Adaptogens were initially defined as substances that enhance the "state of nonspecific resistance" in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. Studies on animals and isolated neuronal cells have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. In addition, a number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly in tolerance to mental exhaustion and enhanced attention. Indeed, recent pharmacological studies of a number of adaptogens have provided a rationale for these effects also at the molecular level. It was discovered that the stress-protective activity of adaptogens was associated with regulation of homeostasis via several mechanisms of action, which was linked with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of stress response, such as molecular chaperons (e.g., HSP70), stress-activated c-Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription factor DAF-16, cortisol and nitric oxide.
Collapse
Affiliation(s)
- Alexander Panossian
- Swedish Herbal Institute Research & Development, Spårvägen 2, SE-432 96 Åskloster, Sweden.
| | - Georg Wikman
- Swedish Herbal Institute Research & Development, Spårvägen 2, SE-432 96 Åskloster, Sweden
| |
Collapse
|
9
|
Wang MC, Lai YC, Chang CL. High throughput screening and antioxidant assay of dibenzo[a,c]cyclooctadiene lignans in modified-ultrasonic and supercritical fluid extracts of Schisandra chinensis Baill by liquid chromatography--mass spectrometry and a free radical-scavenging method. J Sep Sci 2008; 31:1322-32. [PMID: 18446887 DOI: 10.1002/jssc.200700443] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Dibenzo[a,c]cyclooctadiene lignans of Schisandra chinensis Baill are well known because of their hepatoprotective activity, antioxidant activity, and anticancer effect. For the isolation of the dibenzo[a,c]cyclooctadiene lignans of Schisandra chinensis Baill two extraction methods were used: modified-ultrasonic extraction and supercritical fluid extraction. A specific and fast analytical method for structure identification is established for quality control because structure elucidation could be accomplished by means of liquid chromatography-mass spectrometry (LC-MS) technologies. The separation and identification of the compounds were completed by: (i) a water-acetonitrile gradient system using a C18 reversed-phase column; (ii) UV detection at 225 nm; (iii) MS/MS experiments with electrospray ionization interface (ESI) ion trap mass spectrometry in the positive mode. Normalized collision energy was used to obtain fragment ions of structural relevance in the LC-MS/MS. These results provided a reliable LC-MS/MS method for the determination of the dibenzo[a,c]cyclooctadiene lignans from Schisandra chinensis Baill. Finally, we also detected 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging effects (%) of the modified-ultrasonic and supercritical fluid extracts of Schisandra chinensis Baill compared with 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). The antioxidant activities of the modified-ultrasonic and supercritical fluid extracts were lower than that of trolox.
Collapse
Affiliation(s)
- Ming-Chih Wang
- Graduate School of Biotechnology, HungKuang University, Taichung, Taiwan, ROC
| | | | | |
Collapse
|
10
|
Tsi D, Tan A. Evaluation on the combined effect of Sesamin and Schisandra extract on blood fluidity. Bioinformation 2008; 2:249-52. [PMID: 18317575 PMCID: PMC2258427 DOI: 10.6026/97320630002249] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2007] [Accepted: 01/02/2008] [Indexed: 12/04/2022] Open
Abstract
Several studies have demonstrated a link between blood viscosity and various forms of liver dysfunction. Therefore, we investigated the effect of liver protective herbal materials, Sesamin combined with extract of Schisandra chinensis berry (Schisandra) for its potential to improve blood fluidity in humans. Ten human subjects were recruited to study the effect of sesamin combined with schisandra extract (SCH) for two weeks on blood viscosity. Blood fluidity was measured as the transit time for 100mul of heparinized whole blood to pass through a micro-channel array setup at baseline, 1 week and 2 weeks. For safety assessment, blood biochemistry, hematology and urine analysis were taken at baseline, 1 week and 2 weeks after SCH administration. No safety concern and adverse effects were observed during the 2-week continuous intake period. Intake of SCH reduced blood passage time by 9.0% and 9.7% at 1 and 2 weeks, respectively. In conclusion, this pilot clinical study indicates that the combined administration of sesamin with schisandra extract could improve blood fluidity after 1 week of oral intake and this effect was sustained up to 2 weeks.
Collapse
Affiliation(s)
- Daniel Tsi
- BRAND'S Centre for Health and Nutritional Sciences, Cerebos Pacific Limited,18 Cross Street # 12-01/08, Singapore.
| | | |
Collapse
|
11
|
Pan SY, Yu ZL, Dong H, Lee NTK, Wang H, Fong WF, Han YF, Ko KM. Evaluation of acute bis(7)-tacrine treatment on behavioral functions in 17-day-old and 30-day-old mice, with attention to drug toxicity. Pharmacol Biochem Behav 2007; 86:778-83. [PMID: 17449090 DOI: 10.1016/j.pbb.2007.03.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2006] [Revised: 03/05/2007] [Accepted: 03/06/2007] [Indexed: 11/22/2022]
Abstract
Bis(7)-tacrine was evaluated for efficacy on memory retention in mice 17 days of age and 30 days of age. The tests used were a passive-avoidance response test and a measure of spontaneous motor activity. Also, possible drug-induced hepatotoxicity and acute drug toxicity were evaluated. Behavioral studies were performed using a step-through task and an open-field test with a 24-h interval between training and evaluation tests. Bis(7)-tacrine (0.06-20 micromol/kg) was subcutaneously injected 30 min prior to the first session of both test types. During the training session of the step-through task, bis(7)-tacrine treatment reduced (by 46%, P<0.01) the number of avoidable electric shocks (footshocks) only at a high dose of 20 micromol/kg in mice 17 days of age, but dose-dependently decreased the number of footshocks (10-56%, P<0.001) in mice 30 days of age. Bis(7)-tacrine treatment at all doses tested did not produce any detectable changes in retention latency in mice 17 days of age, but the drug significantly prolonged retention latency at low doses (1.25 and 2.50 micromol/kg), and not high doses (5-20 micromol/kg), in mice 30 days of age. In the open-field test, bis(7)-tacrine decreased spontaneous motor activity in the acquisition session only at a high dose of 20 micromol/kg in mice 17 days of age and 30 days of age (by 28 and 45%, respectively), but did not affect spontaneous motor activity in the recall session. Bis(7)-tacrine treatment at a dose of 20 micromol/kg produced a more potent hepatotoxic effect in mice 30 days of age than in mice 17 days of age, (P<0.05), and the drug caused acute toxicity with comparable potencies in mice of both age groups. In conclusion, mice 30 days of age seemed to be more sensitive than mice 17 days of age to bis(7)-tacrine-induced cognitive function enhancement and hepatotoxicity. Bis(7)-tacrine appears to be more potent and more selective as a cognitive function-enhancing agent than tacrine.
Collapse
Affiliation(s)
- S Y Pan
- Department of Pharmacology, Beijing University of Chinese Medicine, Beijing 100029, China.
| | | | | | | | | | | | | | | |
Collapse
|
12
|
Pan SY, Yang R, Han YF, Dong H, Feng XD, Li N, Geng W, Ko KM. High doses of bifendate elevate serum and hepatic triglyceride levels in rabbits and mice: animal models of acute hypertriglyceridemia. Acta Pharmacol Sin 2006; 27:673-8. [PMID: 16723084 DOI: 10.1111/j.1745-7254.2006.00332.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
AIM To investigate the effects of bifendate on serum and hepatic lipids level in rabbits and mice. METHODS Animals were administered bifendate [powdered pill suspended in 0.5% sodium carboxymethylcellulose (CMC)] at increasing doses (0.25-1 g/kg, ig). Blood lipid and apolipoprotein levels were measured using commercially available assay kits. RESULTS The treatment of rabbits with a single dose of bifendate (0.3 g/kg) caused a time-dependent and biphasic change in serum triglyceride (TG) levels, with the value reaching a maximum (3-fold increase compared to the baseline value) between 24 and 36 h post-dosing. When mice were orally treated with bifendate (0.25-1 g/kg), serum TG levels increased by 39%-76% and 14%-39% at 24 and 48 h post-dosing, respectively. When given at daily doses of 0.25 and 1 g/kg for 4 d, bifendate increased serum TG levels (56%-79%), with concomitant elevations in apolipoprotein A-I and apolipoprotein B levels at 24 h after the last dosing. TG levels were also increased (11%-43%) in liver samples of mice receiving single or multiple doses of bifendate. However, bifendate treatment caused slight reductions in serum and hepatic total cholesterol levels (9%-13%). The hypertriglyceridemia induced by bifendate was ameliorated by fenofibrate but not inositol nicotinate treatment in mice. CONCLUSION The findings suggest that bifendate treatment at high oral doses can cause an acute elevation in serum and hepatic TG levels.
Collapse
Affiliation(s)
- Si-Yuan Pan
- Department of Pharmacology, Beijing University of Chinese Medicine, Beijing 100029, China.
| | | | | | | | | | | | | | | |
Collapse
|
13
|
Pan SY, Dong H, Han YF, Li WY, Zhao XY, Ko KM. A novel experimental model of acute hypertriglyceridemia induced by schisandrin B. Eur J Pharmacol 2006; 537:200-4. [PMID: 16624278 DOI: 10.1016/j.ejphar.2006.03.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2005] [Revised: 03/01/2006] [Accepted: 03/06/2006] [Indexed: 10/24/2022]
Abstract
Mice were intragastrically treated with single doses (0.05-0.8 g/kg) of schisandrin B (a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis). Twenty-four hours after schisandrin B administration, the serum triglyceride level was increased by 10-235% in a dose-dependent manner. However, the serum low density lipoprotein cholesterol level was significantly decreased by 28% at a dose of 0.8 g/kg. When given once daily (0.01-0.2 g/kg) for 4 days, schisandrin B also dose-dependently elevated the serum triglyceride level (17-134%). Kinetics parameters estimated by Scott's plot analysis of schisandrin B-induced changes in serum and hepatic triglyceride levels were determined: serum-E(max) (maximal effect)=6 mmol/L (384% increase, P<0.001); K(D) (affinity)=0.59 mmol/kg; pD(2) (an index of affinity)=6.62; liver-E(max)=21 micromol/g (68% increase, P<0.001); K(D)=0.37 mmol/kg; pD(2)=6.83. The efficacy of schisandrin B in increasing the triglyceride level was 5.6-fold higher in serum than in liver tissue. Fenofibrate (0.2g/kg) treatment, when in combination with schisandrin B (0.2g/kg), for 4 days significantly reduced the schisandrin B-induced increase in serum triglyceride level (by 81%, P<0.001). Hepatic triglyceride level was also decreased (by 100%, P<0.001) by co-treatment with fenofibrate. Our results suggest that schisandrin B treatment can be used to establish a mouse model of acute hypertrigylceridemia.
Collapse
Affiliation(s)
- Si-Yuan Pan
- Department of Pharmacology, Beijing University of Chinese Medicine, Beijing 100102, China.
| | | | | | | | | | | |
Collapse
|
14
|
Jung HA, Chung HY, Yokozawa T, Kim YC, Hyun SK, Choi JS. Alaternin and emodin with hydroxyl radical inhibitory and/or scavenging activities and hepatoprotective activity on tacrine-induced cytotoxicity in HepG2 cells. Arch Pharm Res 2005; 27:947-53. [PMID: 15473666 DOI: 10.1007/bf02975849] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The antioxidative and hepatoprotective potentials of two anthraquinones, alaternin (2-hydroxyemodin) and emodin, to scavenge and/or inhibit hydroxyl radicals generated by the Fenton reaction and to protect tacrine-induced cytotoxicity in human liver derived HepG2 cells were evaluated, respectively. The inhibitory activity on hydroxyl radical generated in a cell-free chemical system (FeSO4/H2O2) was investigated by a fluorescence spectrophotometer using a highly fluorescent probe, 2',7'-dichlorofluorescein. The hydroxyl radical scavenging activity was determined by electron spin resonance spectroscopy using 5,5-dimethy-1-pyrroline-N-oxide as hydroxyl radicals trapping agents. Tacrine-induced HepG2 cell toxicity was determined by a 3-[4,5-dimethylthiazole-2yl]-2,5-diphenyltertrazolium bromide assay. Although the scavenging activity of alaternin on hydroxyl radical was similar to that of emodin in dose-dependent patterns, the inhibitory activity exhibited by the former on hydroxyl radical generation was stronger than that of the latter, with IC50 values of 3.05 +/- 0.26 microM and 13.29 +/- 3.20 microM, respectively. In addition, the two anthraquinones, alaternin and emodin showed their hepatoprotective activities on tacrine-induced cytotoxicity, and the EC50 values were 4.02 microM and 2.37 microM, respectively. Silymarin, an antihepatotoxic agent used as a positive control exhibited the EC50 value of 2.00 microM. These results demonstrated that both alaternin and emodin had the simultaneous antioxidant and hepatoprotective activities.
Collapse
Affiliation(s)
- Hyun Ah Jung
- Research Institute of Marine Science and Technology, Korea Maritime University, Busan, 606-791, Korea
| | | | | | | | | | | |
Collapse
|
15
|
Wu YF, Cao MF, Gao YP, Chen F, Wang T, Zumbika EP, Qian KX. Down-modulation of heat shock protein 70 and up-modulation of Caspase-3 during schisandrin B-induced apoptosis in human hepatoma SMMC-7721 cells. World J Gastroenterol 2004; 10:2944-8. [PMID: 15378770 PMCID: PMC4576249 DOI: 10.3748/wjg.v10.i20.2944] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To investigate the effect of schisandrin B (Sch B) on proliferation and apoptosis of human hepatoma SMMC-7721 cells in vitro and regulation of Hsp70 and Caspases-3, 7, 9 expression by Sch B.
METHODS: Human hepatoma cell line SMMC-7721 was cultured and treated with Sch B at various concentrations. Growth suppression was detected with MTT colorimetric assay. Cell apoptosis was confirmed by DNA ladder detection and flow cytometric analysis. The expression of Hsp70, Caspases-3, 7, 9 were analyzed by Western blot analysis.
RESULTS: Sch B inhibited the growth of hepatoma SMMC-7721 cells in a dose-dependent manner, leading to a 50% decrease in cell number (LC50) value of 23.50 mg/L. Treatment with Sch B resulted in degradation of chromosomal DNA into small internucleosomal fragments, evidenced by the formation of a 180-200 bp DNA ladder on agarose gels. FCM analysis showed the peak areas of subdiploid at the increased concentration of Sch B. The results of Western bolt analysis showed that Hsp70 was down-regulated and Caspase-3 was up-regulated, while the activity of Caspases-7, -9 had no significant change.
CONCLUSION: Sch B is able to inhibit the proliferation of human hepatoma SMMC-7721 cells and induce apoptosis, which goes through Caspase-3-dependent and Caspase-9-independent pathway accompanied with the down-regulation of Hsp70 protein expression at an early event.
Collapse
Affiliation(s)
- Yi-Feng Wu
- College of Life Sciences, Zhejiang University, Hangzhou 310027, Zhejiang Province, China
| | | | | | | | | | | | | |
Collapse
|