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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (5): 569-576.doi: 10.3736/jcim20120513

• Original Experimental Research • Previous Articles     Next Articles

Effects of the effective component group of Chinese herbal medicine Xiaoxuming Decoction on brain mitochondria in rats with chronic cerebral ischemia

Yue-hua Wang(), Xiao-li He, Xiao-xiu Li, Hai-lin Qin, Guan-hua Du()   

  1. Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China
  • Received:2011-10-10 Accepted:2011-11-30 Online:2012-05-20 Published:2018-06-15
  • Contact: Yue-hua Wang, Guan-hua Du E-mail:walling@imm.ac.cn;dugh@imm.ac.cn

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Objective: To investigate the effects of the effective component group of Xiaoxuming Decoction (XXM), a compound traditional Chinese herbal medicine, on cerebral mitochondria in rats with chronic cerebral ischemia.

Methods: Rats were subjected to permanent bilateral common carotid artery occlusion to induce chronic cerebral ischemia. Then, the rats with chronic cerebral ischemia were randomly divided into five groups: model group, extract of Ginkgo biloba group and low-, medium- and high-dose effective component group of XXM groups. Another 11 rats without common carotid artery occlusion were used as a sham control. Gradient centrifugation was used to obtain the mitochondria from the rat brain. Clark oxygen electrode method was used to determine mitochondrial respiratory function. Photometric determination was used to measure mitochondrial swelling. Rodamine 123 was used to measure mitochondrial membrane potential. Western blotting was used to detect mitochondrial apoptosis.

Results: Compared with the sham group, the mitochondria dysfunction was caused by chronic cerebral ischemia associated with the decrease of oxidative phosphorylation parameters and the mitochondrial membrane potential, the increase of the mitochondrial degree, the elevation of reactive oxygen species level, the decrease in Bcl-2/Bax ratio, and the release of cytochrome c. The effective component group of XXM could reduce mitochondrial damage induced by chronic cerebral ischemia by improving the indexes mentioned above.

Conclusion: The effective component group of Xiaoxuming Decoction can protect brain mitochondrial homeostasis and improve the function of mitochondria in rats with chronic cerebral ischemia, which may be the mechanism of its protection against chronic cerebral ischemia.

Key words: plant extracts, brain ischemia, mitochondria, reactive oxygen species, bcl-2-associated X protein, rats

Table 1

Effects of effective component group of XXM on brain mitochondrial respiratory properties in rats with chronic cerebral ischemia using L-glutamate plus L-malate as the substrate (x±s)"

Group Dose (g/kg) n V3 (nmol O/
(min·mg
protein))		 V4 (nmol O/
(min·mg
protein))		 RCR ADP/O OPR (nmol ATP/
(min·mg protein))
Sham — 6 66.15±10.99 19.07±2.43 3.45±0.19 2.62±0.19 172.19±24.89
Model — 6 63.78±6.53 19.67±2.17 3.26±0.29 2.18±0.22** 138.26±13.57*
EGB 0.15 6 68.41±15.38 20.17±4.46 3.39±0.02 2.76±0.85△ 192.04±66.01△
Low-dose effective components 0.05 6 68.12±8.17 16.96±3.39 4.06±0.62△ 2.44±0.26 165.51±20.68
Medium-dose effective components 0.15 6 75.79±7.50△ 17.74±3.13 4.37±1.13△ 2.72±0.11△ 206.02±13.71△△
High-dose effective components 0.5 6 77.98±2.19△ 19.94±2.22 3.93±0.33 2.47±0.92 191.69±87.84

Table 2

Effects of effective component group of XXM on brain mitochondrial respiratory properties in rats with chronic cerebral ischemia using succinate as the substrate (x±s)"

Group Dose (g/kg) n V3 (nmol O/
(min·mg
protein))		 V4 (nmol O/
(min·mg
protein))		 RCR ADP/O OPR (nmol ATP/
(min·mg protein))
Sham — 6 106.00±6.14 39.94±2.79 2.67±0.26 1.85±0.14 196.46±22.83
Model — 6 95.35±9.21 36.90±3.34 2.59±0.15 1.66±0.10* 156.98±10.19**
EGB 0.15 6 93.06±9.18 36.19±3.42 2.58±0.27 1.92±0.34△ 178.99±37.36△
Low-dose effective components 0.05 6 98.57±12.48 36.87±3.88 2.68±0.25 1.81±0.11 177.77±13.88
Medium-dose effective components 0.15 6 107.90±10.73 37.28±6.68 2.91±0.22 1.72±0.06△ 185.85±11.70△
High-dose effective components 0.5 6 110.32±16.19 41.35±7.36 2.68±0.17 1.56±0.19 172.60±41.14

Table 3

Effects of effective component group of XXM on mitochondria swelling degree, MMP level and ROS production in rats with chronic cerebral ischemia (x±s)"

Group Dose (g/kg) n Swelling degree
(A520 decrease)		 MMP (mV) ROS production
(fluorescence value)
Sham — 6 0.068±0.018 161.4±10.4 356.7±69.7
Model — 6 0.119±0.011** 134.7±9.9* 580.4±53.2**
EGB 0.15 6 0.092±0.030 147.4±3.5 495.5±17.4△
Low-dose effective components 0.05 6 0.072±0.021△ 150.4±5.2△ 505.3±9.4△
Medium-dose effective components 0.15 6 0.074±0.016△ 153.2±2.1△ 496.8±16.2△
High-dose effective components 0.5 6 0.077±0.020△ 154.4±3.6△ 509.8±31.9△

Figure 1

Effects of effective component group of XXM on Cyt c release from rat brain mitochondria after chronic cerebral ischemia 2-VO: chronic cerebral ischemia model group; XXM-L: low-dose effective components of XXM group; XXM-M: medium-dose effective components of XXM group; XXM-H: high-dose effective components of XXM group. XXM: Xiaoxuming Decoction. Cyt c: cytochrome c. **P<0.01, vs sham group; △P<0.05, △△P<0.01, vs model group."

Figure 2

Effects of effective component group of XXM on Bcl-2/Bax in rat brain mitochondria after chronic cerebral ischemia 2-VO: chronic cerebral ischemia model group; XXM-L: low-dose effective components of XXM group; XXM-M: Medium-dose effective components of XXM group; XXM-H: high-dose effective components of XXM group. XXM: Xiaoxuming Decoction. △P<0.05, △△P<0.01, vs model group."

[1] De la Torre JC, Aliev G . Inhibition of vascular nitric oxide after rat chronic brain hypoperfusion: spatial memory and immunocytochemical changes[J]. J Cereb Blood Flow Metab, 2005,25(6):663-672.
doi: 10.1038/sj.jcbfm.9600057
[2] Farkas E, Luiten PG . Cerebral microvascular pathology in aging and Alzheimer’s disease[J]. Prog Neurobiol, 2001,64(6):575-611.
doi: 10.1016/S0301-0082(00)00068-X pmid: 11311463
[3] Farkas E, Luiten PG, Bari F . Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases[J]. Brain Res Rev, 2007,54(1):162-180.
doi: 10.1016/j.brainresrev.2007.01.003
[4] Zhu X, Smith MA, Perry G, Aliev G . Mitochondrial failures in Alzheimer’s disease[J]. Am J Alzheimers Dis Other Demen, 2004,19(6):345-352.
doi: 10.1177/153331750401900611 pmid: 15633943
[5] Schapira AH . Mitochondrial dysfunction in neurodegenerative diseases[J]. Neurochem Res, 2008,33(12):2502-2509.
doi: 10.1007/s11064-008-9855-x
[6] Chaturvedi RK , Beal MF.Mitochondrial approaches for neuroprotection[J].Ann N Y Acad Sci, 2008, 1147: 395-412.
doi: 10.1196/annals.1427.027
[7] Kasparova S, Brezová V, Valko M, Horecký J, Mlynárik V, Liptaj T, Vancová O, Ulicná O, Dobrota D . Study of the oxidative stress in a rat model of chronic brain hypoperfusion[J]. Neurochem Int, 2005,46(8):601-611.
doi: 10.1016/j.neuint.2005.02.006 pmid: 15863238
[8] Christophe M, Nicolas S . Mitochondria: a target for neuroprotective interventions in cerebral ischemia-reperfusion[J]. Curr Pharm Des, 2006,12(6):739-757.
doi: 10.2174/138161206775474242
[9] Du GH . Overview of effective compound group in traditional Chinese medical prescription[J]. Zhong Cheng Yao, 2002,24(11):878-880.
杜冠华 . 中药复方有效成分组学研究[J]. 中成药, 2002,24(11):878-880.
[10] Wang YH, Zhang HX, Li Q, Di Y, Hu JJ, Du GH . High-throughput screening assay for groups of effective components extracted from Xiaoxuming Recipe[J]. J Chin Integr Med, 2006,4(1):64-47.
王月华, 张海霞, 李奇, 丁怡, 胡娟娟, 杜冠华 . 小续命汤有效成分组的高通量筛选研究[J]. 中西医结合学报, 2006,4(1):64-67.
[11] Li ZH, Ni KY, Du GH . Identification of the major components in the effective component group of Xiao-xu-ming decoction by high performance liquid chromatography-electrospray lionization-mass spectrometry/mass spectrometry[J]. Fen Xi Hua Xue Za Zhi, 2007,35(2):233-239.
李忠红, 倪坤仪, 杜冠华 . 高效液相色谱-质谱法鉴定中药复方小续命汤有效成分组中醇溶性成分[J]. 分析化学杂志, 2007,35(2):233-239.
[12] Li ZH, Fan XL, Cai MM, Yang ZH, Ying J, Qiang GF, Du GH . Pharmacokinetics of fangchinoline and tetrandrine in rats[J]. Zhongguo Zhong Yao Za Zhi, 2009,34(23):3110-3113.
doi: 10.3321/j.issn:1001-5302.2009.23.028
李忠红, 樊夏雷, 蔡美明, 杨志宏, 应剑, 强桂芬, 杜冠华 . 小续命汤有效成分组中防己诺林碱和粉防己碱在大鼠体内药动学研究[J]. 中国中药杂志, 2009,34(23):3110-3113.
doi: 10.3321/j.issn:1001-5302.2009.23.028
[13] Wang Y, Ding C, Du K, Xiao Y, Wu C, Zhang J, Qin H, Du G . Identification of active compounds and their metabolites by high-performance liquid chromatography/electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry from Xiao-xu-ming decoction(XXMD)[J]. Rapid Commun Mass Spectrom, 2009,23(17):2724-2732.
doi: 10.1002/rcm.v23:17
[14] Wang YH, He XL, Yang HG, Qin HL, Du GH . Effects of the active components of Chinese herbal medicine Xiaoxuming Dectction on memory behavior and brain injury in rats with chronic cerebral ischemia[J]. J Chin Integr Med, 2012,10(1):91-99.
doi: 10.3736/jcim20120114
王月华, 贺晓丽, 杨海光, 秦海林, 杜冠华 . 小续命汤有效成分组对慢性脑缺血大鼠学习记忆及病理损伤的影响[J]. 中西医结合学报, 2012,10(1):91-99.
doi: 10.3736/jcim20120114
[15] Zhang HX, Du GH, Zhang JT . Ischemic pre-conditioning preserves brain mitochondrial functions during the middle cerebral artery occlusion in rat[J]. Neurol Res, 2003,25(5):471-476.
doi: 10.1179/016164103101201878
[16] Chvez JC, Pichiule P, Boero J, Arregui A . Reduced mitochondrial respiration in mouse cerebral cortex during chronic hypoxia[J]. Neumsci Lett, 1995,193(3):169-172.
doi: 10.1016/0304-3940(95)11692-P pmid: 7478175
[17] Emaus RK, Gmnwald R, Lemastem JJ . Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties[J]. Biochim Biophys Acta, 1986,850(3):436-448.
doi: 10.1016/0005-2728(86)90112-X
[18] Bao XM, Wu CF, Lu GP . Atorvastatin attenuates homocysteine-induced apoptosis in human umbilical vein endothelial cells via inhibiting NADPH oxidase-related oxidative stress-triggered p38MAPK signaling[J]. Acta Pharmacol Sin, 2009,30(10):1392-1398.
doi: 10.1038/aps.2009.135
[19] Robertson CL, Soane L, Siegel ZT, Fiskum G . The potential role of mitochondria in pediatric traumatic brain injury[J]. Dev Neurosci, 2006,28(4-5):432-446.
doi: 10.1159/000094169
[20] Pithukpakorn M . Disorders of pyruvate metabolism and the tricarboxylic acid cycle[J]. Mol Genet Metab, 2005,85(4):243-246.
doi: 10.1007/978-3-540-28785-8_12 pmid: 16156009
[21] Robinson BH , MacKay N, Chun K, Ling M . Disorders of pyruvate carboxylase and the pyruvate dehydrogenase complex[J]. J Inherit Metab Dis, 1996,19(4):452-462.
doi: 10.1007/BF01799106 pmid: 8884569
[22] Phaneuf S, Leeuwenburgh C . Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age[J]. Am J Physiol Regul Integr Comp Physiol, 2002,282(2):R423-R430.
doi: 10.1152/ajpregu.00296.2001
[23] Adams JM, Cory S . The Bcl-2 protein family: arbiters of cell survival[J]. Science, 1998,281(5381):1322-1326.
doi: 10.1126/science.281.5381.1322
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