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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."

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