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Safety evaluation of chinese medicine injections with a cell imaging-based multiparametric assay revealed a critical involvement of mitochondrial function in hepatotoxicity.

Wang M, Liu CX, Dong RR, He S, Liu TT, Zhao TC, Wang ZL, Shen XY, Zhang BL, Gao XM, Zhu Y - Evid Based Complement Alternat Med (2015)

Bottom Line: The safety of herbal medicine products has been a widespread concern due to their complex chemical nature and lack of proper evaluation methods.Our results suggested that the reported hepatotoxicity by one of the drugs, Fufangkushen injection, could be attributed at least in part to the interference of mitochondrial function in human HepG2 cells by some of its constituents.This method should be useful for both preclinical screen in a drug discovery program and postclinical evaluation of herbal medicine preparations.

View Article: PubMed Central - PubMed

Affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China ; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China.

ABSTRACT
The safety of herbal medicine products has been a widespread concern due to their complex chemical nature and lack of proper evaluation methods. We have adapted a sensitive and reproducible multiparametric cell-based high-content analysis assay to evaluate the hepatic-safety of four Chinese medicine injections and validated it with classical animal-based toxicity assays. Our results suggested that the reported hepatotoxicity by one of the drugs, Fufangkushen injection, could be attributed at least in part to the interference of mitochondrial function in human HepG2 cells by some of its constituents. This method should be useful for both preclinical screen in a drug discovery program and postclinical evaluation of herbal medicine preparations.

No MeSH data available.


Related in: MedlinePlus

Serum AST (a), ALT (b), TG (c), and ALP (d) profile of Danhong injection, Xiangdan injection, Mailuoning injection, and Fufangkushen injection after 4-week treatment to rats. Data are given as mean ± SEM for each point of at least four separate rats for each point, *P < 0.05, **P < 0.01.
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fig6: Serum AST (a), ALT (b), TG (c), and ALP (d) profile of Danhong injection, Xiangdan injection, Mailuoning injection, and Fufangkushen injection after 4-week treatment to rats. Data are given as mean ± SEM for each point of at least four separate rats for each point, *P < 0.05, **P < 0.01.

Mentions: To further assess the antioxidant effect of the four injections on liver function in vivo, SOD, MDA, CAT, and GSH were measured. As shown in Figure 6, the SOD, MDA, CAT, and GSH activities of 4 TCM injections did not show significant change except for the high-dose group of FFKSI. The CAT activity of FFKSI high-dose group (41.61 ± 3.11, P < 0.01) decreased 40.4% compared to the blank; meanwhile the MDA activity (1.57 ± 0.18, P < 0.01) increased significantly by 70.0%. It indicated that the high dose of FFKSI increased reactive oxygen species (ROS) and decreased the antioxidant capacity of liver tissue that was in accordance with the decrease of MMP found in HCA assay established. The SOD value of XDI high-dose group was lower than all other groups; the MDA level was also higher than other groups except for FFKSI high-dose group without significant difference. It indicated that long-term use of XDI at a high concentration may also cause certain oxidative damage on liver (Figure 7).


Safety evaluation of chinese medicine injections with a cell imaging-based multiparametric assay revealed a critical involvement of mitochondrial function in hepatotoxicity.

Wang M, Liu CX, Dong RR, He S, Liu TT, Zhao TC, Wang ZL, Shen XY, Zhang BL, Gao XM, Zhu Y - Evid Based Complement Alternat Med (2015)

Serum AST (a), ALT (b), TG (c), and ALP (d) profile of Danhong injection, Xiangdan injection, Mailuoning injection, and Fufangkushen injection after 4-week treatment to rats. Data are given as mean ± SEM for each point of at least four separate rats for each point, *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352439&req=5

fig6: Serum AST (a), ALT (b), TG (c), and ALP (d) profile of Danhong injection, Xiangdan injection, Mailuoning injection, and Fufangkushen injection after 4-week treatment to rats. Data are given as mean ± SEM for each point of at least four separate rats for each point, *P < 0.05, **P < 0.01.
Mentions: To further assess the antioxidant effect of the four injections on liver function in vivo, SOD, MDA, CAT, and GSH were measured. As shown in Figure 6, the SOD, MDA, CAT, and GSH activities of 4 TCM injections did not show significant change except for the high-dose group of FFKSI. The CAT activity of FFKSI high-dose group (41.61 ± 3.11, P < 0.01) decreased 40.4% compared to the blank; meanwhile the MDA activity (1.57 ± 0.18, P < 0.01) increased significantly by 70.0%. It indicated that the high dose of FFKSI increased reactive oxygen species (ROS) and decreased the antioxidant capacity of liver tissue that was in accordance with the decrease of MMP found in HCA assay established. The SOD value of XDI high-dose group was lower than all other groups; the MDA level was also higher than other groups except for FFKSI high-dose group without significant difference. It indicated that long-term use of XDI at a high concentration may also cause certain oxidative damage on liver (Figure 7).

Bottom Line: The safety of herbal medicine products has been a widespread concern due to their complex chemical nature and lack of proper evaluation methods.Our results suggested that the reported hepatotoxicity by one of the drugs, Fufangkushen injection, could be attributed at least in part to the interference of mitochondrial function in human HepG2 cells by some of its constituents.This method should be useful for both preclinical screen in a drug discovery program and postclinical evaluation of herbal medicine preparations.

View Article: PubMed Central - PubMed

Affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China ; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China.

ABSTRACT
The safety of herbal medicine products has been a widespread concern due to their complex chemical nature and lack of proper evaluation methods. We have adapted a sensitive and reproducible multiparametric cell-based high-content analysis assay to evaluate the hepatic-safety of four Chinese medicine injections and validated it with classical animal-based toxicity assays. Our results suggested that the reported hepatotoxicity by one of the drugs, Fufangkushen injection, could be attributed at least in part to the interference of mitochondrial function in human HepG2 cells by some of its constituents. This method should be useful for both preclinical screen in a drug discovery program and postclinical evaluation of herbal medicine preparations.

No MeSH data available.


Related in: MedlinePlus