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Kadsura heteroclita stem ethanol extract protects against carbon tetrachloride-induced liver injury in mice via suppression of oxidative stress, inflammation, and apoptosis.
J Ethnopharmacol. 2021 Mar 01; 267:113496.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Kadsura heteroclita stem (KHS) is a well-known hepatoprotective Tujia ethnomedicine (folk named Xuetong), has long been used for the prevention and treatment of hepatitis and liver diseases.

AIM OF THE STUDY

To explore the protective effects of KHS against carbon tetrachloride (CCl4)-induced liver injury and the underlying mechanism, particularly antioxidative, anti-inflammatory, and anti-apoptotic potentials.

MATERIALS AND METHODS

The acute toxicity of KHS was measured by the method of maximum tolerated dose (MTD). Liver injury in mice was induced by intraperitoneal injection of 25% carbon tetrachloride (olive oil solubilization) 2 times every week. After modeling, mice in KHS groups were treated with KHS at 100, 200, 400 mg/kg/d, mice in positive control group were treated with bifendate (30 mg/kg/d), and mice in normal and model groups were given ultrapure water. After 4 weeks of treatment, blood of mice was taken from the orbital venous plexus before mice euthanized, the liver, spleen, and thymus of mice were weighed by dissecting the abdominal cavity after mice euthanized. Moreover, the liver of mice was selected for histological examination. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in mice serum were measured using the automatic biochemical analyzer. The levels of superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione peroxidase (GPX-2), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), Bcl-2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), Caspase-3, and Caspase-8 in mice liver were measured by Elisa kits. Furthermore, the protein expression of Bcl-2 and Bax in mice liver tissue was detected by Western blot.

RESULTS

The MTD of KHS was determined to be 26 g/kg in both sexes of mice. Treatment with KHS dose-dependently protected the liver and other main organs against CCl4-induced liver injury in mice. The ALT and AST levels in mice liver were significantly reduced after treatment with KHS at the dose of 100, 200, and 400 mg/kg. In addition, the liver histopathological analyses revealed that KHS markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl4. Further assay indicated that KHS significantly suppressed the production of MDA and MPO, while markedly increased the level of SOD and GPx-2. The TNF-α and IL-6 level in mice liver tissue were decreased by KHS, whereas the IL-10 level was increased. KHS also inhibited hepatocyte apoptosis by significantly reducing the expression of Bax, Caspase-3, Caspase-8, as well as increasing the expression of Bcl-2. Besides, the Western blot results strongly demonstrated that KHS inhibited hepatocyte apoptosis, as evidenced by reducing the expression of Bax protein and increasing the expression of Bcl-2 protein in liver injury tissues.

CONCLUSIONS

This research firstly clarified that KHS has a significant protective effect against CCl4-induced liver injury, which might be closely related to alleviating oxidative stress, reducing inflammatory response, and inhibiting hepatocyte apoptosis.

Authors+Show Affiliations

TCM and Ethnomedicine Innovation & Development International Laboratory, And Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China.TCM and Ethnomedicine Innovation & Development International Laboratory, And Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China.TCM and Ethnomedicine Innovation & Development International Laboratory, And Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China.TCM and Ethnomedicine Innovation & Development International Laboratory, And Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China.TCM and Ethnomedicine Innovation & Development International Laboratory, And Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China. Electronic address: zengrong42@126.com.TCM and Ethnomedicine Innovation & Development International Laboratory, And Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, PR China. Electronic address: wangwei402@hotmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33091494

Citation

Yu, Huang-He, et al. "Kadsura Heteroclita Stem Ethanol Extract Protects Against Carbon Tetrachloride-induced Liver Injury in Mice Via Suppression of Oxidative Stress, Inflammation, and Apoptosis." Journal of Ethnopharmacology, vol. 267, 2021, p. 113496.
Yu HH, Qiu YX, Li B, et al. Kadsura heteroclita stem ethanol extract protects against carbon tetrachloride-induced liver injury in mice via suppression of oxidative stress, inflammation, and apoptosis. J Ethnopharmacol. 2021;267:113496.
Yu, H. H., Qiu, Y. X., Li, B., Peng, C. Y., Zeng, R., & Wang, W. (2021). Kadsura heteroclita stem ethanol extract protects against carbon tetrachloride-induced liver injury in mice via suppression of oxidative stress, inflammation, and apoptosis. Journal of Ethnopharmacology, 267, 113496. https://doi.org/10.1016/j.jep.2020.113496
Yu HH, et al. Kadsura Heteroclita Stem Ethanol Extract Protects Against Carbon Tetrachloride-induced Liver Injury in Mice Via Suppression of Oxidative Stress, Inflammation, and Apoptosis. J Ethnopharmacol. 2021 Mar 1;267:113496. PubMed PMID: 33091494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kadsura heteroclita stem ethanol extract protects against carbon tetrachloride-induced liver injury in mice via suppression of oxidative stress, inflammation, and apoptosis. AU - Yu,Huang-He, AU - Qiu,Yi-Xing, AU - Li,Bin, AU - Peng,Cai-Yun, AU - Zeng,Rong, AU - Wang,Wei, Y1 - 2020/10/19/ PY - 2020/02/14/received PY - 2020/10/12/revised PY - 2020/10/15/accepted PY - 2020/10/23/pubmed PY - 2021/3/3/medline PY - 2020/10/22/entrez KW - Hepatocyte apoptosis KW - Inflammatory cytokines KW - Kadsura heteroclite stem KW - Liver injury KW - Oxidative stress KW - Tujia ethnomedicine KW - Xuetong SP - 113496 EP - 113496 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 267 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Kadsura heteroclita stem (KHS) is a well-known hepatoprotective Tujia ethnomedicine (folk named Xuetong), has long been used for the prevention and treatment of hepatitis and liver diseases. AIM OF THE STUDY: To explore the protective effects of KHS against carbon tetrachloride (CCl4)-induced liver injury and the underlying mechanism, particularly antioxidative, anti-inflammatory, and anti-apoptotic potentials. MATERIALS AND METHODS: The acute toxicity of KHS was measured by the method of maximum tolerated dose (MTD). Liver injury in mice was induced by intraperitoneal injection of 25% carbon tetrachloride (olive oil solubilization) 2 times every week. After modeling, mice in KHS groups were treated with KHS at 100, 200, 400 mg/kg/d, mice in positive control group were treated with bifendate (30 mg/kg/d), and mice in normal and model groups were given ultrapure water. After 4 weeks of treatment, blood of mice was taken from the orbital venous plexus before mice euthanized, the liver, spleen, and thymus of mice were weighed by dissecting the abdominal cavity after mice euthanized. Moreover, the liver of mice was selected for histological examination. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in mice serum were measured using the automatic biochemical analyzer. The levels of superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione peroxidase (GPX-2), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), Bcl-2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), Caspase-3, and Caspase-8 in mice liver were measured by Elisa kits. Furthermore, the protein expression of Bcl-2 and Bax in mice liver tissue was detected by Western blot. RESULTS: The MTD of KHS was determined to be 26 g/kg in both sexes of mice. Treatment with KHS dose-dependently protected the liver and other main organs against CCl4-induced liver injury in mice. The ALT and AST levels in mice liver were significantly reduced after treatment with KHS at the dose of 100, 200, and 400 mg/kg. In addition, the liver histopathological analyses revealed that KHS markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl4. Further assay indicated that KHS significantly suppressed the production of MDA and MPO, while markedly increased the level of SOD and GPx-2. The TNF-α and IL-6 level in mice liver tissue were decreased by KHS, whereas the IL-10 level was increased. KHS also inhibited hepatocyte apoptosis by significantly reducing the expression of Bax, Caspase-3, Caspase-8, as well as increasing the expression of Bcl-2. Besides, the Western blot results strongly demonstrated that KHS inhibited hepatocyte apoptosis, as evidenced by reducing the expression of Bax protein and increasing the expression of Bcl-2 protein in liver injury tissues. CONCLUSIONS: This research firstly clarified that KHS has a significant protective effect against CCl4-induced liver injury, which might be closely related to alleviating oxidative stress, reducing inflammatory response, and inhibiting hepatocyte apoptosis. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/33091494/Kadsura_heteroclita_stem_ethanol_extract_protects_against_carbon_tetrachloride_induced_liver_injury_in_mice_via_suppression_of_oxidative_stress_inflammation_and_apoptosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(20)33382-1 DB - PRIME DP - Unbound Medicine ER -