Protective Mechanism of Andrographolide against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Abstract

The aim of this study was to investigate the protective effects of andrographolide (AP), a bioactive component isolated from Andrographis paniculata, on carbon tetrachloride (CCl(4))-induced liver injury as well as the possible mechanisms involved in this protection in mice. Acute liver injury was induced by CCl(4) intoxication in mice. Serum biological analysis, lipid peroxides and antioxidant estimation, histopathological studies, reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay were carried out. CCl(4) treatment resulted in severe hepatic injury, as evidenced by significant elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and typical histopathological changes, such as hepatocyte necrosis. Additionally, CCl(4) administration led to oxidative stress in mice, as indicated by a remarkable increase in the hepatic malondialdehyde (MDA) level, together with a significant decrease in liver reduced glutathione (GSH) content. However, CCl(4)-induced hepatotoxicity was significantly attenuated by pretreatment with AP, as demonstrated by significant reduction of serum ALT, AST levels and hepatic MDA activity, along with a remarkable increase in hepatic GSH content. Histopathological changes induced by CCl(4) were also ameliorated by AP pretreatment. The marked increase of tumor necrosis factor-α (TNF-α) induced by CCl(4) was attenuated by AP, and the dramatic elevation of heme oxygenase-1 (HO-1) at transcriptional and protein levels was augmented following AP pretreatment. AP can effectively prevent liver injury induced by CCl(4), which may be due to inhibition of oxidative stress and inflammatory responses.

Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis

“…The use of andrographolide as shown in this paper is promising because andrographolide has been used alone or as a botanical extract for the treatment of colds, fever, laryngitis and other infections with no or minimal side effects. Andrographolide not only regulates inflammation, but also suppresses the fibrotic pathology observed in chronic liver and kidney diseases [14-16]. Other advantages include the low cost of the drug, or a botanical extract highly enriched in andrographolide, and the fact that it can be given orally in capsules, thus providing hope for future therapeutic options of an oral formulation with no undesired side effects for patients with muscular disorders.…”

“…It has been reported to be particularly efficient at regulating immune responses [12,13] and possesses anti-inflammatory properties by reducing the generation of reactive oxygen species in human neutrophils [11]. Andrographolide not only regulates inflammation, but is also effective against the fibrotic pathology observed in chronic liver and kidney diseases [14-16]. Mechanistically, andrographolide forms a covalent adduct with NF-κB, thus blocking the binding of NF-κB to nuclear proteins [17].…”

Anti-tumor Initiating Potential of Andrographolide in 7,12-dimethylbenz[a]anthracene Induced Hamster Buccal Pouch Carcinogenesis

“…Oral administration of andrographolide at a dose of 50 mg/kg bw to hamsters treated with DMBA, not only completely prevented the tumor formation but also significantly reduced the severity of precancerous lesions such as hyperplasia and dysplasia. Andrographolide protected normal cells against chemical induced toxicity (Ye et al, 2011). Andrographolide induced G0/G1 cell cycle arrest in various types of cancer cells (Jada et al, 2008).…”

Study on the effects of blueberry treatment on histone acetylation modification of CCl₄-induced liver disease in rats

“…The CCl 4 -induced liver injury model has been widely used in the study of hepatic necrosis, hepatic fibrosis and cirrhosis etiology, histology research and liver-protecting drug development, and medicinal plant extract assessments (Lee et al, 2007;Ye et al, 2011). Continuous CCl 4 treatment increases liver cell damage, and results in pathological processes, such as lipid peroxidation, cytokine release, and calcium imbalance, in hepatic cells that had undergone apoptosis, regeneration, and gradually returned to normal.…”