Isoniazid induced hepatotoxicity and its amelioration with ethanolic extract of stem bark of Berberis lycium Royale in mice

Rafiq, Saima; Ajmal, Khalida; Afzal, Ayesha

doi:10.18203/2319-2003.ijbcp20173270

Cited by 3 publications

(3 citation statements)

References 14 publications

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“…However, BLE at a low dose (60 mg/kg) was not as effective compared to a high dose (120 mg/kg). This study agrees well with the previous findings on the stem bark-based ethanol extract of Berberis Lycium Royle, where a high dose (200 mg/kg) of the extract was good at reducing hepatocyte ballooning and other signs of inflammation induced by the isoniazid drug [15]. Further, we found that berberine at both a low and high dose was much more effective at reducing the LFT markers of liver injury, along with AFP levels in the blood serum (Table 1).…”

Section: Establishment and Amelioration Of Hepatocarcinomasupporting

confidence: 93%

“…The roots of B. lycium Royle from the Himalayan region have a higher content of berberine, as compared to the stem and other parts of the plant [14]. B. lycium Royle stem bark-based ethanol extract effectively reduced LFT serum markers at a high dose of 200 mg/kg, as compared to 150 mg/kg of extract in isoniazid-induced liver toxicity in mice [15]. The antitumor potential of berberine has already been proven against brain tumor cells [16], and doxorubicin-induced liver toxicity in mice [17].…”

Section: Introductionmentioning

confidence: 99%

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Comparative Study on the Role of Berberine and Berberis lycium Royle Roots Extract against the Biochemical Markers and Cyclin D1 Expression in HCC Animal Model

Mustafa

Mohamed

et al. 2021

Applied Sciences

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Diethylamine nitrosamine (DEN), as an initiator of liver tumor, and carbon tetrachloride (CCl4), as a tumor promoter, have been used to study the molecular events of liver cancer in animal models. Recently, our in vitro study reported BLE (Berberis lycium Royle ethanol extract) as the most effective agent against liver cancer, thus we continued our study in vivo to assess the hepatoprotective effect of BLE and its most active alkaloid, berberine, in albino mice (70 male). Moreover, we investigated the biochemical/immunohistochemical effects of a single alkaloid versus the effect of Berberis extract in mice liver. Hepatic cancer was induced in mice by a single intraperitoneal injection with DEN (100 mg/kg b.wt), followed by biweekly injections of CCl4 (0.5 mL/kg) for 30 days. The development of liver cancer was assessed after 60 days of DEN injection by measuring the elevated level of the serum tumor marker alpha-fetoprotein (AFP) and liver function test (ALT, AST, ALP, and BUN) markers. After the confirmation of liver cancer development, the BLE extract and berberine were fed to mice for 90 days and the serum biomarkers for liver injury (LFTs and AFP) were measured again. Overall, berberine (120 mg/kg b.wt) proved to be a stronger agent in reducing the symptoms of HCC in mice, as compared with BLE. Histopathological analysis agreed well with the biochemical observations. Immunohistochemistry analysis suggested significant suppression of the quantitative expression of the key oncogene cyclin D1 at low (60 mg/kg) and high (120 mg/kg) doses of berberine. These findings implicate the amelioration of hepatocarcinoma by berberine more prominently in mice, by suppression of cyclin-dependent kinase activator (CD1) expression, reducing LFTs, as well as AFP, in the serum. Thus, our findings are novel, as berberine may help in controlling the perturbation in CD1 associated with aggressive forms of HCC. However, future studies should be directed at finding out whether berberine has any effect on inhibitors (p27 and CDKI) of cyclin-dependent kinase too.

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Section: Establishment and Amelioration Of Hepatocarcinomasupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Comparative Study on the Role of Berberine and Berberis lycium Royle Roots Extract against the Biochemical Markers and Cyclin D1 Expression in HCC Animal Model

Mustafa

Mohamed

et al. 2021

Applied Sciences

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“…This result shows that our extract is more toxic to the liver cancer cell line as compared to normal cells. It is consistent with the hepatoprotective effect of berberine from B. aristata used in a study on mice which increased the life span and other hepatoprotective markers of the survived mice [ 27 ], and another study used an ethanolic extract of stem bark of B. Lycium Royle on mice and it conferred hepatoprotective effects [ 28 ].…”

Section: Discussionsupporting

confidence: 78%

In Vitro Anticancer Potential of Berberis lycium Royle Extracts against Human Hepatocarcinoma (HepG2) Cells

Mustafa

Mohamed

Shah

et al. 2020

BioMed Research International

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Human liver cancer has emerged as a serious health concern in the world, associated with poorly available therapies. The Berberis genus contains vital medicinal plants with miraculous healing properties and a wide range of bioactivities. In this study, different crude extracts of B. lycium Royle were prepared and screened against Human Hepatocarcinoma (HepG2) cell lines. The water/ethanolic extract of B. lycium Royle (BLE) exhibited significant antiproliferative activity against the HepG2 cancer cell line with an IC50 value of 47 μg/mL. The extract decreased the clonogenic potential of HepG2 cells in a dose-dependent manner. It induced apoptotic cell death in HepG2 cells that were confirmed by cytometric analysis and microscopic examination of cellular morphology through DAPI-stained cells. Biochemical evidence of apoptosis came from elevating the intracellular ROS level that was accompanied by the loss of mitochondrial membrane potential. The mechanism of apoptosis was further confirmed by gene expression analysis using RT-qPCR that revealed the decline in Bcl-2 independent of p53 mRNA and a rise in CDK1 while downregulating CDK5, CDK9, and CDK10 mRNA levels at 48 h of BLE treatment. The most active fraction was subjected to HPLC which indicated the presence of berberine (48 μg/mL) and benzoic acid (15.8 μg/mL) as major compounds in BLE and a trace amount of luteolin, rutin, and gallic acid. Our study highlighted the importance of the most active BLE extract as an excellent source of nutraceuticals against Human Hepatocarcinoma that can serve as an herbal natural cure against liver cancer.

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Hepatoprotective activity of Picrorhiza kurroa and Berberis lycium is mediated by inhibition of COX-2 and TGF-β expression in lantadenes-induced sub-chronic toxicity in guinea pigs

et al. 2022

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Isoniazid induced hepatotoxicity and its amelioration with ethanolic extract of stem bark of Berberis lycium Royale in mice

Cited by 3 publications

References 14 publications

Comparative Study on the Role of Berberine and Berberis lycium Royle Roots Extract against the Biochemical Markers and Cyclin D1 Expression in HCC Animal Model

Comparative Study on the Role of Berberine and Berberis lycium Royle Roots Extract against the Biochemical Markers and Cyclin D1 Expression in HCC Animal Model

In Vitro Anticancer Potential of Berberis lycium Royle Extracts against Human Hepatocarcinoma (HepG2) Cells

Hepatoprotective activity of Picrorhiza kurroa and Berberis lycium is mediated by inhibition of COX-2 and TGF-β expression in lantadenes-induced sub-chronic toxicity in guinea pigs

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