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

Abstract

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.

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

“…Moreover, as we have previously reported, the strong in vitro anticancer potential of 50% ethanol-based (BLE) crude root extract from B. lycium Royle against HepG2 cells (IC 50 = 47 µg/mL) and berberine was detected by HPLC as a major bioactive compound [11]. We speculated whether this BLE extract is also effective against hepatocellular carcinoma in vivo, in comparison with its activity with frequently reported [11,12,23] isoquinoline berberine. We continued our study to evaluate the difference in the strong anti-cancer potential of BLE and berberine in DEN + CCl 4 -induced liver cancer in Balb-c mice, for the first time according to our knowledge.…”

“…The plant was identified by Dr. Xioa Haifang from the Department of Agriculture Engineering and Food Science, Shandong University of Technology, China. The extract was prepared exactly the same as previously prepared by us for in vitro experiments [11].…”

“…There is much evidence supporting the consumption of plants [18], as the crude plant extract contains a cocktail of various phytometabolites exerting a strong anti-cancer effect, as compared to isolated phytochemicals [19][20][21][22]. Moreover, as we have previously reported, the strong in vitro anticancer potential of 50% ethanol-based (BLE) crude root extract from B. lycium Royle against HepG2 cells (IC 50 = 47 µg/mL) and berberine was detected by HPLC as a major bioactive compound [11]. We speculated whether this BLE extract is also effective against hepatocellular carcinoma in vivo, in comparison with its activity with frequently reported [11,12,23] isoquinoline berberine.…”

“…B. lycium Royle is a medium-sized (2.7-3.6 m height) green shrub that belongs to the family Berberidaceae [11]. It is abundantly distributed in Asia, Europe, and America.…”

Reproductive Biology and Pollination Ecology of Berberis lycium Royle: A Highly Valued Shrub of Immense Medicinal Significance

“…which signifies its potential role in the formulation of antibacterial, antifungal, antidiabetic and cardio-protective drugs [ 7 , 8 ]. Active constituents include berberine [ 9 , 10 ], an isoquinoline alkaloid which is widely known for its activity against severe diarrhea [ 11 ], cholera [ 12 ], latent malaria and amoebiasis [ 12 ]. Owing to its wide spectrum of medicinal significance this plant is being exploited at an alarming rate.…”