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Anti-angiogenic and anti-proliferative effects of Benja-ummarit extract in rats with hepatocellular carcinoma.

ABSTRACT: The herbal extract Benja-ummarit (BU) is a traditional Thai medicine with a putative cancer-suppressing effect. However, this effect has only been tested in vitro in human hepatocarcinoma cell lines. The present study determined the efficacy of a BU extract to treat hepatocellular carcinoma (HCC) in rats in vivo and established its anti-angiogenic and anti-proliferative properties. The BU extract was prepared in 95% ethanol and its composition determined using liquid chromatography-mass spectrometry. HCC was induced in Wistar rats by an injection of diethylnitrosamine (DEN), followed 2 weeks later by injections of thioacetamide (TAA) thrice weekly for 4 weeks. Following 2 months, the DEN-TAA-treated rats were divided into 6 groups that were treated orally for another 2 months with: i) No treatment; ii) vehicle; iii) 30 mg/kg sorafenib (SF); iv) 1 mg/kg BU; v) 10 mg/kg BU; or vi) 50 mg/kg BU. Liver samples were collected for gross morphological, histological, reverse transcription-quantitative PCR and western blot analyses, and serum samples were collected for liver function tests. The size and number of the cancer nodules were reduced ~10-fold in BU-treated HCC groups and ~14-fold in the SF-treated group compared with the HCC group. Furthermore, the serum parameters of liver damage were lower in BU-compared with SF-treated rats. These results indicate that while each of these formulations strongly reduce HCC expansion, BU extract results in less liver damage. Vascular endothelial growth factor expression was reduced significantly in the BU-and SF-treated HCC groups compared with the HCC group (P<0.05). BU extract antagonizes HCC growth in vivo potently through inhibiting tumor angiogenesis. BU, therefore, qualifies as a promising medical herb requiring further evaluation as a treatment of HCC.

SUBMITTER: Kaewnoonual N

PROVIDER: S-EPMC7006111 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Anti-angiogenic and anti-proliferative effects of Benja-ummarit extract in rats with hepatocellular carcinoma.

Kaewnoonual Nattpawit N Itharat Arunporn A Pongsawat Suriya S Nilbu-Nga Cheng C Kerdput Vichununt V Pradidarcheep Wisuit W

Biomedical reports 20200116 3

The herbal extract Benja-ummarit (BU) is a traditional Thai medicine with a putative cancer-suppressing effect. However, this effect has only been tested <i>in vitro</i> in human hepatocarcinoma cell lines. The present study determined the efficacy of a BU extract to treat hepatocellular carcinoma (HCC) in rats <i>in vivo</i> and established its anti-angiogenic and anti-proliferative properties. The BU extract was prepared in 95% ethanol and its composition determined using liquid chromatography ...[more]

PMID: 32042419

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Project description:BackgroundSchistosomiasis is one of the most prevalent helminthic infections worldwide. Praziquantel (PZQ) resistance poses a possible danger to the disease's ability to be controlled. Little is known about the role of Ziziphus spina-christi leaf extract (ZLE) in the treatment of hepatic schistosomiasis. However, no study has explored ZLE's anti-angiogenic and anti-proliferative activity as a possible mechanism for reducing hepatic injury in this context. Therefore, this study aimed to evaluate the therapeutic potential of ZLE as an anti-angiogenic, and anti-proliferative agent in hamsters infected with S. mansoni.MethodsFifty hamsters were used and divided into 5 groups (10 hamsters each); noninfected untreated (controls), noninfected treated with ZLE, infected untreated, infected treated with PZQ- and infected treated with ZLE. Anti-angiogenic and anti-fibrotic effects of the drugs were assessed pathologically through the immunohistochemical expression of VEGF, Ki-67, and TGF β1 in liver sections. Some oxidative stress parameters were measured in hepatic homogenates (NO, GSH, GST, and SOD), and serum liver enzymes were also assessed.ResultsA significant decrease in worm burden, granuloma size, granuloma area, and numbers in the ZLE- and PZQ-treated groups compared to the infected untreated group, and the decrease in granulomas number and tissue egg load was significantly lower in PZQ treated group compared to ZLE treated group (p<0.05). ZLE exhibited significant anti-angiogenic and anti-fibrotic effects on granulomas, illustrated by significantly lower expression of VEGF and TGF-β1 than infected untreated and PZQ-treated groups. ZLE exhibits antiproliferative activity evidenced by a significant reduction of positive Ki-67 hepatocytes percentage compared to the infected untreated group. Moreover, ZLE exhibits potent antioxidant effects evidenced by a significantly lowered NO and conservation of hepatic GSH, GST, and SOD in hepatic homogenates compared to infected untreated and PZQ-treated groups (p<0.05).ConclusionOur results point to ZLE as a promising hepatoprotective therapeutic tool in the treatment of schistosome hepatic fibrosis as it has anti-angiogenic, anti-proliferative, anti-fibrotic, and antioxidant effects in hamsters infected with S. mansoni, providing scientific support for its use in conventional medicine.

Dataset Information

Anti-angiogenic and anti-proliferative effects of Benja-ummarit extract in rats with hepatocellular carcinoma.

Publications

Anti-angiogenic and anti-proliferative effects of Benja-ummarit extract in rats with hepatocellular carcinoma.

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