Promising Anti-Hepatitis C Virus Compounds from Natural Reseurcees

Hepatitis C virus (HCV) infection is a major worldwide problem, which involves approximately 170 million people. High morbidity of patients is caused by chronic infection, which leads to liver cirrhosis, hepatocellular carcinoma and other HCV-related diseases. The sustained virological response (SVR) has been markedly improved to be >90% by the current standard interferon (IFN)-free treatment regimens with a combination of direct-acting antiviral agents (DAAs) targeting the viral NS3 protease, NS5A multi-function protein and NS5B RNA-dependent RNA polymerase, compared with 50–70% of SVR rates achieved by the previous standard IFN-based treatment regimens with or without an NS3 protease inhibitor. However, the emergence of DAA-resistant HCV strains and the limited access to the DAAs due to their high cost could be major concerns. Also, the long-term prognosis of patients treated with DAAs, such as the possible development of hepatocellular carcinoma, still needs to be further evaluated. Natural resources are considered to be good candidates to develop anti-HCV agents. Here, we summarize anti-HCV compounds obtained from natural resources, including medicinal plant extracts, their isolated compounds and some of their derivatives that possess high antiviral potency against HC

Aktivitas Sitotoksisitas Ekstrak Metanol Daun Sirsak (Annona muricata L.) terhadap Karsinoma Hepatoseluler Strain HUH7IT-1 Cell Line

ABSTRAKLatar Belakang: Karsinoma hepatoseluler (HCC) merupakan tumor ganas hati primer dengan prognosis pada umumnya dapat menyebabkan kematian. Studi awal penelitian antiviral hepatitis C pada tumbuhan Sirsak (Annona muricata L.) pada konsentrasi 20 μg/mL memperlihatkan toksisitas yang sangat tinggi terhadap Huh7it-1 cell line, yang diindikasi memiliki potensi anti kanker terhadap sel hati, sehingga penelitian ini bertujuan menguji beberapa konsentrasi lebih rendah pada ekstrak metanol daun Annona muricata L. (EMDAM) terhadap Karsinoma Hepatoseluler strain Huh7it-1 cell line.Metode: Sel diuji dengan konsentrasi 20, 10, 5, 2.5, 1.25, 0.6, 0.3 μg/mL selama 48 jam. Sitotoksisitas EMDAM terhadap Huh7it-1 dilihat dengan mikrokop inverted dan selanjutnya diukur dengan metode MTT [3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium].Hasil: Hasil uji menunjukkan sel memperlihatkan bentuk tidak monolayer pada mikroskop inverted dengan sitotoksisitas hingga konsentrasi terendah pada 0.3 μg/mL mencapai 84,7%, sehingga konsentrasi 50% Sitotoksisitas (CC50) < 0.3 μg/mL.Simpulan: Hasil uji mengindikasi bahwa EMDAM memiliki potential terhadap aktivitas anti kanker hati. Studi lebih lanjut diperlukan untuk purifikasi untuk senyawa aktif sebagai antikanker atau target mekanisme terhadap aktivitas anti kanker hati.Kata kunci: Karsinoma Hepatoseluler, Huh7it-1, Sitotoksisitas, Annona muricataABSTRACTBackground: Hepatocellular carcinoma (HCC) is a malignant tumor of liver cells with prognosis can cause death within 2-3 months. Previous studies of Annona muricata L. on anti-HCV studies at concentrations of 20 μg / mL showed very high toxicity to Huh7it-1 cell line, it was indicated to have anti-cancer potential of liver cells, so this study tested the potency of anticancer activity extract methanol leaf Annona muricata L. (EMDAM) against Hepatocellular Carcinoma Huh7it-1 strain cell line with low dose.Methods: Cells were tested with concentrations of 20, 10, 5, 2.5, 1.25, 0.6, 0.3 μg / mL for 48 hours. The EMDAM cytotoxicity of Huh7it-1 was seen with an inverted microcomputer and then measured with MTT assay [3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium].Results: The results showed that the cells presented non-monolayer form in an inverted microscope with cytotoxicity until the lowest concentration of 0.3 μg / mL reached 84.7%, thus concentrating 50% cytotoxicity (CC50) <0.3 μg / mL.Conclusion: The results indicate that EMDAM has the potential for anti-liver cancer activity. Further studies are needed for purification for active compounds as anticancer or target mechanisms against anti-liver cancer activity.Keywords: Hepatocellular carcinoma, Huh7it-1, Cytotoxicity, Annona muricat

Anti-viral activity of Phyllanthus niruri against hepatitis C virus

Hepatitis C virus (HCV) infection is a global problem that causes liver disease and hepatocellular carcinoma. Although the current standard treatment provided a significant improvement on response rate with sustain virology response more than 90%, however, the high cost was remaining limited access to this therapy, resistance emergence and serious side effects which provide the necessities to find the new anti-HCV agents. The current study, we evaluated the ethanol extract of Phyllanthus niruri for its anti-HCV activities. Anti-HCV activity was determined by in vitro culture cells of Huh 7it. Anti-HCV activity of P. niruri extract revealed strong inhibition against HCV with IC50 values of 4.14 µg/mL and yield stronger activity in the entry step of the HCV life cycle. Moreover, the P. niruri extract enhanced anti-HCV activity of simeprevir (NS3 protease inhibitor) with increase the activity up to 4-fold compared to a single treatment of simeprevir. Docking analysis was performed to predict the interaction phyllanthin and hypophyllantin, known compounds of P. niruri against HCV receptor. Both of phyllantin and hypophyllantin were mediated a strong interaction with 4GAG, a protein that involved in entry step of HCV. These results suggested that the ethanol extract of P. niruri may be good candidates for the development of anti-HCV drugs