Potential Drug Targets Against Hepatitis B Virus Based on Both Virus and Host Factors.

BACKGROUND: Hepatitis B is a very harmful and epidemic disease caused by hepatitis B virus (HBV). Although an effective anti-HBV vaccine is available, chronic infection poses still a huge health burden in the whole world. The present anti-HBV drugs including nucleoside analogues and interferonalpha have their limitations without exception. There is no effective drug and therapeutic method that can really and truly cure hepatitis B so far. The variability of HBV genome results in that a significant number of patients develop drug resistance during the long-term use of anti-HBV drugs. Hence, it is urgently needed to discover novel targets and develop new drugs against hepatitis B. OBJECTIVE: The review aims to provide the theory support for designing of the anti-HBV innovative drugs by offering a summary of the current situation of antiviral potential targets. RESULTS AND CONCLUSION: Since HBV is obligate intracellular parasite, and as such it depends on host cellular components and functions to replicate itself. The targeting both virus and host might be a novel therapeutic option for hepatitis B. Accordingly, we analyse the advances in the study of the potential drug targets for anti-HBV infection, focusing on targeting virus genome, on targeting host cellular functions and on targeting virus-host proteins interactions, respectively. Meanwhile, the immune targets against chronic hepatitis B are also emphasized. In short, the review provides a summary of antiviral therapeutic strategies to target virus factors, host factors and immune factors for future designing of the innovative drug against HBV infection.

Optimization of Ultrasonic-Assisted Enzymatic Extraction Conditions for Improving Total Phenolic Content, Antioxidant and Antitumor Activities In Vitro from Trapa quadrispinosa Roxb. Residues.

Stems are the important residues of Trapa quadrispinosa Roxb., which are abundant in phenolic compounds. Ultrasonic-assisted enzymatic extraction (UAEE) is confirmed as a novel extraction technology with main advantages of enhancing extraction yield and physiological activities of the extracts from various plants. In this study, UAEE was applied to obtain the highest yield of phenolic content, strongest antioxidant, and antitumor activities and to optimize the extraction conditions using response surface methodology (RSM). The extracts from the stems of T. quadrispinosa were characterized by determination of their antioxidant activities through 2,2-azinobis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), 1,1-Diphenyl-2-picrylhydrazxyl (DPPH) radical scavenging, total antioxidant capacity (TAC), ferric reducing antioxidant capacity (FRAC) methods and of their antitumor activity by MTT method. The selected key independent variables were cellulase concentration (X1: 1.5%-2.5%), extraction time (X2: 20-30 min) and extraction temperature (X3: 40-60 °C). The optimal extraction conditions for total phenolic content (TPC) value of the extracts were determined as 1.74% cellulase concentration, 25.5 min ultrasonic extraction time and 49.0 °C ultrasonic temperature. Under these conditions, the highest TPC value of 53.6 ± 2.2 mg Gallic acid equivalent (GAE)/g dry weight (DW) was obtained, which agreed well with the predicted value (52.596 mg GAE/g·DW. Furthermore, the extracts obtained from UAEE presented highest antioxidant activities through ABTS, DPPH, TAC and FRAC methods were of 1.54 ± 0.09 mmol Trolox equivalent (TE)/g·DW; 1.45 ± 0.07 mmol·TE/g·DW; 45.2 ± 2.2 mg·GAE/g·DW; 50.4 ± 2.6 µmol FeSO4 equivalent/g·DW and lowest IC50 values of 160.4 ± 11.6 µg/mL, 126.1 ± 10.8 µg/mL, and 178.3 ± 13.1 µg/mL against Hela, HepG-2 and U251 tumor cells, respectively. The results indicated that the UAEE was an efficient alternative to improve extraction yield and enhance the antioxidant and antitumor activities of the extracts. The phenolic extracts from the stems of T. quadrispinosa had significant antioxidant and antitumor activities, which could be used as a source of potential antioxidant and antitumor agents.

Anti-HBV agents derived from botanical origin.

There are 350,000 hepatitis B virus (HBV) carriers all over the world. Chronic HBV infection is at a high risk of developing liver cirrhosis and hepatocelluar carcinoma (HCC), and heavily threatened people's health. Two kinds of drugs approved by FDA for anti-HBV therapy are immunomodulators (interferon α, pegylated-interferon α) and nucleos(t)ide analogues (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate). These drugs have been proved to be far from being satisfactory due to their low specificity, side effects, and high rate of drug resistance. There is an urgent need to discover and develop novel effective anti-HBV drugs. With vast resources, various structures, diverse biological activities and action mechanisms, as well as abundant clinical experiences, botanical agents become a promising source of finding new anti-HBV drugs. This review summarizes the recent research and development of anti-HBV agents derived from botanical origin on their sources and active components, inhibitory effects and possible toxicities, as well as action targets and mechanisms, and also addresses the advantages and the existing shortcomings in the development of botanical inhibitors. This information may not only broaden the knowledge of anti-HBV therapy, and offer possible alternative or substitutive drugs for CHB patients, but also provides considerable information for developing new safe and effective anti-HBV drugs.