Background: Hepatitis B virus (HBV) infection is a severe health problem in the world; however, there is still no satisfactory therapeutic strategy for the HBV infection. In search for new anti-HBV agents with higher efficiency and less side effects, the anti-HBV activities of traditional Chinese medicine Rheum palmatum L. ethanol extract (RPE) and isolated anthraquinones were evaluated. Methods: The anti-HBV activities of RPE and isolated anthraquinones were demonstrated in a stable HBV-producing cell line HepG2 2.2.15 by using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and Southern blot analysis. Results: RPE could inhibit HBV-DNA production and HBsAg expression in a dose-dependent manner. The concentration of 50% HBV-DNA inhibition (IC50) of RPE was calculated at 212.36 ± 11 µg/ml. Six anthraquinones were isolated from RPE by using RP-HPLC. Five free anthraquinones showed weakly or slightly inhibitory activities against HBV. The only combined anthraquinone chrysophanol 8-O-β-D-glucoside exhibited significant activity against HBV DNA production and antigens expression with an IC50 value of 36.98 ± 2.28 µg/ml on HBV DNA inhibition. Endogenous HBV DNA polymerase activity assay indicated that chrysophanol 8-O-β-D-glucoside might be a potential inhibitor of the HBV DNA polymerase. Conclusions: The results suggested that RPE could effectively inhibit HBV. The combined anthraquinone chrysophanol 8-O-β-D-glucoside is the major active compound in RPE and could be a promising candidate for the development of new anti-HBV drugs in the treatment of HBV infection.
The Chinese government has launched six rounds of national drug price negotiation since 2016 to lower the price and expand access to innovative drugs, many of which are anticancer drugs. This study aims to examine the effect of the second round of negotiation at the provincial level on the expenditure, volume, and availability of anti-cancer drugs. Procurement data at the provincial level from January 2017 to September 2018 were extracted from the China Drug Supply Information Platform (CDSIP). The volume, expenditure, and availability of three targeted anti-cancer drugs, rituximab, trastuzumab, and recombinant human endostatin (RHE), in 11 provinces that implemented the policy in September 2017 were analyzed through a controlled interrupted time series (ITS) analysis. A significant 6.0% increase (p < 0.1) in monthly average expenditure, an increase in the volume of 99.51 DDDs (defined daily doses) (p < 0.1), and a 0.24% (p < 0.1) increase in availability were observed for rituximab following the implementation of the policy. The volume and availability of rituximab increased by 949.6 DDDs (p < 0.05) and 1.56%, respectively, immediately after implementation. The availability of trastuzumab increased by 5.14% (p < 0.01) immediately after the implementation while no instant changes in expenditure and volume were observed. A 15% (p < 0.01) increase in monthly expenditure, 3673.17 DDDs increase in volume, and 0.66% increase in availability were observed after the inclusion of Trastuzumab. However, for RHE, only a 0.32% (p < 0.01) increase was observed after its inclusion. Eastern and middle provinces benefited more than western provinces. National negotiation related to the drug price significantly increased the volume and expenditure of anti-cancer drugs and improved their availability. The effect of the policy might be different across different regions and across different anticancer drugs.
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