Chronic hepatitis C virus (HCV) infection ultimately leads to chronic hepatitis, hepatic cirrhosis and hepatocellular carcinoma (HCC). As the standard treatment is not completely efficacious, a safer and more effective agent against HCV infection needs to be developed. In this report, we demonstrated that 3-hydroxy caruilignan C (3-HCL-C) isolated from Swietenia macrophylla stems exhibited high anti-HCV activity at both protein and RNA levels at nontoxic concentrations, with an EC(50) value of 10.5 ± 1.2 μm. Combinations of 3-HCL-C and interferon-α (IFN-α), an HCV NS5B polymerase inhibitor (2'-C-methylcytidine; NM-107) or an HCV NS3/4A protease inhibitor (Telaprevir; VX-950) increased the suppression of HCV RNA replication. The results suggested that 3-HCL-C may be a potential anti-viral agent. We then demonstrated that 3-HCL-C interfered with HCV replication by inducing IFN-stimulated response element transcription and IFN-dependent anti-viral gene expression.
Fuzi (lateral root of Aconitum carmichaelii) has been used for millennia in Traditional Chinese Medicine (TCM) and Ayurveda to treat cancer and cardiovascular diseases. Fuzi must be processed before use to decrease the concentration of its toxic alkaloids. Detoxification during processing occurs through the transformation of diester-diterpenoid alkaloids (DDAs) to monoester-diterpenoid alkaloids (MDAs). However, traditional detoxification methods are time-consuming and expensive on large-scale production. To develop efficient detoxification protocols to reduce unnecessary processing procedure and keep the maximum functional contents from raw Fuzi, we replicated the traditional procedure and quantified the DDAs and MDAs by UPLC-MS/MS and UPLC-PDA during different steps and conditions of processing. With due consideration of obtained data, we concluded that soaking in Danba solution and the washing steps were inefficient traditional processing methods. The detoxification effect of steaming (56.3 ± 0.27 μg/g DDAs, lowest after steaming) was weaker and slower than boiling (5.8 ± 0.33 μg/g DDAs, lowest after boiling). Moreover, roasting at 105℃ showed better effect in lowering the DDAs (5.8 ± 0.33 μg/g DDAs) and increasing the MDAs (729.1 ± 1.22 μg/g MDAs, highest) than roasting at 60℃ (17.3 ± 0.65 μg/g DDAs; 504.0 ± 0.99 μg/g MDAs). With these highly reliable analytic data, we established an efficient and referenceable detoxification protocol for Fuzi TCM products, in which DDAs and MDAs should legitimately follow the safe and specific ranges stipulated in pharmacopeias.
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