Pharmacokinetics, Safety, and Antiviral Effects of Hypericin, a Derivative of St. John's Wort Plant, in Patients with Chronic Hepatitis C Virus Infection

Abstract

Hypericin is a natural derivative of the common St. Johns wort plant, Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral activity of hypericin in patients with chronic HCV infection. The first 12 patients received an 8-week course of 0.05 mg of hypericin per kg of body weight orally once a day; 7 patients received an 8-week course of 0.10 mg/kg orally once a day. At the end of the 8-week period of treatment, no subject had a change of plasma HCV RNA level of more than 1.0 log 10 . Five of 12 subjects receiving the 0.05-mg/kg/day dosing schedule and 6 of 7 subjects receiving the 0.10-mg/kg/day dosing schedule developed phototoxic reactions. No other serious adverse events associated with hypericin use occurred. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 h, respectively, for the doses of 0.05 and 0.1 mg/kg) and mean area under the curve determinations of 1.5 and 3.1 g/ml ؋ hr, respectively. In sum, hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection.

Reduction in hypericin-induced phototoxicity by Hypericum perforatum extracts and pure compounds

“…Based on these studies, it seems as though hypericin administered via Hp extracts may be less toxic [8,9] than administration of pure hypericin [10,11].…”

“…The light-induced toxicity of hypericin and Hp extracts containing the hypericin compounds have also been studied in human clinical trials for treatment purposes as well as safety assessment [8][9][10][11]. Based on these studies, it seems as though hypericin administered via Hp extracts may be less toxic [8,9] than administration of pure hypericin [10,11].…”

“…Biological activities and toxicities possessed by this plant may also depend on the properties of several constituents collectively provoking a variety of physiological responses. An example of this may be found in studies that report the general absence of phototoxic side effects in human subjects administered Hp extracts [9,13] but moderate to severe phototoxicity in those administered pure hypericin [10,11].…”

“…Aggressive analysis of this plant over the last three decades has revealed that it possesses several biological properties, including antidepressant, antiviral and antiproliferative activities [4][5][6][7][8]. Although H. perforatum (Hp) is most commonly used as an alternative to standard tricyclic antidepressants, other biological properties possessed by this plant have also been utilized for the treatment of cancer and viral infections [8][9][10][11][12]. Widespread use of Hp as an alternative medicine has raised concern regarding its safe use by the public [1,2].…”

Breast Cancer and Current Therapeutic Approaches: From Radiation to Photodynamic Therapy

“…Among others it possesses properties suitable for PDT (Čavarga et al, 2005;Chan et al, 2009) and PDD (Thong et al, 2009). Peculiar attributes of this photosensitizer are high efficiency in production of singlet oxygen (Redmond & Gamlin, 1999) and superoxide anions after irradiation with light wavelength around 600 nm and low or no toxicity in the dark (Jacobson et al, 2001;Miadoková et al, 2009). Photoactivated HY is known to induce changes at cellular as well as vascular level or even affect CD8+ T cell-mediated cytotoxicity (Lavie et al, 2000).…”