每年出版 12 期
ISSN 打印: 1521-9437
ISSN 在线: 1940-4344
Indexed in
GENERAL LECTURES
Antihyperlipidemic Effect of Pleurotus ostreatus (Jacq.:Fr.) P.Kumm. in HIV: Results of a Pilot Proof-of-Principle Clinical Trial
摘要
Antiretroviral treatment regimens in HIV patients commonly include low-dose ritonavir with another protease inhibitor (PI). The addition of ritonavir to some PIs "boosts" their blood concentration and improves the efficacy of the regimen. However, use of PIs, especially ritonavir, causes significant lipid elevations in many patients, including both increases in triglycerides as well as cholesterol. Standard treatments for hypercholesterolemia include the HMG CoA reductase inhibitors, or "statins." Because many PIs and statins share a common metabolic pathway that uses the CYP3A4 enzyme system, coadministration of ritonavir with most statins increases statin levels significantly. This increases the likelihood for adverse effects, including elevated liver function tests and muscle breakdown, which, if left untreated, may progress to renal failure.
A safe and effective alternative to statins for treatment of hyperlipidemia in patients on ritonavircontaining antiretroviral regimens would be of value. Pleurotus ostreatus has been shown in animal models to decrease lipid levels, a finding that has been supported by preliminary data in a small study in humans. Our pilot study was designed (1) to determine whether there are detectable lipid-lowering effects of P. ostreatus, specifically in patients with HIV and hyperlipidemia, who are taking ritonavir in combination with another PI; (2) to assess whether the concomitant administration of daily P. ostreatus and such regimens in this population is safe; and (3) to investigate the mechanism of action by which P. ostreatus may exert an antihyperlipidemic effect.
Pleurotus ostreatus was cloned and maintained in vitro at the spawn laboratories before being expanded into edible mushrooms. Clusters of young mushrooms were harvested and flash-frozen. We designed a single-arm, open-label study of 8 weeks' duration with a target enrollment of 20 subjects. Study participants (patients) with ritonavir-induced elevated LDL cholesterol levels (>160 mg/dL) were eligible to enroll. After screening and obtaining informed consent, patients were admitted to the inpatient General Clinical Research Center (GCRC) at San Francisco General Hospital for a one-night stay to obtain pretreatment PI blood levels. Patients were given their first mushroom dose in the GCRC and then received packets of freeze-dried P. ostreatus (15 gm/day) to be administered orally each day for the 8-week trial period. Patients were followed with lipid levels drawn every 2 weeks to assess efficacy. Safety assessments include a pharmacokinetic substudy to determine if P. ostreatus alters the hepatic metabolism of the PI, self-reported incidence of muscle aches, and measurement of liver and muscle enzymes. HMG CoA reductase inhibition activity after P. ostreatus ingestion will be measured. Seven of the 20 patients have completed the trial to date with no safety issues observed. The goal is to fully enroll the study by the end of summer 2005. Efficacy and safety data will be available at the time of presentation.
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Jagadeesh Raman, Babu Gajandran, Lakshmanan Hariprasath, Oh Oh Min-Ji, Jang Jang Kab-Yeul, Kong Kong Won-Sik, Raaman Nanjian, Bioactive Sterol Derivatives Isolated from the Pleurotus djamor var. Roseus Induced Apoptosis in Cancer Cell Lines, Cardiovascular & Hematological Agents in Medicinal Chemistry , 18, 2, 2020. Crossref