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      Calycosin Influences the Metabolism of Five Probe Drugs in Rats

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          Abstract

          Background

          Calycosin (CAL), a type of O-methylated isoflavone extracted from the herb Astralagusmembranaceus (AM), is a bioactive chemical with antioxidative, antiphlogistic and antineoplastic activities commonly used in traditional alternative Chinese medicine. AM has been shown to confer health benefits as an adjuvant in the treatment of a variety of diseases.

          Aim

          The main objective of this study was to determine whether CAL influences the cytochrome P450 (CYP450) system involved in drug metabolism.

          Methods

          Midazolam, tolbutamide, omeprazole, metoprolol and phenacetin were selected as probe drugs. Rats were randomly divided into three groups, specifically, 5% Carboxymethyl cellulose (CMC) for 8 days (Control), 5% CMC for 7 days + CAL for 1 day (single CAL) and CAL for 8 days (conc CAL), and metabolism of the five probe drugs evaluated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

          Results

          No significant differences were observed for omeprazole and midazolam, compared to the control group. T max and t 1/2 values of only one probe drug, phenacetin, in the conc CAL group were significantly different from those of the control group ( T max h: 0.50±0.00 vs 0.23±0.15; control vs conc CAL). C max of tolbutamide was decreased about two-fold in the conc CAL treatment group (conc vs control: 219.48 vs 429.56, P<0.001).

          Conclusion

          Calycosin inhibits the catalytic activities of CYP1A2, CYP2D6 and CYP2C9. Accordingly, we recommend caution, particularly when combining CAL as a modality therapy with drugs metabolized by CYP1A2, CYP2D6 and CYP2C9, to reduce the potential risks of drug accumulation or ineffective treatment.

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          Most cited references 16

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          Annual Report to the Nation on the Status of Cancer, 1975–2007, Featuring Tumors of the Brain and Other Nervous System

          Background The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year’s report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004. Methods Cancer incidence data were obtained from the National Cancer Institute, CDC, and NAACCR, and information on deaths was obtained from the CDC’s National Center for Health Statistics. The annual percentage changes in age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers for men and for women were estimated by joinpoint analysis of long-term (1992–2007 for incidence; 1975–2007 for mortality) trends and short-term fixed interval (1998–2007) trends. Analyses of malignant neuroepithelial brain and ONS tumors were based on data from 1980–2007; data on nonmalignant tumors were available for 2004–2007. All statistical tests were two-sided. Results Overall cancer incidence rates decreased by approximately 1% per year; the decrease was statistically significant (P < .05) in women, but not in men, because of a recent increase in prostate cancer incidence. The death rates continued to decrease for both sexes. Childhood cancer incidence rates continued to increase, whereas death rates continued to decrease. Lung cancer death rates decreased in women for the first time during 2003–2007, more than a decade after decreasing in men. During 2004–2007, more than 213 500 primary brain and ONS tumors were diagnosed, and 35.8% were malignant. From 1987–2007, the incidence of neuroepithelial malignant brain and ONS tumors decreased by 0.4% per year in men and women combined. Conclusions The decrease in cancer incidence and mortality reflects progress in cancer prevention, early detection, and treatment. However, major challenges remain, including increasing incidence rates and continued low survival for some cancers. Malignant and nonmalignant brain tumors demonstrate differing patterns of occurrence by sex, age, and race, and exhibit considerable biologic diversity. Inclusion of nonmalignant brain tumors in cancer registries provides a fuller assessment of disease burden and medical resource needs associated with these unique tumors.
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            Isoflavones

            Phytoestrogens are naturally occurring nonsteroidal phenolic plant compounds that, due to their molecular structure and size, resemble vertebrate steroids estrogens. This review is focused on plant flavonoids isoflavones, which are ranked among the most estrogenic compounds. The main dietary sources of isoflavones for humans are soybean and soybean products, which contain mainly daidzein and genistein. When they are consumed, they exert estrogenic and/or antiestrogenic effects. Isoflavones are considered chemoprotective and can be used as an alternative therapy for a wide range of hormonal disorders, including several cancer types, namely breast cancer and prostate cancer, cardiovascular diseases, osteoporosis, or menopausal symptoms. On the other hand, isoflavones may also be considered endocrine disruptors with possible negative influences on the state of health in a certain part of the population or on the environment. This review deals with isoflavone classification, structure, and occurrence, with their metabolism, biological, and health effects in humans and animals, and with their utilization and potential risks.
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              Surveillance of certain health behaviors and conditions among states and selected local areas --- Behavioral Risk Factor Surveillance System, United States, 2009.

              Chronic diseases and conditions (e.g., heart disease, cancer, stroke, and diabetes) are the leading causes of death in the United States. Controlling health risk behaviors and conditions (e.g., smoking, physical inactivity, poor diet, excessive drinking, and obesity) and using preventive health-care services (e.g., physical examination, vaccination, screening for high blood pressure and high cholesterol, consumption of fruits and vegetables, and participation in regular leisure-time physical activity) can reduce morbidity and mortality from chronic diseases. January 2009--December 2009. The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing state-based random-digit--dialed telephone survey of noninstitutionalized adults aged ≥18 years residing in the United States. BRFSS collects data on health risk behaviors and conditions, chronic diseases and conditions, access to health care, and use of preventative health services and practices related to the leading causes of death and disabilities in the United States. This report presents results for 2009 for all 50 states, the District of Columbia, the Commonwealth of Puerto Rico, Guam, the U.S. Virgin Islands, 180 metropolitan and micropolitan statistical areas (MMSAs), and 283 selected counties. In 2009, the estimated prevalence of general health status, use of preventive health-care services, health risk behaviors and conditions, chronic diseases, and health impairments and disabilities varied substantially by state and territory, MMSA, and county. The following is a summary of results listed by BRFSS question topics. Each set of proportions refers to the range of estimated prevalence for the disease, condition, or behavior, as reported by the survey respondent. Adults who reported having fair or poor health: 10.1%--30.9% for states and territories, 7.9%--25.8% for MMSAs, and 4.5%--26.1% for counties. Adults with health-care coverage: 71.4%--94.7% for states and territories, 52.7%--96.3% for MMSAs, and 52.7%--97.6% for counties. Annual routine physical checkup among adults aged ≥18 years: 55.8%--79.3% for states and territories, 51.8%--80.7% for MMSAs, and 49.2%--83.5% for counties. Annual influenza vaccination among adults aged ≥65 years: 26.8%--76.8% for states and territories, 55.4%--81.4% for MMSAs, and 50.5%--83.5% for counties. Pneumococcal vaccination among adults aged ≥65 years: 19.1%--73.9% for states and territories, 52.9%--81.3% for MMSAs, and 41.9%--82.0% for counties. Adults who had their cholesterol checked within the preceding 5 years: 67.5%--85.3% for states and territories, 58.2%--88.8% for MMSAs, and 58.2%--92.4% for counties. Adults who consumed at least five servings of fruits and vegetables per day: 14.6%--31.5% for states and territories, 12.6%--33.0% for MMSAs, and 13.4%--34.9% for counties. Adults who engaged in moderate or vigorous physical activity: 28.0%--60.7% for states and territories, 34.6%--64.9% for MMSAs, and 33.6%--67.3% for counties. Adults who engaged in only vigorous physical activity: 13.7%--40.1% for states and territories, 13.8%--43.3% for MMSAs, and 14.2%--50.0% for counties. Current cigarette smoking among adults: 6.4%--25.6% for states and territories, 5.7%--29.0% for MMSAs, and 5.6%--29.8% for counties. Binge drinking among adults: 6.8%--23.9% for states and territories, 3.5%--23.2% for MMSAs, and 3.4%--26.3% for counties. Heavy drinking among adults: 1.9%--8.1% for states and territories, 1.0%--11.1% for MMSAs, and 0.9%--11.1% for counties. Adults who reported no leisure-time physical activity: 15.8%--45.6% for states and territories, 13.3%--40.2% for MMSAs, and 10.5%--40.2% for counties. Adults aged ≥18 years who were overweight: 31.6%--38.7% for states and territories, 28.7%--44.1% for MMSAs, and 25.6%--46.7% for counties. Adults aged ≥20 years who were obese: 19.7%--36.0% for states and territories, 15.4%--43.6% for MMSAs, and 13.8%--45.7% for counties. Adults aged ≥18 years who did not get enough rest or sleep: 34.3%--52.6% for states and territories, 28.2%--54.8% for MMSAs, and 24.5%--55.6% for counties. Adults who had received a high blood pressure diagnosis: 22.1%--38.5% for states and territories, 18.8%--43.9% for MMSAs, and 17.2%--43.6% for counties. Adults who had a high blood cholesterol diagnosis: 24.9%--42.2% for states and territories, 27.5%--47.8% for MMSAs, and 26.7%--51.4% for counties. Adults who had received a diagnosis of coronary heart disease: 2.5%--10.3% for states and territories, 2.6%--11.6% for MMSAs, and 1.6%--12.3% for counties. Adults who had received a stroke diagnosis: 1.4%--3.9% for states and territories, 0.8%--5.9% for MMSAs, and 0.8%--6.6% for counties. Adults who had received a diabetes diagnosis: 5.8%--12.9% for states and territories, 2.8%--15.4% for MMSAs, and 2.8%--14.7% for counties. Adults who had received a cancer diagnosis: 3.0%--12.6% for states and territories, 5.8%--15.1% for MMSAs, and 3.9%--16.2% for counties. Adults who had asthma: 4.4%--11.1% for states and territories, and 3.2%--15.3% for MMSAs, and 3.2%--15.7% for counties. Adults who had arthritis: 10.7%--35.6% for states and territories, 16.2%--36.0% for MMSAs, and 12.6%--39.4% for counties. Adults with activity limitation associated with physical, mental, or emotional problems: 10.2%--27.1% for states and territories, 13.1%--33.7% for MMSAs, and 10.4%--36.1% for counties. Adults who required special equipment because of health problems: 3.6%--10.2% for states and territories, 3.4%--11.5% for MMSAs, and 1.7%--13.0% for counties. The findings in this report indicate substantial variations in self-rated general health status, health-care coverage, use of preventive health-care services, health risk behaviors and health conditions, cardiovascular conditions, other chronic diseases, and health impairments and disabilities among U.S. adults at the state and territory, MMSA, and county levels. The findings show that Healthy People 2010 objectives had not been met in many areas by 2009, which underscores the continued need for surveillance of general health status, use of preventive health-care services, health risk behaviors and conditions, chronic diseases, and health impairment and disability. Data on health risk behaviors, chronic health conditions, preventive care practices, and chronic diseases are used to develop health promotion activities, intervention programs, and health policies at the state, city, and county levels.. The overarching goals of Healthy People 2010 are to increase quality and years of healthy life and to eliminate health disparities. Local and state health departments and federal agencies should continue to use BRFSS data to identify populations at high risk for certain health risk behaviors and conditions, cardiovascular conditions, and other chronic diseases and to evaluate the use of preventive health-care services. In addition, BRFSS data can be used to direct, implement, monitor, and evaluate public health programs and policies that can lead to a reduction in morbidity and mortality.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                29 January 2020
                2020
                : 14
                : 429-434
                Affiliations
                [1 ]Faculty of Medicine, Jinhua Polytechnic , Zhejiang, People’s Republic of China
                Author notes
                Correspondence: Bi-e Tang Faculty of Medicine, Jinhua Polytechnic , No. 1188 Wuzhou Street, Jinhua City, Zhejiang Provinc, People’s Republic of China Email tangbiejh@163.com
                Article
                236221
                10.2147/DDDT.S236221
                6996205
                © 2020 Wu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 1, Tables: 2, References: 19, Pages: 6
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine

                cyp450, calycosin, cocktail, uplc-ms/ms, herb-drug interactions

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