Potential Clinical Applications of (-), (+) and (±)-Z-Bisdehydrodoisynolic Acids in Metabolic Disorders
Jeremy E. Davis, Yuqing Hou, Cal Y. Meyers and William J. Banz
Affiliation: Department of Animal Science, Food and Nutrition, Southern Illinois University, Carbondale, IL 62901-4317, USA.
Doisynolic acids (DAs), such as (±)-Z-bisdehydrodoisynolic acid [(±)-Z-BDDA], are a group of synthetically
produced compounds with structural similarity to 17β-estradiol (E2), which exhibit significant estrogenic activity. They
regulate estrogen receptor-α and -β (ERα/β) reporter gene activation, as well mediate significant uterotropic effects
in vivo. Despite these estrogen-specific effects, (±)-Z-BDDA and related compounds exhibit low ER binding activity
in vitro. This may reflect changes in chemical structure or cellular environment necessary for optimum binding of DAs.
are possible explanations for the binding/activity paradox. Selective estrogen receptor modulators (SERMs), such as
tamoxifen, provide estrogenic activity without undesired adverse effects of E2. The strong SERM activity and limited side
effects of (±)-Z-BDDA make it an ideal alternative to hormone replacement therapy. Recent investigation of (±)-Z-BDDA
has revealed a marked protection against obesity, diabetes, cardiovascular disease, and prostate cancer. The underlying
mechanisms involved in attenuation of these degenerative diseases are not fully elucidated but may relate to the
compounds significant estrogenic and anti-inflammatory properties. This review summarizes some of the proposed
mechanisms for different therapeutic applications of DAs, including obesity and diabetes, as well as some patents on (±)-
Z-BDDA protection against prostate cancer.
Keywords: (+)-Z-bisdehydrodoisynolic acid ((+)-Z-BDDA), insulin resistance, selective estrogen receptor modulator (SERM),
metabolic rate, obese Zucker rat (OZR).
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