Estrogenic Extracts of Morus Alba and Uses Thereof

Abstract

Extracts of various species of the Moraceae family have estrogenic properties. For example, aqueous and ethanolic extracts of Morus alba L. species possess estrogenic properties in both ERα+ and ERβ+ cells. These estrogenic effect include estrogen response element (ERE) stimulation as well as tumor necrosis factor (TNF) repression. Methods are provided for treating climacteric symptoms, breast and/or uterine cancer, and osteoporosis.

1 . A plant extract composition, comprising an extract of a plant species selected from the taxonomic species  Morus alba  L. 
     
     
         2 . The composition of  claim 1 , wherein the extract is either an aqueous or ethanolic extract. 
     
     
         3 . The composition of  claim 1 , wherein the extract is an ethanolic extract. 
     
     
         4 . A method of activating a gene under control of an estrogen response element, comprising administering to a cell having an estrogen response element operatively linked to the gene and an estrogen receptor an amount of a composition of  claim 1  sufficient to activate said gene. 
     
     
         5 . The method of  claim 4 , wherein said cell is in vitro. 
     
     
         6 . The method of  claim 4 , wherein said cell is in vivo. 
     
     
         7 . The method of  claim 4 , wherein said cell is in an ERα+ breast tissue. 
     
     
         8 . The method of  claim 4 , wherein said cell is in an ERβ+ breast tissue. 
     
     
         9 . The method of  claim 4 , wherein said cell is in an ERα/ERβ+ breast tissue. 
     
     
         10 . The method of  claim 4 , wherein said estrogen response element is expressed in a transformed cell. 
     
     
         11 . The method of  claim 10 , wherein both the estrogen response element and the estrogen receptor are expressed in a transformed cell. 
     
     
         12 . The method of  claim 4 , wherein said estrogen response element is heterologously expressed in the cell. 
     
     
         13 . The method of  claim 12 , wherein both the estrogen response element and the estrogen receptor are heterologously expressed in the cell. 
     
     
         14 . The method of  claim 4 , wherein said cell is selected from the group consisting of a U937, a U205, a MDA-MB-435 and a MCF-7 cell transformed with an ERE-controlled gene. 
     
     
         15 . The method of  claim 14 , wherein the cell expresses ERα. 
     
     
         16 . The method of  claim 14 , wherein the cell expresses ERβ. 
     
     
         17 . The method of  claim 14 , wherein the ERE-controlled gene is ERE-tk-Luc. 
     
     
         18 . A method of repressing expression of a TNF-RE-controlled gene, comprising administering to a cell comprising a gene under control of a TNF response element and an estrogen receptor an amount of a composition of  claim 1  effective to repress said TNF-RE-controlled gene. 
     
     
         19 . The method of  claim 18 , wherein the TNF-RE-controlled gene is TNF-α. 
     
     
         20 . The method of  claim 18 , wherein the TNF-RE-controlled gene is TNF-RE-Luc. 
     
     
         21 . The method of  claim 18 , wherein said cell is in vitro. 
     
     
         22 . The method of  claim 18 , wherein said cell is in vivo. 
     
     
         23 . The method of  claim 18 , wherein said cell is in an ER+ breast tissue. 
     
     
         24 . The method of  claim 18 , wherein said cell is in an ERα+ breast tissue. 
     
     
         25 . The method of  claim 18 , wherein said cell is in an ERβ+ breast tissue. 
     
     
         26 . The method of  claim 18 , wherein said TNF response element is endogenously expressed in the cell. 
     
     
         27 . The method of  claim 26 , wherein both the TNF response element and the estrogen receptor are endogenously expressed in the cell. 
     
     
         28 . The method of  claim 18 , wherein said TNF response element is heterologously expressed in the cell. 
     
     
         29 . The method of  claim 28 , wherein both the TNF response element and the estrogen receptor are heterologously expressed in the cell. 
     
     
         30 . The method of  claim 18 , wherein said cell contains an estrogen receptor gene, is transformed with an TNF response element-controlled gene, and is selected from the group consisting of a U937, a U2OS, a MDA-MB-435 and a MCF-7 cell. 
     
     
         31 . The method of  claim 30 , wherein the estrogen receptor gene is a gene expressing ERα. 
     
     
         32 . The method of  claim 30 , wherein the estrogen receptor gene is a gene expressing ERβ. 
     
     
         33 . A method of making a plant extract of  claim 1 , comprising obtaining a quantity of plant matter from a plant of the species  Morus alba  L., and contacting said plant matter with an extraction medium comprising water at a temperature between about 25° C. and 100° C. and separating said extraction medium from said plant. 
     
     
         34 . The method of  claim 33 , wherein said temperature is between about 50° C. and 80° C. 
     
     
         35 . The method of  claim 33 , wherein said temperature is about 75° C. 
     
     
         36 . A method of making a plant extract of  claim 1 , comprising obtaining a quantity of plant matter from a plant of the genus  Morus alba  L., and contacting said plant matter with an extraction medium comprising ethanol at a temperature between about 25° C. and about 78° C.; and separating said extraction medium from said plant matter. 
     
     
         37 . The method of  claim 36 , wherein said temperature is between about 50° C. and 78° C. 
     
     
         38 . The method of  claim 36  wherein said temperature is about 75° C.