Letter to the editor

Recent pharmacological advances on genistein in clinical trials

Shimy Mathew1, Cijo George Vazhappilly1[*]

1Department of Biotechnology, American University of Ras Al Khaimah, Ras Al Khaimah, United Arab Emirates

EXCLI J 2020;19:Doc1120


Dear Editor,

Genistein [4′,5,7-trihydroxyisoflavone or 5,7-dihydroxy-3-(4-hydroxyphenyl) chromen-4-one] is a plant-derived, hydrolyzed aglycone form of isoflavonoid, genistin (a glycoside) (Nayeem et al., 2019[16]; Sansai et al., 2020[20]). Genistein is mainly found in leguminous plants, especially in soybeans along with other important isoflavones, daidzein and glycitein (Kalaiselvan et al., 2010[12]). Other sources of genistein include broad beans, chickpeas, vegetables, fruits, nuts, soy-based foods and genistein supplements. It has also been reported that unfermented soybeans contain more genistein than the fermented ones (Kuligowski et al., 2017[13]; Li and Zhang, 2017[14]). Further, genistein can be metabolically synthesized by introducing the IFS gene (isoflavone synthase gene) into yeast cells and rice lines, which results in an increased genistein content in rice (up to 30 folds) (Spagnuolo et al., 2015[23]).

Plant flavonoids, especially isoflavonoids, have shown promising pharmacological properties to ameliorate diseases including cancer (George et al., 2016[9], 2017[8]). Genistein exhibits various pharmacological properties including antioxidant properties, mainly by increasing the activity of antioxidant enzymes. It also has numerous clinical implications in the treatment and prevention of diseases like diabetes, cardiovascular diseases, cancer, and osteoporosis (Kalaiselvan et al., 2010[12]). Genistein has been reported in exhibiting anti-angiogenesis property by regulating vascular endothelial growth factor 165 and matrix metalloprotease-2 and 9 in human bladder cancer cell lines (Su et al., 2005[24]). Due to genistein's high structural similarity to estradiol, the binding capacity of genistein to the estrogen receptor is notable and thus, genistein is mainly studied in postmenopausal women. Here, we have summarized the most recent findings on the pharmacological activities of genistein in clinical trials, see Table 1(Tab. 1) (References in Table 1: Amanat et al., 2018[1]; Arcoraci et al., 2017[2]; Bilir et al., 2017[3]; Braxas et al., 2019[4]; Cho et al., 2019[5]; De Gregorio et al., 2017[6]; Dong et al., 2020[7]; Hashem et al., 2018[10]; Jochum et al., 2017[11]; Li and Zhang, 2017[14]; Lu et al., 2018[15]; Nayeem et al., 2019[16]; Orsatti et al., 2018[17]; Perez-Alonso et al., 2017[18]; Pintova et al., 2019[19]; Schneider et al., 2019[21]; Silva et al., 2017[22]; Zhang et al., 2019;[25]).


The authors thank the American University of Ras Al Khaimah for the support and facilities provided. The authors also thank Ms. Gulbahor Amirova, Instructor of English, the American University of Ras Al Khaimah, for proof-reading the article.

Conflict of interest

The authors declare no conflict of interest.



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2. Arcoraci V, Atteritano M, Squadrito F, D’Anna R, Marini H, Santoro D, et al. Antiosteoporotic activity of genistein aglycone in postmenopausal women: Evidence from a post-hoc analysis of a multicenter randomized controlled trial. Nutrients. 2017;9(2):179.
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16. Nayeem F, Chen N-W, Nagamani M, Anderson KE, Lu L-JW. Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: A 2-year randomized, double-blind, placebo-controlled study. Nutr Res. 2019;68:70–81.
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20. Sansai K, Na Takuathung M, Khatsri R, Teekachunhatean S, Hanprasertpong N, Koonrungsesomboon N. Effects of isoflavone interventions on bone mineral density in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int. 2020;epub ahead of print. doi: 10.1007/s00198-020-05476-z.
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22. Silva LA, Ferraz Carbonel AA, de Moraes ARB, Simões RS, Sasso GR da S, Goes L, et al. Collagen concentration on the facial skin of postmenopausal women after topical treatment with estradiol and genistein: a randomized double-blind controlled trial. Gynecol Endocrinol. 2017;33:845–8.
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Table 1: Recent findings on the pharmacological activities of genistein in clinical trials

[*] Corresponding Author:

Cijo George Vazhappilly, Department of Biotechnology, American University of Ras Al Khaimah, Ras Al Khaimah, 10021, UAE; Tel.: +971-7-246-8842, eMail: cijo.vazhappilly@aurak.ac.ae