Planta Med
DOI: 10.1055/a-2328-2750
Original Papers

Estrogenic Activity of Derris scandens Stem Extract and its Major Compounds Using MCF-7 Cell Proliferation Assay and Estrogen-Related Gene Expression

Worapol Sae-Foo
1   Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
,
Gorawit Yusakul
2   School of Pharmacy, Walailak University, Nakhon Si Thammarat, Thailand
,
Natsajee Nualkaew
1   Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
,
1   Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand
› Author Affiliations
Supported by: National Research Council of Thailand N41A650080

Abstract

Derris scandens, which contains isoflavones and prenylated derivatives, has analgesic and anti-inflammatory properties and is an ingredient in traditional Thai medicine for perimenopause and menopause. However, the estrogenic activity of D. scandens has not yet been explored. Therefore, this study aimed to examine the estrogenic activity of the stem extract of D. scandens and its isoflavone derivatives. In this study, we conducted a proliferation assay in MCF-7 cells, and used quantitative reverse transcription polymerase chain reaction to assess gene expression. We found that the relative cell proliferation of the compounds (1 µM) was ranked in the following order as compared to 0.1 nM 17β-estradiol (100%): genistein (97.84%) > derrisisoflavone A (83.17%) > genistein-7-O-[α-rhamnopyranosyl-(1 → 6)-glucopyranoside] (69.55%) > 6,8-diprenylgenistein (51.91%) > lupalbigenin (18.72%). Furthermore, cotreatment with 1 µM lupalbigenin and 0.1 nM 17β-estradiol was performed, which decreased cell proliferation to 80.38%. In vitro results suggest that lupalbigenin has an estrogen-antagonistic effect. At a dose of 1 µM, genistein had the strongest efficacy in increasing the expression of human estrogen receptor β by 4.0-fold compared to the control. Furthermore, genistein-7-O-[α-rhamnopyranosyl-(1 → 6)]-β-glucopyranoside augmented the gene expression of human estrogen receptor α and human estrogen receptor β by 1.5- and 3.4-fold, respectively. Prenylated derivatives of genistein (derrisisoflavone A, 6,8-diprenylgenistein, and lupalbigenin) significantly suppressed the gene expression of the human androgen receptor. The administration of the crude extract at 10 µg/mL significantly suppressed human androgen receptor (0.6-fold) and transmembrane protease serine 2 (0.1-fold) expression but did not significantly affect human estrogen receptor α and human estrogen receptor β gene expression. This herbal medicine may be safe for estrogen-exposed breast cancer patients.



Publication History

Received: 29 February 2024

Accepted after revision: 15 May 2024

Accepted Manuscript online:
15 May 2024

Article published online:
28 June 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Sae-Foo W, Yusakul G, Nualkaew N, Putalun W. Identification of major bioactive anti-inflammatory compounds of Derris scandens stem using RAW 264.7 cells and HPLC-UV analysis. Planta Med 2024; 90: 126-137
  • 2 Puttarak P, Sawangjit R, Chaiyakunapruk N. Efficacy and safety of Derris scandens (Roxb.) Benth. for musculoskeletal pain treatment: A systematic review and meta-analysis of randomized controlled trials. J Ethnopharmacol 2016; 194: 316-323
  • 3 Chaichamnong N, Temkitthawon P, Khorana N, Pitpakdeeanan P, Taepavarapruk P, Nuengchamnong N, Siriwattanasathien Y, Suksamrarn A, Ingkaninan K. Phosphodiesterase 5 inhibitors from Derris scandens . Planta Med 2018; 84: 1134-1140
  • 4 Bhandari S, Nuengchamnong N, Chaichamnong N, Seasong T, Ingkaninan K, Temkitthawon P. At‐line LC‐QTOF‐MS micro‐fractionation of Derris scandens (Roxb.) Benth, coupled to radio assay for the early identification of PDE5A1 inhibitors. Phytochem Anal 2020; 31: 297-305
  • 5 Tantipongpiradet A, Monthakantirat O, Daodee S, Boonyarat C, Matsumoto K, Pitiporn S, Chulikhit Y. Yakae-Prajamduen-Jamod recipe reduced anxiety behavior and brain oxidative damage in ovariectomized mice. Songklanakarin J Sci Technol 2020; 42: 172-179
  • 6 Daodee S, Monthakantirat O, Tantipongpiradet A, Maneenet J, Chotritthirong Y, Boonyarat C, Khamphukdee C, Kwankhao P, Pitiporn S, Awale S, Matsumoto K, Chulikhit Y. Effect of Yakae-Prajamduen-Jamod traditional Thai remedy on cognitive impairment in an ovariectomized mouse model and its mechanism of action. Molecules 2022; 27: 4310
  • 7 Benchakanta S, Puttiwong S, Boontan N, Wichit M, Wapee S, Kansombud S. A comparison of efficacy and side effects of knee osteoarthritis treatments with crude Derris scandens and ibuprofen. J Thai Trad Alt Med 2012; 10: 115-123
  • 8 Zhang J, Ge Y, Han F, Li B, Yan S, Sun J, Wang L. Isoflavone content of soybean cultivars from maturity group 0 to VI grown in northern and southern China. J Am Oil Chem Soc 2014; 91: 1019-1028
  • 9 Juengsanguanpornsuk W, Yusakul G, Kraithong W, Putalun W. Simple preparation and analysis of a phytoestrogen-rich extract of Pueraria candollei var. mirifica and its in vitro estrogenic activity. J Herb Med 2021; 29: 100463
  • 10 Kuptniratsaikul V, Pinthong T, Bunjob M, Thanakhumtorn S, Chinswangwatanakul P, Thamlikitkul V. Efficacy and safety of Derris scandens Benth extracts in patients with knee osteoarthritis. J Altern Complement Med 2011; 17: 147-153
  • 11 Kuljittichanok D, Diskul-Na-Ayudthaya P, Weeraphan C, Chokchaichamnankit D, Chiablaem K, Lirdprapamongkol K, Svasti J, Srisomsap C. Effect of Derris scandens extract on a human hepatocellular carcinoma cell line. Oncol Lett 2018; 16: 1943-1952
  • 12 Hematulin A, Ingkaninan K, Limpeanchob N, Sagan D. Ethanolic extract from Derris scandens Benth mediates radiosensitzation via two distinct modes of cell death in human colon cancer HT-29 cells. Asian Pac J Cancer Prev 2014; 15: 1871-1877
  • 13 Ausawasamrit A, Itthiwarapornkul N, Chaotham C, Sukrong S, Chanvorachote P. Lupalbigenin from Derris scandens sensitizes detachment-induced cell death in human lung cancer cells. Anticancer Res 2015; 35: 2827-2834
  • 14 Kraithong W, Juengsanguanpornsuk W, Krittanai S, Yusakul G, Putalun W. Phytoestrogen constituents and estrogenic activity of Pueraria candollei var. mirifica callus and its extract preparation for removing cytotoxic constituents. Songklanakarin J Sci Technol 2021; 43: 2642
  • 15 Sae-Foo W, Yusakul G, Nualkaew N, Putalun W. Estrogenic activity of isoflavones derived from Derris scandens using MCF-7 cell. Planta Med 2022; 88: 1475
  • 16 Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO. The E-SCREEN assay as a tool to identify estrogens: An update on estrogenic environmental pollutants. Environ Health Perspect 1995; 103: 113-122
  • 17 Department of Medical Sciences, Ministry of Public Health. Thai Herbal Pharmacopoeia 2021. Nonthaburi, Thailand; Department of Medical Sciences, Ministry of Public Health. Department of Medical Sciences 2021; 669-679
  • 18 Simons R, Gruppen H, Bovee TF, Verbruggen MA, Vincken JP. Prenylated isoflavonoids from plants as selective estrogen receptor modulators (phytoSERMs). Food Funct 2012; 3: 810-827
  • 19 Pinto B, Bertoli A, Noccioli C, Garritano S, Reali D, Pistelli L. Estradiol‐antagonistic activity of phenolic compounds from leguminous plants. Phytother Res 2008; 22: 362-366
  • 20 Jiang Q, Payton-Stewart F, Elliott S, Driver J, Rhodes LV, Zhang Q, Zheng S, Bhatnagar D, Boue SM, Collins-Burow BM, Sridhar J, Stevens C, McLachlan JA, Wiese TE, Burow ME, Wang G. Effects of 7-O substitutions on estrogenic and anti-estrogenic activities of daidzein analogues in MCF-7 breast cancer cells. J Med Chem 2010; 53: 6153-6163
  • 21 Sekine T, Inagaki M, Ikegami F, Fujii Y, Ruangrungsi N. Six diprenylisoflavones, derrisisoflavones A–F, from Derris scandens . Phytochemistry 1999; 52: 87-94
  • 22 Jutathis K, Kitisripanya T, Udomsin O, Inyai C, Sritularak B, Tanaka H, Putalun W. An enzyme-linked immunosorbent assay for genistein 7-O-[α-rhamnopyranosyl-(1 → 6)]-β-glucopyranoside determination in Derris scandens using a polyclonal antibody. Phytochem Anal 2016; 27: 336-342
  • 23 Rafii F. The role of colonic bacteria in the metabolism of the natural isoflavone daidzin to equol. Metabolites 2015; 5: 56-73
  • 24 Sukhonthasilakun S, Mahakunakorn P, Naladta A, Nuankaew K, Nualkaew S, Yenjai C, Nualkaew N. Anti-inflammatory effects of Derris scandens extract on narrowband-ultraviolet B exposed HaCaT human keratinocytes. J Ayurveda Integr Med 2023; 14: 100693
  • 25 Leach DA, Mohr A, Giotis ES, Cil E, Isac AM, Yates LL, Barclay WS, Zwacka RM, Bevan CL, Brooke GN. The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells. Nat Commun 2021; 12: 4068
  • 26 Baratchian M, McManus JM, Berk M, Nakamura F, Mukhopadhyay S, Xu W, Erzurum S, Drazba J, Peterson J, Klein EA, Gaston B, Sharifi N. Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes. Sci Rep 2021; 11: 11130
  • 27 Ji G, Zhang Y, Yang Q, Cheng S, Hao J, Zhao X, Jiang Z. Genistein suppresses LPS-induced inflammatory response through inhibiting NF-κB following AMP kinase activation in RAW 264.7 macrophages. PLoS One 2012; 7: e53101
  • 28 Kim H, Datta A, Talwar S, Saleem SN, Mondal D, Abdel-Mageed AB. Estradiol-ERβ2 signaling axis confers growth and migration of CRPC cells through TMPRSS2-ETV5 gene fusion. Oncotarget 2017; 8: 62820
  • 29 Paramita P, Louisa M, Nafrialdi N. Increased vimentin mRNA expression in MCF-7 breast cancer cell line after repeated endoxifen-treatment. Med J Indones 2016; 25: 207-213