Estrogenic post-menopausal anti-osteoporotic mechanism of Achyranthes aspera L.: Phytochemicals and network pharmacology approaches

Hormone replacement therapy is used to treat postmenopausal syndrome caused by estrogen deficiency, but it has been linked to an increased risk of breast cancer. In India, Achyranthes aspera L. is traditionally used to treat menstrual problems; however, there is a lack of mechanistic evidence of its...

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Main Authors: Moyeenul Huq, A. K. M., Stanslas, Johnson, Nizhum, Nisarat, Uddin, Md. Nazim, Maulidiani, Maulidiani, Roney, Miah, Faridah, Abas, Jamal, Jamia Azdina
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Language:English
Published: Elsevier Ltd 2024
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Online Access:http://umpir.ump.edu.my/id/eprint/42974/1/Estrogenic%20post-menopausal%20anti-osteoporotic%20mechanism%20of%20Achyranthes%20aspera%20L..pdf
http://umpir.ump.edu.my/id/eprint/42974/
https://doi.org/10.1016/j.heliyon.2024.e38792
https://doi.org/10.1016/j.heliyon.2024.e38792
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spelling my.ump.umpir.429742024-11-25T04:14:01Z http://umpir.ump.edu.my/id/eprint/42974/ Estrogenic post-menopausal anti-osteoporotic mechanism of Achyranthes aspera L.: Phytochemicals and network pharmacology approaches Moyeenul Huq, A. K. M. Stanslas, Johnson Nizhum, Nisarat Uddin, Md. Nazim Maulidiani, Maulidiani Roney, Miah Faridah, Abas Jamal, Jamia Azdina Q Science (General) RM Therapeutics. Pharmacology TP Chemical technology Hormone replacement therapy is used to treat postmenopausal syndrome caused by estrogen deficiency, but it has been linked to an increased risk of breast cancer. In India, Achyranthes aspera L. is traditionally used to treat menstrual problems; however, there is a lack of mechanistic evidence of its phytoestrogenicity. Therefore, this study investigated the estrogenic activity of A. aspera on estrogen-responsive MCF-7 breast cancer cells. In a cell proliferation assay, the MeOH fraction (100 μg/mL) exhibited the highest proliferation effect (PE) of 138 % (p < 0.001) and relative proliferation effect (RPE) of 96.5 %, compared to 17β-estradiol (0.01 μM: 143 % PE, p < 0.001; 100 % RPE). The MeOH fraction was shown to upregulate the oestrogen marker genes trefoil factor 1 and progesterone receptor by 20.14–23.94 folds and 10.83–14.83 folds, respectively. Twelve phenolics were identified by LC-MS/MS in the active MeOH fraction, i.e. quinic acid, kaempferol hexoside, kaempferol 3-O-(2″-O-galloyl)-glucoside)-β-D-glucoside, geniposide, 3-O-(6′-O-(9Z,12Z-octadecadienoyl)-β-D-glucopyranosyl)-stigmast-5,22E-dien-3β-ol, kaempferol-3-O-glucoside (astragalin), 3,30-di-O-methylellagic acid isomer, procyanidin, naringin, propapyriogenin A2, (3β,22E,24R)-23-methylergosta-5,7,22-trien-3-ol and 6-prenylapigenin. Through network pharmacology, the potential effects, and mechanisms of these compounds in osteoporosis were revealed. About 55 target genes were linked to osteoporosis. GO and KEGG enrichment suggest regulation of female reproductive hormone related signaling pathways, which are also associated with estrogen dependent osteoporosis. Molecular docking analysis of the compounds revealed potential interactions with hERα receptor for 3-O-(6′-O-(9Z,12Z-octadecadienoyl)-β-D-glucopyranosyl)-stigmast-5,22E-dien-3β-ol and kaempferol-3-O-glucoside (astragalin) (docking scores of −9.3 and −10.1 kcal/mol, respectively) as compared to 17β-estradiol (−9.3 kcal/mol). These results suggest the estrogenicity of A. aspera via an ERα-associated mechanism and support its traditional usage in the management of menopausal-related problems. Elsevier Ltd 2024-10-30 Article PeerReviewed pdf en cc_by_nc_nd_4 http://umpir.ump.edu.my/id/eprint/42974/1/Estrogenic%20post-menopausal%20anti-osteoporotic%20mechanism%20of%20Achyranthes%20aspera%20L..pdf Moyeenul Huq, A. K. M. and Stanslas, Johnson and Nizhum, Nisarat and Uddin, Md. Nazim and Maulidiani, Maulidiani and Roney, Miah and Faridah, Abas and Jamal, Jamia Azdina (2024) Estrogenic post-menopausal anti-osteoporotic mechanism of Achyranthes aspera L.: Phytochemicals and network pharmacology approaches. Heliyon, 10 (20). pp. 1-14. ISSN 2405-8440. (Published) https://doi.org/10.1016/j.heliyon.2024.e38792 https://doi.org/10.1016/j.heliyon.2024.e38792
institution Universiti Malaysia Pahang Al-Sultan Abdullah
building UMPSA Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Pahang Al-Sultan Abdullah
content_source UMPSA Institutional Repository
url_provider http://umpir.ump.edu.my/
language English
topic Q Science (General)
RM Therapeutics. Pharmacology
TP Chemical technology
spellingShingle Q Science (General)
RM Therapeutics. Pharmacology
TP Chemical technology
Moyeenul Huq, A. K. M.
Stanslas, Johnson
Nizhum, Nisarat
Uddin, Md. Nazim
Maulidiani, Maulidiani
Roney, Miah
Faridah, Abas
Jamal, Jamia Azdina
Estrogenic post-menopausal anti-osteoporotic mechanism of Achyranthes aspera L.: Phytochemicals and network pharmacology approaches
description Hormone replacement therapy is used to treat postmenopausal syndrome caused by estrogen deficiency, but it has been linked to an increased risk of breast cancer. In India, Achyranthes aspera L. is traditionally used to treat menstrual problems; however, there is a lack of mechanistic evidence of its phytoestrogenicity. Therefore, this study investigated the estrogenic activity of A. aspera on estrogen-responsive MCF-7 breast cancer cells. In a cell proliferation assay, the MeOH fraction (100 μg/mL) exhibited the highest proliferation effect (PE) of 138 % (p < 0.001) and relative proliferation effect (RPE) of 96.5 %, compared to 17β-estradiol (0.01 μM: 143 % PE, p < 0.001; 100 % RPE). The MeOH fraction was shown to upregulate the oestrogen marker genes trefoil factor 1 and progesterone receptor by 20.14–23.94 folds and 10.83–14.83 folds, respectively. Twelve phenolics were identified by LC-MS/MS in the active MeOH fraction, i.e. quinic acid, kaempferol hexoside, kaempferol 3-O-(2″-O-galloyl)-glucoside)-β-D-glucoside, geniposide, 3-O-(6′-O-(9Z,12Z-octadecadienoyl)-β-D-glucopyranosyl)-stigmast-5,22E-dien-3β-ol, kaempferol-3-O-glucoside (astragalin), 3,30-di-O-methylellagic acid isomer, procyanidin, naringin, propapyriogenin A2, (3β,22E,24R)-23-methylergosta-5,7,22-trien-3-ol and 6-prenylapigenin. Through network pharmacology, the potential effects, and mechanisms of these compounds in osteoporosis were revealed. About 55 target genes were linked to osteoporosis. GO and KEGG enrichment suggest regulation of female reproductive hormone related signaling pathways, which are also associated with estrogen dependent osteoporosis. Molecular docking analysis of the compounds revealed potential interactions with hERα receptor for 3-O-(6′-O-(9Z,12Z-octadecadienoyl)-β-D-glucopyranosyl)-stigmast-5,22E-dien-3β-ol and kaempferol-3-O-glucoside (astragalin) (docking scores of −9.3 and −10.1 kcal/mol, respectively) as compared to 17β-estradiol (−9.3 kcal/mol). These results suggest the estrogenicity of A. aspera via an ERα-associated mechanism and support its traditional usage in the management of menopausal-related problems.
format Article
author Moyeenul Huq, A. K. M.
Stanslas, Johnson
Nizhum, Nisarat
Uddin, Md. Nazim
Maulidiani, Maulidiani
Roney, Miah
Faridah, Abas
Jamal, Jamia Azdina
author_facet Moyeenul Huq, A. K. M.
Stanslas, Johnson
Nizhum, Nisarat
Uddin, Md. Nazim
Maulidiani, Maulidiani
Roney, Miah
Faridah, Abas
Jamal, Jamia Azdina
author_sort Moyeenul Huq, A. K. M.
title Estrogenic post-menopausal anti-osteoporotic mechanism of Achyranthes aspera L.: Phytochemicals and network pharmacology approaches
title_short Estrogenic post-menopausal anti-osteoporotic mechanism of Achyranthes aspera L.: Phytochemicals and network pharmacology approaches
title_full Estrogenic post-menopausal anti-osteoporotic mechanism of Achyranthes aspera L.: Phytochemicals and network pharmacology approaches
title_fullStr Estrogenic post-menopausal anti-osteoporotic mechanism of Achyranthes aspera L.: Phytochemicals and network pharmacology approaches
title_full_unstemmed Estrogenic post-menopausal anti-osteoporotic mechanism of Achyranthes aspera L.: Phytochemicals and network pharmacology approaches
title_sort estrogenic post-menopausal anti-osteoporotic mechanism of achyranthes aspera l.: phytochemicals and network pharmacology approaches
publisher Elsevier Ltd
publishDate 2024
url http://umpir.ump.edu.my/id/eprint/42974/1/Estrogenic%20post-menopausal%20anti-osteoporotic%20mechanism%20of%20Achyranthes%20aspera%20L..pdf
http://umpir.ump.edu.my/id/eprint/42974/
https://doi.org/10.1016/j.heliyon.2024.e38792
https://doi.org/10.1016/j.heliyon.2024.e38792
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