Exploring the boost of steaming with wine on Ligustri Lucidi Fructus in treating postmenopausal osteoporosis based on superior "multi-component structure" and iron/bone metabolism coregulation
Clinical studies indicated that postmenopausal osteoporosis (PMOP) often accompanied by iron overload risk factor, which exacerbated bone metabolism disorders and accelerated PMOP. Previous research found that multicomponent in Ligustri Lucidi Fructus (FLL) or wine-steamed FLL (WFLL) acted on the co...
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| creator | Jiang, Jun Zhao, Baixiu Xiao, Jianpeng Shi, Liang Shang, Wei Shu, Ye Zhao, Zhiming Shen, Junyi Xu, Jingjuan Cai, Hui |
| description | Clinical studies indicated that postmenopausal osteoporosis (PMOP) often accompanied by iron overload risk factor, which exacerbated bone metabolism disorders and accelerated PMOP. Previous research found that multicomponent in Ligustri Lucidi Fructus (FLL) or wine-steamed FLL (WFLL) acted on the common targets of iron overload and PMOP simultaneously, which indicated that FLL and WFLL probably regulated iron/bone metabolism dually. Additionally, WFLL had more superior effect according to the theory of Chinese medicine for thousands of years.
To reveal the "superior multi-component structure (SMCS)" and its molecular mechanisms in parallelly down-regulating iron overload and rescuing bone metabolism by WFLL.
HPLC fingerprinting was established to compare the chemical profiles of FLL and WFLL; Then, the chemical compositions and quality markers of FLL and WFLL were analyzed by UPLC-Orbitrap-MS/MS coupled with OPLS-DA; the dynamic contents of quality markers and the multi-component structure at different wine steaming times (WST) were simultaneously determined by HPLC-DAD. Meanwhile, the dynamic efficacy of FLL at different WST were hunt by systematic zebrafish model. Subsequently, potential mechanism of WFLL in treating PMOP accompanied with iron overload was obtained from network pharmacology (NP) and molecular docking (MD). Finally, zebrafish and ovariectomy rat model were carried out to validate this potential mechanism.
HPLC fingerprints similarity of 15 batches in FLL and WFLL were among 0.9-1.0. 126 compositions were identified, including 58 iridoids, 25 terpenes, 30 phenylethanoids, 7 flavonoids and 6 others. 20 quality markers associated with WFLL was revealed, and the ratio of phenylethanols: Iridoids: Triterpenes (P/I/T) was converted from 1: 15: 4.5 to 1: 0.8: 0.9 during steaming (0 - 24 h) calculated by the quantification of 11 quality markers; the bone mineralization and motor performance of zebrafish larvae indicated that the optimum efficacy of WFLL at 12 h (p |
| doi_str_mv | 10.1016/j.phymed.2023.155275 |
| format | Article |
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To reveal the "superior multi-component structure (SMCS)" and its molecular mechanisms in parallelly down-regulating iron overload and rescuing bone metabolism by WFLL.
HPLC fingerprinting was established to compare the chemical profiles of FLL and WFLL; Then, the chemical compositions and quality markers of FLL and WFLL were analyzed by UPLC-Orbitrap-MS/MS coupled with OPLS-DA; the dynamic contents of quality markers and the multi-component structure at different wine steaming times (WST) were simultaneously determined by HPLC-DAD. Meanwhile, the dynamic efficacy of FLL at different WST were hunt by systematic zebrafish model. Subsequently, potential mechanism of WFLL in treating PMOP accompanied with iron overload was obtained from network pharmacology (NP) and molecular docking (MD). Finally, zebrafish and ovariectomy rat model were carried out to validate this potential mechanism.
HPLC fingerprints similarity of 15 batches in FLL and WFLL were among 0.9-1.0. 126 compositions were identified, including 58 iridoids, 25 terpenes, 30 phenylethanoids, 7 flavonoids and 6 others. 20 quality markers associated with WFLL was revealed, and the ratio of phenylethanols: Iridoids: Triterpenes (P/I/T) was converted from 1: 15: 4.5 to 1: 0.8: 0.9 during steaming (0 - 24 h) calculated by the quantification of 11 quality markers; the bone mineralization and motor performance of zebrafish larvae indicated that the optimum efficacy of WFLL at 12 h (p < 0.05) in which the SMCS of P/I/T was converted to 1: 4: 1.8. NP discovered that BMP-Smad pathway is one of the potential mechanisms of FLL in anti PMOP and then regulated bone formation and iron overload simultaneously. MD revealed that 17 active ingredients and 10 core targets genes could spontaneously bind with appropriate affinity. Rats model verified that FLL and WFLL significantly reversed PMOP, based on the improvement in bone formation indexes (ALP, OPG, OGN), iron metabolism indicators (hepcidin, ferritin), bone microstructure (BMD, BV/TV, Tb. Th, Tb. N); Moreover, WFLL significant enhanced reversal effect in anti-PMOP compared to FLL (p < 0.05). FLL and WFLL increased genes and proteins expression (Hep, BMP-6, p-Smad1/5, Smad4) related to BMP-Smad pathway compared with model group, and WFLL was more superior than FLL (p< 0.05).
The SMCS of FLL was optimized by wine-steam, WFLL represented a dual effect in downregulating iron overload and promoting bone formation, and the BMP-Smad pathway is one of the potential molecular mechanisms.</description><identifier>ISSN: 0944-7113</identifier><identifier>EISSN: 1618-095X</identifier><identifier>DOI: 10.1016/j.phymed.2023.155275</identifier><identifier>PMID: 38142661</identifier><language>eng</language><publisher>Germany</publisher><subject>animal models ; Animals ; bone mineralization ; Danio rerio ; Drugs, Chinese Herbal - chemistry ; Female ; ferritin ; flavonoids ; hepcidin ; Humans ; iridoids ; Iridoids - therapeutic use ; Iron ; iron absorption ; iron overload ; Iron Overload - drug therapy ; Ligustrum - chemistry ; microstructure ; Molecular Docking Simulation ; Oriental traditional medicine ; osteoporosis ; Osteoporosis - drug therapy ; Osteoporosis, Postmenopausal - drug therapy ; ovariectomy ; pharmacology ; postmenopause ; Rats ; risk factors ; Steam ; Tandem Mass Spectrometry ; triterpenoids ; Wine ; wines ; Zebrafish</subject><ispartof>Phytomedicine (Stuttgart), 2024-01, Vol.123, p.155275-155275, Article 155275</ispartof><rights>Copyright © 2023 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c340t-8306506d90e9b98fc08775d865a71e58ff06759652ecca5c2d2bb87d927513243</citedby><cites>FETCH-LOGICAL-c340t-8306506d90e9b98fc08775d865a71e58ff06759652ecca5c2d2bb87d927513243</cites><orcidid>0000-0003-1530-3277 ; 0009-0005-3531-7846 ; 0000-0002-6342-165X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38142661$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jiang, Jun</creatorcontrib><creatorcontrib>Zhao, Baixiu</creatorcontrib><creatorcontrib>Xiao, Jianpeng</creatorcontrib><creatorcontrib>Shi, Liang</creatorcontrib><creatorcontrib>Shang, Wei</creatorcontrib><creatorcontrib>Shu, Ye</creatorcontrib><creatorcontrib>Zhao, Zhiming</creatorcontrib><creatorcontrib>Shen, Junyi</creatorcontrib><creatorcontrib>Xu, Jingjuan</creatorcontrib><creatorcontrib>Cai, Hui</creatorcontrib><title>Exploring the boost of steaming with wine on Ligustri Lucidi Fructus in treating postmenopausal osteoporosis based on superior "multi-component structure" and iron/bone metabolism coregulation</title><title>Phytomedicine (Stuttgart)</title><addtitle>Phytomedicine</addtitle><description>Clinical studies indicated that postmenopausal osteoporosis (PMOP) often accompanied by iron overload risk factor, which exacerbated bone metabolism disorders and accelerated PMOP. Previous research found that multicomponent in Ligustri Lucidi Fructus (FLL) or wine-steamed FLL (WFLL) acted on the common targets of iron overload and PMOP simultaneously, which indicated that FLL and WFLL probably regulated iron/bone metabolism dually. Additionally, WFLL had more superior effect according to the theory of Chinese medicine for thousands of years.
To reveal the "superior multi-component structure (SMCS)" and its molecular mechanisms in parallelly down-regulating iron overload and rescuing bone metabolism by WFLL.
HPLC fingerprinting was established to compare the chemical profiles of FLL and WFLL; Then, the chemical compositions and quality markers of FLL and WFLL were analyzed by UPLC-Orbitrap-MS/MS coupled with OPLS-DA; the dynamic contents of quality markers and the multi-component structure at different wine steaming times (WST) were simultaneously determined by HPLC-DAD. Meanwhile, the dynamic efficacy of FLL at different WST were hunt by systematic zebrafish model. Subsequently, potential mechanism of WFLL in treating PMOP accompanied with iron overload was obtained from network pharmacology (NP) and molecular docking (MD). Finally, zebrafish and ovariectomy rat model were carried out to validate this potential mechanism.
HPLC fingerprints similarity of 15 batches in FLL and WFLL were among 0.9-1.0. 126 compositions were identified, including 58 iridoids, 25 terpenes, 30 phenylethanoids, 7 flavonoids and 6 others. 20 quality markers associated with WFLL was revealed, and the ratio of phenylethanols: Iridoids: Triterpenes (P/I/T) was converted from 1: 15: 4.5 to 1: 0.8: 0.9 during steaming (0 - 24 h) calculated by the quantification of 11 quality markers; the bone mineralization and motor performance of zebrafish larvae indicated that the optimum efficacy of WFLL at 12 h (p < 0.05) in which the SMCS of P/I/T was converted to 1: 4: 1.8. NP discovered that BMP-Smad pathway is one of the potential mechanisms of FLL in anti PMOP and then regulated bone formation and iron overload simultaneously. MD revealed that 17 active ingredients and 10 core targets genes could spontaneously bind with appropriate affinity. Rats model verified that FLL and WFLL significantly reversed PMOP, based on the improvement in bone formation indexes (ALP, OPG, OGN), iron metabolism indicators (hepcidin, ferritin), bone microstructure (BMD, BV/TV, Tb. Th, Tb. N); Moreover, WFLL significant enhanced reversal effect in anti-PMOP compared to FLL (p < 0.05). FLL and WFLL increased genes and proteins expression (Hep, BMP-6, p-Smad1/5, Smad4) related to BMP-Smad pathway compared with model group, and WFLL was more superior than FLL (p< 0.05).
The SMCS of FLL was optimized by wine-steam, WFLL represented a dual effect in downregulating iron overload and promoting bone formation, and the BMP-Smad pathway is one of the potential molecular mechanisms.</description><subject>animal models</subject><subject>Animals</subject><subject>bone mineralization</subject><subject>Danio rerio</subject><subject>Drugs, Chinese Herbal - chemistry</subject><subject>Female</subject><subject>ferritin</subject><subject>flavonoids</subject><subject>hepcidin</subject><subject>Humans</subject><subject>iridoids</subject><subject>Iridoids - therapeutic use</subject><subject>Iron</subject><subject>iron absorption</subject><subject>iron overload</subject><subject>Iron Overload - drug therapy</subject><subject>Ligustrum - chemistry</subject><subject>microstructure</subject><subject>Molecular Docking Simulation</subject><subject>Oriental traditional medicine</subject><subject>osteoporosis</subject><subject>Osteoporosis - drug therapy</subject><subject>Osteoporosis, Postmenopausal - drug therapy</subject><subject>ovariectomy</subject><subject>pharmacology</subject><subject>postmenopause</subject><subject>Rats</subject><subject>risk factors</subject><subject>Steam</subject><subject>Tandem Mass Spectrometry</subject><subject>triterpenoids</subject><subject>Wine</subject><subject>wines</subject><subject>Zebrafish</subject><issn>0944-7113</issn><issn>1618-095X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctq3DAUhkVpaCZp36AUkVU2nuhi2dKyhKQpDHSTQndGlo9nNNiSqwtN3q6PFrmTrLuRkM5_gfMh9JmSLSW0uTlul8PzDMOWEca3VAjWindoQxsqK6LEr_doQ1RdVy2l_BxdxHgkhNaqJR_QOZe0Zk1DN-jv3dMy-WDdHqcD4N77mLAfcUyg5_X3j02HcjjA3uGd3eeYgsW7bOxg8X3IJuWIrcMpgE6rYSkJMzi_6Bz1hMsL_OKDjzbiXkcY1qCYFwjWB3w15ynZyvh58Q5cKsX_MgNcYe0GbIN3N30Z4RmS7v1k44yND7DPU-nz7iM6G_UU4dPrfYl-3t893j5Uux_fvt9-3VWG1yRVkpNGkGZQBFSv5GiIbFsxyEboloKQ40iaVqhGMDBGC8MG1veyHVTZKuWs5pfo-pS7BP87Q0zdbKOBadIOfI4dJzXhrWRC_lfKFBFFKWtVpPVJasqCYoCxW4KddXjuKOlWzN2xO2HuVszdCXOxfXltyP06ezO9ceUv5q2qsA</recordid><startdate>202401</startdate><enddate>202401</enddate><creator>Jiang, Jun</creator><creator>Zhao, Baixiu</creator><creator>Xiao, Jianpeng</creator><creator>Shi, Liang</creator><creator>Shang, Wei</creator><creator>Shu, Ye</creator><creator>Zhao, Zhiming</creator><creator>Shen, Junyi</creator><creator>Xu, Jingjuan</creator><creator>Cai, Hui</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0003-1530-3277</orcidid><orcidid>https://orcid.org/0009-0005-3531-7846</orcidid><orcidid>https://orcid.org/0000-0002-6342-165X</orcidid></search><sort><creationdate>202401</creationdate><title>Exploring the boost of steaming with wine on Ligustri Lucidi Fructus in treating postmenopausal osteoporosis based on superior "multi-component structure" and iron/bone metabolism coregulation</title><author>Jiang, Jun ; Zhao, Baixiu ; Xiao, Jianpeng ; Shi, Liang ; Shang, Wei ; Shu, Ye ; Zhao, Zhiming ; Shen, Junyi ; Xu, Jingjuan ; Cai, Hui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c340t-8306506d90e9b98fc08775d865a71e58ff06759652ecca5c2d2bb87d927513243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>animal models</topic><topic>Animals</topic><topic>bone mineralization</topic><topic>Danio rerio</topic><topic>Drugs, Chinese Herbal - chemistry</topic><topic>Female</topic><topic>ferritin</topic><topic>flavonoids</topic><topic>hepcidin</topic><topic>Humans</topic><topic>iridoids</topic><topic>Iridoids - therapeutic use</topic><topic>Iron</topic><topic>iron absorption</topic><topic>iron overload</topic><topic>Iron Overload - drug therapy</topic><topic>Ligustrum - chemistry</topic><topic>microstructure</topic><topic>Molecular Docking Simulation</topic><topic>Oriental traditional medicine</topic><topic>osteoporosis</topic><topic>Osteoporosis - drug therapy</topic><topic>Osteoporosis, Postmenopausal - drug therapy</topic><topic>ovariectomy</topic><topic>pharmacology</topic><topic>postmenopause</topic><topic>Rats</topic><topic>risk factors</topic><topic>Steam</topic><topic>Tandem Mass Spectrometry</topic><topic>triterpenoids</topic><topic>Wine</topic><topic>wines</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Jun</creatorcontrib><creatorcontrib>Zhao, Baixiu</creatorcontrib><creatorcontrib>Xiao, Jianpeng</creatorcontrib><creatorcontrib>Shi, Liang</creatorcontrib><creatorcontrib>Shang, Wei</creatorcontrib><creatorcontrib>Shu, Ye</creatorcontrib><creatorcontrib>Zhao, Zhiming</creatorcontrib><creatorcontrib>Shen, Junyi</creatorcontrib><creatorcontrib>Xu, Jingjuan</creatorcontrib><creatorcontrib>Cai, Hui</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Phytomedicine (Stuttgart)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, Jun</au><au>Zhao, Baixiu</au><au>Xiao, Jianpeng</au><au>Shi, Liang</au><au>Shang, Wei</au><au>Shu, Ye</au><au>Zhao, Zhiming</au><au>Shen, Junyi</au><au>Xu, Jingjuan</au><au>Cai, Hui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exploring the boost of steaming with wine on Ligustri Lucidi Fructus in treating postmenopausal osteoporosis based on superior "multi-component structure" and iron/bone metabolism coregulation</atitle><jtitle>Phytomedicine (Stuttgart)</jtitle><addtitle>Phytomedicine</addtitle><date>2024-01</date><risdate>2024</risdate><volume>123</volume><spage>155275</spage><epage>155275</epage><pages>155275-155275</pages><artnum>155275</artnum><issn>0944-7113</issn><eissn>1618-095X</eissn><abstract>Clinical studies indicated that postmenopausal osteoporosis (PMOP) often accompanied by iron overload risk factor, which exacerbated bone metabolism disorders and accelerated PMOP. Previous research found that multicomponent in Ligustri Lucidi Fructus (FLL) or wine-steamed FLL (WFLL) acted on the common targets of iron overload and PMOP simultaneously, which indicated that FLL and WFLL probably regulated iron/bone metabolism dually. Additionally, WFLL had more superior effect according to the theory of Chinese medicine for thousands of years.
To reveal the "superior multi-component structure (SMCS)" and its molecular mechanisms in parallelly down-regulating iron overload and rescuing bone metabolism by WFLL.
HPLC fingerprinting was established to compare the chemical profiles of FLL and WFLL; Then, the chemical compositions and quality markers of FLL and WFLL were analyzed by UPLC-Orbitrap-MS/MS coupled with OPLS-DA; the dynamic contents of quality markers and the multi-component structure at different wine steaming times (WST) were simultaneously determined by HPLC-DAD. Meanwhile, the dynamic efficacy of FLL at different WST were hunt by systematic zebrafish model. Subsequently, potential mechanism of WFLL in treating PMOP accompanied with iron overload was obtained from network pharmacology (NP) and molecular docking (MD). Finally, zebrafish and ovariectomy rat model were carried out to validate this potential mechanism.
HPLC fingerprints similarity of 15 batches in FLL and WFLL were among 0.9-1.0. 126 compositions were identified, including 58 iridoids, 25 terpenes, 30 phenylethanoids, 7 flavonoids and 6 others. 20 quality markers associated with WFLL was revealed, and the ratio of phenylethanols: Iridoids: Triterpenes (P/I/T) was converted from 1: 15: 4.5 to 1: 0.8: 0.9 during steaming (0 - 24 h) calculated by the quantification of 11 quality markers; the bone mineralization and motor performance of zebrafish larvae indicated that the optimum efficacy of WFLL at 12 h (p < 0.05) in which the SMCS of P/I/T was converted to 1: 4: 1.8. NP discovered that BMP-Smad pathway is one of the potential mechanisms of FLL in anti PMOP and then regulated bone formation and iron overload simultaneously. MD revealed that 17 active ingredients and 10 core targets genes could spontaneously bind with appropriate affinity. Rats model verified that FLL and WFLL significantly reversed PMOP, based on the improvement in bone formation indexes (ALP, OPG, OGN), iron metabolism indicators (hepcidin, ferritin), bone microstructure (BMD, BV/TV, Tb. Th, Tb. N); Moreover, WFLL significant enhanced reversal effect in anti-PMOP compared to FLL (p < 0.05). FLL and WFLL increased genes and proteins expression (Hep, BMP-6, p-Smad1/5, Smad4) related to BMP-Smad pathway compared with model group, and WFLL was more superior than FLL (p< 0.05).
The SMCS of FLL was optimized by wine-steam, WFLL represented a dual effect in downregulating iron overload and promoting bone formation, and the BMP-Smad pathway is one of the potential molecular mechanisms.</abstract><cop>Germany</cop><pmid>38142661</pmid><doi>10.1016/j.phymed.2023.155275</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-1530-3277</orcidid><orcidid>https://orcid.org/0009-0005-3531-7846</orcidid><orcidid>https://orcid.org/0000-0002-6342-165X</orcidid></addata></record> |
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| subjects | animal models Animals bone mineralization Danio rerio Drugs, Chinese Herbal - chemistry Female ferritin flavonoids hepcidin Humans iridoids Iridoids - therapeutic use Iron iron absorption iron overload Iron Overload - drug therapy Ligustrum - chemistry microstructure Molecular Docking Simulation Oriental traditional medicine osteoporosis Osteoporosis - drug therapy Osteoporosis, Postmenopausal - drug therapy ovariectomy pharmacology postmenopause Rats risk factors Steam Tandem Mass Spectrometry triterpenoids Wine wines Zebrafish |
| title | Exploring the boost of steaming with wine on Ligustri Lucidi Fructus in treating postmenopausal osteoporosis based on superior "multi-component structure" and iron/bone metabolism coregulation |
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