{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T23:53:52Z","timestamp":1778630032185,"version":"3.51.4"},"reference-count":118,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Traditional Chinese medicine (TCM) has been practiced in the treatment of bone diseases and alcoholism. Chronic excessive alcohol use results in alcohol-induced bone diseases, including osteopenia and osteoporosis, which increases fracture risk, deficient bone repair, and osteonecrosis. This preclinical study investigated the therapeutic effects of TCM herbal extracts in animal models of chronic excessive alcohol consumption-induced osteopenia. TCM herbal extracts (Jing extracts) were prepared from nine Chinese herbal medicines, a combinative herbal formula for antifatigue and immune regulation, including <jats:italic>Astragalus<\/jats:italic>, <jats:italic>Cistanche deserticola<\/jats:italic>, <jats:italic>Dioscorea polystachya<\/jats:italic>, <jats:italic>Lycium barbarum<\/jats:italic>, <jats:italic>Epimedium<\/jats:italic>, <jats:italic>Cinnamomum cassia<\/jats:italic>, <jats:italic>Syzygium aromaticum<\/jats:italic>, <jats:italic>Angelica sinensis<\/jats:italic>, and <jats:italic>Curculigo orchioides<\/jats:italic>. In this study, Balb\/c male mice were orally administrated alcohol (3.2\u00a0g\/kg\/day) with\/without TCM herbal extracts (0.125\u00a0g\/kg, 0.25\u00a0g\/kg, or 0.5\u00a0g\/kg) by gavage. Our results showed that after 50\u00a0days of oral administration, TCM herbal extracts prevented alcohol-induced osteopenia demonstrated by \u03bc-CT bone morphological analysis in young adults and middle-aged\/old Balb\/c male mice. Biochemical analysis demonstrated that chronic alcohol consumption inhibits bone formation and has a neutral impact on bone resorption, suggesting that TCM herbal extracts (Jing extracts) mitigate the alcohol-induced abnormal bone metabolism in middle-aged\/old male mice. Protocatechuic acid, a natural phenolic acid in Jing extracts, mitigates <jats:italic>in vivo<\/jats:italic> alcohol-induced decline of alkaline phosphatase (ALP) gene expression in the bone marrow of Balb\/c male mice and <jats:italic>in vitro<\/jats:italic> ALP activity in pre-osteoblast MC3T3-E1 cells. Our study suggests that TCM herbal extracts prevent chronic excessive alcohol consumption-induced osteopenia in male mice, implying that traditional medicinal plants have the therapeutic potential of preventing alcohol-induced bone diseases.<\/jats:p>","DOI":"10.3389\/fphar.2021.754088","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T11:35:42Z","timestamp":1639568142000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["A Traditional Chinese Medicine Plant Extract Prevents Alcohol-Induced Osteopenia"],"prefix":"10.3389","volume":"12","author":[{"given":"Dongyang","family":"Qian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anish","family":"Patel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiguang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqiang","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yimin","family":"Shan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lily","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuancai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuanhu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.2174\/13894501113146660231","article-title":"Pathogenesis of Alcohol-Induced Osteoporosis and its Treatment: a Review","volume":"14","author":"Abukhadir","year":"2013","journal-title":"Curr. Drug Targets."},{"key":"B2","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1093\/alcalc\/agp038","article-title":"Osteopenia in Alcoholics: Effect of Alcohol Abstinence","volume":"44","author":"Alvisa-Negr\u00edn","year":"2009","journal-title":"Alcohol Alcohol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.lfs.2016.01.024","article-title":"Natural Products for Treatment of Osteoporosis: The Effects and Mechanisms on Promoting Osteoblast-Mediated Bone Formation","volume":"147","author":"An","year":"2016","journal-title":"Life Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/nprot.2013.032","article-title":"Mouse Model of Chronic and Binge Ethanol Feeding (The NIAAA Model)","volume":"8","author":"Bertola","year":"2013","journal-title":"Nat. Protoc."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.3390\/nu10111680","article-title":"Protective Effects of Dioscorea Batatas Flesh and Peel Extracts Against Ethanol-Induced Gastric Ulcer in Mice","volume":"10","author":"Byeon","year":"2018","journal-title":"Nutrients."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/beverages6010001","article-title":"Compound Analysis of Jing Liqueur and Nrf2 Activation by Jing Liqueur-One of the Most Popular Beverages in China","volume":"6","author":"Cai","year":"2020","journal-title":"Beverages."},{"key":"B7","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.maturitas.2008.03.010","article-title":"Curculigo Orchioides, a Traditional Chinese Medicinal Plant, Prevents Bone Loss in Ovariectomized Rats","volume":"59","author":"Cao","year":"2008","journal-title":"Maturitas."},{"key":"B8","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3390\/nu10020247","article-title":"Oleanolic Acid Exerts Osteoprotective Effects and Modulates Vitamin D Metabolism","volume":"10","author":"Cao","year":"2018","journal-title":"Nutrients."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2077","DOI":"10.1097\/01.alc.0000192039.21305.55","article-title":"Alcohol-Induced Bone Loss and Deficient Bone Repair","volume":"29","author":"Chakkalakal","year":"2005","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1016\/j.bone.2012.08.113","article-title":"The Collection of NFATc1-Dependent Transcripts in the Osteoclast Includes Numerous Genes Non-Essential to Physiologic Bone Resorption","volume":"51","author":"Charles","year":"2012","journal-title":"Bone."},{"key":"B11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41413-020-00128-8","article-title":"Nrf2 Epigenetic Derepression Induced by Running Exercise Protects Against Osteoporosis","volume":"9","author":"Chen","year":"2021","journal-title":"Bone Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1016\/j.biopha.2018.08.069","article-title":"Beneficial Effects of Hyperoside on Bone Metabolism in Ovariectomized Mice","volume":"107","author":"Chen","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/pan3.10166","article-title":"Understanding Traditional Chinese Medicine to Strengthen Conservation Outcomes","volume":"3","author":"Cheung","year":"2021","journal-title":"People Nat."},{"key":"B14","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"The Lancet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.1007\/s00198-014-2794-2","article-title":"Clinician's Guide to Prevention and Treatment of Osteoporosis","volume":"25","author":"Cosman","year":"2014","journal-title":"Osteoporos. Int."},{"key":"B16","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1172\/JCI10483","article-title":"Chronic Alcohol Ingestion Induces Osteoclastogenesis and Bone Loss Through IL-6 in Mice","volume":"106","author":"Dai","year":"2000","journal-title":"J. Clin. Invest."},{"key":"B17","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1302\/0301-620x.84b6.11994","article-title":"Mutual Associations Among Microstructural, Physical and Mechanical Properties of Human Cancellous Bone","volume":"84","author":"Ding","year":"2002","journal-title":"J. Bone Jt. Surg Br."},{"key":"B18","doi-asserted-by":"publisher","first-page":"114299","DOI":"10.1016\/j.jep.2021.114299","article-title":"Potentiation of Flutamide-Induced Hepatotoxicity in Mice by Xian-Ling-Gu-Bao through Induction of CYP1A2","volume":"278","author":"Ding","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.jep.2015.08.053","article-title":"Spirits and Liqueurs in European Traditional Medicine: Their History and Ethnobotany in Tuscany and Bologna (Italy)","volume":"175","author":"Egea","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"B20","first-page":"64","article-title":"A Review of Presence of Oleanolic Acid in Natural Products","volume":"2","author":"Fai","year":"2009","journal-title":"Nat. Prod. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1093\/oxfordjournals.aje.a117664","article-title":"Alcohol Intake and Bone Mineral Density in Elderly Men and Women. The Framingham Study","volume":"142","author":"Felson","year":"1995","journal-title":"Am. J. Epidemiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3527809","DOI":"10.1155\/2019\/3527809","article-title":"Protocatechuic Acid-Mediated miR-219a-5p Activation Inhibits the P66shc Oxidant Pathway to Alleviate Alcoholic Liver Injury","volume":"2019","author":"Fu","year":"2019","journal-title":"Oxid Med. Cel Longev."},{"key":"B23","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1111\/acer.13000","article-title":"Alcohol: A Simple Nutrient With Complex Actions on Bone in the Adult Skeleton","volume":"40","author":"Gaddini","year":"2016","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/nature25154","article-title":"Alcohol and Endogenous Aldehydes Damage Chromosomes and Mutate Stem Cells","volume":"553","author":"Garaycoechea","year":"2018","journal-title":"Nature."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/S0140-6736(18)31310-2","article-title":"Alcohol Use and Burden for 195 Countries and Territories, 1990-2016: a Systematic Analysis for the Global Burden of Disease Study 2016","volume":"392","year":"2018","journal-title":"Lancet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.ijbiomac.2016.09.039","article-title":"Preliminary Characterizations, Antioxidant and Hepatoprotective Activity of Polysaccharide From Cistanche Deserticola","volume":"93","author":"Guo","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jep.2016.03.033","article-title":"The In Vivo Effects of a Fraction From Dioscorea Spongiosa on Glucocorticoid-Induced Osteoporosis","volume":"185","author":"Han","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"B28","first-page":"S74","article-title":"Drug Discovery in Traditional Chinese Medicine: From Herbal Fufang to Combinatory Drugs","volume":"350","author":"He","year":"2015","journal-title":"Sponsored Suppl. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1080\/01495739708936692","article-title":"Quantification of Bone Microarchitecture With the Structure Model Index","volume":"1","author":"Hildebrand","year":"1997","journal-title":"Comput. Methods Biomech. Biomed. Engin"},{"key":"B30","doi-asserted-by":"publisher","first-page":"109205","DOI":"10.1016\/j.biopha.2019.109205","article-title":"Ferulic Acid, a Natural Polyphenol, Protects Against Osteoporosis by Activating SIRT1 and NF-\u039ab in Neonatal Rats With Glucocorticoid-Induced Osteoporosis","volume":"120","author":"Hou","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"B31","doi-asserted-by":"publisher","first-page":"211","DOI":"10.7326\/0003-4819-140-6-200403160-00011","article-title":"Effect of Alcohol Consumption on Diabetes Mellitus: a Systematic Review","volume":"140","author":"Howard","year":"2004","journal-title":"Ann. Intern. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s13020-021-00435-0","article-title":"Simultaneous Quantification of Bioactive Components in Chinese Herbal Spirits by Ultra-High Performance Liquid Chromatography Coupled to Triple-Quadrupole Mass Spectrometry (UHPLC-QQQ-MS\/MS)","volume":"16","author":"Hu","year":"2021","journal-title":"Chin. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1002\/ptr.5218","article-title":"The Standardized BHH10 Extract, a Combination of Astragalus Membranaceus, Cinnamomum Cassia, and Phellodendron Amurense, Reverses Bone Mass and Metabolism in a Rat Model of Postmenopausal Osteoporosis","volume":"29","author":"Huh","year":"2015","journal-title":"Phytother Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"8299","DOI":"10.1038\/s41598-019-44575-8","article-title":"Variable Osteogenic Performance of MC3T3-E1 Subclones Impacts Their Utility as Models of Osteoblast Biology","volume":"9","author":"Hwang","year":"2019","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1111\/acer.12105","article-title":"Intraperitoneal Injection of Ethanol Results in Drastic Changes in Bone Metabolism Not Observed When Ethanol Is Administered by Oral Gavage","volume":"37","author":"Iwaniec","year":"2013","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.18203\/2319-2003.ijbcp20192672","article-title":"Evaluation of Antioxidant and Hepatoprotective Property of Ethanolic Extract of Curculigoorchioides in Albino Rats","volume":"8","author":"Jacob Jesurun","year":"2019","journal-title":"Int. J. Basic Clin. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"7280342","DOI":"10.1155\/2018\/7280342","article-title":"Protocatechuic Acid Attenuates Trabecular Bone Loss in Ovariectomized Mice","volume":"2018","author":"Jang","year":"2018","journal-title":"Oxid Med. Cel Longev."},{"key":"B38","doi-asserted-by":"publisher","first-page":"361","DOI":"10.3892\/mmr.2016.5269","article-title":"Syzygium Aromaticum Water Extract Attenuates Ethanol Induced Gastric Injury Through Antioxidant Effects in Rats","volume":"14","author":"Jin","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"B39","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s11684-014-0362-y","article-title":"Mechanisms of \"Kidney Governing Bones\" Theory in Traditional Chinese Medicine","volume":"8","author":"Ju","year":"2014","journal-title":"Front. Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"952943","DOI":"10.1155\/2014\/952943","article-title":"A Review on Protocatechuic Acid and its Pharmacological Potential","volume":"2014","author":"Kakkar","year":"2014","journal-title":"ISRN Pharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/s12011-012-9527-1","article-title":"Effects of Astragalus Membranaceus With Supplemental Calcium on Bone Mineral Density and Bone Metabolism in Calcium-Deficient Ovariectomized Rats","volume":"151","author":"Kang","year":"2013","journal-title":"Biol. Trace Elem. Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"482","DOI":"10.3945\/jn.108.100495","article-title":"Cinnamon Extract Protects Against Acute Alcohol-Induced Liver Steatosis in Mice","volume":"139","author":"Kanuri","year":"2009","journal-title":"J. Nutr."},{"key":"B43","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1093\/aje\/kwn294","article-title":"Light to Moderate Alcohol Consumption and Disability: Variable Benefits by Health Status","volume":"169","author":"Karlamangla","year":"2009","journal-title":"Am. J. Epidemiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1080\/14786419.2010.511216","article-title":"Clove (Syzygium Aromaticum Linn) Extract Rich in Eugenol and Eugenol Derivatives Shows Bone-Preserving Efficacy","volume":"26","author":"Karmakar","year":"2012","journal-title":"Nat. Prod. Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/s0031-9422(97)00723-1","article-title":"Kudzu Root: an Ancient Chinese Source of Modern Antidipsotropic Agents","volume":"47","author":"Keung","year":"1998","journal-title":"Phytochemistry."},{"key":"B46","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.intimp.2019.01.020","article-title":"Acteoside Ameliorates Inflammatory Responses Through NFkB Pathway in Alcohol Induced Hepatic Damage","volume":"69","author":"Khullar","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.jcma.2016.11.006","article-title":"Improvement of Osteoporosis by Lycium Chinense Administration in Ovariectomized Mice","volume":"80","author":"Kim","year":"2017","journal-title":"J. Chin. Med. Assoc."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e1002585","DOI":"10.1371\/journal.pmed.1002585","article-title":"The Association of Lifetime Alcohol Use With Mortality and Cancer Risk in Older Adults: A Cohort Study","volume":"15","author":"Kunzmann","year":"2018","journal-title":"Plos Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"133","DOI":"10.11005\/jbm.2018.25.3.133","article-title":"Treatment of Osteoporosis: Unmet Needs and Emerging Solutions","volume":"25","author":"Langdahl","year":"2018","journal-title":"J. Bone Metab."},{"key":"B51","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.phymed.2013.01.001","article-title":"Antiosteoporotic Activity of Echinacoside in Ovariectomized Rats","volume":"20","author":"Li","year":"2013","journal-title":"Phytomedicine."},{"key":"B52","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1691\/ph.2016.6627","article-title":"Calycosin Attenuates Osteoporosis and Regulates the Expression of OPG\/RANKL in Ovariectomized Rats via MAPK Signaling","volume":"71","author":"Li","year":"2016","journal-title":"Pharmazie."},{"key":"B53","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1111\/j.2042-7158.2012.01483.x","article-title":"Cistanche Deserticola Extract Increases Bone Formation in Osteoblasts","volume":"64","author":"Li","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"4362","DOI":"10.3390\/nu6104362","article-title":"Anti-osteoporotic Effects of Angelica Sinensis (Oliv.) Diels Extract on Ovariectomized Rats and its Oral Toxicity in Rats","volume":"6","author":"Lim","year":"2014","journal-title":"Nutrients."},{"key":"B55","doi-asserted-by":"publisher","first-page":"496","DOI":"10.5582\/bst.2017.01216","article-title":"Chinese Single Herbs and Active Ingredients for Postmenopausal Osteoporosis: From Preclinical Evidence to Action Mechanism","volume":"11","author":"Lin","year":"2017","journal-title":"Biosci. Trends."},{"key":"B56","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.cbi.2014.07.017","article-title":"Oleanolic Acid Co-administration Alleviates Ethanol-Induced Hepatic Injury via Nrf-2 and Ethanol-Metabolizing Modulating in Rats","volume":"221","author":"Liu","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"B57","first-page":"CN100392399C","article-title":"Method for Checking Quality of Chinese Jing Wine by Using Fingerprint Pattern Technology","author":"Liu","year":"2008","journal-title":"China Patent."},{"key":"B58","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.18632\/oncotarget.13732","article-title":"Icariside II Activates EGFR-Akt-Nrf2 Signaling and Protects Osteoblasts from Dexamethasone","volume":"8","author":"Liu","year":"2017","journal-title":"Oncotarget."},{"key":"B59","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s10856-020-06472-9","article-title":"Development of Epimedin A Complex Drugs for Treating the Osteoporosis","volume":"32","author":"Liu","year":"2021","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1002\/stem.2392","article-title":"Chronic High Dose Alcohol Induces Osteopenia via Activation of mTOR Signaling in Bone Marrow Mesenchymal Stem Cells","volume":"34","author":"Liu","year":"2016","journal-title":"Stem Cells."},{"key":"B62","first-page":"1080","article-title":"The Effects of China Jing Wine on the Functions of Hypothalamic-Pituitary-Adrenal axis and Immune System in the Shen-Yang Deficiency Model Rats","volume":"27","author":"Liu","year":"2011","journal-title":"Chin. J. Immunol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"609","DOI":"10.4321\/s1130-01082013001000006","article-title":"Alcoholic Liver Disease and Changes in Bone mineral Density","volume":"105","author":"L\u00f3pez-Larramona","year":"2013","journal-title":"Rev. Esp Enferm Dig."},{"key":"B64","first-page":"82","article-title":"The Effects of Chinese JING Liqueur in Relieving the Fatigue of the Patients With Fatigued Sub-Health Status","volume":"30","author":"Lu","year":"2017","journal-title":"West. J. Traditional Chin. Med."},{"key":"B65","first-page":"562","article-title":"Clinical Observation of Main Symptoms Relief by Chinese Jing Liqueur in Patients With Kidney Yang Deficiency Syndrome","volume":"40","author":"Lu","year":"2018","journal-title":"Chin. Traditional Patent Med."},{"key":"B66","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s40709-018-0079-1","article-title":"Changes in the Microstructure of Compact and Trabecular Bone Tissues of Mice Subchronically Exposed to Alcohol","volume":"25","author":"Martiniakova","year":"2018","journal-title":"J. Biol. Res. (Thessalon)."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00198-011-1787-7","article-title":"Alcohol and Bone: Review of Dose Effects and Mechanisms","volume":"23","author":"Maurel","year":"2012","journal-title":"Osteoporos. Int."},{"key":"B68","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1124\/jpet.112.197038","article-title":"Vitamin D Supplementation Protects Against Bone Loss Associated With Chronic Alcohol Administration in Female Mice","volume":"343","author":"Mercer","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B69","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s10354-013-0258-5","article-title":"Alcohol and Bone","volume":"164","author":"Mikosch","year":"2014","journal-title":"Wien Med. Wochenschr."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.2105\/AJPH.2016.303336","article-title":"Key Findings on Alcohol Consumption and a Variety of Health Outcomes From the Nurses' Health Study","volume":"106","author":"Mostofsky","year":"2016","journal-title":"Am. J. Public Health."},{"key":"B71","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A Simple Practice Guide for Dose Conversion Between Animals and Human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"B72","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/nrgastro.2009.166","article-title":"Current Understanding of Osteoporosis Associated with Liver Disease","volume":"6","author":"Nakchbandi","year":"2009","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B73","unstructured":"Alcohol Facts and Statistics2021"},{"key":"B74","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1272\/jnms.JNMS.2018_85-52","article-title":"The Contribution of Alcohol Dehydrogenase 3 to the Development of Alcoholic Osteoporosis in Mice","volume":"85","author":"Okuda","year":"2018","journal-title":"J. Nippon Med. Sch."},{"key":"B76","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1089\/jmf.2004.7.456","article-title":"Hepatoprotective Role of Ferulic Acid: a Dose-dependent Study","volume":"7","author":"Rukkumani","year":"2004","journal-title":"J. Med. Food."},{"key":"B77","doi-asserted-by":"publisher","first-page":"162","DOI":"10.3389\/fendo.2015.00162","article-title":"Structure Model Index Does Not Measure Rods and Plates in Trabecular Bone","volume":"6","author":"Salmon","year":"2015","journal-title":"Front. Endocrinol. (Lausanne)."},{"key":"B78","first-page":"292","article-title":"Alcohol and Other Factors Affecting Osteoporosis Risk in Women","volume":"26","author":"Sampson","year":"2002","journal-title":"Alcohol. Res. Health."},{"key":"B79","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/j.1530-0277.1998.tb05912.x","article-title":"Alcohol's Harmful Effects on Bone","volume":"22","author":"Sampson","year":"1998","journal-title":"Alcohol. Health Res. World."},{"key":"B80","first-page":"1600","article-title":"Effects of Chinese Jing Liqueur on Fatigue, Immunity, and Sexual Function","volume":"40","author":"Shan","year":"2018","journal-title":"Chin. Traditional Patent Med."},{"key":"B81","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1017\/S136898001200331X","article-title":"Alcohol Consumption and Bone mineral Density in Elderly Women","volume":"16","author":"Sommer","year":"2013","journal-title":"Public Health Nutr."},{"key":"B82","doi-asserted-by":"publisher","first-page":"112836","DOI":"10.1016\/j.jpba.2019.112836","article-title":"Simultaneous Determination of Multiple Components in Rat Plasma and Pharmacokinetic Studies at a Pharmacodynamic Dose of Xian-Ling-Gu-Bao Capsule by UPLC-MS\/MS","volume":"177","author":"Tang","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B83","doi-asserted-by":"publisher","first-page":"111956","DOI":"10.1016\/j.fct.2020.111956","article-title":"Echinacoside Ameliorates Alcohol-Induced Oxidative Stress and Hepatic Steatosis by Affecting SREBP1c\/FASN Pathway via PPAR\u03b1","volume":"148","author":"Tao","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"322","DOI":"10.4077\/CJP.2015.BAD325","article-title":"Improving Bone Microarchitecture in Aging With Diosgenin Treatment: A Study in Senescence-Accelerated OXYS Rats","volume":"58","author":"Tikhonova","year":"2015","journal-title":"Chin. J. Physiol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.3945\/ajcn.2008.26765","article-title":"Effects of Beer, Wine, and Liquor Intakes on Bone mineral Density in Older Men and Women","volume":"89","author":"Tucker","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1111\/j.1530-0277.2000.tb01971.x","article-title":"Skeletal Response to Alcohol","volume":"24","author":"Turner","year":"2000","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"B87","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.jep.2006.11.037","article-title":"Are Herb-Pairs of Traditional Chinese Medicine Distinguishable From Others? Pattern Analysis and Artificial Intelligence Classification Study of Traditionally Defined Herbal Properties","volume":"111","author":"Ung","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"B88","unstructured":"U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-20252020"},{"key":"B89","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.drugalcdep.2019.04.023","article-title":"Differences in Alcohol Use Between Younger and Older People: Results From a General Population Study","volume":"202","author":"Veerbeek","year":"2019","journal-title":"Drug Alcohol Depend."},{"key":"B90","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.taap.2007.02.011","article-title":"Chronic Ethanol Exposure Inhibits Distraction Osteogenesis in a Mouse Model: Role of the TNF Signaling axis","volume":"220","author":"Wahl","year":"2007","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"113899","DOI":"10.1016\/j.jep.2021.113899","article-title":"Total Glycosides and Polysaccharides of Cistanche Deserticola Prevent Osteoporosis by Activating Wnt\/\u03b2-Catenin Signaling Pathway in SAMP6 Mice","volume":"271","author":"Wang","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"6528","DOI":"10.1002\/fsn3.1942","article-title":"Hepatoprotective Effect of Crude Polysaccharide Isolated From Lycium Barbarum L. Against Alcohol-Induced Oxidative Damage Involves Nrf2 Signaling","volume":"8","author":"Wang","year":"","journal-title":"Food Sci. Nutr."},{"key":"B93","doi-asserted-by":"publisher","first-page":"118996","DOI":"10.1016\/j.ijpharm.2019.118996","article-title":"Self-Assembled Angelica Sinensis Polysaccharide Nanoparticles With an Instinctive Liver-Targeting Ability as a Drug Carrier for Acute Alcoholic Liver Damage protection","volume":"577","author":"Wang","year":"","journal-title":"Int. J. Pharm."},{"key":"B94","doi-asserted-by":"publisher","first-page":"4370263","DOI":"10.1155\/2016\/4370263","article-title":"From \"Kidneys Govern Bones\" to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science","volume":"2016","author":"Wang","year":"2016","journal-title":"Evid. Based Complement. Alternat Med."},{"key":"B95","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1007\/s00198-017-4255-1","article-title":"The Effect of Icariin on Bone Metabolism and its Potential Clinical Application","volume":"29","author":"Wang","year":"2018","journal-title":"Osteoporos. Int."},{"key":"B96","doi-asserted-by":"publisher","first-page":"5304","DOI":"10.1002\/jcb.27806","article-title":"Daidzin Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents LPS-Induced Bone Loss In Vivo","volume":"120","author":"Wei","year":"2019","journal-title":"J. Cel Biochem."},{"key":"B97","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1007\/s00223-010-9359-y","article-title":"Age-Related Changes in Bone Structure and Strength in Female and Male BALB\/c Mice","volume":"86","author":"Willinghamm","year":"2010","journal-title":"Calcif Tissue Int."},{"key":"B98","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1002\/ptr.4966","article-title":"Animal Studies on Medicinal Herbs: Predictability, Dose Conversion and Potential Value","volume":"28","author":"Wojcikowski","year":"2014","journal-title":"Phytother Res."},{"key":"B99","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1016\/S0140-6736(18)30134-X","article-title":"Risk Thresholds for Alcohol Consumption: Combined Analysis of Individual-Participant Data for 599\u2008912 Current Drinkers in 83 Prospective Studies","volume":"391","author":"Wood","year":"2018","journal-title":"Lancet."},{"key":"B100","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.1002\/jbmr.2269","article-title":"The Recent Prevalence of Osteoporosis and Low Bone Mass in the United States Based on Bone Mineral Density at the Femoral Neck or Lumbar Spine","volume":"29","author":"Wright","year":"2014","journal-title":"J. Bone Miner Res."},{"key":"B101","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1159\/000489248","article-title":"Icariin Restores Bone Structure and Strength in a Rat Model of Chronic High-Dose Alcohol-Induced Osteopenia","volume":"46","author":"Wu","year":"2018","journal-title":"Cell Physiol Biochem."},{"key":"B102","first-page":"359","article-title":"Effect of Xianling Gubao Capsules on Bone Mineral Density in Osteoporosis Patients","volume":"31","author":"Wu","year":"2017","journal-title":"J. Biol. Regul. Homeost Agents."},{"key":"B103","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s11655-010-0799-7","article-title":"History of Chinese Medicinal Wine","volume":"19","author":"Xia","year":"2013","journal-title":"Chin. J. Integr. Med."},{"key":"B104","doi-asserted-by":"publisher","first-page":"162","DOI":"10.3109\/00952990.2015.1114118","article-title":"An Open-Label Pilot Study of Icariin for Co-Morbid Bipolar and Alcohol Use Disorder","volume":"42","author":"Xiao","year":"2016","journal-title":"Am. J. Drug Alcohol. Abuse."},{"key":"B105","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/j.jep.2012.09.041","article-title":"Effect of a Derived Herbal Recipe from an Ancient Chinese Formula, Danggui Buxue Tang, on Ovariectomized Rats","volume":"144","author":"Xie","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"6991","DOI":"10.1038\/s41598-019-43518-7","article-title":"Ligustilide, a Major Bioactive Component of Angelica Sinensis, Promotes Bone Formation via the GPR30\/EGFR Pathway","volume":"9","author":"Yang","year":"","journal-title":"Sci. Rep."},{"key":"B107","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.3390\/ijms20122974","article-title":"Protective Effect of Acteoside on Ovariectomy-Induced Bone Loss in Mice","volume":"20","author":"Yang","year":"","journal-title":"Int. J. Mol. Sci."},{"key":"B109","doi-asserted-by":"publisher","first-page":"83","DOI":"10.37094\/adyujsci.729426","article-title":"Histopathological and Biochemical Effects of Eugenol on Alcohol-Treated Rat Liver","volume":"10","author":"Yildiz","year":"2020","journal-title":"ADYU J. SCI."},{"key":"B110","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1089\/jmf.2016.0023","article-title":"A Standardized Composition From Extracts of Myristica Fragrans, Astragalus Membranaceus, and Poria Cocos Protects Liver From Acute Ethanol Insult","volume":"19","author":"Yimam","year":"2016","journal-title":"J. Med. Food."},{"key":"B111","doi-asserted-by":"publisher","first-page":"D1118","DOI":"10.1093\/nar\/gky965","article-title":"CMAUP: a Database of Collective Molecular Activities of Useful Plants","volume":"47","author":"Zeng","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B112","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.3389\/fphar.2019.01412","article-title":"Anti-Osteoporotic Activity of an Edible Traditional Chinese Medicine Cistanche Deserticola on Bone Metabolism of Ovariectomized Rats Through RANKL\/RANK\/TRAF6-Mediated Signaling Pathways","volume":"10","author":"Zhang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B113","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1016\/j.bone.2005.11.019","article-title":"Flavonoids Derived From Herbal Epimedium Brevicornum Maxim Prevent OVX-Induced Osteoporosis in Rats Independent of its Enhancement in Intestinal Calcium Absorption","volume":"38","author":"Zhang","year":"2006","journal-title":"Bone."},{"key":"B114","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jep.2016.05.025","article-title":"Traditional Chinese Medicine Formulas for the Treatment of Osteoporosis: Implication for Antiosteoporotic Drug Discovery","volume":"189","author":"Zhang","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"B115","doi-asserted-by":"publisher","first-page":"190","DOI":"10.3389\/fnins.2019.00190","article-title":"Challenge and Prospect of Traditional Chinese Medicine in Depression Treatment","volume":"13","author":"Zhang","year":"2019","journal-title":"Front. Neurosci."},{"key":"B116","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1055\/s-0035-1558294","article-title":"Beneficial Effects of a Flavonoid Fraction of Herba Epimedii on Bone Metabolism in Ovariectomized Rats","volume":"82","author":"Zhao","year":"2016","journal-title":"Planta Med."},{"key":"B117","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/nyas.13464","article-title":"Chronic Kidney Disease and Vitamin D Metabolism in Human Bone Marrow-Derived MSCs","volume":"1402","author":"Zhou","year":"2017","journal-title":"Ann. N. Y Acad. Sci."},{"key":"B118","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/bs.vh.2018.01.005","article-title":"Dehydroepiandrosterone and Bone","volume":"108","author":"Zhou","year":"2018","journal-title":"Vitam Horm."},{"key":"B119","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1111\/j.1474-9726.2008.00377.x","article-title":"Age-Related Intrinsic Changes in Human Bone-Marrow-Derived Mesenchymal Stem Cells and Their Differentiation to Osteoblasts","volume":"7","author":"Zhou","year":"2008","journal-title":"Aging Cell."},{"key":"B120","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.jsbmb.2012.09.009","article-title":"Vitamin D Metabolism and Action in Human Marrow Stromal Cells: Effects of Chronic Kidney Disease","volume":"136","author":"Zhou","year":"2013","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B121","doi-asserted-by":"publisher","first-page":"10573","DOI":"10.1038\/srep10573","article-title":"Paracrine Effects of Haematopoietic Cells on Human Mesenchymal Stem Cells","volume":"5","author":"Zhou","year":"2015","journal-title":"Sci. Rep."},{"key":"B122","doi-asserted-by":"publisher","first-page":"524","DOI":"10.3390\/antiox8110524","article-title":"White Peony (Fermented Camellia Sinensis) Polyphenols Help Prevent Alcoholic Liver Injury via Antioxidation","volume":"8","author":"Zhou","year":"2019","journal-title":"Antioxidants (Basel)."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.754088\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T17:40:55Z","timestamp":1640194855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.754088\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,15]]},"references-count":118,"alternative-id":["10.3389\/fphar.2021.754088"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.754088","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,15]]},"article-number":"754088"}}