{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:00:39Z","timestamp":1787666439303,"version":"build-2736575974"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"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>Although osteoarthritis (OA) significantly affects the quality of life of the elderly, there is still no effective treatment strategy. The standardized <jats:italic>Ginkgo biloba<\/jats:italic> L. extract preparation has been shown to have a wide range of therapeutic effects. Bilobalide, a unique ingredient of <jats:italic>Ginkgo biloba<\/jats:italic>, has anti-inflammatory and antioxidant pharmacological properties, but its mechanism of action on OA remains unknown. In this study, we investigated the effects of bilobalide on the development of OA through <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> experiments, as well as its potential anti-inflammatory mechanisms. The <jats:italic>in vitro<\/jats:italic> experiments demonstrated that bilobalide significantly inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metalloproteinase 13 (MMP13) in ATDC5 chondrocytes induced by Interleukin-1\u03b2 (IL-1\u03b2). At the molecular level, bilobalide induced chondrocyte autophagy by activating the AMPK\/SIRT1\/mTOR signaling pathway, which increased the expression of autophagy-related Atg genes, up-regulated the expression of LC3 protein, and reduced the expression of the p62 protein. <jats:italic>In vivo<\/jats:italic>, bilobalide exerted significant anti-inflammatory and anti-extracellular matrix (ECM) degradation effects in a rat model of post-traumatic OA (PTOA) induced by anterior cruciate ligament transection (ACLT). Bilobalide could relieve joint pain in PTOA rats, inhibit the expression of iNOS and COX-2 protein in cartilage via the AMPK\/SIRT1\/mTOR pathway, and reduce the level of ECM degradation biomarkers in serum. In conclusion, bilobalide exhibits vigorous anti-inflammatory activity, presenting it as an interesting potential therapeutic agent for OA.<\/jats:p>","DOI":"10.3389\/fphar.2022.783506","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T14:06:27Z","timestamp":1645625187000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Bilobalide Exerts Anti-Inflammatory Effects on Chondrocytes Through the AMPK\/SIRT1\/mTOR Pathway to Attenuate ACLT-Induced Post-Traumatic Osteoarthritis in Rats"],"prefix":"10.3389","volume":"13","author":[{"given":"Tianwen","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangyu","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XinYu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanbo","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiantao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1055\/a-1109-3405","article-title":"Effects of Ginkgo Biloba on Diseases Related to Oxidative Stress","volume":"86","author":"Achete de Souza","year":"2020","journal-title":"Planta Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.chembiol.2015.06.008","article-title":"AMPK Activation via Modulation of De Novo Purine Biosynthesis with an Inhibitor of ATIC Homodimerization","volume":"22","author":"Asby","year":"2015","journal-title":"Chem. Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"735","DOI":"10.2147\/DDDT.S157113","article-title":"The Efficacy and Safety of Ginkgo Biloba Extract as an Adjuvant in Type 2 Diabetes Mellitus Patients Ineffectively Managed with Metformin: a Double-Blind, Randomized, Placebo-Controlled Trial","volume":"12","author":"Aziz","year":"2018","journal-title":"Drug Des. Devel Ther."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/nu12071988","article-title":"L-theanine Reduced the Development of Knee Osteoarthritis in Rats via its Anti-inflammation and Anti-matrix Degradation Actions: In Vivo and In Vitro Study","volume":"12","author":"Bai","year":"2020","journal-title":"Nutrients"},{"key":"B5","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1136\/pmj.77.904.112","article-title":"A Case of Cerebral Haemorrhage-Can Ginkgo Biloba Be Implicated?","volume":"77","author":"Benjamin","year":"2001","journal-title":"Postgrad. Med. J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta12110","article-title":"Cyclooxygenase-2 Selective Non-steroidal Anti-inflammatory Drugs (Etodolac, Meloxicam, Celecoxib, Rofecoxib, Etoricoxib, Valdecoxib and Lumiracoxib) for Osteoarthritis and Rheumatoid Arthritis: a Systematic Review and Economic Evaluation","volume":"12","author":"Chen","year":"2008","journal-title":"Health Technol. Assess."},{"key":"B7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s40266-019-00660-1","article-title":"Safety of Oral Non-selective Non-steroidal Anti-inflammatory Drugs in Osteoarthritis: What Does the Literature Say?","volume":"36","author":"Cooper","year":"2019","journal-title":"Drugs Aging"},{"key":"B8","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1159\/000241299","article-title":"Skin Penetration of Epigallocatechin-3-Gallate and Quercetin from green tea and Ginkgo Biloba Extracts Vehiculated in Cosmetic Formulations","volume":"22","author":"dal Belo","year":"2009","journal-title":"Skin Pharmacol. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.1056\/NEJMra020398","article-title":"Herbal Remedies","volume":"347","author":"De Smet","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"608388","DOI":"10.3389\/fcell.2020.608388","article-title":"The Role of Autophagy in Osteoarthritis","volume":"8","author":"Duan","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s10020-019-0125-y","article-title":"The Neuroprotective Mechanisms of Ginkgolides and Bilobalide in Cerebral Ischemic Injury: a Literature Review","volume":"25","author":"Feng","year":"2019","journal-title":"Mol. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cytogfr.2018.07.001","article-title":"Autophagy and Proinflammatory Cytokines: Interactions and Clinical Implications","volume":"43","author":"Ge","year":"2018","journal-title":"Cytokine Growth Factor. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1097\/FBP.0b013e32836360ab","article-title":"Bilobalide, a Unique Constituent of Ginkgo Biloba, Inhibits Inflammatory Pain in Rats","volume":"24","author":"Goldie","year":"2013","journal-title":"Behav. Pharmacol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10091938","article-title":"Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology","volume":"10","author":"Gr\u00e4ssel","year":"2021","journal-title":"J. Clin. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"112230","DOI":"10.1016\/j.jep.2019.112230","article-title":"Best Practice in Research - Overcoming Common Challenges in Phytopharmacological Research","volume":"246","author":"Heinrich","year":"2020","journal-title":"J. Ethnopharmacol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s11926-018-0782-9","article-title":"Natural Products for Promoting Joint Health and Managing Osteoarthritis","volume":"20","author":"Henrotin","year":"2018","journal-title":"Curr. Rheumatol. Rep."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20225543","article-title":"A Double Negative Feedback Loop between mTORC1 and AMPK Kinases Guarantees Precise Autophagy Induction upon Cellular Stress","volume":"20","author":"Holczer","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.exer.2004.03.009","article-title":"The Effects of Ginkgo Biloba Extract on Lipopolysaccharide-Induced Inflammation In Vitro and In Vivo","volume":"79","author":"Ilieva","year":"2004","journal-title":"Exp. Eye Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2995","DOI":"10.1002\/art.27608","article-title":"Alteration of Sensory Neurons and Spinal Response to an Experimental Osteoarthritis Pain Model","volume":"62","author":"Im","year":"2010","journal-title":"Arthritis Rheum."},{"key":"B20","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.cellsig.2018.10.005","article-title":"Interleukin-1\u03b2 Signaling in Osteoarthritis - Chondrocytes in Focus","volume":"53","author":"Jenei-Lanzl","year":"2019","journal-title":"Cell Signal"},{"key":"B21","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s12974-014-0167-6","article-title":"Neuroprotective Effects of Bilobalide on Cerebral Ischemia and Reperfusion Injury Are Associated with Inhibition of Pro-inflammatory Mediator Production and Down-Regulation of JNK1\/2 and P38 MAPK Activation","volume":"11","author":"Jiang","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"B22","doi-asserted-by":"publisher","first-page":"101315","DOI":"10.1016\/j.arr.2021.101315","article-title":"Mechanisms Linking Mitochondrial Mechanotransduction and Chondrocyte Biology in the Pathogenesis of Osteoarthritis","volume":"67","author":"Jiang","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"B23","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1080\/15548627.2015.1121361","article-title":"How Autophagy Both Activates and Inhibits Cellular Senescence","volume":"12","author":"Kang","year":"2016","journal-title":"Autophagy"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1016\/j.joca.2019.05.016","article-title":"A Dual Amylin and Calcitonin Receptor Agonist Inhibits Pain Behavior and Reduces Cartilage Pathology in an Osteoarthritis Rat Model","volume":"27","author":"Katri","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"key":"B25","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1001\/jama.2020.22171","article-title":"Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review","volume":"325","author":"Katz","year":"2021","journal-title":"JAMA"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3374","DOI":"10.1073\/pnas.0712145105","article-title":"A Role for the NAD-dependent Deacetylase Sirt1 in the Regulation of Autophagy","volume":"105","author":"Lee","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2579","DOI":"10.1002\/ptr.6988","article-title":"Puerarin Inhibits the Development of Osteoarthritis through Antiinflammatory and Antimatrix\u2010degrading Pathways in Osteoarthritis\u2010induced Rat Model","volume":"35","author":"Ma","year":"2020","journal-title":"Phytotherapy Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"111911","DOI":"10.1016\/j.fct.2020.111911","article-title":"IRE1 and CaMKK\u03b2 Pathways to Reveal the Mechanism Involved in Microcystin-LR-Induced Autophagy in Mouse Ovarian Cells","volume":"147","author":"Ma","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"R14","DOI":"10.1111\/j.1750-3841.2007.00597.x","article-title":"Multifaceted Therapeutic Benefits of Ginkgo Biloba L.: Chemistry, Efficacy, Safety, and Uses","volume":"73","author":"Mahadevan","year":"2008","journal-title":"J. Food Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e22405","DOI":"10.1002\/jbt.22405","article-title":"Bilobalide Alleviates IL-17-induced Inflammatory Injury in ATDC5 Cells by Downregulation of microRNA-125a","volume":"33","author":"Mao","year":"2019","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"615250","DOI":"10.3389\/fendo.2020.615250","article-title":"17\u03b2-Estradiol Induces Mitophagy Upregulation to Protect Chondrocytes via the SIRT1-Mediated AMPK\/mTOR Signaling Pathway","volume":"11","author":"Mei","year":"2020","journal-title":"Front. Endocrinol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1080\/15548627.2015.1071759","article-title":"Modulation of Inflammation by Autophagy: Consequences for Human Disease","volume":"12","author":"Netea-Maier","year":"2016","journal-title":"Autophagy"},{"key":"B33","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s12905-019-0755-9","article-title":"Effect of a Multi-Ingredient Based Food Supplement on Sexual Function in Women with Low Sexual Desire","volume":"19","author":"Palacios","year":"2019","journal-title":"BMC Womens Health"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1016\/j.joca.2014.06.013","article-title":"Development and Reliability of a Multi-Modality Scoring System for Evaluation of Disease Progression in Pre-clinical Models of Osteoarthritis: Celecoxib May Possess Disease-Modifying Properties","volume":"22","author":"Panahifar","year":"2014","journal-title":"Osteoarthritis Cartilage"},{"key":"B35","doi-asserted-by":"publisher","first-page":"730312","DOI":"10.3389\/fphar.2021.730312","article-title":"Selective STAT3 Inhibitor Alantolactone Ameliorates Osteoarthritis via Regulating Chondrocyte Autophagy and Cartilage Homeostasis","volume":"12","author":"Pei","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10020265","article-title":"Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis","volume":"10","author":"P\u00e9rez-Lozano","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B37","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.gene.2013.11.091","article-title":"Pain Assessment in Animal Models of Osteoarthritis","volume":"537","author":"Piel","year":"2014","journal-title":"Gene"},{"key":"B38","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","article-title":"Osteoarthritis Cartilage Histopathology: Grading and Staging","volume":"14","author":"Pritzker","year":"2006","journal-title":"Osteoarthritis Cartilage"},{"key":"B39","first-page":"2021","article-title":"Bilobalide Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer's Disease by Upregulating lincRNA-P21","volume":"13","author":"Qin","year":"2021","journal-title":"Am. J. Transl Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1039\/d0fo02141e","article-title":"Citrus Peel Flavonoid Nobiletin Alleviates Lipopolysaccharide-Induced Inflammation by Activating IL-6\/STAT3\/FOXO3a-mediated Autophagy","volume":"12","author":"Rong","year":"2021","journal-title":"Food Funct."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz7714","article-title":"Reconstitution of Autophagosome Nucleation Defines Atg9 Vesicles as Seeds for Membrane Formation","volume":"369","author":"Sawa-Makarska","year":"2020","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12906-015-0520-z","article-title":"Arthropod Steroid Hormone (20-Hydroxyecdysone) Suppresses IL-1\u03b2-induced Catabolic Gene Expression in Cartilage","volume":"15","author":"Sheu","year":"2015","journal-title":"BMC Complement. Altern. Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2391","DOI":"10.3390\/molecules26082391","article-title":"Chondroprotection and Molecular Mechanism of Action of Phytonutraceuticals on Osteoarthritis","volume":"26","author":"Sukhikh","year":"2021","journal-title":"Molecules"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.1089\/ars.2010.3482","article-title":"Autophagosome Formation and Molecular Mechanism of Autophagy","volume":"14","author":"Tanida","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"B45","doi-asserted-by":"publisher","first-page":"795058","DOI":"10.3389\/fphar.2021.795058","article-title":"Phytochemicals Mediate Autophagy against Osteoarthritis by Maintaining Cartilage Homeostasis","volume":"12","author":"Tian","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1080\/08923973.2019.1641723","article-title":"Isorhamnetin Ameliorates Inflammatory Responses and Articular Cartilage Damage in the Rats of Monosodium Iodoacetate-Induced Osteoarthritis","volume":"41","author":"Tsai","year":"2019","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"41","DOI":"10.3389\/fphar.2019.00041","article-title":"Schisandrin A Inhibits the IL-1\u03b2-Induced Inflammation and Cartilage Degradation via Suppression of MAPK and NF-\u039ab Signal Pathways in Rat Chondrocytes","volume":"10","author":"Tu","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/S0140-6736(05)79516-7","article-title":"Subarachnoid Haemorrhage Associated with Ginkgo Biloba","volume":"352","author":"Vale","year":"1998","journal-title":"Lancet"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2700","DOI":"10.3390\/ijms22052700","article-title":"Control of the Autophagy Pathway in Osteoarthritis: Key Regulators, Therapeutic Targets and Therapeutic Strategies","volume":"22","author":"Valenti","year":"2021","journal-title":"Ijms"},{"key":"B50","doi-asserted-by":"publisher","first-page":"706","DOI":"10.3389\/fphys.2018.00706","article-title":"Role of the Inflammation-Autophagy-Senescence Integrative Network in Osteoarthritis","volume":"9","author":"Vinatier","year":"2018","journal-title":"Front. Physiol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.3389\/fphar.2020.01114","article-title":"Metformin Mitigates Cartilage Degradation by Activating AMPK\/SIRT1-Mediated Autophagy in a Mouse Osteoarthritis Model","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s13075-019-1952-5","article-title":"IL-1\u03b2 Receptor Antagonist (IL-1Ra) Combined with Autophagy Inducer (TAT-Beclin1) Is an Effective Alternative for Attenuating Extracellular Matrix Degradation in Rat and Human Osteoarthritis Chondrocytes","volume":"21","author":"Wang","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"B53","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.cytogfr.2018.10.002","article-title":"Pro-inflammatory Cytokines: The Link between Obesity and Osteoarthritis","volume":"44","author":"Wang","year":"2018","journal-title":"Cytokine Growth Factor. Rev."},{"key":"B54","doi-asserted-by":"publisher","first-page":"661072","DOI":"10.3389\/fphar.2021.661072","article-title":"Rhoifolin Ameliorates Osteoarthritis via Regulating Autophagy","volume":"12","author":"Yan","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.ceb.2009.11.014","article-title":"Mammalian Autophagy: Core Molecular Machinery and Signaling Regulation","volume":"22","author":"Yang","year":"2010","journal-title":"Curr. Opin. Cell Biol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1002\/jsfa.9431","article-title":"Ginkgo Biloba Sarcotesta Polysaccharide Inhibits Inflammatory Responses through Suppressing Both NF-\u039ab and MAPK Signaling Pathway","volume":"99","author":"Ye","year":"2019","journal-title":"J. Sci. Food Agric."},{"key":"B57","doi-asserted-by":"publisher","first-page":"718","DOI":"10.3389\/fphar.2020.00718","article-title":"Bilobalide Alleviated Dextran Sulfate Sodium-Induced Experimental Colitis by Inhibiting M1 Macrophage Polarization through the NF-\u039ab Signaling Pathway","volume":"11","author":"Zhang","year":"","journal-title":"Front. Pharmacol."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.11205","article-title":"Translocation of Interleukin-1\u03b2 into a Vesicle Intermediate in Autophagy-Mediated Secretion","volume":"4","author":"Zhang","year":"2015","journal-title":"Elife"},{"key":"B59","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1691\/ph.2020.0762","article-title":"Metformin Protects Chondrocytes against IL-1\u03b2 Induced Injury by Regulation of the AMPK\/NF-\u03ba B Signaling Pathway","volume":"75","author":"Zhang","year":"","journal-title":"Pharmazie"},{"key":"B60","doi-asserted-by":"publisher","first-page":"8835408","DOI":"10.1155\/2021\/8835408","article-title":"Bilobalide Enhances AMPK Activity to Improve Liver Injury and Metabolic Disorders in STZ-Induced Diabetes in Immature Rats via Regulating HMGB1\/TLR4\/NF-\u039ab Signaling Pathway","volume":"2021","author":"Zhao","year":"2021","journal-title":"Biomed. Res. Int."},{"key":"B61","doi-asserted-by":"publisher","first-page":"101249","DOI":"10.1016\/j.arr.2020.101249","article-title":"The Role of Metabolism in Chondrocyte Dysfunction and the Progression of Osteoarthritis","volume":"66","author":"Zheng","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"B62","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1159\/000490016","article-title":"By Activating Akt\/eNOS Bilobalide B Inhibits Autophagy and Promotes Angiogenesis Following Focal Cerebral Ischemia Reperfusion","volume":"47","author":"Zheng","year":"2018","journal-title":"Cell Physiol Biochem"},{"key":"B63","doi-asserted-by":"publisher","first-page":"659597","DOI":"10.3389\/fphar.2021.659597","article-title":"Microbial Metabolite Sodium Butyrate Attenuates Cartilage Degradation by Restoring Impaired Autophagy and Autophagic Flux in Osteoarthritis Development","volume":"12","author":"Zhou","year":"2021","journal-title":"Front. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.783506\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T14:06:32Z","timestamp":1645625192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.783506\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,23]]},"references-count":63,"alternative-id":["10.3389\/fphar.2022.783506"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.783506","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,23]]},"article-number":"783506"}}