OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

To evaluate the effect of chlorogenic acid supplementation in patients with retinitis pigmentosa, we evaluated objective change in visual function with multifocal electroretinography, along with visual acuity, visual field, standard electroretinography, and contrast sensitivity. Eighteen patients diagnosed with retinitis pigmentosa were enrolled in this prospective, non-comparative, single-arm study. Multifocal electroretinography, best-corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters, total point score on visual field examination with Humphrey Field Analyzer II, electroretinography, and contrast sensitivity were measured and repeated after 3 months supplementation with chlorogenic acid. The amplitude of ring 5 was significantly higher on multifocal electroretinography after 3 months of chlorogenic acid supplementation (7.2 +/- 9.5 vs 8.3 +/- 10.8 nV/deg2, mean +/- standard deviation, P = 0.022). There were no significant changes in the best-corrected visual acuity, total point score on Humphrey Field Analyzer, 30 Hz flicker amplitude on standard electroretinography, or contrast sensitivity. Chlorogenic acid may have a beneficial effect on the peripheral area at the margins of retinal degeneration, and should be considered as an anti-oxidant for the management of retinitis pigmentosa.
Adult ; Antioxidants/adverse effects/therapeutic use ; Chlorogenic Acid/adverse effects/*therapeutic use ; Dietary Supplements/adverse effects ; Electroretinography/*drug effects ; Female ; Humans ; Male ; Middle Aged ; Oxidative Stress/drug effects ; Prospective Studies ; Retina/physiopathology ; Retinitis Pigmentosa/*drug therapy ; Vision, Ocular/*drug effects ; Visual Acuity/*drug effects ; Visual Fields/drug effects ; Young Adult