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Using network pharmacology, metabolomics, UHPLC\u2010Q\u2010TOF\/MS, and functional studies (in vitro and in\u00a0vivo), we systematically explored DHJSD's molecular mechanisms. DHJSD has 254 constituents; those may regulate inflammation, apoptosis, and metabolic processes. DHJSD attenuates ECM\/fibrosis\u2010related changes, lowers BMP2 expression, is associated with reduced TGF\u2010\u03b2\/Smad2\/3 phosphorylation, and partially improves annulus fibrosus morphology. SB431542 attenuated IL\u20101\u03b2\u2010induced TGF\u2010\u03b2 pathway activation and BMP2 expression, supporting the involvement of this pathway in DHJSD\u2010related regulation of fibrosis markers. The levels of serum IL\u20101\u03b2 and TNF\u2010\u03b1 significantly decreased in animal models. Through glycerophospholipid and sphingolipid metabolism, DHJSD reshapes lipid homeostasis and may be associated with reduced TGF\u2010\u03b2 overactivation by downregulating pro\u2010fibrotic compounds and upregulating anti\u2010inflammatory metabolites. DHJSD modulates autophagy\u2010related markers via controlling the LC3\u2010II\/LC3\u2010I ratio and BCL2, P62 expression. DHJSD may affect glycolysis\u2010related and oxidative phosphorylation\u2010related changes and may be associated with phosphatidylcholine\/ethanolamine\u2010related mitochondrial membrane changes. DHJSD treats IVDD via a \u201cmetabolic reprogramming\u2013TGF\u2010\u03b2\u2010related regulation\u2013autophagy\/mitochondrial\u2010related remodeling\u201d network, suggesting a potential multi\u2010target strategy and demonstrating the value of multi\u2010omics in analyzing traditional medicine.<\/jats:p>","DOI":"10.1002\/bmc.70530","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:41:58Z","timestamp":1782938518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Duhuo Jisheng Decoction Mitigates Intervertebral Disc Degeneration via Metabolic Reprogramming and TGF\u2010\u03b2\/Smad\u2010Driven Autophagy\u2010Fibrosis Network Modulation"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0611-4298","authenticated-orcid":false,"given":"Chao","family":"Song","sequence":"first","affiliation":[{"name":"Department of Orthopedics The Second 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