{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T08:19:35Z","timestamp":1788941975180,"version":"build-2803163510"},"reference-count":131,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T00:00:00Z","timestamp":1613779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009381","name":"International Medical University","doi-asserted-by":"publisher","award":["BP I-02-2019(11)"],"award-info":[{"award-number":["BP I-02-2019(11)"]}],"id":[{"id":"10.13039\/501100009381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Catalpol isolated from Rehmannia glutinosa is a potent antioxidant and investigated against many disorders. This review appraises the key molecular pathways of catalpol against diabetes mellitus and its complications. Multiple search engines including Google Scholar, PubMed, and Science Direct were used to retrieve publications containing the keywords \u201cCatalpol\u201d, \u201cType 1 diabetes mellitus\u201d, \u201cType 2 diabetes mellitus\u201d, and \u201cdiabetic complications\u201d. Catalpol promotes IRS-1\/PI3K\/AKT\/GLUT2 activity and suppresses Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase) expression in the liver. Catalpol induces myogenesis by increasing MyoD\/MyoG\/MHC expression and improves mitochondria function through the AMPK\/PGC-1\u03b1\/PPAR-\u03b3 and TFAM signaling in skeletal muscles. Catalpol downregulates the pro-inflammatory markers and upregulates the anti-inflammatory markers in adipose tissues. Catalpol exerts antioxidant properties through increasing superoxide dismutase (sod), catalase (cat), and glutathione peroxidase (gsh-px) activity in the pancreas and liver. Catalpol has been shown to have anti-oxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis properties that in turn bring beneficial effects in diabetic complications. Its nephroprotective effect is related to the modulation of the AGE\/RAGE\/NF-\u03baB and TGF-\u03b2\/smad2\/3 pathways. Catalpol produces a neuroprotective effect by increasing the expression of protein Kinase-C (PKC) and Cav-1. Furthermore, catalpol exhibits a cardioprotective effect through the apelin\/APJ and ROS\/NF-\u03baB\/Neat1 pathway. Catalpol stimulates proliferation and differentiation of osteoblast cells in high glucose condition. Lastly, catalpol shows its potential in preventing neurodegeneration in the retina with NF-\u03baB downregulation. Overall, catalpol exhibits numerous beneficial effects on diabetes mellitus and diabetic complications.<\/jats:p>","DOI":"10.3390\/biom11020323","type":"journal-article","created":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T21:15:01Z","timestamp":1613942101000},"page":"323","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Molecular and Biochemical Pathways of Catalpol in Alleviating Diabetes Mellitus and Its Complications"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7886-2909","authenticated-orcid":false,"given":"Subrat Kumar","family":"Bhattamisra","sequence":"first","affiliation":[{"name":"Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2840-2330","authenticated-orcid":false,"given":"Hui Min","family":"Koh","sequence":"additional","affiliation":[{"name":"School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin Yean","family":"Lim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hira","family":"Choudhury","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8249-9743","authenticated-orcid":false,"given":"Manisha","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,20]]},"reference":[{"key":"ref_1","unstructured":"Duke, L., Fereira de Moura, A., Silvia Gorban de Lapertosa, S., Lucy Hammond, L., Jacobs, E., and Abha Kaundal, A. 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