{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T15:49:19Z","timestamp":1774280959922,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from Cassia fistula stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg\/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin\/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (p &lt; 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner (p &lt; 0.05). Plasma insulin (p &lt; 0.0001)\/C-peptide (p &lt; 0.0006), tissue glycogen (p &lt; 0.0034), glycogen phosphorylase (p &lt; 0.005), glucose 6-phosphatase (p &lt; 0.0001) and lipid markers were significantly increased (p &lt; 0.0001) in diabetic rats, whereas glucokinase (p &lt; 0.0047), glycogen synthase (p &lt; 0.003), glucose oxidation (p &lt; 0.001), GLUT4 mRNA (p &lt; 0.0463), GLUT4 protein (p &lt; 0.0475) and the insulin-signaling molecules IR mRNA (p &lt; 0.0195), IR protein (p &lt; 0.0001), IRS-1 mRNA (p &lt; 0.0478), p-IRS-1Tyr612 (p &lt; 0.0185), Akt mRNA (p &lt; 0.0394), p\u2013AktSer473 (p &lt; 0.0162), GLUT4 mRNA (p &lt; 0.0463) and GLUT4 (p &lt; 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1\u2013C3 with IRK and PPAR-\u03b3 protein coincided with in vivo findings. C1\u2013C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.<\/jats:p>","DOI":"10.3390\/molecules26226812","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T23:04:46Z","timestamp":1636671886000},"page":"6812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel Triterpenoids from Cassia fistula Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1\/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats"],"prefix":"10.3390","volume":"26","author":[{"given":"Sabapathy","family":"Indu","sequence":"first","affiliation":[{"name":"DBT-BIF Centre, PG & Research Department of Biotechnology & Bioinformatics, Holy Cross College (Autonomous), Bharathidasan University, Trichy 620002, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Periyasamy","family":"Vijayalakshmi","sequence":"additional","affiliation":[{"name":"DBT-BIF Centre, PG & Research Department of Biotechnology & Bioinformatics, Holy Cross College (Autonomous), Bharathidasan University, Trichy 620002, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-1423","authenticated-orcid":false,"given":"Jayaraman","family":"Selvaraj","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospitals, Saveetha University, Chennai 600020, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manikkam","family":"Rajalakshmi","sequence":"additional","affiliation":[{"name":"DBT-BIF Centre, PG & Research Department of Biotechnology & Bioinformatics, Holy Cross College (Autonomous), Bharathidasan University, Trichy 620002, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.2337\/dc09-S302","article-title":"Skeletal muscle insulin resistance is the primary defect in type 2 diabetes","volume":"32","author":"DeFronzo","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1161\/01.HYP.0000163475.04421.e4","article-title":"Mechanisms of insulin resistance in humans and possible links with inflammation","volume":"5","author":"Savage","year":"2005","journal-title":"Hypertension"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/414799a","article-title":"Insulin signalling and the regulation of glucose and lipid metabolism","volume":"414","author":"Saltiel","year":"2001","journal-title":"Nature."},{"key":"ref_4","first-page":"5071","article-title":"Minireview: Recent developments in the regulation of glucose transporter-4 traffic: New signals, locations, and partners","volume":"12","author":"Shiki","year":"2005","journal-title":"Endocrinology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.2522\/ptj.20080018","article-title":"Skeletal muscle insulin resistance: Roles of fatty acid metabolism and exercise","volume":"11","author":"Turcotte","year":"2008","journal-title":"Phys. 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