Antidiabetic, Toxicological, and Metabolomic Profiling of Aqueous Extract of Cichorium intybus Seeds

Background: Cichorium intybus has a wide range of therapeutic applications in Indian traditional systems of medicine, especially in metabolic disorders. Objective: To evaluate the toxicity profile and to investigate the antidiabetic, antihyperlipidemic, and antioxidative efficacy of C. intybus seeds in Wistar rats. Materials and Methods: The aqueous extract of seeds was prepared by decoction, and its quality control analysis was carried out by thin‑layer chromatography and ultra‑performance liquid chromatography‑mass spectrometry (UPLC‑MS) fingerprinting. Wistar rats were fed with high‑fat diet for 5 weeks followed by a single dose of streptozotocin intraperitoneally to induce diabetes. The protective group of rats was given aqueous extract during and after the induction of type 2 diabetes mellitus. Further, repeated dose 28‑day (subacute) and repeated dose 90‑day (chronic) toxicity studies were conducted as per the OECD guidelines. Results: A total of 18 metabolites have been tentatively identified by UPLC‑MS profiling in aqueous extract of C. intybus seeds. No significant changes in mortality and biochemical parameters have been observed during toxicity studies. Moreover, administration of the extract to a protective group of diabetic rats attenuated serum glucose and triglyceride levels by 52.7% and 65.3%, respectively, supported by similar results for parameters related to insulin resistance and oxidative stress. The beneficial effect of extract has also been confirmed through in silico screening. Conclusion: C. intybus can be used as a natural dietary supplement for the prevention and management of diabetes and can be explored to develop a potent phytopharmaceutical for diabetes.