Exploratory assessment of mortalin’s association with glycemic parameters and its modulation by Ashwagandha: Invitro and preliminary observational evidence

Diabetes mellitus, characterized by hypoinsulinemia, is a stress-dependent and irreversible hyperglycemic metabolic disorder, commonly complicating into life-threatening conditions such as neuropathy, nephropathy, retinopathy, cancer, and even death. Mortalin has been known to play a central role in the intracellular stress response and carcinogenesis. It has been detected in the serum of cancer, liver cirrhosis, and COVID-19 patients and correlated with disease severity and mortality risk. Assessment of blood levels of mortalin has been predicted to be a useful prognostic factor. We initially aimed to examine mortalin in the serum of diabetic patients and investigate its function in diabetes mellitus using in vitropancreatic cell differentiation models with retinoic acid and Ashwagandha leaf extracts. The latter were then recruited for a clinical observatory study on diabetic patients. Mortalin analysis of 352 human serum samples revealed lower levels in diabetic than in normal individuals. In the in vitro pancreatic cell differentiation model, treatment of Panc-1 cells with RA or Ashwagandha extracts induced differentiation, associated with upregulation of mortalin and insulin, suggesting that Ashwagandha may be useful for the management of diabetic conditions. In a preliminary observational study, 7 of 29 (~25%) patients benefited from Ashwagandha leaf powder, achieving complete remission, with no observed toxicity or worsening of the disease.