In vitro and in vivo exploitation of cell stress pathways using methanolic extracts of Phlomis stewartii in diabetic rat's model

Various bioactive constituents present in plants are used to treat metabolic disorders linked to oxidative stress and obesity. Low-grade to chronic inflammation and IR are considered as main causes of obesity, which is strongly correlated with the prevalence and incidence of Type-2 Diabetes Mellitus (T2DM). In this study, the biological influence of Phlomis stewartii extracts was evaluated in vitro and in vivo using rat diabetic models. The biological effects included anti-inflammatory, anti-proliferative, anti-apoptotic, metabolic hormonal via molecular signaling pathways, and antioxidant potential. The extracts from P. stewartii exhibited the strongest DPPH and FRAP potential for LM (38.92 µg/mL) and (45.28 µg/mL) respectively. Moreover, the high absorbance for reducing power was observed in leaves methanol (LM) 1.36 which is greater than flower methanol (FM) 1.12, and whole plant methanol (WPM) 1.21 at a concentration of 500 µg/mL when comparing treated groups to the negative control (NC), and positive control (PC) groups. The results of an Enzyme-linked Immunosorbent Assay (ELISA) study measuring a metabolic hormonal profile that includes Triiodothyronine (T3), Thyroxine (T4), Thyroid Stimulating Hormone (TSH), insulin, leptin, and glucokinase showed that LM has been greatly recovered. The study examined the gene expression analysis of cell stress pathways, and it found that the PC groups had higher levels of Janus kinase (JAK), Signal Transducer and Activator of Transcription (STATS) pathways through JAK (JAK-2 and STAT-1), G protein-Coupled Receptor Kinase 2 (GRK-2), Calmodulin 2 (CALM-2), Proteins Inhibitor of Activated STAT 1 (PIAS-1), Forkhead Box 01, 03, 04, (FOXO-1, FOXO-3, FOXO-4), Bcl-2 Associated X-protein (BAX), B-cell Lymphoma 2 (BCL-2), Interleukins (IL-6, IL-1β), and Tumour Necrosis Factor-α (TNF-α). On the other hand, downregulation was observed in NC groups and P. stewartii extract-treated groups. The outcome of this study suggests a strong relationship towards ameliorative effects.