The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

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Background Medicinal plants are used to manage pain and inflammatory disorders in traditional medicine. A scientific investigation could serve as a basis for the determination of molecular mechanisms of antinociceptive and antiinflammatory actions of herbal products. In this work, we used both artificial intelligence (AI) based models inform of adaptive neuro-fuzzy inference system and artificial neural network (ANN) as well as a linear model, namely; stepwise linear regression in modelling the performance of four different inflammatory biomarkers namely; interleukin (1L)-1β, 1L-6, tumour necrosis factor (TNF)-α and prostaglandin E2 (PGE2). This modelling was done using number of abdominal writes, the reaction time of paw licking in mice and paw oedema diameter as the input variables. Results Four different performance indices were employed, which are determination coefficient (DC), root mean squared error (RMSE), mean square error (MSE) and correlation co-efficient (CC). The results have shown the superiority of the AI-based models over the linear model. Conclusions The overall quantitative and visualized comparison of the results showed that adaptive neuro-fuzzy inference system outperformed the ANN and SWLR models in modelling the performance of the four inflammation biomarkers in both the calibration and verification phases.

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis in insulin-secreting beta-cells is essential. Several pathophysiological conditions and pharmacological agents disrupt the ER homeostasis, thereby causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways whenever the ER stress persists. ER stress has been linked to several diseases, such as cancers, obesity, and diabetes. Thus, the regulation of ER stress may provide possible therapeutic targets for many diseases. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, resulting in irreversible UPR activation and cells death. Despite much progress in understanding the pathophysiology of UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provided up-to-date information regarding the current status of UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

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