Azim Ullah Shamsul Islam: Role of β-myrcene in attenuation of neurodegeneration, renal malfunction, and Inflammatory bowel disease in the Adrenalectomized Rat model

Abstract

Glucocorticoids (GCs) are secreted by the adrenal glands in response to signals from the hypothalamus and pituitary gland through the hypothalamic–pituitary–adrenal axis. Physiological GCs are important regulators of immunity, energy metabolism, oxidative stress response, and cellular homeostasis.

Adrenalectomy (ADX) results in the loss of hippocampal neurons including the dentate gyrus, and cornu ammonis. Pathways implicated in neurodegeneration include inflammation, upregulation of microglia and astrocytes, oxidative stress, downregulation of autophagy, disruption of cellular homeostasis, and increased apoptosis. The autophagy lysosomal pathway plays a pivotal role in the degradation of damaged organelles and retrieval of proteins essential for the cell cycle and intracellular homeostasis. Metabolism and homeostasis in the hippocampal neurons are mediated by the mammalian target of rapamycin through the autophagy lysosomal pathway. Myrcene was evaluated to mitigate inflammation and oxidative stress and reinstate metabolism and cellular homeostasis. Myrcene attenuated inflammation, deactivated glial cells and astrocytes, relieved oxidative stress, reinstated autophagy, promoted hippocampal neuronal growth, ensured homeostasis, and prevented apoptosis in adrenalectomized rats.

ADX-mediated GC depletion mediated renal inflammation, induced oxidative stress, and exacerbated renal injury, leading to functional impairment and increased mortality in inflammatory bowel disease (IBD). Meanwhile, myrcene abrogated the inflammatory plethora and inhibited reactive oxygen species (ROS), ultimately preventing renal injury and reducing mortality in adrenalectomized rats with IBD. Furthermore, in ADX-induced inflammation and oxidative stress, myrcene attenuated renal inflammation and inhibited ROS. ADX promotes the recruitment of macrophages in the kidney, which exacerbates inflammation and oxidative stress, ultimately leading to the impairment of renal function. Myrcene attenuated renal inflammation and oxidative stress, reinstating the renal function, in ADX-treated rats.

Overall, myrcene prevents neurodegeneration, improves renal function, and mitigates IBD complications, exhibiting potency in alleviating neuronal and renal inflammation and oxidative stress.