The pharmacological effects of Berberine and its therapeutic potential in different diseases: Role of the phosphatidylinositol 3‐kinase/AKT signaling pathway

Abstract

The phosphatidylinositol 3‐kinase (PI3K)/AKT signaling pathway plays a central role in cell growth and survival and is disturbed in various pathologies. The PI3K is a kinase that generates phosphatidylinositol‐3,4,5‐trisphosphate (PI (3–5) P3), as a second messenger responsible for the translocation of AKT to the plasma membrane and its activation. However, due to the crucial role of the PI3K/AKT pathway in regulation of cell survival processes, it has been introduced as a main therapeutic target for natural compounds during the progression of different pathologies. Berberine, a plant‐derived isoquinone alkaloid, is known because of its anti‐inflammatory, antioxidant, antidiabetic, and antitumor properties. The effect of this natural compound on cell survival processes has been shown to be mediated by modulation of the intracellular pathways. However, the effects of this natural compound on the PI3K/AKT pathway in various pathologies have not been reviewed so far. Therefore, this paper aims to review the PI3K/AKT‐mediated effects of Berberine in different types of cancer, diabetes, cardiovascular, and central nervous system diseases.

Cannabigerol–A useful agent restoring the muscular phospholipids milieu in obese and insulin-resistant Wistar rats?

“…It is well established that PI is an essential component of the cell membrane that functions as a lipid anchor of numerous membrane proteins ( Derkaczew et al, 2023 ). Furthermore, it also constitutes a precursor for many derivatives, such as phosphatidylinositol-3,4,5-trisphosphate (PIP 3 ), that activates downstream signaling proteins, the most notable of which is the protein kinase B (PKB/Akt), which plays a pivotal role in the insulin signal transduction pathway ( Derkaczew et al, 2023 ; Khezri et al, 2023 ). Therefore, taking into account the above-mentioned effects caused by the CBG treatment, it seems reasonable to conclude that this phytocannabinoid may prevent the development of IR in the skeletal muscle under the increased dietary FAs bioavailability conditions through improving the cellular phospholipids milieu.…”

Progress in the Treatment of Central Nervous System Diseases Based on Nanosized Traditional Chinese Medicine

“…[ 224 ] Within the natural pharmaceutical treasure trove of TCM, numerous natural compounds, such as baicalin, arsenic trioxide, berberine, muscone, puerarin, and ginkgolides, are also found to be applicable in the treatment of CNS diseases. [ 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 , 233 ] However, many of these natural compounds exhibit unfavorable physicochemical properties, including low solubility, poor water‐solubility, low oral bioavailability, poor stability, rapid hepatic metabolism, low intestinal absorption, fast systemic clearance, short half‐life, and potential hepatorenal toxicity. [ 7 , 8 , 234 , 235 , 236 ] Moreover, their large molecular size hampers their ability to penetrate the BBB, limiting their accumulation within brain tissues to achieve and maintain effective therapeutic concentrations.…”