左归丸调控PI3K/AKT信号通路的研究进展

Research Progress of Regulation of PI3K/AKT Signaling Pathway with Yin-Restoring Pill

左归丸是滋阴补肾的代表方剂,具有滋阴益髓、温壮肾阳、填精补肾之功效。现代研究表明其主要通过调控磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)信号通路中的相关细胞因子对机体神经、生殖、内分泌及骨科疾病等方面发挥防治功能,其主要机制为通过磷酸化AKT不同位点精准调控其下游B淋巴细胞瘤-2基因(B-cell lymphoma-2,Bcl-2)、BCL2-associated X的蛋白质(BCL2-Associated X,Bax)、半胱氨酸蛋白酶-3(cysteinyl aspartate-specific proteinase-3,Caspase-3)、糖原合成酶激酶3β(glycogen synthase kinase3β,GSK3β)、雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、叉头转录蛋白O(forkhead box O,FOXO)等靶蛋白发挥调节细胞周期,促进细胞代谢、生长及增殖,抑制细胞凋亡,调节氧化应激、炎症反应及能量代谢,调控肿瘤细胞发生等生物学防治功能。左归丸在临床应用较为广泛,但关于左归丸对相关疾病防治的药理作用及分子机制尚未明确,今后,则需对左归丸防治疾病的分子生物学机制进行深入研究,进一步明确其临床应用价值。

Yin-Restoring Pill is a representative formula for nourishing yin and tonifying the kidney,which has the effects of nourishing yin and enriching marrow,warming and strengthening kidney yang,and filling the essence and tonifying the kidney.Modern research has shown that it mainly plays a preventive and curative role in the prevention and treatment of neurological,reproductive,endocrine and orthopedic diseases by regulating related cytokines in the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB,also known as AKT) signaling pathway.The main mechanism is to regulate the downstream target proteins such as B-cell lymphoma-2(Bcl-2),BCL2-Associated X(Bax),cysteinyl aspartate-specific proteinase-3(Caspase-3),glycogen synthase kinase3β(GSK3β),mammalian target of rapamycin(mTOR),and forkhead box O(FOXO) by phosphorylating AKT at different sites,which plays a biological preventive and curative role in regulating cell cycle,promoting cell metabolism,growth and proliferation,inhibiting apoptosis,regulating oxidative stress and inflammatory response,regulating energy metabolism,and regulating tumor cell formation.Although Yin-Restoring Pill has been widely used in clinical practice,its pharmacological effects and molecular mechanisms on the prevention and treatment of related diseases have not been precisely defined.In the future,deep research on the molecular biology of Yin-Restoring Pill in the prevention and treatment of diseases is needed to further clarify the potential clinical application value.