Depression is a highly debilitating and life-threatening psychiatric disorder. The classical antidepressants are still not adequate due to undesirable side effects. Therefore, the development of new drugs for depression treatment is an urgent strategic to achieving clinical needs. Licorisoflavan A is a bioactive ingredient isolated from Glycyrrhizae Radix and has been recently reported for neuroprotective effects. In this study, the antidepressant-like effect and neural mechanism of licorisoflavan A were explored. In the mice behavioral despair test, we observed that licorisoflavan A exhibited powerful antidepressant-like effect in forced swimming test (FST), tail suspension test (TST), without affecting locomotor activity in open field test (OFT). Additionally, licorisoflavan A administration significantly restored Chronic mild stress (CMS)-induced changes in sucrose preference test (SPT), FST, and TST, without altering the locomotion in OFT. In chronical-stimulated mice, the licorisoflavan A treatment effectively attenuated the expressions of Brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), the phosphorylations of cAMP response element binding protein (CREB), extracellular signal-regulated kinase (ERK)-1/2, eukaryotic elongation factor 2 (eEF2), mammalian target of rapamycin (mTOR), initiation factor 4E-binding protein 1 (4E-BP-1), and p70 ribosomal protein S6 kinase (p70S6K) in hippocampus of CMS-induced mice. Additionally, licorisoflavan A could reverse the decreases in synaptic proteins post-synaptic density protein 95 (PSD-95) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) caused by CMS, and its antidepressant-like effect was blocked by the AMPA receptor antagonist NBQX. These findings served as preclinical evidence that licorisoflavan A exerted potent antidepressant-like effects involving BDNF-TrkB pathway and AMPA receptors. Licorisoflavan A might be used as a potential medicine against depression-like disorder.

中文翻译：

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Licorisoflavan A在小鼠中表现出抗抑郁样作用：涉及BDNF-TrkB途径和AMPA受体。

抑郁症是一种高度虚弱和威胁生命的精神疾病。由于不希望的副作用，传统的抗抑郁药仍然不足。因此，开发用于抑郁症治疗的新药物是实现临床需求的紧急战略。Licorisoflavan A是一种从甘草中提取的生物活性成分，最近已报道其具有神经保护作用。本研究探讨了甘草异黄酮A的抗抑郁样作用及其神经机制。在小鼠行为绝望测试中，我们观察到力索异黄烷A在强迫游泳测试（FST），尾部悬吊测试（TST）中表现出强大的抗抑郁样作用，而在开放视野测试（OFT）中不影响运动活性。另外，licorisoflavan A给药可显着恢复慢性轻度应激（CMS）引起的蔗糖偏爱测试（SPT），FST和TST的变化，而不会改变OFT的运动。在慢性刺激的小鼠中，licorisoflavan A治疗可有效减弱脑源性神经营养因子（BDNF），酪氨酸激酶B（TrkB），cAMP反应元件结合蛋白（CREB）的磷酸化，细胞外信号调节激酶（ERK）的表达。 ）-1/2，真核生物延伸因子2（eEF2），雷帕霉素的哺乳动物靶标（mTOR），起始因子4E结合蛋白1（4E-BP-1）和p70核糖体蛋白S6激酶（p70S6K）诱导的小鼠。另外，licorisoflavan A可以逆转突触后密度蛋白95（PSD-95）和α-氨基-3-羟基-5-甲基-4-异恶唑-丙酸（AMPA）受体亚基谷氨酸受体1（GluR1）的减少。由CMS引起，其抗抑郁样作用被AMPA受体拮抗剂NBQX阻断。这些发现提供了临床上的证据，表明甘草异黄烷A具有有效的抗抑郁样作用，涉及BDNF-TrkB途径和AMPA受体。Licorisoflavan A可用作抗抑郁症的潜在药物。这些发现提供了临床上的证据，表明甘草异黄烷A具有有效的抗抑郁样作用，涉及BDNF-TrkB途径和AMPA受体。Licorisoflavan A可用作对抗抑郁症的潜在药物。这些发现提供了临床上的证据，表明甘草异黄烷A具有有效的抗抑郁样作用，涉及BDNF-TrkB途径和AMPA受体。Licorisoflavan A可用作抗抑郁症的潜在药物。