Department of Pharmacy, Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan.
Graduate School of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki, Japan;
Acta Neurobiol Exp (Wars). 2021;81(4):393-404.
The neurotrophic hypothesis of depression, which suggests that decreased hippocampal brain‑derived neurotrophic factor (BDNF) levels cause depression, has become increasingly popular. BDNF, a member of the neurotrophin family, promotes neuronal differentiation and survival. BDNF is synthesized in various peripheral tissues, as well as in the brain. Considering that peripheral BDNF can be transported into the brain across the blood‑brain barrier, substances with the ability to upregulate BDNF activity in peripheral tissues may be useful in the management of depression. Previously, we demonstrated that the human kidney adenocarcinoma cell line ACHN produces BDNF; hence, this cell line was employed for screening upregulators of peripheral BDNF. Here, we aimed to identify Kampo (traditional Japanese) medicines and their crude drug components that upregulate BDNF levels using ACHN cells. Chotosan, Hochuekkito, Kososan, and Ninjinyoeito, Kampo medicines used in treating psychiatric disorders, increased BDNF levels in the culture media of ACHN cells. Furthermore, Chinpi (Citrus unshiu peel), a crude drug contained in these four Kampo medicines, as well as Onji (Polygala tenuifolia root), and Saiko (Bupleurum falcatum root) elevated BDNF levels in ACHN cells. Chinpi, showing strong BDNF elevating effect, increased BDNF mRNA expression. Inhibitors of protein kinase B, mitogen‑activated protein kinase kinase, and cAMP‑dependent protein kinase, involved in the transcription of BDNF, attenuated Chinpi‑induced BDNF elevation. Our results suggest that Chinpi and Kampo medicines containing Chinpi can promote the production of BDNF in peripheral tissues, potentially alleviating depression symptoms.
抑郁症的神经营养假说认为，海马源性神经营养因子（BDNF）水平降低导致抑郁症，该假说越来越受到关注。BDNF 是神经营养因子家族的一员，可促进神经元分化和存活。BDNF 可在多种外周组织以及大脑中合成。鉴于外周 BDNF 可以穿过血脑屏障进入大脑，因此具有增强外周组织 BDNF 活性的物质可能有助于治疗抑郁症。先前，我们证明人肾腺癌细胞系 ACHN 可产生 BDNF；因此，该细胞系被用于筛选外周 BDNF 的上调物。在这里，我们旨在使用 ACHN 细胞鉴定可上调 BDNF 水平的汉方药及其粗提药成分。用于治疗精神疾病的汉方药柴朴汤、八味地黄丸、归脾汤和加味逍遥散可增加 ACHN 细胞培养物中 BDNF 的水平。此外，这四种汉方药中所含的粗药陈皮，以及远志和柴胡也可提高 ACHN 细胞中的 BDNF 水平。显示出强烈 BDNF 升高作用的陈皮可增加 BDNF mRNA 的表达。BDNF 转录涉及的蛋白激酶 B、丝裂原活化蛋白激酶激酶和 cAMP 依赖性蛋白激酶抑制剂可减弱陈皮诱导的 BDNF 升高。我们的研究结果表明，陈皮和含有陈皮的汉方药可促进外周组织中 BDNF 的产生，从而可能缓解抑郁症状。
