Phytother Res

. 2023 Jun 26:4621-4638. doi: 10.1002/ptr.7930. Online ahead of print.

Tenuifolin in the prevention of Alzheimer's disease-like phenotypes: Investigation of the mechanisms from the perspectives of calpain system, ferroptosis, and apoptosis

Congting Li 1, Feng Gao 1, Yan Qu 1, Panpan Zhao 1, Xuncui Wang 1, Guoqi Zhu 1

Affiliations expand

• PMID: 37364988

•  DOI: 10.1002/ptr.7930

Abstract

Polygala tenuifolia was documented to calm the mind and promote wisdom. However, its underlying mechanisms are still unclear. This study aimed to investigate the mechanisms underlying the effects of tenuifolin (Ten) on Alzheimer's disease (AD)-like phenotypes. We first applied bioinformatics methods to screen the mechanisms of P. tenuifolia in the treatment of AD. Thereafter, the d-galactose combined with Aβ1-42 (GCA) was applied to model AD-like behaviors and investigate the action mechanisms of Ten, one active component of P. tenuifolia. The data showed that P. tenuifolia actioned through multi-targets and multi-pathways, including regulation of synaptic plasticity, apoptosis, and calcium signaling, and so forth. Furthermore, in vitro experiments demonstrated that Ten prevented intracellular calcium overload, abnormal calpain system, and down-regulation of BDNF/TrkB signaling induced by GCA. Moreover, Ten suppressed oxidative stress and ferroptosis in HT-22 cells induced by GCA. Calpeptin and ferroptosis inhibitor prevented the decrease of cell viability induced by GCA. Interestingly, calpeptin did not interrupt GCA-induced ferroptosis in HT-22 cells but blocked the apoptosis. Animal experiments further demonstrated that Ten prevented GCA-induced memory impairment in mice and increased synaptic protein expression while reducing m-calpain expression. Ten prevents AD-like phenotypes through multiple signaling by inhibiting oxidative stress and ferroptosis, maintaining the stability of calpain system, and suppressing neuronal apoptosis.

Keywords: Alzheimer's disease; Tenuifolin; calpain system; ferroptosis; synaptic damage.

Biomed Pharmacother

. 2023 Sep:165:115259. doi: 10.1016/j.biopha.2023.115259. Epub 2023 Aug 1.

Tenuigenin promotes non-rapid eye movement sleep via the GABAA receptor and exerts somnogenic effect in a MPTP mouse model of Parkinson's disease

Di Zhang 1, Wenjing Zhang 2, Shumin Deng 1, Lu Liu 1, Hua Wei 3, Fenqin Xue 3, Hui Yang 3, Xiaomin Wang 4, Zheng Fan 5

Affiliations expand

• PMID: 37531785

•  DOI: 10.1016/j.biopha.2023.115259

Free article

Abstract

Sleep disturbances are commonly non-motor symptoms in Parkinson's diseases (PD). However, standard dopamine replacement therapies for the treatment of motor symptoms often prove inadequate in combating sleep disturbances. Previous studies conducted by our research group have reported the neuroprotective effects of tenuigenin, a natural extract from Polygala tenuifolia root, which has been traditionally employed in treating insomnia. The objective of this study was to investigate the potential of tenuigenin in modulating sleep-wake behaviors and elucidate the underlying mechanisms. We employed EEG/EMG recordings to evaluate the impact of tenuigenin on sleep-wake profiles. Furthermore, we utilized c-Fos immunostaining, whole-cell patch clamping and local field potentials (LFP) recording to explore the mechanisms involved in sleep-promoting effects of tenuigenin. Additionally, we examined the effects of tenuigenin on sleep-promoting in MPTP PD mice. Here, we found tenuigenin demonstrated a significant increase in NREM sleep and a reduction in sleep latency in mice, without altering the EEG power density. Moreover, tenuigenin increased c-Fos expression in the ventrolateral preoptic area (VLPO) and stimulated sleep-promoting neurons in VLPO. The sleep-promoting effects of tenuigenin were abolished when mice were pretreated with flumazenil, an antagonist at the benzodiazepine site of the GABAA receptor. Furthermore, tenuigenin was found to ameliorate sleep disturbances in MPTP-induced mice. The results suggesting that tenuigenin facilitated a type of NREM sleep comparable to physiological NREM sleep through interaction with the GABAA receptor. Additionally, tenuigenin demonstrated improvements in sleep disturbances in MPTP-induced PD mice, suggesting its potential as a sleep-promoting substance, particularly for PD patients experiencing sleep disturbances.

Keywords: GABA(A) receptor; NREM sleep; Parkinson’s diseases; Sleep disturbances; Tenuigenin; VLPO.