Rumex japonicus Houtt. Protects Dopaminergic Neurons by Regulating Mitochondrial Function and Gut–Brain Axis in In Vitro and In Vivo Models of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Rumex japonicus Houtt. (RJ) has been used to treat gastrointestinal and inflammatory diseases in East Asia. However, it is unknown whether RJ can prevent PD. We investigated the neuroprotective effects of RJ in cellular and animal PD models, focused on mitochondrial function and the gut–brain axis. SH-SY5Y cells were treated with RJ (0.01 mg/mL) for 24 h, after which they were treated with the 1-methyl-4-phenylpyridinium ion (MPP+). MPP+-induced apoptosis increased mitochondrial reactive oxygen species and decreased ATP, PINK1, and DJ-1, which were inhibited by RJ. Ten-week-old C57BL/6N male mice were treated with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 5 days and orally administered 50 or 100 mg/kg of RJ for 14 days. RJ alleviated MPTP-induced behavioral impairment, dopaminergic neuronal death, and mitochondrial dysfunction in the substantia nigra (SN) and suppressed the MPTP-induced increase in lipopolysaccharide, interleukin-1β, tumor necrosis factor-α, α-synuclein, and apoptotic factors in the SN and colon. Moreover, RJ inhibited the MPTP-mediated disruption of the tight junction barrier in the colon and blood–brain barrier of mice. Therefore, RJ alleviates MPTP-induced inflammation and dopaminergic neuronal death by maintaining mitochondrial function and tight junctions in the brain and colon.

Rumex japonicus Houtt. Extract Suppresses Colitis-Associated Colorectal Cancer by Regulating Inflammation and Tight-Junction Integrity in Mice

“…In the present study, treatment of RJ effectively protected the TJ barrier and suppressed the activation of cancerous TJ like claudin-2 in the colon tissue (Figures 4, 5). In addition, in our previous studies, RJ protected the TJ barrier not only in the colon but also in the brain (Kim et al, 2020;Kim et al, 2022). Therefore, RJ may enhance the connection between TJs.…”

“…Claudin-2 expression level can be increased by the activation of IL-6 ( Suzuki et al, 2011 ), and increased claudin-2 level enhances IBD-associated dysplasia and sporadic adenomas ( Weber et al, 2008 ). When the connection of TJs is weak, the immune cells move to the intestine through the paracellular pathway and produce proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β ( Kim et al, 2022 ). Therefore, the weakness of the TJ barrier causes epithelial inflammatory damage, such as erosion, ulceration, and apoptosis, which are major characteristics of IBD and colorectal cancer ( Landy et al, 2016 ).…”

“…RJ (10 g) was immersed in 500 ml methanol, sonicated for 15 min, and extracted for 24 h. The extract was filtered through filter paper, dried using a vacuum evaporator (Eyela, Tokyo, Japan), and freeze-dried (Labconco, Kansas City, MO, United States). Constituents of RJ extract were identified by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry ( Supplementary Figure S1 ) ( Kim et al, 2022 ). Freeze-dried RJ was dissolved in water for each oral administration.…”

“…RJ has anti-oxidative, anti-bacterial, anti-sepsis, anti-inflammatory, and anti-cancer effects ( Sun et al, 2020 ). Moreover, RJ alleviates the disruption of tight junctions (TJs), apoptosis, and inflammation in the colons of dextran sulfate sodium (DSS)-induced colitis mouse model and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease mouse model ( Kim et al, 2020 ; Kim et al, 2022 ). However, it is unclear whether RJ can suppress the incidence of CAC.…”

Comparative Study of 12 Herbal Formulae Covered by the National Health Insurance Service in Korea

“…. 실제로 인삼 11) , 양제근 12) , 천마 13) 등의 한약재와 억간산 mg/ml), 보허탕(1.538 mg/ml), 반하백출천마탕(2.476 mg/ml) 순 으로 우수한 것으로 나타났다(Fig. 2).…”