Artemisia Leaf Extract protects against neuron toxicity by TRPML1 activation and promoting autophagy/mitophagy clearance in both in vitro and in vivo models of MPP+/MPTP-induced Parkinson's disease

Jang

2022

IJMS

Parkinson’s disease (PD), a neurodegenerative disorder, is characterized by the loss of dopaminergic (DA) neurons. The pathogenesis of PD is associated with several factors including oxidative stress, inflammation, and mitochondrial dysfunction. Ca2+ signaling plays a vital role in neuronal signaling and altered Ca2+ homeostasis has been implicated in many neuronal diseases including PD. Recently, we reported that apamin (APM), a selective antagonist of the small-conductivity Ca2+-activated K+ (SK) channel, suppresses neuroinflammatory response. However, the mechanism(s) underlying the vulnerability of DA neurons were not fully understood. In this study, we investigated whether APM affected 1-methyl-4-phenyl pyridinium (MPP+)-mediated neurotoxicity in SH-SY5Y cells and rat embryo primary mesencephalic neurons. We found that APM decreased Ca2+ overload arising from MPP+-induced neurotoxicity response through downregulating the level of CaMKII, phosphorylation of ERK, and translocation of nuclear factor NFκB/signal transducer and activator of transcription (STAT)3. Furthermore, we showed that the correlation of MPP+-mediated Ca2+ overload and ERK/NFκB/STAT3 in the neurotoxicity responses, and dopaminergic neuronal cells loss, was verified through inhibitors. Our findings showed that APM might prevent loss of DA neurons via inhibition of Ca2+-overload-mediated signaling pathway and provide insights regarding the potential use of APM in treating neurodegenerative diseases.

Section: Discussionmentioning

confidence: 99%

Effects of Apamin on MPP+-Induced Calcium Overload and Neurotoxicity by Targeting CaMKII/ERK/p65/STAT3 Signaling Pathways in Dopaminergic Neuronal Cells

Jang

2022

IJMS

Environmental Toxicology

“…AA and OC are popular herbal medicines in Southeast Asia. This plant extract has been used as an anti‐cancer, anti‐apoptotic, and anti‐aging agent and for Parkinson's disease treatments 12,14,40–42 . ISL drug has also been used against multiple diseases such as cardiomyopathy and intracerebral hemorrhage 43,44 .…”

Section: Discussionmentioning

confidence: 99%

“…This plant extract has been used as an anti-cancer, antiapoptotic, and anti-aging agent and for Parkinson's disease treatments. 12,14,[40][41][42] ISL drug has also been used against multiple diseases such as cardiomyopathy and intracerebral hemorrhage. 43,44 To the A previous study demonstrated that DOX-induced cardiac failure is important in hypertrophy-related signaling pathways, including GATA-4, ANP, and BNP.…”

Section: Isl Combined With Water Extract Of Aa and Oc Protects Agains...mentioning

confidence: 99%

A combination of isoliquiritigenin with Artemisia argyi and Ohwia caudata water extracts attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/Ho‐1 signaling pathways in SD rats with doxorubicin‐induced acute cardiotoxicity

Yuan Hsieh,

Islam,

Kuo

et al. 2023

Self Cite

Ohwia caudata (Thunb.) H. Ohashi (Leguminosae) also called as “Evergreen shrub” and Artemisia argyi H.Lév. and Vaniot (Compositae) also named as “Chinese mugwort” those two‐leaf extracts frequently used as herbal medicine, especially in south east Asia and eastern Asia. Anthracyclines such as doxorubicin (DOX) are commonly used as effective chemotherapeutic drugs in anticancer therapy around the world. However, chemotherapy‐induced cardiotoxicity, dilated cardiomyopathy, and congestive heart failure are seen in patients who receive DOX therapy, with the mechanisms underlying DOX‐induced cardiac toxicity remaining unclear. Mitochondrial dysfunction, oxidative stress, inflammatory response, and cardiomyocytes have been shown to play crucial roles in DOX‐induced cardiotoxicity. Isoliquiritigenin (ISL, 10 mg/kg) is a bioactive flavonoid compound with protective effects against inflammation, neurodegeneration, cancer, and diabetes. Here, in this study, our aim is to find out the Artemisia argyi (AA) and Ohwia caudata (OC) leaf extract combination with Isoliquiritigenin in potentiating and complementing effect against chemo drug side effect to ameliorate cardiac damage and improve the cardiac function. In this study, we showed that a combination of low (AA 300 mg/kg; OC 100 mg/kg) and high‐dose(AA 600 mg/kg; OC 300 mg/kg) AA and OC water extract with ISL activated the cell survival‐related AKT/PI3K signaling pathway in DOX‐treated cardiac tissue leading to the upregulation of the antioxidant markers SOD, HO‐1, and Keap‐1 and regulated mitochondrial dysfunction through the Nrf2 signaling pathway. Moreover, the water extract of AA and OC with ISL inhibited the inflammatory response genes IL‐6 and IL‐1β, possibly through the NFκB/AKT/PI3K/p38α/NRLP3 signaling pathways. The water extract of AA and OC with ISL could be a potential herbal drug treatment for cardiac hypertrophy, inflammatory disease, and apoptosis, which can lead to sudden heart failure.

BioMed Research International

“…According to the results of the KEGG pathway enrichment analyses, YGJ group was mainly focused on PI3K-Akt signaling pathway, while YGJ-BBB group was mainly concerned in endocrine resistance. Activating the PI3K-Akt cell survival pathway can inhibit mitochondrial damage-mediated apoptosis, promote autophagy of amyloid, and play a neuroprotective role [57][58][59]. In the meantime, the activation of the PI3K-Akt pathway can also inhibit inflammation response and oxidative stress [60,61].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Molecular Docking Analyses Unveil the Mechanisms of Yiguanjian Decoction against Parkinson’s Disease from Inner/Outer Brain Perspective

Shen

Zhang

2022

Objective. This study aims to explore the pharmacodynamic mechanism of Yiguanjian (YGJ) decoction against Parkinson’s disease (PD) through integrating the central nervous (inner brain) and peripheral system (outer brain) relationship spectrum. Methods. The active components of YGJ were achieved from the TCMSP, TCMID, and TCM@Taiwan databases. The blood-brain barrier (BBB) permeability of the active components along with their corresponding targets was evaluated utilizing the existing website, namely, SwissADME and SwissTargetPrediction. The targets of PD were determined through database retrieval. The interaction network was constructed upon the STRING database, followed by the visualization using Cytoscape software. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on potential targets. Finally, the molecular docking approach was employed to assess the binding affinity between key components and key targets. Results. Overall, we identified 79 active components, 128 potential targets of YGJ, and 97 potential targets of YGJ-BBB potentially suitable for the treatment of PD. GO and KEGG analyses showed that the YGJ treatment of PD mainly relied on PI3K-Akt pathway while the YGJ-BBB was mostly involved in endocrine resistance. The molecular docking results displayed high affinity between multiple compounds and targets in accordance with previous observations. Conclusions. Our study unveiled the potential mechanisms of YGJ against PD from a systemic perspective: (1) for the YGJ, they have potential exerting effects on the peripheral system and inhibiting neuronal apoptosis through regulating the PI3K-Akt pathway; (2) for the YGJ-BBB, they can directly modulate endocrine resistance of the central nervous and holistically enhance body resistance to PD along with YGJ on PI3K-Akt pathway.