Aims: Although the genetic locus of X-linked dystonia parkinsonism (XDP), a neurodegenerative disease endemic in the Philippines, is well-characterized, the exact mechanisms leading to neuronal loss are not yet fully understood. Recently, we demonstrated an increase in myeloperoxidase (MPO) levels in XDP postmortem prefrontal cortex (PFC), suggesting a role for inflammation in XDP pathogenesis. Therefore, we hypothesized that inhibiting MPO could provide a therapeutic strategy for XDP.
Methods: MPO activity was measured by using an MPO-activatable fluorescent agent (MAFA) in human postmortem PFC. Reactive oxygen species (ROS) and MPO activity were measured in XDP-derived fibroblasts and SH-SY5Y cells following MPO inhibition.
Results: MPO activity was significantly increased in XDP PFC. Additionally, treatment of cell lines with postmortem XDP PFC resulted in a significant increase in ROS levels. To determine whether increases in MPO activity caused increases in ROS, MPO content was immunodepleted from XDP PFC, which resulted in a significant decrease in ROS in SH-SY5Y cells. Consistently, the treatment with verdiperstat, a potent and selective MPO inhibitor, significantly decreased ROS in both XDP-derived fibroblasts and XDP PFC-treated SH-SY5Y cells.
Conclusions: Collectively, our results suggest that MPO inhibition mitigates oxidative stress and may provide a novel therapeutic strategy for XDP treatment.
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http://dx.doi.org/10.1111/cns.70109 | DOI Listing |
Life Sci
December 2024
School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China; State Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Lanzhou University, Lanzhou 730000, PR China; Southeast Research Institute, Lanzhou University, Lanzhou 730000, PR China. Electronic address:
Objectives: The Shh pathway may shed new light on developing new cell death inhibitors for the therapy of ischemic stroke. We aimed to examine whether the Shh co-reporter SMO or its agonist halcinonide can upregulate Bcl-2 to suppress neuronal cell death, ultimately improving behavioral deficits and reducing cerebral infarction in an ischemic stroke model.
Methods: Halcinonide or genetic manipulation of SMO was conducted in PC12 cells to examine their impacts on oxidative or OGD/R stress, and the chemical, along with AAV-SMO or AAV-EGFP were tested in MCAO rats to investigate their potential protective effects against neuronal damages due to cerebral I/R injury.
J Ethnopharmacol
December 2024
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China; State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs; Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China; Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences; NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance. Electronic address:
Ethnopharmacological Relevance: Myristica fragrans (Nutmeg) is a commonly used Chinese herbal medicine and edible spice. According to Pharmacopoeia of People's Republic of China, it has the effects of warming the middle and promoting qi, astringent intestines, and antidiarrheal. In the record of Compendium of Materia Medica, it is the myristica fragrans water extract (MFWE) that is utilized for therapeutic purposes of gastrointestinal disorders frequently.
View Article and Find Full Text PDFCell Biochem Biophys
December 2024
Department of Biochemistry, Faculty of Veterinary Medicine, Alexandria University, Alexandria, 21944, Egypt.
Berberine (BER) and Cyperus rotundus rhizomes extract (CRE) are phytochemicals characterized by broad-spectrum pharmacological activity that could tackle the side effects of conventional mastitis therapies, however, they undergo a modest bioavailability. In the current study, nanoformulations of BER and CRE chitosan hydrogel (BER/CH-NPs, CRE/CH-NPs) were investigated for their antibacterial, antioxidant, anti-inflammatory and anti-apoptotic effects against S. aureus-induced mastitis in a rat model.
View Article and Find Full Text PDFBrain Res Bull
December 2024
Department of Neurology, Shanghai Tenth People's Hospital Chongming Branch, 2866 Chongming Road, Shanghai 202157, China.
Background: This study aimed to clarify whether the neuroprotective effect of LXA4 is associated with the targeting of neutrophil extracellular traps (NETs) in ischemic stroke (IS).
Methods: The MCAO rat model was established to assess cerebral infarction, brain water content and neurological deficits. ELISA was employed to examine the activities of MPO, NE, MMP-9.
Zhongguo Zhong Yao Za Zhi
September 2024
School of Life Sciences, Lanzhou University Lanzhou 730000, China.
This study aims to decipher the mechanism of the broth of Codonopsis Radix fermented with Lactobacillus plantarum(FCR) on the gastric mucosa in the rat model of acute gastric ulcer. A total of 64 SD rats were randomized into 8 groups: control, model, positive control(omeprazole), probiotic, unfermented Codonopsis Radix, and low-, medium-and high-dose FCR, with 8 rats in each group. The rat model of acute gastric ulcer was established by gavage with anhydrous ethanol.
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