Protopanaxtriol protects against 3-nitropropionic acid-induced oxidative stress in a rat model of Huntington's disease

Abstract

Aim: Protopanaxtriol (Ppt) is extracted from Panax ginseng Mayer. In the present study, we investigated whether Ppt could protect against 3-nitropropionic acid (3-NP)-induced oxidative stress in a rat model of Huntington's disease (HD) and explored the mechanisms of action. Methods: Male SD rats were treated with 3-NP (20 mg/kg on d 1, and 15 mg/kg on d 2-5, ip). The rats received Ppt (5, 10, and 20 mg/kg, po) daily prior to 3-NP administration. Nimodipine (12 mg/kg, po) or N-acetyl cysteine (NAC, 100 mg/kg, po) was used as positive control drugs. The body weight and behavior were monitored within 5 d. Then the animals were sacrificed, neuronal damage in striatum was estimated using Nissl staining. Hsp70 expression was detected with immunohistochemistry. Reactive oxygen species (ROS) generation was measured using dihydroethidium (DHE) staining. The levels of components in the Nrf2 pathway were measured with immunohistochemistry and Western blotting. Results: 3-NP resulted in a marked reduction in the body weight and locomotion activity accompanied by progressive striatal dysfunction. In striatum, 3-NP caused ROS generation mainly in neurons rather than in astrocytes and induced Hsp70 expression. Administration of Ppt significantly alleviated 3-NP-induced changes of body weight and behavior, decreased ROS production and restored antioxidant enzymes activities in striatum. Moreover, Ppt directly scavenged free radicals, increased Nrf2 entering nucleus, and the expression of its downstream products heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidase 1 (NQO1) in striatum. Similar effects were obtained with the positive control drugs nimodipine or NAC. Conclusion: Ppt exerts a protective action against 3-NP-induced oxidative stress in the rat model of HD, which is associated with its anti-oxidant activity.

The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease: A Mini Review

“…Sagredo et al [192] provided preclinical evidence for the neuroprotective effect of phytocannabinoid-based medicines in HD. Gao et al [193] investigated the neuroprotective effect of protopanaxatriol against 3-nitropropionic acid-induced oxidative stress in experimental HD. Túnez et al [194] showed the protective effect of melatonin in 3-nitropropionic acid-induced oxidative stress in synaptosomes in rat with HD.…”

Nrf2—a therapeutic target for the treatment of neurodegenerative diseases

“…Malonate also increased Nrf2 and HO-1 mRNA levels in mouse striatum seven days after injection into striatum [158]. In the 3NP model, HO-1 and NQO1 protein levels were increased in rat striatum [159]. However, another study using 3NP did not demonstrate changes in Nrf2 protein or mRNA levels of NQO1, HO-1, GCLM, or glutathione-S-transferase P1 [160].…”

“…DMF treatment of YAC128 mice resulted in reduced clasping score and neuronal loss in the striatum and cortex at 1 year of age. Two additional compounds, naringin, a flavonone from grapefruit, and protopanaxtriol, a compound isolated from ginseng, protect against 3NP-induced neurodegeneration [159, 160]. Much more work is required in the HD and genetic HD models to better understand how Nrf2 can modulate HD pathology.…”

A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

“…The operation was performed at 4 °C, and the hippocampus tissues were stored at -80 °C until use. The hippocampus tissues were homogenized and dissociated with lysis buffer (50 mmol/L Tris-HCl, pH 7.5, 150 mmol/L NaCl, and protease inhibitor mixture) for 30 min and then centrifuged at 12 000×g for 30 min; the supernatants were collected after centrifugation [12] . Protein concentrations were determined using the BCA protein assay.…”