The necessity of eliminating the interference of panaxatriol saponins to maximize the preventive effect of panaxadiol saponins against Parkinson's disease in rats

IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL
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Abstract

Background

The effects of individual panaxadiol saponin and panaxatriol saponin on rodent models of Parkinson's disease (PD) have been recognized. However, it is not clear whether purified total ginsenosides as an entirety has effect against PD in rat model. This study compared the protective effects of a purified panaxadiol saponin fraction (PDSF), a purified panaxatriol saponin fraction (PTSF), and their mixtures against the rotenone (ROT)-induced PD in rats.

Methods

Potential effects of PDSF, PTSF, and their mixtures against motor dysfunction and impairments of nigrostriatal dopaminergic neurons (DN), blood-brain barrier (BBB), cerebrovascular endothelial cells (CEC), and glial cells were measured in the models of ROT-induced PD rats and cell damage. Pro-inflammatory NF-kB p65 (p65) activation was localized in DN and other cells in the striatum.

Results

PDSF and PTSF had a dose-dependent effect against motor dysfunction with a larger effective dose range for PDSF. PDSF protected CEC, glial cells, and DN in models of PD rats and cell damage, while PTSF had no such protections. Chronic ROT exposure potently activated p65 in CEC with enhanced pro-inflammatory and decreased anti-inflammatory factors and impaired BBB in the striatum, PDSF almost completely blocked the ROT-induced p65 activation and maintained both anti- and pro-inflammatory factors at normal levels and BBB integrity, but PTSF aggravated the p65 activation with impaired BBB. Furthermore, PTSF nullified all the effects of PDSF when they were co-administrated.

Conclusion

PDSF had significant protective effect against the ROT-induced PD in rats by protecting CEC, glial cells, and DN, likely through inhibiting NF-κB p65 in CEC from triggering neuroinflammation, and also directly protecting glial cells and neurons against ROT-induced toxicity. PDSF has great potential for preventing and treating PD.

Abstract Image

Abstract Image

消除三七皂苷干扰以最大限度发挥三七皂苷对大鼠帕金森病的预防作用的必要性
背景单个三七皂苷和三七酚皂苷对帕金森病(PD)啮齿动物模型的影响已得到认可。然而,目前尚不清楚纯化的人参皂苷整体是否对大鼠帕金森病模型有作用。本研究比较了纯化的三七皂苷组分(PDSF)、纯化的三七皂苷组分(PTSF)及其混合物对鱼藤酮(ROT)诱导的帕金森病大鼠的保护作用。方法 在ROT诱导的帕金森病大鼠模型和细胞损伤模型中,测量PDSF、PTSF及其混合物对运动功能障碍和黑质纹状体多巴胺能神经元(DN)、血脑屏障(BBB)、脑血管内皮细胞(CEC)和神经胶质细胞损伤的潜在作用。结果PDSF和PTSF对运动功能障碍有剂量依赖性作用,PDSF的有效剂量范围更大。PDSF 能保护脊髓灰质炎大鼠和细胞损伤模型中的 CEC、神经胶质细胞和 DN,而 PTSF 则没有这种保护作用。PDSF几乎完全阻断了ROT诱导的p65活化,并使抗炎和促炎因子维持在正常水平,同时保持了BBB的完整性,但PTSF加剧了p65的活化,并使BBB受损。结论PDSF通过保护CEC、神经胶质细胞和DN,对ROT诱导的大鼠帕金森病具有显著的保护作用,这可能是通过抑制CEC中的NF-κB p65引发神经炎症,并直接保护神经胶质细胞和神经元免受ROT诱导的毒性。PDSF 在预防和治疗帕金森病方面具有巨大潜力。
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来源期刊
Journal of Ginseng Research
Journal of Ginseng Research CHEMISTRY, MEDICINAL-INTEGRATIVE & COMPLEMENTARY MEDICINE
CiteScore
11.40
自引率
9.50%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Journal of Ginseng Research (JGR) is an official, open access journal of the Korean Society of Ginseng and is the only international journal publishing scholarly reports on ginseng research in the world. The journal is a bimonthly peer-reviewed publication featuring high-quality studies related to basic, pre-clinical, and clinical researches on ginseng to reflect recent progresses in ginseng research. JGR publishes papers, either experimental or theoretical, that advance our understanding of ginseng science, including plant sciences, biology, chemistry, pharmacology, toxicology, pharmacokinetics, veterinary medicine, biochemistry, manufacture, and clinical study of ginseng since 1976. It also includes the new paradigm of integrative research, covering alternative medicinal approaches. Article types considered for publication include review articles, original research articles, and brief reports. JGR helps researchers to understand mechanisms for traditional efficacy of ginseng and to put their clinical evidence together. It provides balanced information on basic science and clinical applications to researchers, manufacturers, practitioners, teachers, scholars, and medical doctors.
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