Investigation of the protective effect of Paeonia lactiflora on Semen Strychni-induced neurotoxicity based on monitoring nine potential neurotoxicity biomarkers in rat serum and brain tissue

Abstract

Semen Strychni has been widely used as a traditional Chinese herb medicine, but its clinical use was limited for its potential neurotoxicity and nephrotoxicity. This study aimed to investigate S. Strychni-induced neurotoxicity and the neuro-protective effect of Paeonia lactiflora based on monitoring nine potential neurotoxicity biomarkers in rat serum and brain tissue. A sensitive liquid chromatography-tandem mass spectrometry method was developed and validated to monitor serotonin, tryptophan, dopamine, tyrosine and glutamate in serum and five brain regions (prefrontal cortex, hippocampus, striatum, cerebellum and hypothalamus). Analytes were separated on a CAPCELL CORE PC column (150 mm × 2 mm, 2.7 μm) with a gradient program of acetonitrile-water (0.2 % formic acid) and a total runtime of 7.5 min. In addition, enzyme-linked immunosorbent assay was conducted to determine four kinds of protein (tryptophan hydroxylase, tyrosine hydroxylase, endogenous brain-derived neurotrophic factor and nerve growth factor). Results demonstrated that the administration of S. Strychni could cause certain endogenous substances disorder. These analytes were found significantly changed (p < 0.05) in serum (except glutamate) and in certain tested brain regions in S. Strychni extract group. Pretreatment of P. lactiflora could significantly reverse the S. Strychni-induced neurotoxicity and normalize the levels of such endogenous substances. The study could be further used in predicting and monitoring neurotoxicity caused by other reasons, and it was expected to be useful for improving clinical use of S. Strychni through pretreatment with P. lactiflora.

Mechanisms of P‐Glycoprotein Modulation by Semen Strychni Combined with Radix Paeoniae Alba

“…Semen Strychni can effectively be used to treat inflammation and pain, but its use is limited by its toxic effects. Some studies have reported that Radix Paeoniae Alba can reduce the toxic effects and increase the therapeutic effects of Semen Strychni [ 4 – 6 ]. In the research, the mechanism of P-gp modulation by Semen Strychni combined with Radix Paeoniae Alba was investigated.…”

“…Radix Paeoniae Alba has been reported to have wide-ranging pharmacological activities on the nervous system [ 3 ] and has been combined with Semen Strychni in the clinic and in the prescription of Chinese patent drugs, such as Gu Ci tablets, Shu Luo Yang Gan pills, and Qi Wei Tang. Radix Paeoniae Alba reportedly decreases the toxic effects and increases the therapeutic effects of Semen Strychni [ 4 – 6 ]. Additionally, Radix Paeoniae Alba and its active ingredients have shown protective effects in previous cytotoxicology experiments [ 7 , 8 ].…”

Neuroprotective effect of total glycosides from paeonies against neurotoxicity induced by strychnos alkaloids related to recovering the levels of neurotransmitters and neuroendocrine hormones in rat serum and brain

“…Datura metel L. (mainly consists of scopolamine) was selected as positive control herb for its proved excited neurotoxicity. [42][43][44] The raw Datura metel L. was pulverized and extracted by reuxing with 75% ethanol (1 : 10, w/v) for three times and 1 h for each time. The extract was obtained by concentrating the ltrates.…”

Prophylactic Neuroprotection of Total Glucosides of Paeoniae Radix Alba against Semen Strychni-Induced Neurotoxicity in Rats: Suppressing Oxidative Stress and Reducing the Absorption of Toxic Components

“…The results in our previous study showed that continuous administration of SAs could induce neurotoxicity. The main toxic effects manifested changes in rat behavior and disorders of endogenous components [ 7 , 8 ].…”

“…Recent studies demonstrated that TGP, especially paeoniflorin (the most abundant ingredient), have been widely used in the treatment of central nervous system (CNS) diseases [ 14 , 15 ]. The neuroprotective potential of TGP may be related to mediation of inflammatory responses, oxidative stress, and endogenous metabolic processes both in vivo [ 7 , 16 ] and in vitro [ 17 , 18 ].…”