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

Abstract

Strychnos alkaloids (SAs) are the main toxic constituents in Semen Strychni, a traditional Chinese medicine, which is known for its fatal neurotoxicity. Hence, the present study was carried out to evaluate the neurotoxicity induced by SAs and the pre-protective effects of the total glucosides of Paeoniae Radix Alba (TGP). An SA brain damage model was firstly established. The neurotoxicity induced by SAs and the pre-protective effects of TGP were confirmed by physical and behavioral testing, biochemical assay, and histological examination. Then, a liquid chromatography-tandem mass spectrometry method was developed and validated to investigate the time-course change and distribution of strychnine and brucine (two main SAs) in the brain after oral SA administration with or without TGP pretreatment. Biochemical analysis results indicated that TGP could ameliorate the oxidative stress status caused by SAs. Time-course change and distribution studies demonstrated that strychnine and brucine were rapidly absorbed into the brain, peaked early at 0.5 h, and were mainly located in the hippocampus and cerebellum. TGP showed a pre-protective effect against neurotoxicity by reducing the absorption of toxic alkaloids into the brain. These findings could provide beneficial information in facilitating future studies of Semen Strychni neurotoxicity and developing herbal medicines to alleviate neurotoxicity in the clinic.

Studies on the Changes of Pharmacokinetics Behaviors of Phytochemicals and the Influence on Endogenous Metabolites After the Combination of Radix Bupleuri and Radix Paeoniae Alba Based on Multi-Component Pharmacokinetics and Metabolomics

“…Besides, several studies have shown that RB, RPA, and their main active ingredients (such as saikosaponins, albiflorin, methyl gallate, etc.) have significant neuroprotective and antidepressant activity ( Wang et al, 2016 ; Li et al, 2017 ; Li et al, 2018 ). Therefore, we speculated that the combination of RB and RPA by increasing the bioavailability of these five phytochemicals, the impact on picolinic acid was strengthened to enhance each other’s neuroprotective.…”

“…Besides, several studies have shown that RB, RPA, and their main active ingredients (such as saikosaponins, albiflorin, methyl gallate, etc.) have significant neuroprotective and antidepressant activity (Wang et al, 2016;Li et al, 2017;Li et al, 2018). Therefore, we speculated that the FIGURE 9 | The correlation between the phytochemicals improved bioavailability after compatibility and the altered endogenous metabolites.…”

Investigation of the detoxification effect of licorice on Semen Strychni-induced acute toxicity in rats using a HPLC-Q-TOF/MS-based metabolomics approach

“…Evidence have shown that Semen Strychni could enhance oxidative stress. 4 Uric acid is the nal oxidation product of purine metabolism and can provide an antioxidant defense. 30 Similar to uric acid, ascorbic acid-2-sulfate could also protect the body from oxidative stress injury.…”

“…When used in large dosage or for a long time, it can easily cause multiple organ damage, such as liver injury, kidney injury as well as nerve injury. 4,5 Thus, it is of great signicance to clarify the toxic mechanism and seek a suitable antidote.…”

Efficacy, Chemical Constituents, and Pharmacological Actions of Radix Paeoniae Rubra and Radix Paeoniae Alba

“…The therapeutic effects of RPA on the nervous system can be summarized as follows: neuroprotective, antidepressant, sedative, and analgesic and anticonvulsant. Total glucosides of paeony can exhibit pre-protection against neurotoxicity by reducing the absorption of toxic alkaloids by the brain (Hou et al, 2017;Li et al, 2018). Albiflorin is the main ingredient of RPA, and it can lower the levels of neuronal nitric oxide synthase (nNOS), and the antinociceptive activity is at least partially related to calcium channels (Zhang et al, 2016b).…”