Systematically explore the potential hepatotoxic material basis and molecular mechanism of Radix Aconiti Lateralis based on the concept of toxicological evidence chain (TEC)

Zhang, Kai; Liu, Chuanxin; Yang, Tiange; Li, Xinxin; Wei, Longyin; Chen, Dongliang; Zhou, Jiali; Yin, Yue; Yu, Xinyu; Li, Fēi

doi:10.1016/j.ecoenv.2020.111342

Cited by 17 publications

(10 citation statements)

References 53 publications

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“…The selection criteria of 14 quantitative components included four factors: (1) detected in QLQX [7] and derived from the main herbals, (2) highly exposed to plasma by UHPLC-Q-TOF-MS in our previous study [8], (3) exhibited anti-heart failure activity in H9c2 cardiomyocytes in our previous study [9], and (4) identified as toxic components [15][16][17]. In the present study, several bioactive components were not selected, including hydroxysafflor yellow A from Carthami Flos [19] and salvianolic acids from Salvia Miltiorrhiza Radix et Rhizoma [20].…”

Section: Selection Of 14 Bioactive Components and Methods Developmentmentioning

confidence: 99%

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Pharmacokinetics, hepatic disposition, and heart tissue distribution of 14 compounds in rat after oral administration of Qi‐Li‐Qiang‐Xin capsule via ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry

Tang

Dai

Zeng

et al. 2022

J of Separation Science

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In the present study, a specific and sensitive approach using ultra-highperformance liquid chromatography coupled with triple quadrupole tandem mass spectrometry was developed and validated for the quantitative analysis of 14 constituents in rat plasma, liver, and heart. The method was fully validated and successfully applied to pharmacokinetic, hepatic disposition, and heart tissue distribution studies of 14 compounds after the oral administration of Qi-Li-Qiang-Xin capsule. Ginsenoside Rb1, alisol A, astragaloside IV, and periplocymarin were found to be highly exposed in rat plasma, while toxic components such as hypaconitine, mesaconitine, and periplocin had low circulation levels in vivo. Moreover, sinapine thiocyanate, neoline, formononetin, calycosin, and alisol A exhibited significant liver first-pass effects. Notably, high levels of alisol A, periplocymarin, benzoylmesaconine, and benzoylhypaconine were observed in the heart. Based on high exposure and appropriate pharmacokinetic features in the systemic plasma and heart, astragaloside IV, ginsenoside Rb1, periplocymarin, benzoylmesaconine, benzoylhypaconine, and alisol A can be considered as the main potentially effective components. Ultimately, the results provide relevant information for discovery of effective substances, as well as further anti-heart failure action mechanism investigations of Qi-Li-Qiang-Xin capsule.

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Section: Selection Of 14 Bioactive Components and Methods Developmentmentioning

confidence: 99%

“…Notably, the alkaloids from Aconiti Lateralis radix exhibit hepatotoxicity [15] and are highly enriched in the liver [16]. Moreover, the cardiac glycosides in Periploca cortex are not only the active components but also toxic components [17].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, hepatic disposition, and heart tissue distribution of 14 compounds in rat after oral administration of Qi‐Li‐Qiang‐Xin capsule via ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry

Tang

Dai

Zeng

et al. 2022

J of Separation Science

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“…Studies have shown that after oral administration of Fuzi, the level of toxic alkaloids in the liver is very high, which can partly explain the hepatotoxicity of Fuzi, but the mechanism is still unclear [ 23 ]. In previous research, our research group screened out 22 potential hepatotoxic ingredients of Fuzi which can induce liver injury in rats [ 24 ]. As one of the potential hepatotoxic components of Fuzi, MA needs to be further studied.…”

Section: Introductionmentioning

confidence: 99%

Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network

Chen

Zhang

Jiao

et al. 2022

Toxins

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Mesaconitine (MA), one of the main diterpenoid alkaloids in Aconitum, has a variety of pharmacological effects, such as analgesia, anti-inflammation and relaxation of rat aorta. However, MA is a highly toxic ingredient. At present, studies on its toxicity are mainly focused on the heart and central nervous system, and there are few reports on the hepatotoxic mechanism of MA. Therefore, we evaluated the effects of MA administration on liver. SD rats were randomly divided into a normal saline (NS) group, a low-dose MA group (0.8 mg/kg/day) and a high-dose MA group (1.2 mg/kg/day). After 6 days of administration, the toxicity of MA on the liver was observed. Metabolomic and network toxicology methods were combined to explore the effect of MA on the liver of SD rats and the mechanism of hepatotoxicity in this study. Through metabonomics study, the differential metabolites of MA, such as L-phenylalanine, retinyl ester, L-proline and 5-hydroxyindole acetaldehyde, were obtained, which involved amino acid metabolism, vitamin metabolism, glucose metabolism and lipid metabolism. Based on network toxicological analysis, MA can affect HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway and FoxO signal pathway by regulating ALB, AKT1, CASP3, IL2 and other targets. Western blot results showed that protein expression of HMOX1, IL2 and caspase-3 in liver significantly increased after MA administration (p < 0.05). Combined with the results of metabonomics and network toxicology, it is suggested that MA may induce hepatotoxicity by activating oxidative stress, initiating inflammatory reaction and inducing apoptosis.

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“…Serum Pharmacochemistry (SPC) is a scientific approach to study the effective material basis for TCM [14][15][16][17] . The studies of SPC have suggested that only constitutions absorbed in blood could be considered as effective ingredients [15][16][17] . The metabolic processes of drugs in vivo could be individually different between pathological and normal conditions.…”

mentioning

confidence: 99%

“…The metabolic processes of drugs in vivo could be individually different between pathological and normal conditions. In order to make the experimental results reflect the effective material basis of TCM truly, researches on SPC should be carried out under a pathological condition [16,17] .…”

mentioning

confidence: 99%

Identification of the Absorbed Components of Raw Fuzi (Lateral Root of Aconitum carmichaelii Debx.) in a Rat Adjuvant Arthritis Model

Wang¹,

Yang²,

Zhang³

et al. 2022

IJPS

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Wang et al.: Absorbed Components of Raw Fuzi in a Rat Adjuvant Arthritis ModelThe aim of the present study was to identify the absorbed components of raw fuzi in a rat adjuvant arthritis model and evaluate the therapeutic effects of three alkaloids of fuzi's absorbed components, aconitine, hypaconitine and mesaconitine. The adjuvant arthritis model was established by complete Freund's adjuvant injection in Wistar rats. Then the animal's body weight, condition of fur, hind paw volume and immunological parameters, nitric oxide and tumor necrosis factor-alpha, were assessed as markers of inflammation and arthritis. Serum samples from rats treated with oral fuzi extracts were analyzed by ultra performance liquid chromatography-mass spectrometric and 12 prototypes of fuzi were identified. Aconitine and mesaconitine could substantially reduce the serum levels of nitric oxide and tumor necrosis factor-alpha in the adjuvant arthritis model, while hypaconitine did not show obvious effects. The method for the identification of absorbed components of raw fuzi was simple and sensitive. Among the alkaloids, aconitine and mesaconitine might be the major compounds from diester-diterpenoid alkaloids for the treatment of rheumatoid arthritis. The current study connected serum pharmacochemistry study of fuzi with pharmacological experiment in adjuvant arthritis model and discovered the effective substance of fuzi, which could provide plausible evidence for its using, a candidate treatment for rheumatoid arthritis.

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Systematically explore the potential hepatotoxic material basis and molecular mechanism of Radix Aconiti Lateralis based on the concept of toxicological evidence chain (TEC)

Cited by 17 publications

References 53 publications

Pharmacokinetics, hepatic disposition, and heart tissue distribution of 14 compounds in rat after oral administration of Qi‐Li‐Qiang‐Xin capsule via ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry

Pharmacokinetics, hepatic disposition, and heart tissue distribution of 14 compounds in rat after oral administration of Qi‐Li‐Qiang‐Xin capsule via ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry

Study on the Mechanism of Mesaconitine-Induced Hepatotoxicity in Rats Based on Metabonomics and Toxicology Network

Identification of the Absorbed Components of Raw Fuzi (Lateral Root of Aconitum carmichaelii Debx.) in a Rat Adjuvant Arthritis Model

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