Quantification of complanatoside A in rat plasma using LC‐MS/MS and its application to a pharmacokinetic study

Li, Nan; Liu, Yue; Cao, Yuchen; Wei, Zhengkai; Pang, Li; Wang, Jianmeng

doi:10.1002/bmc.3624

Cited by 4 publications

(3 citation statements)

References 14 publications

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“…Additionally, the fragment ion at m / z 299.0553 was generated by deglycosylation from the ion at m / z 461.1089. Based on the above statement, M1 was identified as complanatuside [20].…”

Section: Resultsmentioning

confidence: 99%

“…[18], and functions as a chemical marker for quality control of the drug [19]. A previous pharmacokinetic study on it [20] shows its T max (time to reach the maximum drug concentration) at 1.08 h, C max (maximum plasma concentration) of 110.8 ng/mL, and AUC 0-t (area under the plasma concentration-time curve) of 566.0 ng h/mL at a dosage of 30 mg/kg after oral administration. The above results suggest that complanatuside metabolized rapidly with lower absorption in rats.…”

Section: Introductionmentioning

confidence: 99%

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Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

et al. 2018

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The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites—rhamnocitrin 3-O-β-glc and rhamnocitrin—in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites—rhamnocitrin—was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.

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“…Additionally, the fragment ion at m / z 299.0553 was generated by deglycosylation from the ion at m / z 461.1089. Based on the above statement, M1 was identified as complanatuside [20].…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

et al. 2018

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“…Flavonoids from Semen Astragali Complanati could improve the activity of superoxidase dismutase (SOD), reduce the level of malondialdehyde (MDA) and nitric oxide (NO), and enhance the nonspecific immune function in the aging mice model ( Qi et al, 2011 ). The total flavonoids of A. complanatus has the ability to scavenge DDPH (2,2-diphenyl-1-picrylhydrazyl) oxygen free radicals and has an antiaging effect in Drosophila melanogaster ( Li et al, 2016 ). The flavonoid complanatoside A (CA) is the main bioactive part of Semen Astragali Complanati ( Qi et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans

et al. 2022

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Aging is associated with the increased risk of most age-related diseases in humans. Complanatoside A (CA) is a flavonoid compound isolated from the herbal medicine Semen Astragali Complanati. CA was reported to have potential anti-inflammatory and anti-oxidative activities. In this study, we investigated whether CA could increase the stress resistance capability and life span of Caenorhabditis elegans. Our results showed that CA could extend the longevity of C. elegans in a dosage-dependent manner, while 50 μM of CA has the best effect and increased the life span of C. elegans by about 16.87%. CA also improved the physiological functions in aging worms, such as enhanced locomotor capacity, and reduced the accumulation of the aging pigment. CA could also reduce the accumulation of toxic proteins (α-synuclein and β-amyloid) and delay the onset of neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, in models of C. elegans. Further investigation has revealed that CA requires DAF-16/FOXO, SKN-1, and HSF-1 to extend the life span of C. elegans. CA could increase the antioxidation and detoxification activities regulated by transcription factor SKN-1 and the heat resistance by activating HSF-1 that mediated the expression of the chaperone heat shock proteins. Our results suggest that CA is a potential antiaging agent worth further research for its pharmacological mechanism and development for pharmaceutical applications.

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Screening Inhibitors of α‐Amylase in PolygalaRadix Based on an Online Targeted Detection System and Molecular Docking

Su,

Xu,

Chen

et al. 2024

Phytochemical Analysis

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IntroductionTargeted screening of inhibitors of key enzymes in the progression of diabetes from natural products is one of the effective methods for the treatment of diabetes. Polygala has been proved to reduce glucose levels; however, the bioactive compounds in Polygalae Radix (PR) that have anti‐diabetic properties are unknown.ObjectiveThe purpose of this study was to explore the material basis of the anti‐diabetic effect of PR by inhibiting α‐amylase through an online detection system and molecular docking.MethodsAn online analysis platform was established and optimized for the screening of potent enzyme inhibitors from complex mixtures based on ultra‐performance liquid chromatography‐photodiode array‐quadrupole‐time‐of‐flight‐mass spectrometry‐α‐amylase‐fluorescence detector (UHPLC‐PDA‐Q‐TOF‐MSn‐α‐amylase‐FLD) detection system and molecular docking, which could efficiently separate extracts, quickly detect α‐amylase inhibitors, and determine their structures. Molecular docking confirms the inhibition of these compounds. The molecular interaction between α‐amylase and the active compound was evaluated.ResultsAmong the 101 compounds identified, 28 compounds had a strong inhibitory effect on α‐amylase. Molecular docking screening confirmed the inhibition of these compounds and evaluated the molecular interactions between α‐amylase and 30 active compounds, which strongly supported the experimental results. Among the evaluated compounds, onjisaponin R (83) and polygalaxanthone III (11) have the strongest inhibitory activity to α‐amylase (the binding energies were −9.639 and −8.972 kcal/mol, respectively) and are potential lead compounds against diabetes.ConclusionThis study proved the feasibility of using the existing platform to screen the active ingredients in PR extract, and provided a practical method for the rapid screening of potential anti‐diabetic active ingredients in traditional Chinese medicine.

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Quantification of complanatoside A in rat plasma using LC‐MS/MS and its application to a pharmacokinetic study

Cited by 4 publications

References 14 publications

Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans

Screening Inhibitors of α‐Amylase in PolygalaRadix Based on an Online Targeted Detection System and Molecular Docking

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