Profiling the metabolites of astrapterocarpan in rat hepatic 9000g supernatant

Zhang, Yazhou; Xu, Feng; Dong, Jing; Liang, Jing; Hashi, Yuki; Liu, Guang-Xue; Li, Yao-Li; Shang, Ming‐Ying; Wang, Xuan; Cai, Shao‐Qing

doi:10.1016/s1875-5364(19)30102-5

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…Subsequently, the livers were minced and homogenized using a homogenizer (Ultra-Turrax T8, Ika-Werke, Gmbh & Co. KG, Staufen, Germany) in cold 1.15% KCl in 0.05 M Tris-HCl buffer (pH 7.4) to the 4-fold volume of the wet liver weight. The homogenate was centrifuged at 9000× g for 30 min at 4 • C. The 9000× g supernatant (S9) was removed and either stored at −70 • C or used immediately [18,19].…”

Section: Preparation Of the Rat Hepatic S9 Fractionmentioning

confidence: 99%

“…This study aims to profile the main metabolites of formononetin in vitro and the main metabolites of ononin in vivo. The formononetin was incubated in hepatic S9 in vitro (mainly phase I metabolites) and the ononin was administered via oral gavage to rats in vivo (mainly phase II metabolites) [14,15,18,19]. The metabolites in the above samples were analyzed using high-resolution mass spectrometry (HPLC-DAD-ESI-IT-TOF-MS n ), and for the rat liver S9 experimental sample of formononetin, we isolated the major metabolites using chromatographic techniques.…”

Section: Introductionmentioning

confidence: 99%

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Identification of the Metabolites of Both Formononetin in Rat Hepatic S9 and Ononin in Rat Urine Samples and Preliminary Network Pharmacology Evaluation of Their Main Metabolites

Yang,

Wang,

Chen

et al. 2023

Molecules

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Astragalus membranaceus is a traditional Chinese medicine derived from the roots of Astragalus membranaceus (Fisch.) Bge., which has the same medicinal and edible uses in China. It is also widely used in daily food, and its pharmacological effects mainly include antioxidant effects, vascular softening effects, etc. Currently, it is increasingly widely used in the prevention of hypertension, cerebral ischemia, and stroke in China. Formononetin and its glucopyranoside (ononin) are both important components of Astragalus membranaceuss and may play important roles in the treatment of cardiovascular diseases (CVDs). This study conducted metabolic studies using formononectin and its glucopyranoside (ononin), including a combination of the in vitro metabolism of Formonetin using rat liver S9 and the in vivo metabolism of ononin administered orally to rats. Five metabolites (Sm2, 7, 9, 10, and 12) were obtained from the solution incubated with formononetin and rat hepatic S9 fraction using chromatographic methods. The structures of the five metabolites were elucidated as (Sm2)6,7,4′-trihydroxy-isoflavonoid; (Sm7)7,4′-dihydroxy-isoflavonoid; (Sm9)7,8,4′-trihydroxy-isoflavonoid; (Sm10)7,8,-dihydroxy-4′-methoxy-isoflavonoid; and (Sm12)6,7-dihydroxy-4′-methoxy- isoflavonoid on the basis of UV, NMR, and MS data. Totally, 14 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis, from which the formononetin was incubated with rat hepatic S9 fraction, and the main metabolic pathways were hydroxylation, demethylation, and glycosylation. Then, 21 metabolites were identified via HPLC-DAD-ESI-IT-TOF-MSn analysis from the urine samples from SD rats to which ononin was orally administered, and the main metabolic pathways were glucuronidation, hydroxylation, demethylation, and sulfonation. The main difference between the in vitro metabolism of formononetin and the in vivo metabolism of ononin is that ononin undergoes deglycemic transformation into Formonetin in the rat intestine, while Formonetin is absorbed into the bloodstream for metabolism, and the metabolic products also produce combined metabolites during in vivo metabolism. The six metabolites obtained from the aforementioned separation indicate the primary forms of formononetin metabolism, and due to their higher contents of similar isoflavone metabolites, they are considered the main active compounds that are responsible for pharmacological effects. To investigate the metabolites of the active ingredients of formononetin in the rat liver S9 system, network pharmacology was used to evaluate the cardiovascular disease (CVD) activities of the six primary metabolites that were structurally identified. Additionally, the macromolecular docking results of six main components and two core targets (HSP90AA1 and SRC) related to CVD showed that formononetin and its main metabolites, Sm10 and Sm12, may have roles in CVD treatment due to their strong binding activities with the HSP90AA1 receptor, while the Sm7 metabolite may have a role in CVD treatment due to its strong binding activity with the SRC receptor.

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Section: Preparation Of the Rat Hepatic S9 Fractionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of the Metabolites of Both Formononetin in Rat Hepatic S9 and Ononin in Rat Urine Samples and Preliminary Network Pharmacology Evaluation of Their Main Metabolites

Yang,

Wang,

Chen

et al. 2023

Molecules

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Exploring the In Vivo Existence Forms (23 Original Constituents and 147 Metabolites) of Astragali Radix Total Flavonoids and Their Distributions in Rats Using HPLC-DAD-ESI-IT-TOF-MSn

Liu

et al. 2020

Molecules

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Astragali Radix total flavonoids (ARTF) is one of the main bioactive components of Astragali Radix (AR), and has many pharmacological effects. However, its metabolism and effective forms remains unclear. The HPLC-DAD-ESI-IT-TOF-MSn technique was used to screen and tentatively identify the in vivo original constituents and metabolites of ARTF and to clarify their distribution in rats after oral administration. In addition, modern chromatographic methods were used to isolate the main metabolites from rat urine and NMR spectroscopy was used to elucidate their structures. As a result, 170 compounds (23 original constituents and 147 metabolites) were tentatively identified as forms existing in vivo, 13 of which have the same pharmacological effect with ARTF. Among 170 compounds, three were newly detected original constituents in vivo and 89 were new metabolites of ARTF, from which 12 metabolites were regarded as new compounds. Nineteen original constituents and 65 metabolites were detected in 10 organs. Four metabolites were isolated and identified from rat urine, including a new compound (calycoisn-3’-O-glucuronide methyl ester), a firstly-isolated metabolite (astraisoflavan-7-O-glucoside-2’-O-glucuronide), and two known metabolites (daidzein-7-O-sulfate and calycosin-3’-O-glucuronide). The original constituents and metabolites existing in vivo may be material basis for ARTF efficacy, and these findings are helpful for further clarifying the effective forms of ARTF.

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Profiling the metabolites of astrapterocarpan in rat hepatic 9000g supernatant

Cited by 2 publications

References 27 publications

Identification of the Metabolites of Both Formononetin in Rat Hepatic S9 and Ononin in Rat Urine Samples and Preliminary Network Pharmacology Evaluation of Their Main Metabolites

Identification of the Metabolites of Both Formononetin in Rat Hepatic S9 and Ononin in Rat Urine Samples and Preliminary Network Pharmacology Evaluation of Their Main Metabolites

Exploring the In Vivo Existence Forms (23 Original Constituents and 147 Metabolites) of Astragali Radix Total Flavonoids and Their Distributions in Rats Using HPLC-DAD-ESI-IT-TOF-MSn

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