Rapid and Sensitive Determination of Timosaponin AIII in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Application

Liu, Yanping; Pu, Yang; Zhang, Tong; Ding, Yue; Bing, Wang; Cai, Zhenzhen

doi:10.3390/ijms14023656

Cited by 8 publications

(5 citation statements)

References 5 publications

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“…TAIII could be prepared by enzyme hydrolysis from TBII with high purity; 1 kg of TAIII can be prepared in 1 week in a laboratory, 20 thus providing adequate materials for further pharmaceutical research and new drug development. However, in our previous study, 21 TAIII showed hydrophobicity and low bioavailability, limiting its in vivo antitumor efficacy.…”

Section: Introductionmentioning

confidence: 90%

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Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII

Lu¹,

Ding²,

Zhang³

et al. 2018

IJN

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IntroductionTimosaponin AIII (TAIII), as a steroid saponin in Anemarrhena asphodeloides, has favorable potential as an antitumor candidate. However, its hydrophobicity and low bioavailability severely limit its in vivo antitumor efficacy.MethodsTo overcome this drawback, TAIII-loaded liposomes (LP) were prepared to improve TAIII solubility and extend its circulation time. Furthermore, anti-CD44 antibody-modified LP (CD44-LP) was prepared to enhance the therapeutic index of TAIII. The LP and CD44-LP were also characterized through their biological activity, target selective binding and uptake, and in vivo pharmacokinetics.ResultsCompared with free TAIII, both LP and CD44-LP possessed a desirable sustained-release profile in vitro, with ~14.2- and 10.7-fold longer TAIII half-life, respectively, and 1.7- and 1.9-fold larger area under the curve, respectively. LP and CD44-LP enhanced TAIII antitumor activity against HepG2 cells and in a xenograft mouse model without detectable toxicity. In particular, CD44-LP exhibited notably higher cytotoxicity than did LP, with a lower half-maximal inhibitory concentration (48 h). CD44-LP exhibited stronger tumor inhibition, and the tumor inhibitory effect was 1.3-fold that of LP. Furthermore, confocal laser scanning microscopy and in vivo near-infrared imaging of a xenograft mouse model revealed that compared with LP, CD44-LP could effectively enhance tumor accumulation.ConclusionTaken together, the results indicate that both CD44-LP and LP can considerably extend TAIII circulation time, increase tumor-targeted accumulation, and enhance antitumor activity. Thus, the anti-CD44 antibody-modified liposome is a promising candidate for treating CD44-positive cancer with considerable antitumor effects.

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Section: Introductionmentioning

confidence: 90%

“…The plasma was treated and analyzed through HPLC-tandem mass spectrophotometry (MS/MS), as described previously. 21 Briefly, 100 μL of plasma sample was deproteinized with 300 μL methanol, vortexed for 5 min, and centrifuged at 15,000 rpm for 5 min. Subsequently, the supernatant was examined through HPLC-MS/MS.…”

Section: In Vivo Pharmacokinetic Studiesmentioning

confidence: 99%

Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII

Lu¹,

Ding²,

Zhang³

et al. 2018

IJN

Self Cite

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“…The chromatograms of the rat blank plasma, blank plasma spiked with the seven standards and IS, and rat plasma acquired at 6 h after gavage of TAE, were analyzed and compared to investigate the selectivity of the method [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic Comparisons of Multiple Triterpenic Acids from Jujubae Fructus Extract Following Oral Delivery in Normal and Acute Liver Injury Rats

Guo

Quan-jin

et al. 2018

IJMS

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Jujubae Fructus, the dried fruit of Ziziphus jujuba, has been used as Chinese medicine and food for centuries. Triterpenic acids have been found to be the major bioactive constituents in Jujubae Fructus responsible for their hepatoprotective activity in previous phytochemical and biological studies, while few pharmacokinetic studies have been conducted. To reveal the kinetics of the triterpenic acids under the pathological liver injury state, an established ultra-performance liquid chromatography coupled with a mass spectrometry method was applied for the simultaneous quantitation of seven triterpenic acids (ceanothic acid, epiceanothic acid, pomonic acid, alphitolic acid, maslinic acid, betulinic acid, and betulonic acid) in plasma samples of normal and acute liver injury rats induced by CCl4. The results showed that there were significant differences (p < 0.05) in the pharmacokinetic parameters of seven triterpenic acids between model and normal groups. The AUC0–t and AUC0–∞ of epiceanothic acid (5227 ± 334 μg⋅h/L vs. 1478 ± 255 μg⋅h/L and 6127 ± 423 μg⋅h/L vs. 1482 ± 255 μg⋅h/L, respectively) and pomonic acid (4654 ± 349 μg⋅h/L vs. 1834 ± 225 μg⋅h/L and 4776 ± 322 μg⋅h/L vs. 1859 ± 230 μg⋅h/L, respectively) in model rats were significantly higher than those in normal rats, and the CLz/F of them were significantly decreased (0.28 ± 0.02 L/h/kg vs. 1.36 ± 0.18 L/h/kg and 19.96 ± 1.30 L/h/kg vs. 53.15 ± 5.60 L/h/kg, respectively). In contrast, the above parameters for alphitolic acid, betulinic acid and betulonic acid exhibited the quite different trend. This pharmacokinetic research might provide useful information for the clinical usage of triterpenic acids from Jujubae Fructus.

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“…After the oral administration of free TSAIII (6.8 mg/kg) in healthy male SD rats, the Cmax, Tmax, AUC0-t, and T1/2 of TSAIII were 18.2 ± 3.1 ng/mL, 2.3 ± 0.57 h, 150.5 ± 29.2 ng·h/mL, and 4.9 ± 2.0 h, respectively [ 25 ]. Another study reported that the values of T1/2, Cmax, and AUC were 2.74 ± 1.68 h, 105.7 ± 14.9 ng/mL, and 921.8 ± 289.0 ng·h/mL after the intragastrical administration of TSAIII (25 mg/kg) in male SD rats [ 26 ]. Comparably, the values of these were 15.1 ± 2.3 h, 77.28 ± 21.47 ng/mL, and 916.61 ± 208.43 ng·h/mL after the intragastrical administration of sarsasapogenin (25 mg/kg) [ 27 ].…”

Section: Pharmacokinetic Profiles Of Tsaiiimentioning

confidence: 99%

The Potential Role of Timosaponin-AIII in Cancer Prevention and Treatment

et al. 2023

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Cancer, as one of the leading causes of death worldwide, has challenged current chemotherapy drugs. Considering that treatments are expensive, alongside the resistance of tumor cells to anticancer drugs, the development of alternative medicines is necessary. Anemarrhena asphodeloides Bunge, a recognized and well-known medicinal plant for more than two thousand years, has demonstrated its effectiveness against cancer. Timosaponin-AIII (TSAIII), as a bioactive steroid saponin isolated from A. asphodeloides, has shown multiple pharmacological activities and has been developed as an anticancer agent. However, the molecular mechanisms of TSAIII in protecting against cancer development are still unclear. In this review article, we provide a comprehensive discussion on the anticancer effects of TSAIII, including proliferation inhibition, cell cycle arrest, apoptosis induction, autophagy mediation, migration and invasion suppression, anti-angiogenesis, anti-inflammation, and antioxidant effects. The pharmacokinetic profiles of TSAII are also discussed. TSAIII exhibits efficacy against cancer development. However, hydrophobicity and low bioavailability may limit the application of TSAIII. Effective delivery systems, particularly those with tissue/cell-targeted properties, can also significantly improve the anticancer effects of TSAIII.

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Rapid and Sensitive Determination of Timosaponin AIII in Rat Plasma by LC-MS/MS and Its Pharmacokinetic Application

Cited by 8 publications

References 5 publications

Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII

Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII

Pharmacokinetic Comparisons of Multiple Triterpenic Acids from Jujubae Fructus Extract Following Oral Delivery in Normal and Acute Liver Injury Rats

The Potential Role of Timosaponin-AIII in Cancer Prevention and Treatment

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