Glucosylation of Steroidal Saponins by Cyclodextrin Glucanotransferase

Wang, Yongze; Feng, Bing; Huang, Hongzhi; Kang, Liping; Cong, Yu‐Sheng; Zhou, Wenbin; Zou, Peng; Cong, Yang; Song, Xin-Bo; B, Ma

doi:10.1055/s-0030-1249938

Cited by 18 publications

(13 citation statements)

References 22 publications

(28 reference statements)

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“…Rhizoma Anemarrhenae (Zhimu in Chinese), a wellknown traditional Chinese medicinal herb, which is officially listed in the Chinese Pharmacopoeia, has been effectively used for febrile diseases in oriental clinical practices. Timosaponin A-III (TAIII), a steroidal saponin isolated from the rhizomes of Anemarrhena asphodeloides (AA), has been credited with a wide spectrum of bioactivities, including improving learning and memory (16), inhibiting inflammation (17), suppressing allergic reaction (18), controlling hyperglycemic (19,20), activating autophagy (21) and inducing cancer cells apoptosis (22)(23)(24). However, the ability of TAIII to reverse MDR has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Timosaponin A-III reverses multi-drug resistance in human chronic myelogenous leukemia K562/ADM cells via downregulation of MDR1 and MRP1 expression by inhibiting PI3K/Akt signaling pathway

Chen

Xing

Wang

et al. 2016

International Journal of Oncology

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One of the major causes of failure in chemotherapy for patients with human chronic myelogenous leukemia (CML) is the acquisition of multidrug resistance (MDR). MDR is often associated with the overexpression of drug efflux transporters of the ATP-binding cassette (ABC) protein family. Timosaponin A-III (TAIII), a saponin isolated from the rhizome of Anemarrhena asphodeloides, has previously demonstrated the ability to suppress certain human tumor processes and the potential to be developed as an anticancer agent. Nevertheless, the ability of TAIII to reverse MDR has not yet been explored. In this study, the adriamycin (ADM) resistance reversal effect of TAIII in human CML K562/ADM cells and the underlying mechanism was investigated. The Cell Counting Kit-8 (CCK-8) assay showed that TAIII had a reversal effect on the drug resistance of K562/ADM cells. Flow cytometry assay showed increased intracellular accumulation of ADM after cells were pretreated with TAIII, and the changes in the accumulation of rhodamine-123 (Rho-123) and 5(6)-carboxyfluorescein diacetate (CFDA) dye in K562/ADM cells were determined to be similar to the changes of intracellular accumulation of ADM. After pretreatment of cells with TAIII, the decreasing expression of P-gp and MRP1 mRNA was examined by reverse transcription polymerase chain reaction (RT-PCR). Western blotting showed TAIII inhibiting P-gp and MRP1 expression depended on the PI3K/Akt signaling pathway by decreasing the activity of p-Akt. Moreover, wortmannin an inhibitor of PI3K/Akt signaling pathway has a strong inhibitory effect on the expression of p-Akt, P-gp and MRP1. Besides, the combined treatment with TAIII did not have an affect on wortmannin downregulation of p-Akt, P-gp and MRP1. Taken together, our findings demonstrate, for the first time, that TAIII induced MDR reversal through inhibition of P-gp and MRP1 expression and function with regained adriamycin sensitivity which might mainly correlate to the regulation of PI3K/Akt signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Timosaponin A-III reverses multi-drug resistance in human chronic myelogenous leukemia K562/ADM cells via downregulation of MDR1 and MRP1 expression by inhibiting PI3K/Akt signaling pathway

Chen

Xing

Wang

et al. 2016

International Journal of Oncology

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“…Lu et al also developed an enzyme associated five-step preparation method to produce high yield and purity Timo AIII from A. asphodeloides Bunge, which allowed us obtain efficient amount of Timo AIII for further study and product development (Lu et al, 2016). Although Timo AIII and Timo BII are mainly metabolized to sarsasapogenin in vivo, the sugar chain plays important roles in their pharmacological activities (Sy et al, 2008;Lee et al, 2010;Wang et al, 2010). The sugar chain in Timo AIII is indispensable to its pharmacological activities, and conversion of Timo BII to Timo AIII enhanced its cytotoxicity (King et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…So, Timo AIII presented most potential anti-cancer activity due to its specific sugar chain binding site. However, the hydrophobicity and low bioavailability of Timo AIII limited its efficacy in vivo, and many studies also focused on derivatization or drug delivery system design based on Timo AIII (Wang et al, 2010;Hu et al, 2011;Kim et al, 2014;Lu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Activity, Pharmacokinetics, and Toxicity of Timosaponin AIII, a Natural Product Isolated From Anemarrhena asphodeloides Bunge: A Review

et al. 2020

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Anemarrhena asphodeloides Bunge is a famous Chinese Materia Medica and has been used in traditional Chinese medicine for more than two thousand years. Steroidal saponins are important active components isolated from A. asphodeloides Bunge. Among which, the accumulation of numerous experimental studies involved in Timosaponin AIII (Timo AIII) draws our attention in the recent decades. In this review, we searched all the scientific literatures using the key word "timosaponin AIII" in the PubMed database update to March 2020. We comprehensively summarized the pharmacological activity, pharmacokinetics, and toxicity of Timo AIII. We found that Timo AIII presents multiple-pharmacological activities, such as anti-cancer, antineuronal disorders, anti-inflammation, anti-coagulant, and so on. And the anti-cancer effect of Timo AIII in various cancers, especially hepatocellular cancer and breast cancer, is supposed as its most potential activity. The anti-inflammatory activity of Timo AIII is also beneficial to many diseases. Moreover, VEGFR, X-linked inhibitor of apoptosis protein (XIAP), B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1), thromboxane (Tx) A2 receptor, mTOR, NF-kB, COX-2, MMPs, acetylcholinesterase (AChE), and so on are identified as the crucial pharmacological targets of Timo AIII. Furthermore, the hepatotoxicity of Timo AIII was most concerned, and the pharmacokinetics and toxicity of Timo AIII need further studies in diverse animal models. In conclusion, Timo AIII is potent as a compound or leading compound for further drug development while still needs in-depth studies.

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“…A number of reports have suggested that transglycosylation by enzymes can be used to improve physiochemical functions such as taste, solubility in water, and oxidative stability of numerous active substances [15,16]. Among these enzymes, cyclodextrin glycosyltransferase (CGTase, 1,4-α- D -glucan: 1,4-α- D -glycopyranosyltransferase, cyclizing, EC 2.4.1.19) [17] has been reported to accelerate reactions between natural products and starch hydrolysate or β-cyclodextrin to produce glucosylated modifications of natural compounds such as hesperidin, glycosylglycerol [14,16] rutin [18], and steroidal saponins [19].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of a Novel α-Glucosyl Ginsenoside F1 by Cyclodextrin Glucanotransferase and Its In Vitro Cosmetic Applications

et al. 2018

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Ginsenosides from Panax ginseng (Korean ginseng) are unique triterpenoidal saponins that are considered to be responsible for most of the pharmacological activities of P. ginseng. However, the various linkage positions cause different pharmacological activities. In this context, we aimed to synthesize new derivatives of ginsenosides with unusual linkages that show enhanced pharmacological activities. Novel α-glycosylated derivatives of ginsenoside F1 were synthesized from transglycosylation reactions of dextrin (sugar donor) and ginsenoside F1 (acceptor) by the successive actions of Toruzyme®3.0L, a cyclodextrin glucanotransferase. One of the resultant products was isolated and identified as (20S)-3β,6α,12β-trihydroxydammar-24ene-(20-O-β-D-glucopyranosyl-(1→2)-α-D-glucopyranoside) by various spectroscopic characterization techniques of fast atom bombardment-mass spectrometry (FAB-MS), infrared spectroscopy (IR), proton-nuclear magnetic resonance (1H-NMR), 13C-NMR, gradient heteronuclear single quantum coherence (gHSQC), and gradient heteronuclear multiple bond coherence (gHMBC). As expected, the novel α-glycosylated ginsenoside F1 (G1-F1) exhibited increased solubility, lower cytotoxicity toward human dermal fibroblast cells (HDF), and higher tyrosinase activity and ultraviolet A (UVA)-induced inhibitory activity against matrix metalloproteinase-1 (MMP-1) than ginsenoside F1. Since F1 has been reported as an antiaging and antioxidant agent, the enhanced efficacies of the novel α-glycosylated ginsenoside F1 suggest that it might be useful in cosmetic applications after screening.

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Glucosylation of Steroidal Saponins by Cyclodextrin Glucanotransferase

Cited by 18 publications

References 22 publications

Timosaponin A-III reverses multi-drug resistance in human chronic myelogenous leukemia K562/ADM cells via downregulation of MDR1 and MRP1 expression by inhibiting PI3K/Akt signaling pathway

Timosaponin A-III reverses multi-drug resistance in human chronic myelogenous leukemia K562/ADM cells via downregulation of MDR1 and MRP1 expression by inhibiting PI3K/Akt signaling pathway

Pharmacological Activity, Pharmacokinetics, and Toxicity of Timosaponin AIII, a Natural Product Isolated From Anemarrhena asphodeloides Bunge: A Review

Synthesis of a Novel α-Glucosyl Ginsenoside F1 by Cyclodextrin Glucanotransferase and Its In Vitro Cosmetic Applications

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