Drug-protein binding of Danhong injection and the potential influence of drug combination with aspirin: Insight by ultrafiltration LC–MS and molecular modeling

Zhu, Junfeng; Yi, Xiaojiao; Huang, Peng; Shuqing, Chen; Wu, Yongjiang

doi:10.1016/j.jpba.2016.11.028

Cited by 24 publications

(17 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The degree to which a drug is protein-bound in plasma has a marked effect on its toxicological, pharmacological, and pharmacokinetic parameters. It is widely believed that only the free concentration, rather than the total drug concentration, can elicit pharmacological responses [ 10 , 11 ]. Human serum albumin (HSA) is the most abundant protein in the circumstance of blood circulation, playing a crucial role of the protein to transport and transmit many endogenous and exogenous constituents such as fatty acids, hormones, and drugs [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, trials based on active compounds need sophisticated and multiple isolation steps which are labor-intensive, time-consuming, and expensive [ 15 ]. With the advance of the analytical techniques for active ingredients in complex systems, one method based on ultrafiltration coupled with liquid chromatography mass spectrometry (UF-LC-MS) is considered to investigate the combination between HSA and bioactive compounds [ 11 , 16 ]. Due to its low sample consumption, reuse of receptors (e.g., HSA, enzymes), and obviated need for immobilization, bioactive ingredients have been high-throughput screened and identified via the UF-LC-MS technique [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rapid Investigation and Screening of Bioactive Components in Simo Decoction via LC-Q-TOF-MS and UF-HPLC-MD Methods

Cheng

Wang

et al. 2018

Molecules

View full text Add to dashboard Cite

Simo decoction (SMD), as a traditional medicine, is widely used in the treatment of gastrointestinal dysmotility in China. In this study, a combined method of liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) and ultrafiltration high-performance liquid chromatography molecular docking (UF-HPLC-MD) was efficiently employed to identify and screen bioactive ingredients in SMD. Ninety-four major constituents were identified or tentatively characterized by comparing their retention times and mass spectra with standards or literature data by using LC-Q-TOF-MS, and the ascription of those compounds were classified for the first time. Among them, 13 bioactive ingredients, including norisoboldine, eriocitrin, neoeriocitrin, narirutin, hesperidin, naringin, neohesperidin, hesperitin-7-O-glucoside, linderane, poncirin, costunolide, nobiletin, and tangeretin, were primarily identified as the human serum albumin (HSA) ligands at a range of docking scores from −29.7 to −40.6 kJ/mol by UF-HPLC-MD. The results indicate the systematic identification and screening of HSA ligands from Simo decoction guided by LC-Q-TOF-MS and UF-HPLC-MD represents a feasible and efficient method that could be extended for the identification and screening of other bioactive ingredients from natural medicines.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rapid Investigation and Screening of Bioactive Components in Simo Decoction via LC-Q-TOF-MS and UF-HPLC-MD Methods

Cheng

Wang

et al. 2018

Molecules

View full text Add to dashboard Cite

show abstract

“…Among these emerging ligand-searching strategies, affinity ultrafiltration (AUF)-liquid chromatography mass spectrometry (LC-MS) is widely used to screen potential molecules from nature-product extracts. The concept is based on the specific binding between target proteins and ligands [ 13 ] that allows screening according to a molecular weight cut-off for separation [ 14 ]. The advantages of UF include no need for enzyme immobilization and a simplified process that enables rapid detection and identification of enzyme-binding molecules comparing to bioassay-guided fraction [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Enzyme-Site Blocking Combined with Optimization of Molecular Docking for Efficient Discovery of Potential Tyrosinase Specific Inhibitors from Puerariae lobatae Radix

et al. 2018

View full text Add to dashboard Cite

Enzyme inhibitors from natural products are becoming an attractive target for drug discovery and development; however, separating enzyme inhibitors from natural-product extracts is highly complex. In this study, we developed a strategy based on tyrosinase-site blocking ultrafiltration integrated with HPLC-QTOF-MS/MS and optimized molecular docking to screen tyrosinase inhibitors from Puerariae lobatae Radix extract. Under optimized ultrafiltration parameters, we previously used kojic acid, a known tyrosinase inhibitor, to block the tyrosinase active site in order to eliminate false-positive results. Using this strategy, puerarin, mirificin, daidzin and genistinc were successfully identified as potential ligands, and after systematic evaluation by several docking programs, the rank of the identified compounds predicted by computational docking was puerarin > mirificin > kojic acid > daidzin ≈ genistin, which agreed with the results of tyrosinase-inhibition assays. Structure-activity relationships indicated that C-glycosides showed better tyrosinase inhibition as compared with O-glycosides, with reduced inhibition achieved through the addition of glycosyl, which provides ideas about the screen of leading compounds and structural modification.

show abstract

“…Salvianolic acids in DHI are considered as strong ligands of albumin, and the binding ability to human serum albumin of salvianolic acids are stronger than sodium salicylate ( Zhu et al, 2017 ). It is possible that the SA bound with albumin in blood circulation might be squeezed down by salvianolic acids, and the proportion of SA directly excreted by glomerular filtration might be consequently increased.…”

Section: Discussionmentioning

confidence: 99%

Characteristic and Mechanism of Drug-Herb Interaction Between Acetylsalicylic Acid and Danhong Injection Mediated by Organic Anion Transporters

Peng

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

The mixture of Salvia miltiorrhiza and Carthamus tinctorius (Danhong injection, DHI) is widely prescribed in China for the treatment of cardiovascular and cerebrovascular diseases. In most cases, DHI is used in combination with acetylsalicylic acid (aspirin, ASA). However, the interaction between DHI and ASA remains largely undefined. The purpose of this study is to explore the interaction profile and mechanism between DHI and ASA. The frequency of drug combination of DHI and ASA was analyzed based on 5,183 clinical cases. The interaction characteristics were evaluated by analyzing the pharmacokinetics and disposition profile of salicylic acid (SA, the primary metabolite of ASA) in rats. The interaction mechanisms were explored through evaluating the hydrolysis of ASA regulated by ASA esterase, the tubular secretion of SA mediated by influx and efflux transporters, and the tubular reabsorption of SA regulated by urinary acidity-alkalinity. The inhibitory potential of DHI on organic anion transporters (OATs) was further verified in aristolochic acid I (AAI) induced nephropathy. Clinical cases analysis showed that DHI and ASA were used in combination with high frequency of 70.73%. In drug combination of DHI and ASA, the maximum plasma concentration of SA was significantly increased by 1.37 times, while the renal excretion of SA was significantly decreased by 32.54%. The mechanism study showed that DHI significantly inhibited the transport function, gene transcription and protein expression of OATs. In OATs mediated AAI nephropathy, DHI significantly reduced the renal accumulation of AAI by 55.27%, and alleviated renal damage such as glomerulus swelling, tubular blockage and lymphocyte filtration. In drug combination of DHI and ASA, DHI increased the plasma concentration of SA not through enhancing the hydrolysis of ASA, and the tubular reabsorption of SA was not significantly affected. Inhibition of tubular secretion of SA mediated by OATs might be the reason that contributes to the decrease of SA renal excretion.

show abstract

Drug-protein binding of Danhong injection and the potential influence of drug combination with aspirin: Insight by ultrafiltration LC–MS and molecular modeling

Cited by 24 publications

References 26 publications

Rapid Investigation and Screening of Bioactive Components in Simo Decoction via LC-Q-TOF-MS and UF-HPLC-MD Methods

Rapid Investigation and Screening of Bioactive Components in Simo Decoction via LC-Q-TOF-MS and UF-HPLC-MD Methods

Enzyme-Site Blocking Combined with Optimization of Molecular Docking for Efficient Discovery of Potential Tyrosinase Specific Inhibitors from Puerariae lobatae Radix

Characteristic and Mechanism of Drug-Herb Interaction Between Acetylsalicylic Acid and Danhong Injection Mediated by Organic Anion Transporters

Contact Info

Product

Resources

About