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Inhibition effects of eight anti-coronavirus drugs on glycosides metabolism and glycosidases in human gut microflora.
Pharmazie. 2021 05 01; 76(5):195-201.P

Abstract

The effects of eight oral anti-coronavirus drugs (lopinavir, ritonavir, chloroquine, darunavir, ribavirin, arbidol, favipiravir, oseltamivir) on the metabolism of four specific glycosides (polydatin, geniposide, quercitrin, glycyrrhizin) and on the activities of three major glycosidases (β-glucosidase, α-rhamnosidase, β-glucuronidase) from gut microflora were explored in vitro and determined by LC-MS/MS. The metabolism of polydatin, geniposide, quercitrin and glycyrrhizin was significantly inhibited by one or several anti-coronavirus drugs of 100 μM around 1 h and 4 h (P<0.05), among which darunavir could strongly reduce the production of genipin (70.6% reduction), quercitin (80.6% reduction) and glycyrrhetinic acid (37.9% reduction), which may cause a high risk of herb-drug interactions (HDI). Additionally, chloroquine reduced the production of genipin and quercitin by more than 75% (P<0.05), whereas arbidol had no significant influence on the metabolism of polydatin, quercitrin and glycyrrhizin (P>0.05) so that its risk may be lower. The inhibition of darunavir on β-glucosidase was relatively strong (IC50 = 193±23 μM), and the inhibition became weaker on β-glucuronidase and α-rhamnosidase (IC50>500 μM). The consistency between gut microflora and glycosidase system indicated that the inhibition of darunavir on the activity of β-glucosidase and β-glucuronidase may be the main reason for affecting the metabolism of geniposide, glycyrrhizin and polydatin in gut microflora. However, for the inhibition of darunavir and chloroquine on the metabolism of quercetrin, there was no correlation between gut microflora and α-rhamnosidase system. Assessing the risk of HDI mediated by glycosidases in gut microflora may be conducive to the safety and efficacy of combining traditional herbal and Western medicine for the treatment of patients with Covid-19.

Authors+Show Affiliations

Guangzhou Institute of Traumatic Surgery, Guangzhou, China.Department of Orthopaedics, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China.Guangzhou Institute of Traumatic Surgery, Guangzhou, China.Guangzhou Institute of Traumatic Surgery, Guangzhou, China.School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China.Department of Orthopaedics, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China;, Email: meng_qingqi@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33964992

Citation

Dai, Tianming, et al. "Inhibition Effects of Eight Anti-coronavirus Drugs On Glycosides Metabolism and Glycosidases in Human Gut Microflora." Die Pharmazie, vol. 76, no. 5, 2021, pp. 195-201.
Dai T, Wang M, Wang P, et al. Inhibition effects of eight anti-coronavirus drugs on glycosides metabolism and glycosidases in human gut microflora. Pharmazie. 2021;76(5):195-201.
Dai, T., Wang, M., Wang, P., Dai, L., Dai, R., & Meng, Q. (2021). Inhibition effects of eight anti-coronavirus drugs on glycosides metabolism and glycosidases in human gut microflora. Die Pharmazie, 76(5), 195-201. https://doi.org/10.1691/ph.2021.01005
Dai T, et al. Inhibition Effects of Eight Anti-coronavirus Drugs On Glycosides Metabolism and Glycosidases in Human Gut Microflora. Pharmazie. 2021 05 1;76(5):195-201. PubMed PMID: 33964992.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition effects of eight anti-coronavirus drugs on glycosides metabolism and glycosidases in human gut microflora. AU - Dai,Tianming, AU - Wang,Min, AU - Wang,Pengzhen, AU - Dai,Libing, AU - Dai,Renke, AU - Meng,Qingqi, PY - 2021/5/9/entrez PY - 2021/5/10/pubmed PY - 2021/5/21/medline SP - 195 EP - 201 JF - Die Pharmazie JO - Pharmazie VL - 76 IS - 5 N2 - The effects of eight oral anti-coronavirus drugs (lopinavir, ritonavir, chloroquine, darunavir, ribavirin, arbidol, favipiravir, oseltamivir) on the metabolism of four specific glycosides (polydatin, geniposide, quercitrin, glycyrrhizin) and on the activities of three major glycosidases (β-glucosidase, α-rhamnosidase, β-glucuronidase) from gut microflora were explored in vitro and determined by LC-MS/MS. The metabolism of polydatin, geniposide, quercitrin and glycyrrhizin was significantly inhibited by one or several anti-coronavirus drugs of 100 μM around 1 h and 4 h (P<0.05), among which darunavir could strongly reduce the production of genipin (70.6% reduction), quercitin (80.6% reduction) and glycyrrhetinic acid (37.9% reduction), which may cause a high risk of herb-drug interactions (HDI). Additionally, chloroquine reduced the production of genipin and quercitin by more than 75% (P<0.05), whereas arbidol had no significant influence on the metabolism of polydatin, quercitrin and glycyrrhizin (P>0.05) so that its risk may be lower. The inhibition of darunavir on β-glucosidase was relatively strong (IC50 = 193±23 μM), and the inhibition became weaker on β-glucuronidase and α-rhamnosidase (IC50>500 μM). The consistency between gut microflora and glycosidase system indicated that the inhibition of darunavir on the activity of β-glucosidase and β-glucuronidase may be the main reason for affecting the metabolism of geniposide, glycyrrhizin and polydatin in gut microflora. However, for the inhibition of darunavir and chloroquine on the metabolism of quercetrin, there was no correlation between gut microflora and α-rhamnosidase system. Assessing the risk of HDI mediated by glycosidases in gut microflora may be conducive to the safety and efficacy of combining traditional herbal and Western medicine for the treatment of patients with Covid-19. SN - 0031-7144 UR - https://www.unboundmedicine.com/medline/citation/33964992/Inhibition_effects_of_eight_anti-coronavirus_drugs_on_glycosides_metabolism_and_glycosidases_in_human_gut_microflora. L2 - https://www.ingentaconnect.com/openurl?genre=article&amp;issn=0031-7144&amp;volume=76&amp;issue=5&amp;spage=195&amp;aulast=Dai DB - PRIME DP - Unbound Medicine ER -