Inhibition effects of eight anti-coronavirus drugs on glycosides metabolism and glycosidases in human gut microflora
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
|---|---|
| Enthalten in: |
Die Pharmazie - 76(2021), 5 vom: 01. Mai, Seite 195-201 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dai, Tianming [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
886U3H6UFF |
|---|
| Anmerkungen: |
Date Completed 20.05.2021 Date Revised 07.12.2022 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1691/ph.2021.01005 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM325166668 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM325166668 | ||
| 003 | DE-627 | ||
| 005 | 20231225191847.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1691/ph.2021.01005 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1083.xml |
| 035 | |a (DE-627)NLM325166668 | ||
| 035 | |a (NLM)33964992 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Dai, Tianming |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inhibition effects of eight anti-coronavirus drugs on glycosides metabolism and glycosidases in human gut microflora |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 20.05.2021 | ||
| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Glycosides |2 NLM | |
| 650 | 7 | |a Plant Preparations |2 NLM | |
| 650 | 7 | |a Chloroquine |2 NLM | |
| 650 | 7 | |a 886U3H6UFF |2 NLM | |
| 650 | 7 | |a Glycoside Hydrolases |2 NLM | |
| 650 | 7 | |a EC 3.2.1.- |2 NLM | |
| 650 | 7 | |a Darunavir |2 NLM | |
| 650 | 7 | |a YO603Y8113 |2 NLM | |
| 700 | 1 | |a Wang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Pengzhen |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Libing |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Renke |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Qingqi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Die Pharmazie |d 1947 |g 76(2021), 5 vom: 01. Mai, Seite 195-201 |w (DE-627)NLM000009180 |x 0031-7144 |7 nnns |
| 773 | 1 | 8 | |g volume:76 |g year:2021 |g number:5 |g day:01 |g month:05 |g pages:195-201 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1691/ph.2021.01005 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 76 |j 2021 |e 5 |b 01 |c 05 |h 195-201 | ||