Table 2.
Effects of selected natural products on CYP450s (from 2010~2020).
| Natural Products | CYP450 Species | CYP450 | Effects on CYP450 | Method | Ref. |
|---|---|---|---|---|---|
| Milk thistle extracts and eight isolated constituents | Human | CYP3A | Inhibit (The extract silymarin and constituents … demonstrated >50% inhibition of CYP3A activity …) | In vitro (human liver and intestinal microsomes) | [29] |
| Milk thistle extract | Human | CYP1A2 CYP2C9 CYP2D6 CYP3A4/5 |
——(Exposure to milk thistle extract produced no significant influence on CYP1A2, CYP2C9, CYP2D6, or CYP3A4/5 activities.) | Clinical trial | [73] |
| Milk thistle extract | Human | CYP1A2 CYP2A6 CYP2B6 CYP2C8 CYP2C9 CYP2C19 CYP2D6 CYP2E1 CYP3A4 |
Inhibit (… the extract significantly inhibited CYP 2B6, 2C8, 2C9, 2C19, 2E1, and 3A4…) ——(but not likely, and are remote for CYPs 2C19, 2D6, and 3A4.) |
In vitro (human hepatocytes and human liver microsomes), HPLC-MS | [92] |
| Milk thistle | Human | CYP2C9 | Inhibit (The results indicated milk thistle as the most potent CYP2C9 inhibitor.) | In vitro (human liver microsomes), HPLC | [93] |
| Milk thistle | Human | CYP2C8 | Inhibit (Isosilibinin, a mixture of the diastereoisomers isosilybin A and isosilybin B, was found to be the most potent inhibitor, followed by isosilybin B...) | In vitro (human liver microsomes), LC/MS-MS. | [94] |
| 7-O-methylated analogues of flavonolignans from Milk thistle | Human | CYP2C9 CYP3A4/5 |
Inhibit (CYP2C9 activity was most sensitive to inhibition, … followed by CYP3A4/5 and …) | In vitro (human liver or intestinal microsomes), HPLC | [95] |
| Milk thistle aqueous/ methanolic extracts | Human | CYP2C9 CYP2B6 CYP2C19 CYP3A4 |
Inhibit (The present work indicates that inhibition of CYP2C9 occurs with the aqueous extracts, IC50 = 64.2 µg/mL…The methanolic extract caused significant inhibition of CYP2B6, CYP2C9, CYP2C19, and CYP3A4.) | In vitro (N-in-one cocktail), LC/MS-MS | [96] |
| Black cohosh | Human | CYP2D6 CYP3A4 |
—— (Previous in vivo studies in humans have concluded that CYP2D6 and CYP3A4 are not inhibited by black cohosh. The present data are in agreement with these findings.) | In vitro (N-in-one cocktail), LC/MS-MS | [96] |
| Commercial liquid (ethanol) extracts of black cohosh | Human | CYP2C19 | Inhibit (one of the three most potent interactions were: Black cohosh and CYP2C19 (IC50 0.37 μg/mL). | In vitro (microplate-based assays using cDNA-expressed CYP450 isoforms and fluorogenic substrates) | [97] |
| 75% ethanolic extract of black cohosh | Human | CYP2D6 CYP3A4 |
Inhibit (In vitro metabolic interactions between black cohosh and tamoxifen via inhibition of cytochromes P450 2D6 and 3A4.) | In vitro (human liver microsomes), LC-MS | [98] |
| Methanol extracts of garlic, echinacea, saw palmetto, valerian, black cohosh and cranberry | Human | CYP2C8 | Inhibit (All herbal extracts showed inhibition of CYP2C8 activity...) | In vitro (human liver microsomes), LC/MS/MS | [99] |
| Red ginseng | Human | CYP2C9 CYP3A4 CYP1A2 CYP2C19 CYP2D6 |
——(Red ginseng poses minimal risks for clinically relevant CYP- or OATP-mediated drug interactions and is well tolerated.) | Clinical trials, Cocktail | [78] |
| Sailuotong (SLT), a fixed combination of Panax ginseng, Ginkgo biloba, and Crocus sativus extracts | Rat | CYP1A2 CYP3A1/2 |
Induce-CYP1A2 (repeated administration of SLT induced CYP1A2 by enhancing... The influence is attributed to its herbal component of ginseng to a large extent.) Inhibit- CYP3A (The inhibition of SLT on CYP3A was likely attributed to ginseng and gingko cooperatively.) |
In vivo (cocktail), LC-MS/MS | [40] |
| Red ginseng | Human | CYP1A2 CYP2C9 CYP2C19 CYP2D6 CYP3A4 |
——(No significantly different drug interactions were observed between fermented red ginseng and the CYP probe substrates) | Clinical trial | [79] |
| Red ginseng | Human | CYP1A2 CYP2C9 CYP2C19 CYP2D6 CYP3A4 |
——(RG has no relevant potential to cause CYP enzyme- or P-gp-related interactions.) | Clinical trial | [80] |
| Panax ginseng | Human | CYP3A | Induce (Ginseng appeared to induce CYP3A activity in the liver and possibly the gastrointestinal tract.) | Clinical trial | [81] |
| Korean red ginseng (KRG) | Human & Mice | CYP3A CYP2D |
Induce-CYP3A Inhibit-CYP2D (The area under the curve for OH-midazolam/midazolam catalysed by CYP3A was increased significantly by the administration of 2.0 g/kg KRG extract for 2 and 4 weeks. CYP3A-catalysed midazolam 1′-hydroxylation also increased significantly in a dose- and time-dependent manner…Whereas CYP2D-catalysed dextromethorphan O-deethylation decreased in a dose- and time-dependent manner in vivo.) |
In vitro (human liver microsomes), in vivo, LC-MS/MS | [82] |
| Tanshinones of Danshen | Human | CYP1A2 CYP2C9 CYP2E1 CYP3A4 CYP1A2 |
Inhibit (Tanshinone I, tanshinone IIA, and cryptotanshinone were potent competitive CYP1A2 inhibitors; medium competitive inhibitors of CYP2C9; medium competitive inhibitors of CYP2E1 for tanshinone I and 10.8 μM for crytotanshinone; but weak competitive inhibitors of CYP3A4. Dihydrotanshinone was a competitive inhibitor of human CYP1A2 and CYP2C9, a noncompetitive inhibitor of CYP3A4 but an uncompetitive CYP2E1 inhibitor.) | In vitro (human Liver Microsomes), HPLC | [87] |
| Danshen capsules | Human | CYP3A4 | Induce (The results suggested that multiple dose administration of Danshen capsules could induce cytochrome P450 (CYP) isoenzymes, thereby increasing the clearance of clopidogrel.) | Clinical trial | [16] |
| Danshen extract | Rat | CYP3A | —— (Orally administered Danshen had no substantial effect on the pharmacokinetics of docetaxel and clopidogrel, suggesting the negligible safety concern of Danshen in P-gp- and CYP3A-mediated interactions in vivo.) | In vivo (cocktail), LC-MS/MS | [85] |
| Miltirone (from Danshen) | Human | CYP1A2 CYP2C9 CYP2D6 CYP3A4 |
Inhibit (Miltirone showed moderate inhibition on CYP1A2 (IC50 = 1.73 μM) and CYP2C9 (IC50 = 8.61 μM), and weak inhibition on CYP2D6 (IC50 = 30.20 μM) and CYP3A4 (IC50 = 33.88 μM).) | In vitro (human liver microsomes), HPLC | [88] |
| Danshen components | Human | CYP2C8 CYP2J2 |
Inhibit (salvianolic acid A was a competitive inhibitor of CYP2C8 and mixed-type inhibitor of CYP2J2. alvianolic acid C had moderate noncompetitive and mixed-type inhibitions on CYP2C8 and CYP2J2, respectively. Tanshinone IIA was a moderate competitive inhibitor of CYP2C8. Dihydrotanshinone I had moderate noncompetitive inhibition on CYP2J2, but mechanism-based inhibition on CYP2C8. Tanshinone I was a moderate competitive inhibitor of CYP2C8. | In vitro (recombinant human CYP2C8 and CYP2J2 systems), LC-MS/MS | [100] |
| Danshen | Human | CYP1A2 | Inhibit (CYP1A2 activity was decreased with an increasing inhibitor concentration, confirming the inhibition of caffeine metabolism in vivo.) | In vitro (human liver microsomes), clinical trials, HPLC. | [101] |
| Guanxinning injection (Danshen, Chuanxiong) | Rat | CYP1A2 | Inhibit (The in vivo and in vitro results demonstrated that GXNI could induce CYP1A2 activity in rats.) | In vivo, in vitro, UPLC-MS/MS. | [89] |
| Tanshinone I, tanshinone IIA, and cryptotanshinone, baicalein, osthole, quercetin, cordycepin, and sodium tanshinone IIA sulfonate (From Danshen) | Human | CYP1A2 | Inhibit (tanshinone I, tanshinone IIA, and cryptotanshinone exhibited remarkable inhibition on CYP1A2,... baicalein, osthole, quercetin, cordycepin, and sodium tanshinone IIA sulfonate showed moderate inhibition on the CYP1A2…) | In vitro (high throughput inhibitor screening kit) | [102] |