| First Author | Liu J | Year | 2021 |
| Journal | Front Pharmacol | Volume | 12 |
| Pages | 707844 | PubMed ID | 34393786 |
| Mgi Jnum | J:340223 | Mgi Id | MGI:6817803 |
| Doi | 10.3389/fphar.2021.707844 | Citation | Liu J, et al. (2021) Chronoeffects of the Herbal Medicines Puerariae radix and Coptidis rhizoma in Mice: A Potential Role of REV-ERBalpha. Front Pharmacol 12:707844 |
| abstractText | Identifying drugs with dosing time-dependent effects (chronoeffects) and understanding the underlying mechanisms would help to improve drug treatment outcome. Here, we aimed to determine chronoeffects of the herbal medicines Puerariae radix (PR) and Coptidis rhizoma (CR), and investigate a potential role of REV-ERBalpha as a drug target in generating chronoeffects. The pharmacological effect of PR on hyperhomocysteinemia in mice was evaluated by measuring total homocysteine, triglyceride levels and lipid accumulation. PR dosed at ZT10 generated a stronger effect on hyperhomocysteinemia than drug dosed at ZT2. Furthermore, PR increased the expression levels of REV-ERBalpha target genes Bhmt, Cbs and Cth (encoding three key enzymes responsible for homocysteine catabolism), thereby alleviating hyperhomocysteinemia in mice. Moreover, CR attenuated chronic colitis in mice in a dosing time-dependent manner based on measurements of disease activity index, colon length, malondialdehyde/myeloperoxidase activities and IL-1beta/IL-6 levels. ZT10 dosing generated a stronger anti-colitis effect as compared to ZT2 dosing. This was accompanied by lower production of colonic inflammatory cytokines (i.e., Nlrp3, IL-1beta, IL-6, Tnf-alpha and Ccl2, REV-ERBalpha target genes) in colitis mice dosed at ZT10. The diurnal patterns of PR and CR effects were respectively consistent with those of puerarin (a main active constituent of PR, a REV-ERBalpha antagonist) and berberine (a main active constituent of CR, a REV-ERBalpha agonist). In addition, loss of Rev-erbalpha in mice abolished the dosing time-dependency in PR and CR effects. In conclusion, the therapeutic effects of PR and CR depend on dosing time in mice, which are probably attributed to diurnal expression of REV-ERBalpha as the drug target. Our findings have implications for improving therapeutic outcomes of herbal medicines with a chronotherapeutic approach. |
