RESUMO
Objective: To evaluate the safety and efficacy of Compound Huangdai Tablets (Realgar-Indigo Naturalis formula, RIF) combined with all-trans retinoic acid (ATRA) to treat acute promyelocytic leukemia (APL). Methods: This study was registered in PROSPERO (CRD42018108118). The relevant literatures on RIF treatment of APL were systematically searched in the following databases: China National Knowledge Infrastructure, Wanfang, VIP Medical Information System, Chinese Biomedical Database, EMBASE, Cochrane Library, and PubMed. The quality of the included studies was evaluated and Review Manager 5.3 software and Stata 13.0 software were used to perform the Meta-analysis. In addition, this study used the method of network pharmacology to conduct a preliminary exploration of the mechanism of RIF on APL. Results: The study included 12 studies involving 775 APL patients. The Meta-analysis showed that there was no significant difference (P 0.05) between the RIF group and the arsenic trioxide (ATO) group for primary outcomes, secondary outcomes apart from liver dysfunction. The incidence of liver dysfunction (P = 0.006) in the RIF group were significantly lower than those in the ATO group. In addition, the cost of maintenance therapy in the RIF group was significantly lower (P 0.05) than the ATO group. Besides, the active ingredients in RIF mainly act on targets proteins such as ACHE, NCOA2, RXRA, and then play a role in the treatment of APL through regulating multiple molecular mechanisms, such as TP53 regulates transcription of cell cycle genes, nuclear receptor transcription pathway. Conclusion: There was no significant difference in efficacy of oral RIF combined with ATRA compared with intravenous ATO combined with ATRA for the treatment of APL. The oral RIF exposed patients to less risk, offered more convenience and had lower prices. RIF can treat APL by multi-target and multi-pathway interventions that inducing apoptosis of APL cells and inhibiting the proliferation of APL cells, and so on. Therefore, oral RIF in the treatment of APL is worthy of further research and development.
RESUMO
To investigate the effect of clinical dose of Realgar-Indigo Naturais formula (RIF) and large-dose of Realgar on main drug-metabolizing enzymes CYP450s of rat liver, as well as its regulatory effect on mRNA expression. Wistar rats were administrated orally with tested drugs for 14 days. A Cocktail method combined with HPLC-MS/MS was used in the determination of 4 cytochrome P450 isozymes (CYP1A2, CYP2B, CYP3A and CYP2C) in liver of the rats, and the mRNA expression levels of the above subtypes were detected by real-time fluorescent quantitative PCR. The results showed that RIF can significantly induce CYP1A2 and CYP2B enzyme activity, and inhibit CYP3A enzyme activity. This result was consistent with the mRNA expression. However, its single compound showed weaker or even contrary phenomenon. Different doses of Realgar also showed significant inconsistencies on CYP450 enzymes activity and mRNA expression. These phenomena may be relevant with RIF compatibility synergies or toxicity reduction. The results can also prompt drug interactions when RIF is combined with other medicines in application.