Effect and mechanism of quercetin or quercetin-containing formulas against COVID-19: From bench to bedside.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global coronavirus disease 2019 (COVID-19) pandemic since 2019. Immunopathogenesis and thromboembolic events are central to its pathogenesis. Quercetin exhibits several beneficial activities against COVID-19, including antiviral, anti-inflammatory, immunomodulatory, antioxidative, and antithrombotic effects. Although several reviews have been published, these reviews are incomplete from the viewpoint of translational medicine. The authors comprehensively evaluated the evidence of quercetin against COVID-19, both basically and clinically, to apply quercetin and/or its derivatives in the future. The authors searched the PubMed, Embase, and the Cochrane Library databases without any restrictions. The search terms included COVID-19, SARS-CoV-2, quercetin, antiviral, anti-inflammatory, immunomodulatory, thrombosis, embolism, oxidative, and microbiota. The references of relevant articles were also reviewed. All authors independently screened and reviewed the quality of each included manuscript. The Cochrane Risk of Bias Tool, version 2 (RoB 2) was used to assess the quality of the included randomized controlled trials (RCTs). All selected studies were discussed monthly. The effectiveness of quercetin against COVID-19 is not solid due to methodological flaws in the clinical trials. High-quality studies are also required for quercetin-containing traditional Chinese medicines. The low bioavailability and highly variable pharmacokinetics of quercetin hinder its clinical applications. Its positive impact on immunomodulation through reverting dysbiosis of gut microbiota still lacks robust evidence. Quercetin against COVID-19 does not have tough clinical evidence. Strategies to improve its bioavailability and/or to develop its effective derivatives are needed. Well-designed RCTs are also crucial to confirm their effectiveness in the future.

A population-based case-control study on the association of Angelica sinensis exposure with risk of breast cancer.

BACKGROUND: Due to a lack of evidence from large-scale epidemiological studies by far on this issue, whether there is a link between Angelica sinensis exposure and breast cancer risk remained inconclusive. METHODS: We conducted a population-based case-control study using Taiwan's National Health Insurance claim data, in which all breast cancer patients newly diagnosed between 2005 and 2008 were employed as the case group (n = 34,262) and a random sample of non-breast cancer individuals selected from 1-million beneficiaries registered in 2005 was served as the control group. For fair comparability, we employed the time density sampling method to select controls who were matched to case on date of breast cancer diagnosis and age with a case/control ratio of 1/3 (n = 102,786). RESULTS: We found that the use of Angelica sinensis presents a weakly but significantly protective effect on breast cancer (adjusted odds ratio (aOR) 0.95, 95% confidence interval (CI) 0.93-0.98), with a significant dose-gradient relationship. We also noted a stronger association with breast cancer with initial use of Angelica sinensis at a longer time before breast cancer diagnosis, and found that the seemingly protective effect of Angelica sinensis was more obvious among women who had initial use at 47-55 years (aOR 0.93, 95% CI 0.88-0.98). CONCLUSION: This population-based case-control study revealed that exposure to Angelica sinensis showed a weakly but significantly protective effect on breast cancer risk, which could ease people's concern over the potential carcinogenic effect from exposure to Angelica sinensis.