The Characteristics of Orally Absorbed Decoction-borne MicroRNAs in Animal

BackgroundSome dietary plant microRNAs (miRNAs) can be orally absorbed to exert cross-kingdom gene regulation in animal. However, little is known about which kinds of plant miRNAs tend to be absorbed. Given herbal decoction contains numerous plant small RNAs (sRNAs, including miRNAs), some of which have been found to be capable of cross-kingdom gene regulation, the present study chose herbal decoctions as study materials to answer the questions.MethodsTwo decoctions recommended for coronavirus disease 2019 treatment in China, Qingfei Paidu (QFPD) decoction and Qingre Huashi Kangdu (QRHS) decoction, were selected as study materials. Human volunteers and rats were administered with QFPD and QRHS decoction, respectively, and the sRNAs profiles in human and rat serum were detected and compared between the timepoints of pre- and post-administration to collect the absorbed and non-absorbed plant sRNAs. Using logistical repression model, the absorbed and non-absorbed datasets were analyzed to identify the influence factors of plant sRNAs absorption, including the expression levels of sRNAs in the decoctions, the minimum free energy of sRNAs to form secondary structure, the percent of AU/UA dinucleotides in sRNAs. Moreover, the antivirus effects of a highly expressed plant miRNA (MIR-6240-3p) in both decoctions on human coronaviruses type 229E (HCoV-229E) were detected in vitro.Results586176 sRNAs were detected in QFPD decoction, out of which, 100276 and 416961 were respectively judged as absorbed and non-absorbed plant sRNAs in human. 124026 sRNAs were detected in QRHS decoction, out of which, 7484 and 100274 were respectively judged as absorbed and non-absorbed plant sRNAs in rat. Logistical repression analysis found that in both human and animal, the plant sRNAs with higher expression level, minimum free energy or AU/UA frequency were easier to be orally absorbed. MIR-6240-3p could significantly reduce the viral RNA copies in cell culture medium of HCoV-229E.ConclusionThe results suggested that plant miRNAs with higher expression level, minimum free energy or AU/UA frequency tend to be orally absorbed and subsequently exert cross-kingdom gene regulation.