Extracellular RNA dimension in alternative medicine: processing–dependent integrity and bioactivity of honeysuckle miRNA MIR2911Download PDF Download PDF LetterOpen accessPublished: 02 July 2026Jieqiong Lei1 na1,Yangchao Dong2 na1,Yiting Wu1 na1,Chen-Yu Zhang1 &…Zheng Fu1 Signal Transduction and Targeted Therapy volume 11, Article number: 257 (2026) Cite this articleSubjectsDrug discoveryMolecular biologyDear Editor,For decades, the bioactive constituents of Traditional Chinese Medicine (TCM) have been assumed to consist predominantly of chemical small molecules such as alkaloids, ketones, steroids, and terpenoids.1,2,3 In contrast, nucleic acids received little attention owing to the long–standing belief that they are unstable in decoctions and cannot survive gastrointestinal digestion. Recent studies have overturned this assumption by showing that certain TCM–derived miRNAs can withstand the traditional decoction process, can be absorbed intact, and retain therapeutic activity.4,5 Despite these advances, RNA components have yet to be incorporated into the assessment of TCM quality, processing methods, or clinical application. As a result, a substantial gap persists between emerging molecular evidence and current pharmaceutical practice. In this work, we employ MIR2911 from honeysuckle (Lonicera japonica) as a representative to investigate how different origins, processing approaches and extraction methods affect the integrity, stability, bioavailability, and antiviral efficacy of medicinal RNAs.To enable accurate quantification of MIR2911 across diverse biological matrices, we first established a recovery–corrected measurement system. Synthetic miRNA standards spanning graded concentrations were spiked into samples during lysis to determine extraction losses. Recovery rates were consistent across plant decoctions and tissues (~2%) and slightly higher in serum (~4%) (Fig. 1a). This enabled precise quantification of MIR2911 in complex matrices.Fig. 1Full size imageProcessing–dependent integrity and bioactivity of honeysuckle miRNA MIR2911. a Evaluation of the recovery rate when synthetic MIR2911 was spiked into different samples (n = 4; vegetable soup, liver, and serum). b Quantification of MIR2911 levels in different parts of fresh honeysuckle (flower bud, bloomed flower, stem, and leaf) (n = 4; left panel). Quantification of MIR2911 levels in dried honeysuckle (flower bud) from different regions (Henan Province, Shandong Province, and Hebei Province) and drying methods (oven–dried and air–dried honeysuckle) (n = 8; right panel). c Quantification of MIR2911 levels before and after ethanol treatment of HD (n = 4; upper left panel). MIR2911 content in HD and traditional Chinese patent medicines (Yinhuang granules (YHG), Lianhua Qingwen (LHQW), Compound Honeysuckle Granule (CHG), and Shuanghuanglian Oral Liquid (SHLOL) (n = 4; upper right panel). Plaque assay in BHK cells to determine the virus titers in the supernatant of HEK293T cells infected with JEV p3 after transfection with synthetic MIR2911, YHG-RNA or HD-RNA (n = 4; lower left panel). Quantitative RT-PCR analysis of JEV NS5 mRNA levels in JEV p3 virus–infected cells after transfection (n = 4; lower right panel). d Levels of IFN-β in SH-SY5Y and IL-1β and IL-6 in BV2 cells. SH-SY5Y or BV2 cells were infected with the live JEV p3 strain or ultraviolet–inactivated JEV p3 (iJEV), followed by transfection with MIR2911 (n = 4). Values are presented as the means ± SEM. Statistical analysis: one-way ANOVA or two-sided t-test. ***P