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In 2020, the number of deaths caused by lung cancer worldwide reached 1,796,144, making it the leading cause of cancer‐related deaths. Cyclooxygenase‐2/prostaglandin endoperoxide synthase 2 (COX‐2/PTGS2) is overexpressed in lung cancer, which promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that the oligonucleotide drug HQi‐sRNA‐2 from Traditional Chinese Medicine Huangqin targeting COX‐2/PTGS2 significantly inhibited proliferation, migration, and invasion and induced apoptosis in the human lung cancer cell line NCI‐H460. Oral delivery of HQi‐sRNA‐2 bencaosomes prolonged survival, reduced tumor burden, and maintained weight in a spontaneous mouse lung cancer model. Compared with paclitaxel, HQi‐sRNA‐2 may be less toxic and have approximately equal efficacy in reducing tumor burden. Our previous studies reported that herbal small RNAs (sRNAs) are functional medical components. Our data suggest that sphingosine (d18:1)‐HQi‐sRNA‐2 bencaosomes, targeting COX‐2/PTGS2 and downregulating the PI3K and AKT signaling pathways, may provide novel therapeutics for lung cancer. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL‐sRNA‐h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose‐6‐phosphatase. Oral administration of sphingosine (d18:1)‐JGL‐sRNA‐h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)‐JGL‐sRNA‐h7 bencaosomes‐treated beagle dogs. Our study indicates that JGL‐sRNA‐h7 could be a promising hypoglycemic oligonucleotide drug. [ABSTRACT FROM AUTHOR]