RESUMO
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.
RESUMO
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.
RESUMO
Cross-kingdom herbal miRNA was first reported in 2012. Using a modified herbal extraction protocol, we obtained 73,677,287 sequences by RNA-seq from 245 traditional Chinese Medicine (TCM), of which 20,758,257 were unique sequences. We constructed a Bencao (herbal) small RNA (sRNA) Atlas ( http://bencao.bmicc.cn ), annotated the sequences by sequence-based clustering, and created a nomenclature system for Bencao sRNAs. The profiles of 21,757 miRNAs in the Atlas were highly consistent with those of plant miRNAs in miRBase. Using software tools, our results demonstrated that all human genes might be regulated by sRNAs from the Bencao sRNA Atlas, part of the predicted human target genes were experimentally validated, suggesting that Bencao sRNAs might be one of the main bioactive components of herbal medicines. We established roadmaps for oligonucleotide drugs development and optimization of TCM prescriptions. Moreover, the decoctosome, a lipo-nano particle consisting of 0.5%-2.5% of the decoction, demonstrated potent medical effects. We propose a Bencao (herbal) Index, including small-molecule compounds (SM), protein peptides (P), nucleic acid (N), non-nucleic and non-proteinogenic large-molecule compounds (LM) and elements from Mendeleev's periodic table (E), to quantitatively measure the medical effects of botanic medicine. The Bencao sRNA Atlas is a resource for developing gene-targeting oligonucleotide drugs and optimizing botanical medicine, and may provide potential remedies for the theory and practice of one medicine.
Assuntos
Medicamentos de Ervas Chinesas , MicroRNAs , Pequeno RNA não Traduzido , Humanos , Medicina Tradicional Chinesa , MicroRNAs/genética , Medicamentos de Ervas Chinesas/química , Pequeno RNA não Traduzido/genética , OligonucleotídeosRESUMO
The global COVID-19 pandemic emerged at the end of December 2019. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are common lethal outcomes of bacterial lipopolysaccharide (LPS), avian influenza virus, and SARS-CoV-2. Toll-like receptor 4 (TLR4) is a key target in the pathological pathway of ARDS and ALI. Previous studies have reported that herbal small RNAs (sRNAs) are a functional medical component. BZL-sRNA-20 (Accession number: B59471456; Family ID: F2201.Q001979.B11) is a potent inhibitor of Toll-like receptor 4 (TLR4) and pro-inflammatory cytokines. Furthermore, BZL-sRNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (poly (I:C)). We found that BZL-sRNA-20 rescued the viability of cells infected with avian influenza H5N1, SARS-CoV-2, and several of its variants of concern (VOCs). Acute lung injury induced by LPS and SARS-CoV-2 in mice was significantly ameliorated by the oral medical decoctosome mimic (bencaosome; sphinganine (d22:0)+BZL-sRNA-20). Our findings suggest that BZL-sRNA-20 could be a pan-anti-ARDS ALI drug.
Assuntos
Lesão Pulmonar Aguda , COVID-19 , Virus da Influenza A Subtipo H5N1 , Influenza Aviária , Síndrome do Desconforto Respiratório , Camundongos , Humanos , Animais , Lipopolissacarídeos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Virus da Influenza A Subtipo H5N1/metabolismo , Pandemias , COVID-19/patologia , SARS-CoV-2/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , Citocinas/metabolismo , Pulmão/metabolismoRESUMO
Plant-derived microRNAs have recently been reported to function in human blood and tissues. Controversy was immediately raised due to possible contamination and the lack of large sample sizes. Here, we report thousands of unique small RNAs derived from traditional Chinese medicine (TCM) herbs found in human blood cells and mouse lung tissues using a large-scale analysis. We extracted small RNAs from decoctions of 10 TCM plants (Ban Zhi Lian, Chai Hu, Chuan Xin Lian, Di Ding Zi Jin, Huang Qin, Jin Yin Hua, Lian Qiao, Pu Gong Ying, Xia Ku Cao, and Yu Xing Cao) and obtained millions of RNA sequences from each herb. We also obtained RNA-Seq data from the blood cells of humans who consumed herbal decoctions and from the lung tissues of mice administered RNAs from herbal decoctions via oral gavage. We identified thousands of unique small RNA sequences in human blood cells and mouse lung tissues. Some of these identified small RNAs from Chuan Xin Lian and Hong Jing Tian could be mapped to the genomes of the herbs, confirming their TCM plant origin. Small RNAs derived from herbs regulate mammalian gene expression in a sequence-specific manner, and thus are a superior novel class of herbal drug components that hold great potential as oral gene-targeted therapeutics, highlighting the important role of herbgenomics in their development.