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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]

Coronavirus disease 2019, a newly emerging serious infectious disease, has spread worldwide. To date, effective drugs against the disease are limited. Traditional Chinese medicine was commonly used in treating COVID‐19 patients in China. Here we tried to identify herbal effective lipid compounds from the lipid library of 92 heat‐clearing and detoxication Chinese herbs. Through virtual screening, enzymatic activity and inhibition assays, and surface plasmon resonance tests, we identified lipid compounds targeting the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and verified their functions. Here, we found that natural lipid compounds LPC (14:0/0:0) and LPC (16:0/0:0) could target SARS‐CoV‐2 Mpro, recover cell death induced by SARS‐CoV‐2, and ameliorate acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induced by bacterial lipopolysaccharides and virus poly (I:C) mimics in vivo and in vitro. Our results suggest that LPC (14:0/0:0) and LPC (16:0/0:0) might be potential pan remedy against ARDS. [ABSTRACT FROM AUTHOR]

Rosiglitazone, a specific agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), displays a robust hypoglycemic action in patients with type 2 diabetes mellitus (T2DM) and elicits serious adverse reactions, especially hepatotoxicity and cardiotoxicity. Here, we aims to find a new natural PPAR-γ agonist with less adverse reactions than rosiglitazone in db/db mice. The method of virtual screening was used to identify a PPAR-γ agonist 18:0 Lyso PC from an in-house natural product library. We verified its pharmacological effects and adverse reactions comparing with rosiglitazone in vivo and in vitro. 18:0 Lyso PC exhibited pharmacological effects similar to those of rosiglitazone in db/db mice. Moreover, 18:0 Lyso PC showed a lower extent of liver injury and cardiotoxicity in db/db mice. The mechanism, by which this natural compound alleviates metabolic syndrome, involves a reduction in fatty acid synthesis mediated by activation of the phosphorylation of adenosine 5′-monophosphate (AMP)-activated protein kinase-alpha (AMPKα) and acetyl-CoA carboxylase (ACC) and an increase expression of uncoupled protein 1 (UCP1) and PPAR-γ coactivator-1 alpha (PGC1-α). 18:0 Lyso PC, a natural compound, can show a similar hypoglycemic effect to rosiglitazone by activating PPAR-γ, while eliciting markedly fewer adverse reactions than rosiglitazone. [Display omitted] • An in-house natural products library containing 8,545 compounds for virtual screening. • An unreported natural lipid compound, 18:0 Lyso PC, is an agonist of PPAR-γ. • 18:0 Lyso PC showed similar hypoglycemic and lipid-lowering effects compared with rosiglitazone. • 18:0 Lyso PC elicits markedly fewer adverse reactions than rosiglitazone in db/db mice. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019, a newly emerging serious infectious disease, has spread worldwide. To date, effective drugs against the disease are limited. Traditional Chinese medicine was commonly used in treating COVID-19 patients in China. Here we tried to identify herbal effective lipid compounds from the lipid library of 92 heat-clearing and detoxication Chinese herbs. Through virtual screening, enzymatic activity and inhibition assays, and surface plasmon resonance tests, we identified lipid compounds targeting the main protease (M pro ) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and verified their functions. Here, we found that natural lipid compounds LPC (14:0/0:0) and LPC (16:0/0:0) could target SARS-CoV-2 M pro , recover cell death induced by SARS-CoV-2, and ameliorate acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induced by bacterial lipopolysaccharides and virus poly (I:C) mimics in vivo and in vitro. Our results suggest that LPC (14:0/0:0) and LPC (16:0/0:0) might be potential pan remedy against ARDS., (© 2022 International Union of Biochemistry and Molecular Biology.)