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1.
Mol Nutr Food Res ; : e2400004, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840434

RESUMO

Fatigue, a common symptom in both diseased and healthy individuals, is a biological phenomenon characterized by a sense of extreme physical or mental exhaustion. To explore novel drugs and food sources of anti-fatigue, the hydroalcoholic extract of the root of Mirabilis himalaica (MH extract) is evaluated as anti-fatigue agents in this work, and clarifies that the mechanism of MH intervention in fatigue symptoms, and distribution of the anti-fatigue constituents in the plant of Mirabilis himalaica is examined. The results show that the MH extract have a significantly anti-fatigue effect via the pharmacological experiment and biochemical indicators. The network pharmacology, metabolomics, molecular docking, and pharmacology are integrated to determine that boeravinone A, B, and E are the pharmacoperones of anti-fatigue. Moreover, the compounds of boeravinone are present only in the root and not in the leaf and stem of the Mirabilis himalaica, which validates that root of Mirabilis himalaica is historically and officially utilized medicinal parts.

2.
Bioorg Med Chem Lett ; 104: 129729, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38583786

RESUMO

Aptamers have shown significant potential in treating diverse diseases. However, challenges such as stability and drug delivery limited their clinical application. In this paper, the development of AS1411 prodrug-type aptamers for tumor treatment was introduced. A Short oligonucleotide was introduced at the end of the AS1411 sequence with a disulfide bond as responsive switch. The results indicated that the aptamer prodrugs not only enhanced the stability of the aptamer against nuclease activity but also facilitated binding to serum albumin. Furthermore, in the reducing microenvironment of tumor cells, disulfide bonds triggered drug release, resulting in superior therapeutic effects in vitro and in vivo compared to original drugs. This paper proposes a novel approach for optimizing the structure of nucleic acid drugs, that promises to protect other oligonucleotides or secondary structures, thus opening up new possibilities for nucleic acid drug design.


Assuntos
Antineoplásicos , Aptâmeros de Nucleotídeos , Pró-Fármacos , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacologia , Linhagem Celular Tumoral , Dissulfetos/química , Sistemas de Liberação de Medicamentos , Ácidos Nucleicos/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Estabilidade de Medicamentos
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