Caerin 1.9 is a natural peptide derived from the skin secretions of the Australian tree frog (Litoria) with broad-spectrum antimicrobial and anticancer bioactivity. It improves the efficacy of a therapeutic vaccine and immune checkpoint inhibitor therapy when injected intratumorally and inhibits TC-1 tumor growth when applied topically through intact skin in a TC-1 murine tumor model. This paper investigated the pharmaceutical kinetic profile, the tissue distribution, and the acute safety investigation of Caerin 1.9 peptide in Sprague Dawley (SD) rats. The results showed that subcutaneous injection of Caerin 1.9 at 100 mg/kg is safe and does not cause mortality or organ malfunction in the recipient rats. For the consecutive injection of F3 at 10 mg/kg, the peak concentration (Cmax) of F3 displayed at 1 hr after injection in male rats was 591 ng/mL, the average drug retention time was 0.807 hr, T1/2 was 4.58 hr, and AUC0-last was 1890 h × ng/mL. In female rats, Cmax was 256 ng/mL, with an average drug retention time of 2.96 hr, T1/2 of 1.33 hr, and AUC0-last of 740 h × ng/mL. The results showed that the concentration of Caerin 1.9 in the peripheral blood peaked at 1 hour. As injected concentration increased, T1/2 extended, and Cmax, AUC0-last, and volume of distribution at a steady state all increased. After 14 days of repeated subcutaneous injection at 10.0 mg/kg, no accumulation of Caerin 1.9 in plasma was observed. The results of tissue distribution showed that the Caerin 1.9 is below the LC-MS/MS detection threshold at a minimum concentration of 40 ng/g. In conclusion, Caerin 1.9 is well tolerated in rats and could be used with current immunotherapies for better management of solid tumors and genital warts.

Osteoarthritis (OA) is a disabling disease and seriously affects the quality of life of patients. is A potential medicine for the treatment of OA is Eucommia ulmoides leaves (EULs). However, its active compounds and therapeutic mechanisms are unclear. Therefore, it is necessary to develop a method using LC–MS and network pharmacology for the detection and identification of compounds and the mechanisms of action of EULs. The compounds were detected and identified based on ultra‐high‐performance liquid chromatography coupled with Quadrupole Exactive‐Orbitrap MS (UHPLC‐Q Exactive‐Orbitrap MS) and followed by the network pharmacology analysis. Seventy‐three compounds, including 15 flavonoids, 8 iridoids, 10 lignans, 24 phenolic acids, and 16 additional compounds, were identified by UHPLC‐Q Exactive‐Orbitrap MS. The network of the pharmacological analysis revealed that 29 active compounds regulated 17 main pathways through 38 target genes, including NF‐kappa B signaling pathway, PI3K‐Akt signaling pathway, AMPK signaling pathway, etc. In conclusion, EULs were effective in the treatment of OA by regulating the abovementioned key pathways. This study showed that LC–MS/MS followed by network pharmacology analysis is useful to elucidate the complex mechanisms of action of Chinese herb. Practical applications This study describes a rapid method of detecting and identifying the constituents and systematic mechanism of Eucommia ulmoides based on LC–MS and network pharmacology. Our results show that 73 compounds of E. ulmoides leaves were identified and predicted that E. ulmoides leaves were effective in the treatment of OA by regulating key pathways, including NF‐kappa B signaling pathway, PI3K‐Akt signaling pathway, and AMPK signaling pathway by network pharmacology, which lays the foundation for subsequent research.

Diabetic encephalopathy (DE) is a serious complication of diabetes, which affects patients′ quality of life. We aimed to explore HLJDD in the treatment of DE by LC/MS and bioinformatics. UPLC‐Q Exactive‐Orbitrap MS was employed to clarify the compounds. The modules and hub targets of DE were gained from WGCNA. Subsequently, an Herb‐Compound‐Target network was constructed and enrichment analysis was used. In addition, a protein‐protein interaction (PPI) network was constructed and molecular docking was used to verify the above analysis. As result, 138 compounds and 10 prototypes in brain were identified. In network pharmacology, 8 modules and 5692 hub targets were obtained from WGCNA. An Herb‐Compound‐Target network was constructed by 4 herbs, 10 compounds and 56 targets. The enrichment analysis showed that the treatment of DE with HLJDD involve oxidative stress and neuroprotection. Beside, SRC, JUN, STAT3, MAPK1 and PIK3R1 were identified and as hub targets of HLJDD in treating DE. Moreover, Molecular docking showed that five hub targets had strong affinity with the corresponding alkaloids. Therefore, we explored the underlying mechanisms of HLJDD in the treatment of DE and to provide the theoretical and scientific basis for subsequent experimental studies and clinical applications.

background: Recent studies have shown that osteoporosis has become a global public health problem and PL is a potential medicine for treatment of osteoporosis. objective: This study describes a rapid method of detecting and identifying the constituents and systematic mechanism of PL based on LC–MS and network pharmacology. method: We explored the compounds and possible pathways of PL affecting the pathological process of osteoporosis base on UHPLC-Q-Orbitrap MS metabolomics. result: A total of 48 compounds including 38 isoflavones, 6 puerosides and 4 others were identified by UHPLC-Q Exactive-Orbitrap MS. The network pharmacological analysis revealed that 28 compounds regulated 19 pathways through 27 targets, including estrogen signaling pathway and NF-kappa B signaling pathway, etc. conclusion: PL may attenuate osteoporosis by regulating estrogen signaling pathway, NF-kappa B signaling pathway, MAPK signaling pathway and PI3K-Akt signaling pathwayand be a potential source of functional food for prevention of osteoporosis.