A comprehensive chromatographic strategy for assessing the impact of artificial rearing, host tree species and environmental factors on quality of Cicadae Periostracum

Article

作者: Zhang, Huan-Huan ; Wu, Cheng-Ying ; Zhou, Jing ; Yue, Feng-Ru ; Xu, Jin-Di ; Kong, Ming ; Mao, Qian ; Li, Song-Lin ; Zhang, Min ; Zhou, Shan-Shan ; Chen, Lin-Xia ; Shen, Ji-Chen

Cicadae Periostracum (CP), derived from the slough of Cryptotympana atrata Fabricius, is a widely used insect-based medicinal material in traditional Chinese medicine. Due to the depletion of natural resources, artificial rearing has become prevalent; however, its impact on CP quality remains insufficiently elucidated. To evaluate this impact, along with that of host tree species and environmental factors, a comprehensive chromatographic strategy integrating UPLC-Q-TOF-MS/MS, UPLC-TQ-MS/MS and UPLC-DAD was developed for qualitative and quantitative analysis of N-acetyldopamine oligomers (NAOs), the active components in CP, as well as free/hydrolyzed amino acids (FAA/HAA). The extraction conditions for NAOs were optimized by response surface method. The results indicated that chemical profiles of CP obtained from wild collecting/artificial rearing, different host trees and regions exhibited a high degree of consistency. The artificial rearing CP samples showed higher levels of NAOs, FAA and HAA. Radar Plot Analysis showed that CP sourced from Malus pumila Mill (Mal) and Salix babylonica L. (Sal) achieved higher scores compared to five host trees studied. CP from Tengzhou region demonstrated relatively higher levels of NAOs and HAA. NAOs negatively correlated with annual near-surface air temperature, while HAA positively correlated with soil water content. These findings suggested that artificial rearing enhances CP quality, with Mal and Sal as promising host trees. Regions with lower annual near-surface air temperatures may promote NAOs accumulation. Overall, this research highlights the role of artificial rearing, host tree species and key environmental factors on the quality of CP and provides valuable insights for sustainable CP production and quality assessing.

2025-07-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Effect of stereochemistry at position C20 on the antiproliferative activity and selectivity of N-acylated derivatives of salinomycin

Article

作者: Krzywik, Julia ; Pilaszek, Przemysław ; Klejborowska, Greta ; Sukiennik, Jarosław ; Maj, Ewa ; Sulik, Michał ; Wietrzyk, Joanna ; Sobierajski, Tomasz ; Czerwonka, Dominika ; Mozga, Witold ; Ullrich, Małgorzata ; Sobczak, Szymon ; Huczyński, Adam ; Antoszczak, Michał

Salinomycin (SAL), a natural polyether ionophore, exhibits a broad spectrum of pharmacological activities, including potent anticancer activity. Over the past decade, much effort has been put into developing methods for rational chemical modification of SAL to obtain semisynthetic analogs with higher anticancer activity than the native structure. In this paper, we describe an optimized procedure for synthesizing C20-aminosalinomycin 2 with native stereochemistry at position C20, which was confirmed by single-crystal X-ray diffraction analysis. We further transformed amine precursor 2 into a series of 48 C20-N-(thio)acylated products, including N-(sulfon)amides, N-(thio)ureas, and N-carbamates (urethanes), along with their sulfur analogs, i.e., S-substituted thiocarbamates and dithiocarbamates. This previously unreported class of derivatives showed superior cytotoxicity mostly in the nano- and subnanomolar concentration range and improved selectivity toward human cancer cells compared to those of chemically unmodified SAL and a commonly used oncological drug cisplatin. Of note, the obtained products inhibited the proliferation of reference cancer cells more effectively than their C20-epi-N-acylated counterparts, pointing out the pivotal role of stereochemistry at position C20. Our findings support the premise that the modification of SAL is a fruitful strategy for products with promising biological activity profiles. Moreover, the straightforward protocols should be of significant value for more elaborate modifications of SAL in the future.

2025-06-01·PHYTOMEDICINE

Mechanistic insights into the potentiation and toxicity mitigation of myocardial infarction treatment with salvianolate and ticagrelor

Article

作者: Wan, Yan ; Peng, Cheng ; Ye, Qiang ; Guo, Li ; Guo, Yi-Ping ; Liang, Xue ; Yuan, Ming-Hao ; Wang, Yu-Lu

BACKGROUND:

Ticagrelor (TG), a first-line treatment for myocardial infarction (MI), is limited in its clinical application due to the risk of elevated uric acid (UA) levels. Salvianolate injection (SAL), an adjunctive therapy for MI, has been reported to have potential for UA reduction. Although the combined use of TG and SAL has been reported in clinical practice, no studies have focused on the optimal ratio for the combination or the mechanisms underlying their synergistic effects on MI and UA reduction.

OBJECTIVE:

This study follows the principle of enhancing efficacy and reducing toxicity through combination therapy. It aims to explore the optimal combination ratio (low-dose combination group: 10 mg/kg TG + 10 mg/kg SAL; medium-dose combination group: 10 mg/kg TG + 20 mg/kg SAL; high-dose combination group: 20 mg/kg TG + 20 mg/kg SAL) by evaluating both UA-lowering and anti-MI activities. Additionally, the study investigates the underlying mechanisms of anti-hyperuricemia and anti-MI through metabolomics and transcriptomics, in hopes of providing insights into rational clinical use of these drugs.

METHODS:

Kidney H&E staining, biochemical assays (UA, BUN, XOD, CRE), in vitro XOD detection, UA transporter protein analysis (GLUT9, OAT1, ABCG2, URAT1), and bioinformatics (PI3K/AKT) were used to assess anti-hyperuricemic activity under different combination ratios. ECG, echocardiography, biochemical assays (CK, LDH), ELISA (cTnT), and H&E staining were employed to evaluate anti-MI activity. The optimal combination ratio was determined based on both anti-hyperuricemic and anti-MI effects, and metabolomics and transcriptomics were used to explore the mechanisms of anti-hyperuricemia and anti-MI for this ratio.

RESULTS:

The TG-SAL combination reduced TG-induced hyperuricemia by enhancing renal function, UA excretion, and PI3K-AKT expression, as well as inhibiting UA reabsorption and production. Simultaneously, the combination alleviated cardiac injury and restored abnormal cardiac function, demonstrating anti-MI activity. Among the groups, the medium-dose combination showed the best synergistic effect. Further, metabolomics indicated that the anti-hyperuricemic mechanism of the medium-dose combination was related to the positive regulation of selenium compound metabolic pathways. Transcriptomics revealed that the anti-MI activity of the medium-dose combination was associated with the inhibition of cardiac muscle contraction pathways.

CONCLUSION:

The TG-SAL combination exhibited ideal synergistic effects in enhancing anti-MI activity and reducing TG-induced hyperuricemia, with the medium-dose combination demonstrating the best results. Mechanistically, the medium-dose combination exerted anti-hyperuricemic effects by positively regulating selenium compound metabolic pathways and anti-MI activity by inhibiting cardiac muscle contraction pathways. These findings provide a reference for the rational use of TG and SAL in clinical settings.

100 项与 AL-209 相关的药物交易

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