Identification of active compounds in Vernonia anthelmintica (L.) willd by targeted metabolome MRM and kaempferol promotes HaCaT cell proliferation and reduces oxidative stress.

Introduction: Vernonia anthelmintica (L.) Willd. is a traditional treatment for vitiligo in Xinjiang. However, its therapeutic mechanism remains unclear owing to its complex composition and limited research on its chemical profile. Methods: We employed a targeted metabolome approach, combining selective reaction monitoring/multiple response monitoring (SRM/MRM) with high-performance liquid chromatography and MRM mass spectrometry to quantitatively analyze the flavonoid constituents of Vernonia anthelmintica. We also used network pharmacology and molecular docking to identify potential vitiligo-linked compounds and targets of V. anthelmintica seeds. Additionally, we assessed HaCaT cell proliferation by AAPH-induced, alongside changes in SOD activity and MDA content, following treatment with V. anthelmintica components. Finally, flow cytometry was used to detect apoptosis and ROS levels. Results and Discussion: We identified 36 flavonoid compounds in V. anthelmintica seeds, with 14 compounds exhibiting druggability. AKT1, VEGFA, ESR1, PTGS2, and IL2 have been identified as key therapeutic target genes, with PI3K/AKT signaling being an important pathway. Notably, kaempferol, one of the identified compounds, exhibited high expression in network pharmacology analysis. Kaempferol exhibited a strong binding affinity to important targets. Further, kaempferol enhanced HaCaT cell viability, inhibited apoptosis, reduced MDA levels, suppressed ROS activity, and upregulated SOD activity, increase the expression of cellular antioxidant genes, including HO-1, GCLC, GCLM, Nrf2, NQO1 and Keap1, providing significant protection against oxidative stress damage in vitro. Here, we present the first comprehensive study integrating SRM/MRM approaches and network analysis to identify active flavonoid compounds within V. anthelmintica (L.) Willd. Moreover, we revealed that its active ingredient, kaempferol, offers protection against AAPH-induced damage in keratinocytes, highlighting its potential as a clinical resource.

Redox-Neutral α-Arylation of Alkyl Nitriles with Aryl Sulfoxides: A Rapid Electrophilic Rearrangement.

A facile α-arylation of nitriles has been developed by simply introducing Tf2O and DABCO to the mixture of nitriles and aryl sulfoxides. The transformation consists of two sequential steps: (i) Tf2O-initiated electrophilic assembly and and (ii) DABCO-triggered rearrangement. Each step can be tuned independently by changing the temperature and/or base. This adjustability allows the method to accommodate a wide range of substrates. Notable features of this new protocol include remarkable efficiency (20 min, -30 °C), exclusive regioselectivity, and high functional group compatibility, which can be challenging issues in traditional approaches. NMR studies not only identified a unique, highly unstable sulfonium imine complex but also demonstrated the importance of temperature in the formation and manipulation of this key intermediate. Further DFT calculations suggested that an electrophilic assembly, followed by removal of HOTf (by base), and finally [3,3]-sigmatropic rearrangement are three key stages in the reaction. The versatile transformability of the products and easy scalability of this reaction are also exhibited here.