Antibacterial potential of danthron, embelin, sanguinarine and shikonin against multidrug-resistant Neisseria gonorrhoeae in vitro

Neisseria gonorrhoeae (N. gonorrhoeae) poses a public health challenge due to escalating incidence and growing antimicrobial resistance, necessitating urgent exploration of alternative therapies. Presently, clinical management relies on ceftriaxone monotherapy or its combination with azithromycin. However, emergence and spread of strains resistant to previously recommended regimens, particularly the FC428 clone strain, which also exhibits azithromycin resistance, present significant challenges. Therefore, investigation of alternative strategies is paramount. 55 multidrug-resistant N. gonorrhoeae isolates, including those with high-level resistance to ceftriaxone, high-level resistance to azithromycin, and dual-resistant clones, were collected from Guangdong province between 2017 and 2021. Drug susceptibility of natural products was assessed using broth microdilution methods. Cytotoxicity of the four natural products against renal epithelial (293T) and human vaginal epithelial (VK2/E6E7) cells was evaluated by Cell Counting Kit-8 assay. Our findings indicated that danthron exhibited good antibacterial activity, followed by embelin, sanguinarine and shikonin, with MIC 50/90 values of 2.4/4.8, 3/6, 3.3/6.6 and 6/12 mg/L, respectively. These results indicated that even low concentrations could effectively inhibit growth of N. gonorrhoeae. Furthermore, all four natural products demonstrated potent antibacterial effects against dangerous strains, including those exhibiting ceftriaxone resistance (MIC ≥ 0.125 mg/L), high-level azithromycin resistance (MIC ≥ 256 mg/L), or dual-resistance characteristics. Additionally, preliminary toxicological assessments on cell lines suggested the following order of selective toxicity: danthron < embelin < sanguinarine < shikonin. Danthron, embelin, sanguinarine and shikonin demonstrated preliminary effectiveness in eliminating multidrug-resistant N. gonorrhoeae with appropriate selective toxicity. Our study suggests they may represent promising candidates for further investigation and potential therapeutic development.