Sanguinarine, Isolated From Macleaya cordata, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Inhibiting Ergosterol Synthesis

Abstract

In recent decades, infections caused by the opportunistic fungus Candida albicans have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action of sanguinarine (SAN) against C. albicans both in vitro and in vivo. SAN exhibited antifungal activity against C. albicans clinical isolates, with MICs in the range of 112.8–150.5 μM. Furthermore, scanning electron and transmission electron microscopy showed that SAN induced morphological changes as well as structure disruption in C. albicans cells, including masses of cellular debris, ruptured cell walls, and membrane deformation. Flow cytometry revealed that SAN could lead to cell membrane damage, and ergosterol content analysis indicated that SAN could cause ergosterol content reduction exceeding 90%. Further, we validated the efficacy of SAN against candidiasis caused by C. albicans in a murine model, and SAN significantly improved survival and reduced weight loss compared to vehicle. The treatment of 1.5 and 2.5 mg/kg/d SAN obviously reduced the fungal burden in the kidney. In addition, histopathological examination indicated that no fungal cells were observed in lung and kidney tissues after SAN treatment. Hence, this study suggests that SAN is a promising plant-derived compound for the development of an effective anticandidal agent.

Design, Synthesis and Biological Evaluation of Lophanic Acid Derivatives as Antifungal and Antibacterial Agents

“…The concentration of conidia or spore was adjusted with sterile saline to 1 × 10 4 cells/mL by hemocytometer counts. The antifungal susceptibility testing was performed as outlined in document M38-A2 and previous research, with minor changes [ 16 , 17 , 18 , 19 ]. The medium used was RPMI 1640 with L-glutamine buffered to pH 7.0 with 0.165 M morpholinepropanesulfonic acid (MOPS) and was supplemented with 2% glucose ( m / v ).…”

Antifungal and Immunomodulatory Ingredients from Traditional Chinese Medicine

“…Another study reported that sanguinarine inhibited 10 C. albicans strains, with the MICs within the range of 37.5-50 µg/mL. Sanguinarine also showed anticandidal effects in a murine model at the dose of 1.5 and 2.5 mg/kg, and the mode of action is related to ergosterol synthesis deficiency in cells [46]. Sanguinarine can also inhibit C. albicans biofilms, and 3.2 µg/mL of sanguinarine significantly inhibits C. albicans biofilm formation by over 90% and destroys mature biofilms by 68.3%.…”

Screening and Genomic Analysis of Alkaloid-Producing Endophytic Fungus Fusarium solani Strain MC503 from Macleaya cordata

“…They are among the major bioactive components of Macleaya cordata ( M. cordata ) [ 3 , 4 ]. Academics and industrial researchers developed a strong interest in these substances because of their significant antimicrobial and animal growth-promoting activities [ 5 , 6 ]; parasiticidal effects [ 7 ]; anti-inflammatory effects [ 8 ]; and anti-tumor activities [ 9 ]. Recently, there has been a steady rise in the daily demand for this particular plant due to its significant commercial worth.…”