Sanguiin H-6 Fractionated from Cloudberry (Rubus chamaemorus) Seeds Can Prevent the Methicillin-Resistant Staphylococcus aureus Biofilm Development during Wound Infection

Abstract

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity.

Selected Seeds as Sources of Bioactive Compounds with Diverse Biological Activities

“…For example, sanguiin H-6 is a hydrolyzable tannin abundant in blackberry seeds. It shows a wide array of biological activities, including antioxidant, antibacterial, antitumor, anti-angiogenic, estrogenic, and anti-osteoclastogenic [ 2 , 48 , 49 , 50 , 51 , 52 ]. Condensed tannins are oligomers or polymers of flavan-3-ol linked through an interflavan carbon bond.…”

“…Sanguiin H-6 is an ellagitannin displaying a wide array of biological effects, found mainly in berries, including blackberry and black raspberry. Apart from its ability to protect DNA from mitomycin C-induced damage, Sanguiin H-6 was reported to have antioxidant, antibacterial, antitumor, anti-angiogenic, estrogenic, and anti-osteoclastogenic activity [ 2 , 48 , 49 , 50 , 51 , 52 ]. It could protect rat renal mitochondria from oxidative damage induced by peroxynitrite, decreasing the number of apoptotic cells, and reducing caspase-3 activity by 72% [ 89 ].…”

“…In murine primary osteoclasts, it decreased the concentration of ROS and upregulated the expression of heme oxygenase-1 (HO-1), a protein that protects cells from oxidative stress [ 49 ]. Furthermore, it inhibited the development of the biofilm of methicillin-resistant Staphylococcus aureus in a concentration-dependent manner [ 52 ]. As for the antitumor activity, 50–100 μM sanguiin H-6 increased the rate of apoptosis of human breast carcinoma cells (MDA-MB-231 and MCF-7) by 33.7–40.7%.…”

“…Its antibacterial properties against methicillin-resistant Staphylococcus aureus were observed in vivo as well. 20 μL of 0.5 mg/mL topically administered sanguiin H-6 decreased wound infection in mice by 77.2–85.3% compared to control [ 52 ]. Inhibition of bone resorption was also studied on an animal model—the proportion of eroded surface to bone surface of mice injected with TNF-α was decreased in the group treated with sanguiin H-6 at the dose of 10 μg/body weight (g)/day, injected intraperitoneally [ 49 ].…”

NMR Metabolomics and DNA Sequencing of Escherichia coli and Staphylococcus aureus Cultures Treated with Hydrolyzable Tannins

“…Alternative solutions are required to alleviate this problem more effectively. Natural products such as hydrolyzable tannins (HTs) are one option that have shown very promising anti-inflammatory [ 4 , 5 ], antiviral [ 6 , 7 , 8 , 9 ], and antibacterial properties [ 10 , 11 , 12 , 13 , 14 ]. HTs are a structurally varying group of complex compounds that have many favorable bioactivities, such as antioxidant activity [ 15 , 16 ], protein precipitation capacity [ 17 , 18 , 19 , 20 , 21 ], and other interesting macromolecule interactions [ 22 , 23 ].…”