# Combination of curcuminoid and collagen marine peptides for healing diabetic wounds infected by methicillin-resistant Staphylococcus aureus

## TL;DR

This study explores a new treatment combining curcuminoid and collagen marine peptides to heal diabetic wounds infected with MRSA, a bacteria resistant to antibiotics.

## Contribution

The paper introduces a novel combination therapy using curcuminoid and collagen marine peptides to treat MRSA-infected diabetic wounds.

## Key findings

- Hydrolacin-gel with a 2:1 ratio of curcuminoid to collagen marine peptides showed the best efficacy in inhibiting MRSA and promoting wound healing.
- The treatment reduced oxidative stress and improved tissue repair in MRSA-infected diabetic wounds.
- Curcuminoid nanoemulsions combined with collagen marine peptides demonstrated antibacterial activity against MRSA.

## Abstract

The high prevalence of diabetes mellitus in Indonesia indirectly reflects the high risk of developing chronic wounds that are susceptible to infection. Methicillin-resistant Staphylococcus aureus (MRSA) is an infectious pathogen that is resistant to various antibiotics. Therefore, antibiotic therapy is ineffective enough to treat chronic hyperglycemic wounds caused by MRSA infection. Curcuminoids have anti-inflammatory and antibacterial effects by inhibiting the enzymatic pathways involved in the pathogenesis of inflammation. Collagen is a tissue regeneration inducer. The combination of these two ingredients is expected to be an alternative therapy for MRSA-infected hyperglycemic chronic wounds without the risk of antibiotic resistance. The aim of this study was to investigate the efficacy of hydrolacin-gel in wound healing and inhibiting the growth of MRSA bacteria, as well as to determine the optimal concentration of curcuminoids combined with collagen marine peptides (CMPs).

Hydrolacin-gels were prepared by homogenizing curcuminoid nanoemulsions and CMPs. The evaluation of preparation includes stability tests and antibacterial activity tests. Wound diabetic mice were treated with various combinations of curcuminoid and CMPs. Wound healing was observed based on malondialdehyde levels as a marker of oxidative stress and histopathological changes in the skin wound.

Hydrolacin-gel was formulated by combining curcuminoid nanoemulsion (more water soluble) and CMPs, with the ratio of formula 1 (1:2, curcuminoid 43.3 mg and CMPs 5.58 mg), formula 2 (1:1, curcuminoid 86.8 mg and CMPs 3.72), and formula 3 (2:1, curcuminoid 130.2 mg and CMPs 1.87 mg) calculated based on the effective dose of curcuminoid 200 mg/kg body weight (BW) and CAMPs 0.9 g/kg BW. Hydrolacin-gel had a potential antibacterial activity against MRSA. Hydrolacin-gel induced wound tissue repair and reduced oxidative stress caused by inflammation in diabetic-infected MRSA. Hydrolacin-gel could be used for healing MRSA-infected diabetic wounds, especially formula 3 with the ratio of curcuminoid: CMPs = 2:1.

Hydrolacin-gel combining curcuminoid nanoemulsion and CMPs effectively inhibited the inflammatory process and increased re-epithelialization in MRSA-infected diabetic wound healing. Hydrolacin-gel with curcuminoid (130.2 mg) and CMPs (1.87 mg) at a concentration ratio of 2:1 appeared to be the best formula against MRSA infection in diabetic wounds.