The Role of Myrrh Metabolites in Cancer, Inflammation, and Wound Healing: Prospects for a Multi-Targeted Drug Therapy

Abstract

Background: Myrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life. Method: The current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)-like macrophage cell lines. Furthermore, using an in vivo rat model, the extracts’ anti-inflammatory and wound-healing activity was investigated. In addition, in silico predictions of the myrrh constituents highlighted the pharmacokinetic properties, molecular targets, and safety profile, including cytochrome P 450 (CYP) inhibition and organ toxicity. Results: Nine secondary metabolites were identified, and computational predictions suggested a good absorption profile, anticancer, anti-inflammatory, and wound-healing effects. The myrrh extract had moderate cytotoxic activity against both HL60 and K562 leukemia cell lines and the KAIMRC1 breast cancer cell line. Myrrh caused a dose-dependent effect on macrophages to increase the reactive oxygen species (ROS) levels, promote their polarization to classically activated macrophages (M1) and alternatively activated macrophages (M2) phenotypes, and consequently induce apoptosis, highlighting its ability to modulate macrophage function, which could potentially aid in several desired therapeutic processes, including the resolution of inflammation, and autophagy which is an important aspect to consider in cancer treatment. The topical application of myrrh improved wound healing, with no delayed inflammatory response, and promoted complete re-epithelization of the skin, similar to the positive control. In conclusion, we provide evidence for the methanolic extract of myrrh having cytotoxic activity against cancer cells and anti-inflammatory wound-healing properties, which may be attributed to its role in modulating macrophage function. Furthermore, we suggest the active constituents responsible for these properties, which warrants further studies focusing on the precise roles of the active metabolites.

In silico Prediction of Malvaviscus arboreus Metabolites and Green Synthesis of Silver Nanoparticles – Opportunities for Safer Anti-Bacterial and Anti-Cancer Precision Medicine

“…Other studies have also shown medicinal plants to bind to the CA IX enzyme and regulate ROS production in macrophages. 8 , 9 …”

“…Other studies have also shown medicinal plants to bind to the CA IX enzyme and regulate ROS production in macrophages. 8,9 4-hydroxyphenyl acetic acid (4-HPA) is a polyphenol having antioxidant action and was shown to protect against paracetamol-induced liver damage by enhancing the activity of antioxidant enzymes and increasing Phase II metabolism. As such, it could be used as a naturally occurring plant-based hepatoprotective agent.…”

Review of Traditional First Aid for Burn Injuries in the 21st Century

“…Ajiteru et al 75 constructed a fabrication of myrrh resin hydrocolloid dressing called the Mirderm and reported superior wound healing and mechanical capability compared with commercial hydrocolloid and gauzes. Suliman et al 76 analyzed myrrh resin methanolic extract and found anti-inflammatory, anticancer, and wound healing effects, promoting complete re-epithelialization of the skin.…”

Chemometrics‐based Chemical Analysis of Myrrh and Its Vinegar‐processed Products by UPLC‐MS/MS

“…Studies have reported that Myrrh consists of watersoluble gum, alcohol-soluble resins, and volatile oil. [13][14][15][16][17][18][19] Among them, sesquiterpenoids and triterpenoids were considered to be the main bioactive components of this herb. [20][21][22][23][24][25] Our study can provide a powerful guidance for understanding the toxic substance in Myrrh through investigation of the chemical mechanism of toxicity reduction by vinegar-processing.…”

“…Up till now, the exact mechanism and the relationship between vinegar‐processing and changes in the chemical composition of Myrrh has been poorly defined. Studies have reported that Myrrh consists of water‐soluble gum, alcohol‐soluble resins, and volatile oil [13–19] . Among them, sesquiterpenoids and triterpenoids were considered to be the main bioactive components of this herb [20–25] .…”