Garlic Extract as a Novel Addition to Antikeloid Armamentarium: An Untested Hypothesis

Dear Editor:

Keloid is a benign dermal tumor characterized by proliferation of dermal fibroblasts and overproduction of extracellular matrix. ¹

Nuclear factor-κ B (NF-κ B) plays an important role in regulation of inflammation, immune response, and cell proliferation. Activation of the NF-κ B pathway is thought to be closely linked to abnormal cell proliferation and extracellular matrix production in keloid fibroblasts. The inhibition of NF-κ B by dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-κ B inhibitor, may be an attractive therapeutic approach for keloids. ¹

Exogenous nitric oxide (NO), which plays an important role in the inflammation stage of wound healing, was found to enhance the expression of collagens and elevate the cellular levels of cyclic guanine monophosphate (cGMP). The NO/cGMP pathway could augment keloid formation via the transforming growth factor-β1 expression in the keloid fibroblast. ² Some studies showed that matrix metalloproteinase (MMP)-2 activity (the gelatinase involved in prolonged tissue remodeling) is significantly increased in hypertrophic scars and keloids. ³ Increased production of MMPs had a role in the high migratory activity of cultured keloid fibroblasts. ⁴

Iannello et al. ⁵ demonstrated that angiotensin converting enzyme (ACE) inhibitors may be effective in keloid therapy, ⁵ and also several reports have described the effects of the ACE inhibitors, captopril and enalapril, on post–myocardial infarction events, such as reduction of ventricular collagen content and attenuation of left ventricular remodeling, which improves ventricular function. ^6,7

Interleukin-6 (IL-6) is a key pro-inflammatory cytokine. IL-6-mediated inflammation is a key player and may be considered as a common causative factor for development of keloids. Accordingly, inhibitory strategies of the IL-6 signaling pathway by targeting the IL-6 receptors, its downstream effectors, or other molecules influencing this pathway appear to have considerable potential as new therapeutic or preventive challenges for keloid formation. ⁸

Garlic (Allium sativum) has long been used as a folk medicine. Numerous studies have demonstrated that a garlic extract and its sulfur-containing compounds inhibited NF-κ B activation induced by various receptor agonists including lipopolysaccharide. ⁹ Garlic oil derivatives differentially suppress the production of NO in activated macrophages. ¹⁰ Studies show that aqueous garlic extract and its derivatives (e.g., S-allylcysteine) prevent carcinogen-induced breast tumorigenesis partly by reduction of MMP2 activity, resulting in the inhibition of cell motility and invasion. ¹¹ The ACE inhibitory effect of wild garlic was demonstrated in vitro as well as in vivo, which could contribute to the cardioprotective and blood-pressure-lowering action of wild garlic. ¹² The immunoregulatory effects for garlic extract and its attenuation of inflammatory features of allergic airway inflammation in murine models are demonstrated. ¹³

In conclusion, given the ability of garlic extract to inhibit NF-κ B, NO, MMP-2, IL-6, and ACE, this agent can be an effective treartment for keloid treatment. Zhang et al. ¹⁴ have recently demonstrated that garlicin, a commercial garlic product, could inhibit NIH3T3 cell proliferation and reduce the synthesis and protein expression of type I collagen. This study strongly supports our commentary on the potential utility of garlic extract against keloid formation. Our commentary justifies and encourages the conduction of clinical trials on this subject.