THE THERAPEUTIC POTENTIAL OF CARVACROL IN CHRONIC KIDNEY DISEASE AND THE GUT–KIDNEY AXIS

Chronic Kidney Disease (CKD) represents a major global public health problem, affecting between 6% and 10% of the world's population. Conventional pharmacological treatment, although aiding in blood pressure, glycemia, and metabolic disorder control, frequently results in gut microbiota imbalances in renal patients. These imbalances are associated with gastrointestinal disturbances arising from continuous medication use, making non-pharmacological nutritional strategies, such as phytotherapeutics, promising alternatives. Oregano (Origanum vulgare) has garnered scientific interest due to its anti-inflammatory, antioxidant, and antimicrobial properties. Carvacrol, a phenolic monoterpene present in oregano essential oil, is identified as the main component responsible for these biological activities, acting in the modulation of gut microbiota and inflammatory response. This study aims to synthesize evidence on the therapeutic properties of carvacrol and its applications in CKD management.

A narrative review with a qualitative approach was conducted, consulting the SciELO, PubMed/MEDLINE, ScienceDirect, and Cochrane Library databases from January 2015 to December 2024. Controlled descriptors in Portuguese and English were used: "doença renal crônica," "carvacrol," "fitoterápicos," "microbiota intestinal," "chronic kidney disease," "phytotherapy," "gut microbiota," combined with the Boolean operators AND and OR. Inclusion criteria covered studies on the antioxidant, anti-inflammatory, and antimicrobial properties of carvacrol, research on its influence on renal function and gut microbiota, articles in Portuguese, English, and Spanish, experimental studies with clinical relevance, clinical trials, and systematic reviews. Duplicate articles, conference abstracts, exclusively animal studies without clinical discussion, unsystematic reviews, and publications without full access were excluded. Selection occurred in two stages: screening by titles and abstracts, followed by full-text evaluation. Data were extracted using a standardized form and analyzed narratively.

The search yielded 247 articles, of which 28 were included after applying the criteria: 18 experimental studies, 6 clinical trials, 3 systematic reviews, and 1 observational study. Carvacrol concentrations ranged from 10 μg/mL to 500 mg/kg in animal models and 1-100 μM in vitro. In clinical trials, doses ranged from 200-600 mg daily for 4-12 weeks. Studies demonstrated anti-inflammatory effects through inhibition of the NF-κB pathway, with reduction in pro-inflammatory cytokines: TNF-α (45-60%), IL-1β (35-50%), and IL-6 (40-55%). Antioxidant properties included an increase in antioxidant enzymes: superoxide dismutase (35-45%), catalase (30-40%), and glutathione peroxidase (25-35%), with a reduction in oxidative markers such as malondialdehyde (40-50%). Renal effects showed a reduction in serum creatinine (25-35%), urea (20-30%), and proteinuria (30-45%), with improved glomerular filtration (15-25%). One trial with 84 CKD stages 3-4 patients demonstrated a significant improvement in glomerular filtration and reduction in creatinine with 400mg/day carvacrol. Microbiota modulation revealed an increase in beneficial bacteria such as Lactobacillus (40-60%) and Bifidobacterium (35-50%), a reduction in pathogens, and an elevation in short-chain fatty acid production. The safety profile was favorable, with mild adverse effects in less than 8% of participants.

Carvacrol exhibits promising pharmacological properties as an adjuvant therapy in CKD, demonstrating anti-inflammatory, antioxidant, and gut microbiota-modulating effects. The mechanisms include inhibition of the NF-κB pathway, increased antioxidant enzymes, and beneficial microbiota modulation with short-chain fatty acid production, converging to attenuate the chronic inflammatory state characteristic of CKD. Its favorable safety profile and low cost make it attractive for resource-limited settings. However, limitations of current evidence are recognized, with the majority of studies being experimental models and few long-term clinical trials. Randomized controlled trials are needed to definitively prove efficacy and safety in humans, including dose standardization and evaluation of drug interactions. This study contributes to the advancement of phytotherapy in nephrology, reinforcing the potential of natural compounds as complementary strategies in CKD treatment, especially where accessible alternatives are needed.