Mint Compound L-Carvone Shows Promise Against Uremia-Driven Blood Vessel Damage in Kidney Disease

Chronic kidney disease (CKD) affects roughly 9.1 percent of the global population and ranks as the twelfth leading cause of death among 133 diseases tracked by the Global Burden of Disease study. Yet for many patients, the kidneys are only part of the problem. As kidney function declines, a cocktail of uremic toxins accumulates in the blood, and these compounds attack the vascular endothelium, the delicate single-cell lining of blood vessels. The result is endothelial dysfunction, a driving force behind the dramatically elevated cardiovascular risk that makes heart disease the leading killer of people with CKD. Now, a team of Brazilian researchers reports that a familiar molecule from the world of flavors and fragrances, the monoterpene L-carvone, may help shield endothelial cells from this uremic assault, dampening inflammation and preserving cellular structure in laboratory models.

L-carvone is a ketone monoterpene best known as the characteristic scent of spearmint, produced by plants of the Mentha genus. It exists as two mirror-image forms, or optical isomers, with the (R)-(−) form, known as L-carvone, and the (S)-(+) form, known as D-carvone, displaying distinct biological profiles. Previous research has attributed a remarkable range of activities to carvone, including antibacterial, antifungal, antioxidant, anti-neurodegenerative, vasorelaxant, and anticancer effects. Studies have also linked the compound to cardiovascular protection and atheroprotection through mechanisms such as reducing foam cell formation, modulating macrophage balance, and lowering oxidative stress. The new study, led by Guilherme Miniskiskosky and senior author Andréa Emilia Marques Stinghen at the Federal University of Paraná in Curitiba, is the first to test whether these properties extend to the specific inflammatory storm that uremia unleashes on blood vessel walls.

To create a realistic model of the uremic environment, the researchers recruited 14 patients with stable end-stage kidney disease undergoing hemodialysis at a single dialysis unit in Curitiba, Brazil. Participants had been on dialysis for at least three months, and the team carefully excluded anyone with active infection, cancer, autoimmune disease, liver dysfunction, severe mineral disturbances, or use of drugs such as glucocorticoids and immunosuppressants that could confound inflammatory measurements. Serum collected from all patients was pooled in equal amounts to create an averaged uremic milieu, minimizing the influence of any single patient’s biochemistry. The study was approved by the Ethics Committee of Pontifícia Universidade Católica do Paraná, and all patients provided signed informed consent.

The experimental system centered on EA.hy926 cells, a well-established human endothelial cell line, grown under standard conditions and exposed for 24 hours to one of three treatments: a 10 percent uremic serum pool, L-carvone at 100 micromolar, or the two combined. The carvone dose was chosen after a careful dose-response screen. At concentrations of 200 micromolar and above, the compound significantly reduced endothelial cell viability, but at 100 micromolar it left viability untouched, whether applied alone or alongside uremic serum. This established a safe working concentration for probing anti-inflammatory effects without cytotoxic confounders. The 24-hour exposure window was selected to allow sufficient time for transcriptional and inflammatory responses to unfold.

The results were striking. Uremic serum, as expected, drove up gene expression of the pro-inflammatory interleukins IL-6, IL-8, and IL-1β in the endothelial cells. When L-carvone was added, it significantly reduced IL-1β gene expression compared with uremic serum alone, a finding of particular importance because IL-1β sits near the top of the inflammatory cascade, amplifying vascular damage through activation of the nuclear factor kappa-B (NF-κB) pathway and contributing to arterial calcification. At the protein level, the effects broadened considerably. Carvone treatment significantly lowered production of IL-6, IL-8, and IL-1β, as well as tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor A (VEGF-A), and serum amyloid A (SAA), an acute-phase protein secreted by the liver that promotes pro-inflammatory and pro-thrombotic activity on vascular endothelial cells. Levels of the adhesion molecule ICAM-1 also fell substantially, from about 12.05 picograms per milliliter in uremic serum-treated cells to 6.25 picograms per milliliter when carvone was present.

Beyond quieting inflammatory signaling, the compound appeared to interfere with one of the most consequential steps in atherosclerosis: the recruitment of monocytes to the vessel wall. Endothelial cells exposed to uremic serum produce monocyte chemoattractant protein 1 (MCP-1), a chemical beacon that draws circulating monocytes toward the endothelium, where they can invade the vessel wall and seed atherosclerotic plaques. In the study, carvone significantly reduced MCP-1 production under uremic conditions. To test the functional consequence, the team used modified Boyden chambers, placing treated endothelial cell supernatant in the lower compartment and U-937 monocyte-like cells above a porous membrane. Supernatant from uremic serum-treated endothelial cells significantly increased monocyte migration, but supernatant from cells co-treated with carvone significantly reduced it, demonstrating that the anti-inflammatory effect translates into reduced leukocyte recruitment.

Perhaps the most visually compelling evidence came from scanning electron microscopy. Untreated control cells displayed the classic architecture of intact endothelium, spread flat across the substrate in a confluent monolayer. Cells exposed to uremic serum showed the hallmarks of uremic injury: an abundance of filopodia, loss of intercellular adhesions, rounded cell bodies, perforations in the plasma membrane, and scattered cellular debris. These morphological changes matter because uremic toxins are known to disrupt adherens and occluding junctions between endothelial cells, increasing vascular permeability and accelerating vascular damage. Remarkably, cells treated with uremic serum plus carvone largely reverted to a control-like pattern, remaining adhered and spread across the substrate. Carvone also promoted endothelial cell proliferation, which the authors suggest could support regeneration of an endothelial barrier damaged by toxin accumulation, although they caution that increased proliferation alone does not prove restored barrier function.

The authors are careful to frame these findings as mechanistic observations rather than a prescription. The 100 micromolar concentration used in vitro may exceed the circulating levels achievable in humans, since pharmacokinetic studies indicate that carvone is rapidly metabolized and cleared, and quantitative data on attainable plasma or tissue concentrations remain limited. Previous human studies have documented systemic exposure to carvone after oral intake of peppermint and caraway oil preparations and after topical exposure, but these do not establish clinical efficacy or safety of isolated carvone in CKD patients. The researchers also acknowledge that they did not directly measure NF-κB activation or antioxidant pathways, so the precise molecular mechanism behind the observed effects remains speculative, even though other experimental models have linked carvone’s anti-inflammatory actions to NF-κB inhibition.

Additional limitations shape how the results should be interpreted. The EA.hy926 cell line, while a standard tool, may not fully reproduce the behavior of primary human endothelial cells, and validation in primary cells is needed. The pooled serum from 14 patients smooths away inter-individual variability, so studies using serum from larger numbers of individual patients will be important to confirm that the effects hold across different clinical profiles. The authors also note that future work should explore carvone’s effects in other relevant cell types, such as vascular smooth muscle cells and renal tissue, and that in vivo studies will be essential to understand how the compound behaves in complex biological systems.

Even with those caveats, the study represents a genuine first. The researchers demonstrated for the first time that the dysfunctional, inflammatory profile that uremia imposes on endothelial cells can be attenuated by L-carvone treatment in vitro, with reductions in inflammatory biomarkers, reduced leukocyte recruitment, and reversal of uremia-induced structural damage. Because elevated levels of molecules like IL-6, TNF-α, and MCP-1 are linked to poorer cardiovascular prognosis, blunting their production could, in principle, translate into meaningful vascular protection for the CKD population. The work opens a new avenue for investigating how natural monoterpenes might be harnessed against uremic inflammation, and it provides a foundation for the animal studies and, eventually, clinical trials that would determine whether the spearmint molecule can move from the culture dish to the dialysis clinic.

Subject of Research: Anti-inflammatory effects of L-carvone on uremia-induced endothelial dysfunction in chronic kidney disease

Article Title: Potential anti-inflammatory effect of L-carvone in endothelial dysfunction triggered by uremia related to chronic kidney disease

Article References: Miniskiskosky, G., da Cunha, R. S., Gregório, P. C., Azevedo, C. A. B., Pereira, V. C., de Souza Ramos, E. A., & Stinghen, A. E. M. (2026). Potential anti-inflammatory effect of L-carvone in endothelial dysfunction triggered by uremia related to chronic kidney disease. Molecular Biology Reports, 53(1), Article 1651. https://doi.org/10.1007/s11033-026-12806-7

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12806-7

Keywords: chronic kidney disease, L-carvone, endothelial dysfunction, uremic toxins, inflammation, hemodialysis, monoterpene, cardiovascular disease, IL-1β, MCP-1, monocyte recruitment, natural compounds