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DOI: 10.1055/s-0045-1815686
β-Caryophyllene Attenuates Diabetic Nephropathy via Cannabinoid Receptor 2 (CB2)-Mediated Modulation of Oxidative Stress and Inflammation: Evidence from In Vivo and In Vitro Studies
Authors
Background: Diabetic nephropathy (DN) is a serious complication of diabetes characterized by progressive kidney damage. The natural compound β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2) agonist, has shown potential anti-inflammatory and antioxidant properties. This study investigated whether BCP could protect against DN through CB2 receptor activation in both animal and cell culture models.
Methods:
In Vivo: Male C57BL/6 mice (n = 8/group, 12-week-old) received STZ (50 mg/kg) + HFD for 12 weeks to induce DN. BCP (50 mg/kg/day) was selected based on prior pharmacokinetic studies and was divided into six experimental groups to examine the effects. Kidney function (blood urea nitrogen [BUN], creatinine) and oxidative stress markers (malondialdehyde, glutathione peroxidase, catalase, and superoxide dismutase) were assessed through biochemical assays. The histological and morphological architecture of renal tissues was analyzed by H&E staining. ELISA also assessed inflammatory markers (IL-6, IL-1β, IL-10, and TNF-α). The data were analyzed using one-way ANOVA with Duncan’s test (SPSS v24.0).
In Vitro: NRK-52E renal tubular epithelial cells were treated with (1) normal glucose (5.5 mM), (2) high glucose (HG, 45 mM), (3) HG+BCP (25 µM), and (4) HG + BCP + AM630 (10 µM). Cell viability was quantified at 24 and 48 hours. The CB2 receptor-specific antagonist AM630 was employed to verify receptor-dependent mechanisms.
Results: BCP treatment significantly improved kidney function parameters and reduced markers of inflammation and oxidative stress in diabetic mice. Histological examination showed reduced kidney damage in BCP-treated groups. In cell studies, BCP protected against high glucose-induced damage, and these effects were blocked by AM630, supporting a CB2 receptor-dependent mechanism.
Conclusion: These findings demonstrate that BCP exerts protective effects against DN through CB2 receptor activation, reducing both inflammation and oxidative stress. Given its established safety as a dietary compound, BCP presents a promising therapeutic candidate for mitigating DN progression. These findings have immediate relevance for the UAE, where DN prevalence parallels rising diabetes rates.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
29 December 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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