Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 775 15, Olomouc, Czech Republic.
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 775 15, Olomouc, Czech Republic.
Free Radic Biol Med. 2021 Feb 20;164:258-270. doi: 10.1016/j.freeradbiomed.2021.01.012. Epub 2021 Jan 13.
In this contribution, a comprehensive study of the redox transformation, electronic structure, stability and photoprotective properties of phytocannabinoids is presented. The non-psychotropic cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), and psychotropic tetrahydrocannabinol (THC) isomers and iso-THC were included in the study. The results show that under aqueous ambient conditions at pH 7.4, non-psychotropic cannabinoids are slight or moderate electron-donors and they are relatively stable, in the following order: CBD > CBG ≥ CBN > CBC. In contrast, psychotropic Δ-THC degrades approximately one order of magnitude faster than CBD. The degradation (oxidation) is associated with the transformation of OH groups and changes in the double-bond system of the investigated molecules. The satisfactory stability of cannabinoids is associated with the fact that their OH groups are fully protonated at pH 7.4 (pKa is ≥ 9). The instability of CBN and CBC was accelerated after exposure to UVA radiation, with CBD (or CBG) being stable for up to 24 h. To support their topical applications, an in vitro dermatological comparative study of cytotoxic, phototoxic and UVA or UVB photoprotective effects using normal human dermal fibroblasts (NHDF) and keratinocytes (HaCaT) was done. NHDF are approx. twice as sensitive to the cannabinoids' toxicity as HaCaT. Specifically, toxicity IC values for CBD after 24 h of incubation are 7.1 and 12.8 μM for NHDF and HaCaT, respectively. None of the studied cannabinoids were phototoxic. Extensive testing has shown that CBD is the most effective protectant against UVA radiation of the studied cannabinoids. For UVB radiation, CBN was the most effective. The results acquired could be used for further redox biology studies on phytocannabinoids and evaluations of their mechanism of action at the molecular level. Furthermore, the UVA and UVB photoprotectivity of phytocannabinoids could also be utilized in the development of new cannabinoid-based topical preparations.
在本研究中，对植物大麻素的氧化还原转化、电子结构、稳定性和光保护特性进行了全面研究。研究中包括非精神活性大麻二酚 (CBD)、大麻萜酚 (CBG)、大麻醇 (CBN)、大麻色烯 (CBC) 和精神活性四氢大麻酚 (THC)异构体和 iso-THC。结果表明，在 pH 值为 7.4 的水相环境下，非精神活性大麻素是轻微或中等的电子供体，它们相对稳定，稳定性顺序为：CBD>CGB≥CBN>CBC。相比之下，精神活性 Δ-THC 的降解速度比 CBD 快约一个数量级。降解（氧化）与 OH 基团的转化和所研究分子的双键系统的变化有关。大麻素令人满意的稳定性与它们的 OH 基团在 pH 值为 7.4 时完全质子化（pKa≥9）的事实有关。CBN 和 CBC 的不稳定性在暴露于 UVA 辐射后加速，而 CBD（或 CBG）在长达 24 小时内稳定。为了支持它们的局部应用，对正常人类真皮成纤维细胞 (NHDF) 和角质形成细胞 (HaCaT) 进行了细胞毒性、光毒性和 UVA 或 UVB 光保护作用的体外皮肤科比较研究。NHDF 对大麻素的毒性比 HaCaT 敏感约两倍。具体来说，在 24 小时孵育后，CBD 的毒性 IC 值分别为 NHDF 和 HaCaT 的 7.1 和 12.8 μM。研究中的大麻素均无光毒性。广泛的测试表明，CBD 是研究大麻素中对 UVA 辐射最有效的保护剂。对于 UVB 辐射，CBN 是最有效的。获得的结果可用于进一步研究植物大麻素的氧化还原生物学，并评估其在分子水平上的作用机制。此外，植物大麻素的 UVA 和 UVB 光保护作用也可用于开发新的基于大麻素的局部制剂。
