La peau, les ongles, mais surtout les cheveux laissent une impression décisive sur l’apparence soignée d’une personne. Ils ont tous besoin de cosmétiques externes de haute qualité et de différents micronutriments pour avoir une bonne apparence.
L’huile de CBD pour la chute de cheveux
Les bienfaits de l’huile de CBD pour les cheveux sont incroyables. Le CBD n’a pas d’effet psychoactif ou intoxicant, contrairement au THC. Les acides gras oméga-3 et oméga-6 contenus dans la plante aident à restaurer les cheveux et à renforcer et lisser les cheveux cassants et abîmés. Les acides gras résistants protègent la couche extérieure du cheveu et contribuent à sa meilleure résistance à la pollution environnementale externe. Les graisses et les acides aminés peuvent stimuler la croissance des cheveux car ils réduisent le cuir chevelu. Ils peuvent être responsables de la perte de cheveux. La production de kératine est également encouragée par l’huile de CDB. La kératine renforce les cheveux et les rend moins sujets aux cassures et aux pointes fourchues. De plus, le CDB stimule la croissance des cheveux. L’acide gamma-linolénique peut également contribuer à hydrater le cuir chevelu sec et à renforcer les cheveux cassants. L’huile de CBD hydrate, pénètre dans la tige du cheveu, renforce la couche hydrolipidique et protège contre la sécheresse. L’huile de CBD protège également contre les dommages causés par le soleil.
Comment le CBD peut-il aider votre cuir chevelu ?
Il existe de nombreux produits au CBD sur le marché pour le traitement des cheveux. La manière dont vous appliquez le CBD sur vos cheveux ou votre cuir chevelu dépend de vous. Pour une utilisation plus pratique, vous pouvez choisir un shampoing ou un après-shampoing au CBD. Parmi les formules les plus complexes, on trouve celles qui utilisent un sérum pour le cuir chevelu et des masques hydratants. Et bien sûr, vous pouvez frotter divers types d’huile de CBD directement sur votre cuir chevelu (selon les ingrédients exacts). Pour ceux qui préfèrent les cheveux longs, le gel imprégné de CBD est également une option.
TNF increases TRPA1 protein, which is located in intracellular compartments. CBD activates TRPA1 and Ca 2+ is released into the cytosol. Elevations in cytosolic Ca 2+ are reduced through uptake into mitochondria. In addition, increased cytosolic Ca 2+ might enhance the activity of organic cation transporters (OCT) which might mediate the uptake of the fluorescent dye PoPo3. Additionally, OCT might mediate the uptake of CBD itself. By binding to VDAC1, CBD increases Ca 2+ flux through the outer mitochondrial membrane. Ca 2+ is then taken up into the matrix by the mitochondrial Ca 2+ uniporter (MCU) and, if mitochondria are depolarized, by the Na + /Ca 2+ exchanger (NCLX), which operates in reverse mode under these conditions. Ca 2+ overload occurs, the mitochondrial permeability transition pore (mPTP) assembles and cell death occurs.
a, b Mean cell viability of unstimulated (a) or TNF pre-stimulated (b) RASF after CBD challenge monitored in real-time over the course of 375 min. c–e Mean proliferation of RASF with (red bars) and without (white bars) TNF pre-stimulation in response to CBD in medium containing 0% FCS (c), 2% FCS (d), and 10% FCS. The dotted line represents the unstimulated control, which was set to 100%. f Flow cytometric detection of TRPA1 protein in RASF with or without TNF stimulation for 72 h. g–k Mean cell viability of TNF pre-stimulated RASF after CBD challenge and concomitant addition of inhibitors over the course of 20 h. n is the number of replicates and patient samples investigated. ANOVA with Dunnett’s T3 post-hoc test was used for comparisons in a, b, g–k. ANOVA with Bonferroni post-hoc test was used for comparisons in c–e. Two-tailed t-test was used for comparisons in f. *p < 0.05; **p < 0.01, ***p < 0.001 vs control. The error bars in c–f represent the standard error of mean (sem).
The concentrations used in this study are based on values found in the literature (reference).
We demonstrated that CBD reduces cell viability, but RealTime-Glo assays were conducted in serum-free medium without carrier protein. Therefore, we assessed whether CBD influences RASF proliferation in medium containing FCS, since in vivo, CBD is bound to serum albumin, which lowers its free concentration available for receptor binding 24,41 . We confirmed that the anti-proliferative effect of CBD is dependent on FCS content. Consequently, for in vivo applications, CBD needs to be administered in high concentrations to elicit beneficial effects as shown in the treatment of Dravet syndrome 13 . In order to identify the cellular targets for CBD, we used the TRPA1 antagonist A967079 and the pan-TRP antagonist RR to inhibit the effects of CBD on cell viability as CBD has already been identified as ligand for TRPA1 23 . Moreover, we found that CsA reversed the detrimental effects of CBD on cell viability, which confirms results from Olivas-Aguirre et al. 25 that showed mitochondrial calcium overload correlates with assembly of the mPTP by CBD. It has been demonstrated that CBD influences calcium homeostasis 25 and we also found CBD to elevate intracellular calcium in RASF. This confirms own previous results demonstrating calcium mobilization in response to TRPA1 ligation 22 . Moreover, we showed that TNF up-regulates TRPA1 protein in RASF, which translates into increased sensitivity to TRPA1 ligands 22 . CBD also increased calcium levels without extracellular calcium by using PBS instead of HBSS, suggesting mobilization form intracellular stores. In fact, in dorsal root ganglia neurons it has been shown that TRPA1 is located in lysosomes, where its activation fosters neurotransmitter release 42 . Although we do not provide direct evidence regarding the localization of TRPA1, the use of the cell-impermeable pan-TRP inhibitor RR 43 , which was only able to slightly attenuate the effects of CBD suggests an intracellular target protein. In line with this, the lipophilic antagonist A967079 decreased calcium mobilization and PoPo3 uptake after CBD challenge. Moreover, we used Thapsigargin to deplete ER calcium stores and GPN to disrupt lysosomes and both compounds reduced the elevation of intracellular calcium after CBD exposure. This shows that ER calcium stores are involved and it has been shown that even if calcium originates from lysosomes, the signal is amplified by depletion of ER stores 44 . This is important, because although GPN has been reported to mobilize lysosomal calcium, a recent study claimed that GPN increases calcium through an ER-dependent mechanism 45 . CBD is also an agonist at TRPV1/2 ion channels 7,23,46,47 , but neither CPZ nor RR inhibited the effects of CBD, ruling out these receptors as target molecules. CPZ is also an agonist at TRPA1 48 , and we did detect a small increase in basal intracellular calcium in response to this ligand alone. Accordingly, CPZ slightly elevated the calcium response of RASF to CBD suggesting a sensitizing effect on TRPA1. TRPA1 inhibition with A967079 reduced calcium mobilization and PoPo3 uptake in TNF pre-stimulated but not naïve RASF, where we found the opposite, suggesting that CBD exerts additional effects via different cellular targets besides TRPA1. This demonstrates that TRPA1 contributes to the rise in intracellular calcium only in TNF pre-stimulated RASF, in which TRPA1 is upregulated. Besides binding to TRPs, it has been demonstrated that CBD ligates several proteins 11,49 with mitochondrial targets being the most prominent 8–10,25,30 . In mitochondria, CBD targets VDAC1, NCLX, MCU, and controls assembly of the mPTP 8–10,25 . Although protective effects of CBD against mitochondrial toxins have been shown 10,50 , the majority of studies demonstrated that CBD induces cell death by disturbing calcium homeostasis 8,9,25 . This confirms our results, since CBD augmented calcium levels with a concomitant increase in cell death. Excess cytosolic calcium is taken up by mitochondria which are depolarized in this process 51 . If mitochondrial calcium levels exceed a certain threshold, mPTP is assembled leading to cell death 52 . In fact, we demonstrated that only CsA prevented cell death, suggesting that mitochondrial calcium overload occurs in CBD-stimulated RASF. In line with this, CsA reduced intracellular calcium, which is another indicator that mitochondria provide a significant contribution to the increase in calcium by CBD. Calcium is increased by mPTP formation as mitochondria are permeabilized releasing stored calcium into the cytosol 53 . Thus, inhibiting mPTP formation by CsA decreases calcium leakage from mitochondria and subsequent cell death. In addition, we found that the NCLX inhibitor CGP reduced cytosolic calcium levels. CGP blocks calcium transport from the mitochondrial matrix into the intermembrane space, thus increasing mitochondrial and reducing cytosolic calcium levels 54 . We also used the reverse mode inhibitor of the NCLX, KB-R7943, but results with this inhibitor are difficult to interpret due to its interaction with the MCU and NCLX. In the latter it can act as forward or reverse mode antagonist dependent on cell type, NCLX isoform, and concentration 55,56 . Using the specific MCU inhibitor DS16570511 we found increased cytosolic calcium levels in TNF pre-stimulated but not in unstimulated RASF. This might be explained by TRPA1, which only contributed to calcium level alterations in TNF pre-treated RASF. For the inhibition of VDAC1 we used DIDS which increased intracellular calcium in unstimulated, but decreased calcium in TNF pre-treated RASF. This might depend on the initial calcium signal generated by CBD, because DIDS can permeabilize the inner mitochondrial membrane depending on calcium concentration leading to formation of mPTP 57 . Besides calcium, PoPo3 uptake served as readout for changes in cell viability as it is supposed to enter cells with a compromised plasma membrane only. However, several studies showed that the uptake of PoPo3 related compounds also occurs via specific receptors/ion channels 58,59 . In addition, it has been demonstrated that the family of organic cation transporters (OCT) mediates the uptake of many charged but also electroneutral compounds into the cell 39 . Therefore, it is quite possible that PoPo3 is also taken up by OCT and indeed we show that decynium-22, which inhibits all OCT isoforms 39 strongly reduced PoPo3 uptake and it also blunted the increase of intracellular calcium, which might be due to the electrogenic properties of D22 40 . Another possibility is that OCT mediates the uptake of CBD and D22 would limit the access of CBD to intracellular compartments. D22 did not influence basal uptake of PoPo3, but reduced the CBD-induced uptake and this might be related to changes in intracellular calcium since the activity of OCT is regulated by calcium-dependent proteins 39 . DIDS completely blocked PoPo3 uptake but these results are difficult to interpret since DIDS does not inhibit OCT but membrane anion channels, which should not mediate the uptake of the cationic dye PoPo3. It might be that the negatively charged DIDS binds PoPo3 directly, thereby inhibiting binding to DNA and the increase in fluorescence. PoPo3 might be suitable as a surrogate marker for the uptake of chemical compounds/drugs, which is enhanced by CBD. Since RASF produce high amounts of IL-6, IL-8, and MMP-3 60 , we also investigated the impact of CBD on production of these mediators. CBD dose-dependently reduced IL-6, IL-8, and MMP-3 with concomitant reduction in cell viability. CsA was able to rescue RASF from cell death and increased Il-6 and IL-8 production confirming that cell death is the influencing factor on cytokine production.
Biochemicals used in this study.
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
From our data, we propose a mechanism of how CBD influences RASF function and induces cell death under pro-inflammatory conditions (Fig. (Fig.6). 6 ). TNF sensitizes RASF to the action of CBD by up-regulating TRPA1 22 . CBD increases intracellular calcium by activating TRPA1 but it also binds several mitochondrial targets like VDAC1, MCU, and NCLX, which on their part influence cytosolic calcium. Eventually, mitochondrial calcium overload occurs and mPTP is assembled leading to cell death.