SOOTHING EFFECT OF POGOSTEMON CABLIN EXTRACT 433 could counter the infl ammation induced by UVB or LPS, by stimulating CB2 receptor activity on epidermal cells and decreasing the release of infl ammatory cytokines. The selec- tive AM1241 activator, and the patchouli extract helped prevent an acute infl ammation in skin without producing observable adverse effects. CB2 receptor antagonist AM630 clearly reversed the anti-infl ammatory effect of patchouli in ex vivo skin. The patchouli extract contains many anti-infl ammatory molecules such as sesquiterpenes and polyphenols, which could involve other anti-infl ammatory signaling pathways independent of CB2. Activation of peripheral CB2 receptor was shown to produce a particularly potent analge- sic effect on infl ammatory pain (31,32). The opioid peptide β-endorphin is derived from the precursor POMC. Patchouli application associated with CB2 receptor stimulation has effect on the opioid expression. The β-endorphin was detected in the skin biopsies, in the Figure 3. Anti-infl ammatory effect of the patchouli extract. (A) Expression level of TRPV1, IL1R1, and IL6ST in human skin exposed to 200 mJ/cm2 and treated with placebo or patchouli extract for 48 h. The expressions of the proteins were measured by immunohistochemistry. (B) Expression level of TRPV1, and IL1R1 in human skin exposed to 0.5 mg/mL Escherichia coli LPS for 1 night and treated with placebo or patchouli extract for 48 h. The expressions of the proteins were measured by immunohistochemistry. (C) Immunohistochemistry staining of IL6ST (green) and DNA stained with DAPI (blue), on human skin biop- sies irradiated with 200 mJ/cm2 UVB and treated with placebo or patchouli extract for 48 h (×40 objective lens, scale bar = 16 μm) (n = 3 mean ± SEM ***p d 0.005 **p d 0.01 *p d 0.05).

JOURNAL OF COSMETIC SCIENCE 434 epidermis and some cells of the dermis. Application of the patchouli extract signifi - cantly increased the protein level of β-endorphin and the release by keratinocytes. Our results suggest that β-endorphin release contributes to the soothing effects of the patchouli extract. Our results are consistent with those of a previous study, where AM1241 stimulated β-endorphin release from immortalized human keratino- cyte HaCaT cell line (33). It is also possible that other mediators, in addition to β-endorphin, might be released after the activation of CB2 receptors, contributing to the soothing effect. TRPV1 acts as a key peripheral integrator of pain, itch, and heat sensation in skin. TRPV1 was found in human skin and might be associated with infl ammation. Pharmacological blockade of TRPV1 has recently emerged as a potential novel therapeutic possibility in managing infl ammatory diseases (34). In our experimental model, using UVB- and LPS-induced infl ammation, skin treated with the patchouli extract showed less- ened production of TRPV1 and pro-infl ammatory cytokine receptors, including IL6ST and IL1R1. These results demonstrate that the activation of the CB2 receptor, at least in part, might participate in keratinocyte protection through the inhibition of cytokine receptors. The patchouli extract helped prevent the activation of TRPV1 and interleukin infl ammasome pathway, and, in parallel, limited the formation of sun burn cells, as demonstrated by the suppression of tissue damage (Figure 1A and B). Likewise, the patchouli extract formulated at 1% helped to improve skin sensitivity by reducing stinging sensation induced by the activation of TRPV1 via capsaicin (Figure 4). The use of the patchouli extract associated with protective action although CB2 receptor activation could be a promising strategy for the treatment of sensitive skin. CONCLUSIONS In summary, our results confi rm that CB2 agonist has strong anti-infl ammatory activity in the human skin exposed to UVB or LPS. This effect, at least in part, is associated with the reduction in TRPV1, IL1R1, and IL6ST levels and the release of the β-endorphin opioid. A Pogostemon cablin extract (patchouli) containing the phytocannabinoid BCP, and other anti-infl ammatory molecules present in the patchouli extract such as the polyphenols, was associated with a reduction in the level of infl ammatory markers, via cannabinoid Figure 4. Evaluation of skin sensitivity by stinging test with capsaicin after 28 of cream applications. Decrease in capsaicin-induced stinging sensation after face application of a cream containing patchouli extract at 1% (n = 10 mean ± SEM p d 0.05).