{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:12:05Z","timestamp":1785420725399,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Post-inflammatory hyperpigmentation (PIH) results from inflammatory responses that leave persistent dark spots around pores after acne lesions are resolved. This pigmentation is caused by increased melanogenesis in melanocytes stimulated by acne-causing bacteria, followed by phagocytosis of excess melanin by macrophages that remain in the dermis. Therefore, to eliminate PIH caused by acne, it is essential not only to suppress excessive melanin synthesis by melanocytes but also to promote the degradation of melanin retained within macrophages. In this study, we investigated whether a culture extract of Bacillus velezensis AmoreLumina (AL), containing more than 80% moranoline (1-Deoxynojirimycin), could inhibit acne-induced pigmentation. Moranoline reduces melanin synthesis by inhibiting the glycosylation of tyrosinase, a key melanogenic enzyme, thereby suppressing its activity. The extract suppressed the upregulation of melanogenic enzymes (tyrosinase, TRP1, and TRP2) and melanin production in melanocytes exposed to acne bacteria, while promoting melanin degradation via macrophage lysosomal activity, as assessed by the relative protein expression level of p62 using Western blotting. Furthermore, in an ex vivo human skin model subjected to acne and ultraviolet radiation-induced pigmentation, treatment with the extract (0.2%) significantly reduced pigmentation (relative delta L 2.98, p value &lt; 0.01). These findings suggest that cosmetic or pharmaceutical formulations incorporating AL extract or moranoline may potentially improve PIH caused by acne-related inflammation.<\/jats:p>","DOI":"10.3390\/ijms27156837","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:55:11Z","timestamp":1785419711000},"page":"6837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Moranoline-Enriched Bacillus velezensis AmoreLumina Culture Extract Attenuates Post-Inflammatory Hyperpigmentation in Acne-Prone Skin"],"prefix":"10.3390","volume":"27","author":[{"given":"Daejin","family":"Min","sequence":"first","affiliation":[{"name":"Research and Innovation Center, Amorepacific Corporation, Yongin-si 17074, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuk","family":"Kim","sequence":"additional","affiliation":[{"name":"Research and Innovation Center, Amorepacific Corporation, Yongin-si 17074, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Jeong","family":"Choi","sequence":"additional","affiliation":[{"name":"Research and Innovation Center, Amorepacific Corporation, Yongin-si 17074, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nok Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Research and Innovation Center, Amorepacific Corporation, Yongin-si 17074, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-5105","authenticated-orcid":false,"given":"Geunhyuk","family":"Jang","sequence":"additional","affiliation":[{"name":"Research and Innovation Center, Amorepacific Corporation, Yongin-si 17074, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9763-0874","authenticated-orcid":false,"given":"Won-Seok","family":"Park","sequence":"additional","affiliation":[{"name":"Research and Innovation Center, Amorepacific Corporation, Yongin-si 17074, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjung","family":"Choi","sequence":"additional","affiliation":[{"name":"Research and Innovation Center, Amorepacific Corporation, Yongin-si 17074, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"D\u2019Mello, S.A.N., Finlay, G.J., Baguley, B.C., and Askarian-Amiri, M.E. (2016). Signaling pathways in melanogenesis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17071144"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1590\/S0365-05962013000100009","article-title":"Mechanisms regulating melanogenesis","volume":"88","author":"Videira","year":"2013","journal-title":"An. Bras. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/exd.12343","article-title":"Regulation of pigmentation by substrate elasticity in normal human melanocytes and melanotic MNT1 human melanoma cells","volume":"23","author":"Choi","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bao, M., Gempeler, M., and Campiche, R. (2025). Melanosome transport and processing in skin pigmentation: Mechanisms and targets for pigmentation modulation. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202508.0189.v1"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1111\/pcmr.12002","article-title":"Manassantin B inhibits melanosome transport in melanocytes by disrupting the melanophilin-myosin Va interaction","volume":"25","author":"Chang","year":"2012","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Moreiras, H., Seabra, M.C., and Barral, D.C. (2021). Melanin transfer in the epidermis: The pursuit of skin pigmentation control mechanisms. Int. J. Mol. Sci., 22.","DOI":"10.20944\/preprints202104.0441.v1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1177\/12034754241265716","article-title":"Treatment of post-inflammatory hyperpigmentation in skin of colour: A systematic review","volume":"28","author":"Mar","year":"2024","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"adv42925","DOI":"10.2340\/actadv.v105.42925","article-title":"Acne-induced post-inflammatory hyperpigmentation: From grading to treatment","volume":"105","author":"Auffret","year":"2025","journal-title":"Acta Derm. Venereol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1111\/ijd.17718","article-title":"Pathogenesis of melasma explained","volume":"64","author":"Ali","year":"2025","journal-title":"Int. J. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e70366","DOI":"10.1111\/jocd.70366","article-title":"A novel peel to prevent post-inflammatory hyperpigmentation after CO2 resurfacing for acne scars","volume":"24","author":"Hang","year":"2025","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1084\/jem.20171608","article-title":"Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal","volume":"215","author":"Baranska","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_12","first-page":"123","article-title":"Minocycline-induced skin pigmentation: An update","volume":"17","author":"Geria","year":"2009","journal-title":"Acta Dermatovenerol. Croat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1111\/exd.14667","article-title":"Melanin accumulation in dermal stem cells deteriorates their exosome-mediated skin basement membrane construction in solar lentigo","volume":"31","author":"Miyachi","year":"2022","journal-title":"Exp. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1002\/med.21426","article-title":"Trends in regenerative medicine: Repigmentation in vitiligo through melanocyte stem cell mobilization","volume":"37","author":"Birlea","year":"2017","journal-title":"Med. Res. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/s41586-023-05960-6","article-title":"Dedifferentiation maintains melanocyte stem cells in a dynamic niche","volume":"616","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.36849\/JDD.9382","article-title":"Evaluation of an advanced, multimodal skin tone correcting serum in participants with mild-to-severe dyschromia and hyperpigmentation","volume":"25","author":"Draelos","year":"2026","journal-title":"J. Drugs Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tang, S.C., and Yang, J.H. (2018). Dual effects of alpha-hydroxy acids on the skin. Molecules, 23.","DOI":"10.3390\/molecules23040863"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1007\/s43630-025-00795-8","article-title":"The extract of dendrobium Coelonin inhibits PIH induced by AFR CO2 fractional laser combined with UV-B","volume":"24","author":"Li","year":"2025","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_19","first-page":"18","article-title":"Catamenial hyperpigmentation: A review","volume":"13","author":"Mobasher","year":"2020","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hassanshahi, A., Moradzad, M., Ghalamkari, S., Fadaei, M., Cowin, A.J., and Hassanshahi, M. (2022). Macrophage-mediated inflammation in skin wound healing. Cells, 11.","DOI":"10.3390\/cells11192953"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhou, H., Wang, Y., Li, Y.M., and Zheng, Y.W. (2025). The potential of macrophages for skin anti-aging. Front. Biosci., 30.","DOI":"10.31083\/FBL38891"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Guan, M., Yao, L., Zhen, Y., Song, Y., Liu, X., Liu, Y., Chen, R., Cui, Y., and Li, S. (2023). Sporothrix globosa melanin regulates autophagy via the TLR2 signaling pathway in THP-1 macrophages. PLoS Negl. Trop. Dis., 17.","DOI":"10.1371\/journal.pntd.0011281"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wen, J.H., Li, D.Y., Liang, S., Yang, C., Tang, J.X., and Liu, H.F. (2022). Macrophage autophagy in macrophage polarization, chronic inflammation and organ fibrosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.946832"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1600-0625.2006.00515.x","article-title":"Influence of N-glycan processing disruption on tyrosinase and melanin synthesis in HM3KO melanoma cells","volume":"16","author":"Choi","year":"2007","journal-title":"Exp. Dermatol."},{"key":"ref_25","first-page":"139","article-title":"Enhanced depigmenting effects of N-glycosylation inhibitors delivered by pH-sensitive liposomes into HM3KO melanoma cells","volume":"59","author":"Park","year":"2008","journal-title":"J. Cosmet. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"374","DOI":"10.4103\/jomfp.JOMFP_207_20","article-title":"The effect of vitamin C on melanin pigmentation\u2014A systematic review","volume":"24","author":"Sanadi","year":"2020","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1159\/000477356","article-title":"Antimelanogenic efficacy of melasolv (3,4,5-trimethoxycinnamate thymol ester) in melanocytes and three-dimensional human skin equivalent","volume":"30","author":"Lee","year":"2017","journal-title":"Skin. Pharmacol. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e202400314","DOI":"10.1002\/cmdc.202400314","article-title":"Tyrosinase inhibition and antimelanogenic effects of resorcinol-containing compounds","volume":"19","author":"Beaumet","year":"2024","journal-title":"ChemMedChem"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Park, H.J., Jo, D.S., Choi, H., Bae, J.E., Park, N.Y., Kim, J.B., Choi, J.Y., Kim, Y.H., Oh, G.S., and Chang, J.H. (2020). Melasolv induces melanosome autophagy to inhibit pigmentation in B16F1 cells. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0239019"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1080\/15548627.2024.2421695","article-title":"Deciphering melanophagy: Role of the PTK2-ITCH-MLANA-OPTN cascade on melanophagy in melanocytes","volume":"21","author":"Park","year":"2025","journal-title":"Autophagy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jaci.2022.11.009","article-title":"IL-31-generating network in atopic dermatitis comprising macrophages, basophils, thymic stromal lymphopoietin, and periostin","volume":"151","author":"Hashimoto","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20327","DOI":"10.1038\/s41598-022-24577-9","article-title":"Macrophage polarity and wound age determination","volume":"12","author":"Kuninaka","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/j.1346-8138.1993.tb01295.x","article-title":"Expression of monocyte\/macrophage markers (CD13, CD14, CD68) on human keratinocytes in healthy and diseased skin","volume":"20","author":"Hunyadi","year":"1993","journal-title":"J. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lee, K.W., Kim, M., Lee, S.H., and Kim, K.D. (2022). The function of autophagy as a regulator of melanin homeostasis. Cells, 11.","DOI":"10.3390\/cells11132085"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s00403-024-03559-z","article-title":"Imperatorin promotes melanin degradation in keratinocytes through facilitating autophagy via the PI3K\/Akt signaling pathway","volume":"317","author":"Huang","year":"2024","journal-title":"Arch. Dermatol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/exd.12337","article-title":"Autophagy induced by resveratrol suppresses \u03b1-MSH-induced melanogenesis","volume":"23","author":"Kim","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.freeradbiomed.2021.07.030","article-title":"The anti-melanogenic effects of 3-O-ethyl ascorbic acid via Nrf2-mediated \u03b1-MSH inhibition in UVA-irradiated keratinocytes and autophagy induction in melanocytes","volume":"173","author":"Chen","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/j.1468-2494.2009.00529.x","article-title":"Ultrastructural assessments of the melanosome distribution patterns and pigmentation features in human epidermal cells after UV irradiation and kojic acid treatment","volume":"31","author":"Vie","year":"2009","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1034\/j.1600-0625.12.s2.1.x","article-title":"Melanosome transfer to and translocation in the keratinocyte","volume":"12","author":"Boissy","year":"2003","journal-title":"Exp. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1034\/j.1600-0749.2001.140402.x","article-title":"Keratinocyte-melanocyte interactions during melanosome transfer","volume":"14","author":"Seiberg","year":"2001","journal-title":"Pigment Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6416","DOI":"10.1038\/s41598-022-08163-7","article-title":"Preferential stimulation of melanocytes by M2 macrophages to produce melanin through vascular endothelial growth factor","volume":"12","author":"Han","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bento-Lopes, L., Caba\u00e7o, L.C., Charneca, J., Neto, M.V., Seabra, M.C., and Barral, D.C. (2023). Melanin\u2019s journey from melanocytes to keratinocytes: Uncovering the molecular mechanisms of melanin transfer and processing. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202305.1655.v1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1248\/cpb.51.1085","article-title":"Depigmenting activity and low cytotoxicity of alkoxy benzoates or alkoxy cinnamte in cultured melanocytes","volume":"51","author":"Kang","year":"2003","journal-title":"Chem. Pharm. Bull."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"117117","DOI":"10.1016\/j.foodres.2025.117117","article-title":"Identification and fermentation optimization of a newly isolated strain Bacillus velezensis AmoreLumina for high-yield moranoline production","volume":"220","author":"Ju","year":"2025","journal-title":"Food Res. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.jid.2018.01.007","article-title":"Propionibacterium acnes-derived extracellular vesicles promote acne-like phenotypes in human epidermis","volume":"138","author":"Choi","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/sj.jid.5701188","article-title":"Propionibacterium acnes stimulates pro-matrix Metalloproteinase-2 expression through tumor necrosis factor-\u03b1 in human dermal fibroblasts","volume":"128","author":"Choi","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, T., Huang, T., Li, J., Li, A., Li, C., Huang, X., Li, D., Wang, S., and Liang, M. (2023). Optimization of differentiation and transcriptomic profile of THP-1 cells into macrophage by PMA. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0286056"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jdermsci.2012.03.002","article-title":"Kojic acid-induced IL-6 production in human keratinocytes plays a role in its anti-melanogenic activity in skin","volume":"66","author":"Choi","year":"2012","journal-title":"J. Dermatol. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6837\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:56:02Z","timestamp":1785419762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":48,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156837"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156837","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}