{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:58:45Z","timestamp":1787029125588,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Albany College of Pharmacy and Health Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Derivatives of mycophenolic acid (MPA) and 5-aminolevulinic acid photodynamic therapy (ALA-PDT) have been used separately to treat psoriasis, a chronic, inflammatory skin disease that is characterized by the unregulated hyperproliferation of epidermal keratinocytes and a T-cell-mediated immune response. However, the combination of these two therapies has not previously been explored. This study investigated the in vitro effects of combining MPA with ALA-PDT to suppress keratinocytes and the in vitro inhibition of inosine monophosphate dehydrogenase, a key enzyme. The effects of ALA, MPA, and their combination on protoporphyrin IX (PpIX) generation and cell viability in HaCaT cells, as well as the inhibition of IMPDH, were evaluated. Treatment of HaCaT cells with ALA, MPA, and their 1:1 molar combination showed that ALA alone induced PpIX production, with concentrations increasing from 5.25 ng\/mL at 10 \u03bcM to 157.5 ng\/mL at 1 mM. MPA did not increase PpIX on its own but had a modest synergistic effect with ALA at low concentrations (10 \u03bcM and 50 \u03bcM). The impact of blue light irradiation (465 nm) on cell viability was also assessed, revealing that ALA and ALA + MPA treatment led to significant reductions in HaCaT cell viability at higher concentrations (500 \u03bcM\u20131 mM), while MPA alone with blue light irradiation showed no cytotoxicity. The reduction in skin cell viability was enhanced when ALA was combined with MPA. Additionally, MPA effectively inhibited IMPDH activity in a dose-dependent manner, with 94\u201396% inhibition at concentrations of 100 \u03bcM and above. Interestingly, ALA weakly inhibited IMPDH, with a peak inhibition of 46% at 5 \u03bcM. At higher ALA concentrations, its inhibitory effect diminished, and it interfered with the potency of MPA\u2019s IMPDH2 inhibition, suggesting that ALA could modulate MPA\u2019s therapeutic action. These findings suggest that the combination of MPA with ALA-PDT may be a viable new treatment for psoriasis.<\/jats:p>","DOI":"10.3390\/molecules30061359","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T10:43:51Z","timestamp":1742294631000},"page":"1359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Combination Effects of Aminolevulinic Acid and Mycophenolic Acid on Hacat Cell Proliferation and Inhibition of Inosine Monophosphate Dehydrogenase"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6729-8713","authenticated-orcid":false,"given":"Manisha","family":"Venkatesh","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelle","family":"Capriglione","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Rehberg","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Voigt","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3981-9860","authenticated-orcid":false,"given":"Martha A.","family":"Hass","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bhuntani, T., Liao, W., and Nakamura, M. 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