Perlolyrine

Perlolyrine (CAS 29700-20-7) is a naturally occurring β‑carboline compound, derived primarily from the metabolic products of probiotic bacteria such as Lactobacillus crispatus, as well as from certain medicinal plants. Its core biological activity is anti-inflammatory, and it also exhibits potential anticancer properties.

Its anti-inflammatory effects are cell type–specific. In immune cells (monocytes and macrophages), Perlolyrine inhibits TLR (TLR2, TLR3, TLR4) and IFNAR signaling pathways, downregulates NF-κB activation and interferon signaling, and reduces the production of pro-inflammatory cytokines such as IL‑1β and IL‑6. In vitro, at a concentration of 50 μM, it suppresses 77% of LPS-induced TLR4 activation, and at 100 μM it reduces LPS-induced IFN signaling to 19% of its maximal activity.

In barrier cells (vaginal epithelial cells and fibroblasts), Perlolyrine selectively inhibits TLR-mediated inflammatory responses without affecting IFNAR-driven antiviral responses. In vivo, local vaginal administration (100 μM) can significantly alleviate vaginitis caused by genital herpes infection in mice, reduce disease scores, and prolong survival time. Its concentration in cervicovaginal lavage fluid from healthy women is also significantly higher than that in patients with bacterial vaginosis.

As a member of the β‑carboline alkaloid family with defined anticancer potential, Perlolyrine has been included in screening programs for anticancer bioactive compounds derived from medicinal plants. However, its specific anticancer mechanisms, tumor-type selectivity, and related activity data have not yet been clearly elucidated.

References:

[1] Tshikhudo PP, Mabhaudhi T, Koorbanally NA, Mudau FN, Avendaño Caceres EO, Popa D, Calina D, Sharifi-Rad J. Anticancer Potential of β-Carboline Alkaloids: An Updated Mechanistic Overview. Chem Biodivers. 2024 Feb;21(2):e202301263. doi: 10.1002/cbdv.202301263. Epub 2024 Jan 15. PMID: 38108650.

[2] Glick VJ, Webber CA, Simmons LE, Martin MC, Ahmad M, Kim CH, Adams AND, Bang S, Chao MC, Howard NC, Fortune SM, Verma M, Jost M, Beura LK, James MJ, Lee SY, Mitchell CM, Clardy J, Kim KH, Gopinath S. Vaginal lactobacilli produce anti-inflammatory β-carboline compounds. Cell Host Microbe. 2024 Nov 13;32(11):1897-1909.e7. doi: 10.1016/j.chom.2024.09.014. Epub 2024 Oct 17. PMID: 39423813; PMCID: PMC11694765.