**1. Introduction**

Inflammation is an adaptive response triggered by harmful stimuli, including some conditions of infection and tissue damage [1,2]. Macrophages, neutrophils, and lymphocytes are important natural immune cells to participate in homeostasis and immune response, and play complicated action on the pathogenesis of inflammatory disease [3–5]. Stimulated immune cells regulate inflammation by producing proinflammatory factors and mediators, such as interleukin (ILS), tumor necrosis factor-α (TNF-α), NO, prostaglandin E2 (PGE2), and iNOS [6–8]. Therefore, inhibition of inflammatory cytokines, chemokines, and mediators can be potent therapeutic strategies for the prevention of inflammationrelated diseases.

*Penicillium* species are among the most widespread fungal organisms on earth and contains more than 350 species. Many *Penicillium* species can produce plentiful secondary metabolites, such as alkaloids [9], polyketides [10], cyclic peptides [11], and terpenoids [12], that can ascribe specific structural characteristics and significant biological activities. Isocoumarins are important natural lactones with wide range of biological activities, such as neuroprotective, antibacterial, antivirus and antitumor activities, and distribute widely in various microorganisms and plants from natural sources [13–19]. Up to now, nearly 1000 naturally occurring isocoumarins were reported [14]. As our continuing interest in finding new compounds with potential anti-inflammatory activity, the chemical investigation of the endophytic fungus *Penicillium* sp. BJR-P2 yielded two new unique isocoumarins with spiroketal rings (**1**–**2**), two new citreoviridin derivatives (**3**–**4**), together with four known analogues (**5**–**8**) (Figure 1). In this paper, the stereochemistry of these compounds was determined for the first time by DP4+ analysis, ECD calculations, and single-crystal

**Citation:** Chen, C.; Ye, G.; Tang, J.; Li, J.; Liu, W.; Wu, L.; Long, Y. New Polyketides from Mangrove Endophytic Fungus *Penicillium* sp. BJR-P2 and Their Anti-Inflammatory Activity. *Mar. Drugs* **2022**, *20*, 583. https://doi.org/10.3390/ md20090583

Academic Editor: Dehai Li

Received: 27 August 2022 Accepted: 16 September 2022 Published: 18 September 2022

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X-ray diffraction. By screening of the inhibitory effects on NO production in the LPSinduced RAW 264.7 macrophages, the anti-inflammatory activities of these compounds were evaluated, and the results showed that compound **2** exhibited effective inhibitory activity with IC50 value of 12 μM. This article describes the isolation, structure elucidation, and NO production inhibition of the new compounds.

**Figure 1.** Chemical structures of compounds **1**–**8**.
