Nine monoterpenoids from Radix Paeoniae Alba, including paeoniflorin derivatives, paeoniflorin (PF), 4-O-methylpaeoniflorin (MPF), 4-O-methylbenzoylpaeoniflorin (MBPF); paeonidanin derivatives, paeonidanin (PD), paeonidanin A (PDA), albiflorin derivatives, albiflorin (AF), benzoylalbiflorin (BAF), galloylalbiflorin (GAF), and debenzoylalbiflorin (DAF), were obtained in our previous phytochemistry investigations. Their anti-inflammatory effects were determined in the present study. The expression and production of pro-inflammatory cytokines in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells were measured using an Elisa assay and nitric oxide (NO) release was determined using the Griess method. The results demonstrated that the most of the monoterpenoids suppressed the LPS-induced production of NO, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The anti-inflammatory activities of these monoterpenoids were closely related to their structural characteristics. Paeoniflorins and paeonidanins presented stronger anti-inflammatory activities than those of albiflorin derivatives. Furthermore, the action mechanisms of MBPF, having a strong anti-inflammatory effect, were investigated using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot methods. The results indicated that MBPF could down-regulate the mRNA and protein expression level of inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW 264.7 cells. The mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT and nuclear factor κB (NF-κB) signaling pathways are involved in mediating the role of MBPF in suppressing the expression and production of pro-inflammatory cytokines in RAW 264.7 cells.

Alisol F and 25-anhydroalisol F isolated from Alisma orientale, were proved to exhibit anti-inflammatory potential in our previous work. In the current study, the anti-inflammatory effects and action mechanisms of alisol F and 25-anhydroalisol F were investigated in vitro. Moreover, the pharmacological effects of alisol F in lipopolysaccharide (LPS)/d-galactosamine (d-gal)-induced acute liver-injured mice were evaluated. The results demonstrated that alisol F and 25-anhydroalisol F could suppress LPS-induced production of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β), as well as inhibit the mRNA and protein levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2). In addition, we investigated the role of alisol F and 25-anhydroalisol F in mediating mitogen-activated protein kinases (MAPKs), signal transducers, and activators of transcription 3 (STAT3) and nuclear factor κB (NF-κB) pathways involved in the inflammation process of LPS-stimulated RAW 264.7 cells. The phosphorylation of ERK, JNK, p38, and STAT3, and the NF-κB signaling pathway, were obviously suppressed in alisol F and 25-anhydroalisol F treated cells. Results obtained from in vitro experiments suggested alisol F obviously improved liver pathological injury by inhibiting the production of TNF-α, IL-1β, and IL-6, and significantly decreasing the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in LPS/d-gal-induced mice. Furthermore, the reduction of phosphorylation of ERK and JNK, as well as suppression of the NF-κB signaling pathway, were also observed in liver tissues of the alisol F-treated mice model. Alisol F and 25-anhydroalisol F may serve as potential leads for development of anti-inflammatory agents for acute liver failure treatment.

Five novel tacrine-ferulic acid hybrid compounds (8a–e) were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE), reducing self-induced β-amyloid (Aβ) aggregation and chelating Cu²⁺ were evaluated in vitro. Among them, 8c and 8d displayed the higher selectivity in inhibiting AChE over BuChE. Moreover, 8d also showed dramatic inhibition of self-Aβ aggregation, activity of chelating Cu²⁺ and activity against Aβ-induced neurotoxicity in Neuro-2A cells.

Six new metabolites, actinofuranones D-I (compounds 1–6), were isolated together with three known compounds—JBIR-108 (7), E-975 (8), and E-492 (9)—from a fermentation broth of Streptomyces gramineus derived from the lichen Leptogium trichophorum. The structures of the new compounds 1–6 were established using comprehensive NMR spectroscopic data analysis, as well as UV, IR, and MS data. The anti-inflammatory activity of these isolated compounds were evaluated by examining their ability to inhibit nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 4, 5, 8, and 9 attenuated the production of NO due to the suppression of the expression of nitric oxide synthase (iNOS) in LPS-induced RAW 264.7 cells. Moreover, 4, 5, 8, and 9 also inhibited LPS-induced release of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α).

Four isoquinolinequinones (1–4) were isolated from the fermentation broth of Streptomyces albidoflavus which were derived from lichens. Among them, mansouramycin H (1) was identified as a new isoquinolinequinone by comprehensive spectroscopic data analysis. The mansouramycins from S. albidoflavus presented broad cytotoxic activities, especially against MDA-MB-231, but the SAR and mechanism were still unclear. The total synthesis of mansouramycin H (1) and its twenty-three derivatives were completed and their cytotoxic activities against MDA-MB-231 were evaluated in vitro. Primary SAR revealed that the piperazine moieties introduced into the amino group at C-7 could improve the activities of mansouramycins. Benzoyl and phenylacetyl groups on piperazine fragments had better activities than those of benzyl substitution; the alkyl substituent on piperazine exhibited optimal activity. Among them, compound 1g showed the strongest cytotoxicity against MBA-MB-231 cells with an IC₅₀ value of 5.12 ± 0.11 μM. Mechanistic studies revealed that 1g induced apoptosis in MBA-MB-231 cells through down-regulating the protein expression of Bcl-2, up-regulating the protein expression of bax, and, meanwhile, activating the cleavage of caspase-3 and caspase-9. 1g caused S phase cell cycle arrest in MBA-MB-231 cells by reducing the protein expression of CDK2 and cyclin A2 and increasing the protein levels of p21.