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Callintegers A (1) and B (2), unprecedented clerodane norditerpenoids based on a novel carbon skeleton, were isolated from Callicarpa integerrima. Compounds 1and 2possess a novel 6/6/6-fused tricyclic ring system. Their structures and absolute configurations were determined by quantum chemical calculations, spectroscopic analysis, and single-crystal X-ray diffraction methods. Biological evaluation showed that compound 2inhibited IL-1β secretion in a dose-dependent manner with an IC50value of 5.5 ± 3.2 μM. Caspase-1 maturation and IL-1β secretion were also reduced, indicating that compound 2impaired NLRP3 inflammasome activation.

Eight new aspulvinone analogues, aspulvins A–H (1–8) and aspulvinones D, M, O, and R (9–12), were isolated from cultures of the endophytic fungus Cladosporiumsp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 10 μM. Notably, compounds 9, 10, and 12showed potential SARS-CoV-2 Mproinhibition with IC50values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 μM, respectively. For all compounds except 3and 4, the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC50values ranging from 0.7 to 7.4 μM. Compound 10showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1β maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues 9, 10, and 12could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.

A phytochemical study on the aerial parts of Leonurus japonicusled to the isolation and identification of 38 labdane diterpenoids, including 18 new (1, 2, 11, 12, 16–21, 24, 30–34, 37, 38) and 20 known (3–10, 13–15, 22, 23, 25–29, 35, 36) analogues. Their structures were elucidated based on physical data analysis, including 1D and 2D NMR, HRMS, UV, IR, and X-ray diffraction. The structure of the known compound 4was confirmed by single-crystal X-ray diffraction data. These compounds can be divided into furanolabdane (1–10), tetrahydrofuranolabdane (11–15), lactonelabdane (16–23), labdane (24–29), and seco-labdane (30–38) type diterpenoids. All compounds were screened by lipopolysaccharide (LPS)-induced nitric acid (NO) production in RAW264.7 cells to evaluate anti-inflammatory effects. Compounds 1, 5, 10–13, 16–19, 31–33, and 38inhibited NO production with IC50values lower than 50 μM, with compound 30being the most active, with an IC50value of 3.9 ± 1.7 μM. Further studies show that compound 30inhibits pro-inflammatory cytokine production and IKK α/β phosphorylation and restores the IκB expression levels in the NF-κB signaling pathway.

Callicarpins A–D (1–4), possessing an unprecedented A-homoent-clerodane scaffold with a bicyclo[5.4.0]undecane ring system, and callicarpins E–G (5–7), with 5/6-fused ent-clerodane diterpenoid skeletons, were isolated from Callicarpaarboreaand C. integerrim. Their structures were elucidated by comprehensive spectroscopic data, X-ray crystal diffraction, chemical derivatization, and electronic circular dichroism (ECD) data. Putative biosynthetic pathways for these callicarpins are proposed. Compounds 2, 3b, and 6–8showed potent inhibitory effects against the NLRP3 inflammasome with IC50values from 1.4 to 5.3 μM, and 2significantly blocked NLRP3 inflammasome-induced pyroptosis by inhibiting Casp-1 activation and IL-1β secretion in J774A.1 cells.

Species belonging to the genus Callicarpaare used traditionally in Chinese medicine for the treatment of inflammation, rheumatism, and pain. Investigation of the leaves and twigs of Callicarpa bodinieriresulted in the isolation of nine new abietane diterpenoids, bodinieric acids A–I (1–9), along with six known compounds (10–15). The structures of 1–9were elucidated on the basis of the interpretation of their HRESIMS and NMR data and by ECD calculations. To explore the potential therapeutic target of this plant for immune-mediated disease, the inhibitory activities of the isolates obtained were determined against 13 kinase enzymes. Eight compounds exhibited moderate inhibitory effects on spleen tyrosine kinase (SYK), and the IC50values of compounds 2and 6were 7.2 and 10.7 μM, respectively. In addition, a preliminary structure–activity relationship of this scaffold was analyzed with both molecular docking and a 3D-QSAR pharmacophore model.

Fourteen sesquiterpene and norsesquiterpene derivatives, comprising six different carbon skeletons, were isolated from Sanicula lamelligera. Saniculamoid A1 (1a) is an oxidation product of saniculamoid A (1), created by the transition of a formyl group to a carboxylic acid group after a period of storage in air. The known compounds 5–14were identified in Saniculaplants for the first time. The compounds were evaluated for their anti-HIV-1, cytostatic, and nitric-oxide-production-inhibiting activities using in vitro cellular assays. The results showed that 1,5-naphthalenediol inhibited nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells with an IC50value of 28.1 μM and was active toward five cancer cell lines with IC50values in the 31.1–41.6 μM range.

Investigation of whole plants of Euphorbia fischerianaafforded three new tigliane-diterpenoid glycosides, fischerosides A–C (1–3), together with 11 known diterpenoids. Fischerosides A–C (1–3) are the first tigliane-type diterpenoid glucosides. Their structures were determined by a combination of 1D and 2D NMR, MS, and acid hydrolysis. Inhibitory activity against HIV-1 was assessed for compounds 1–5. The new compound 3showed an EC50value of 0.02 μM and a therapeutic index (TI) of 17.50, while prostratin (4) and 12-deoxyphorbol-13,20-diacetate (5) showed significantly greater anti-HIV-1 activity.