The NLRP3 inflammasome plays a critical role in the innate immune response, and its excessive activation will cause pyroptotic cell death and be associated with the onset of inflammatory diseases. However, NLRP3 inflammasome targeting therapies are still to be implemented in the clinic setting. Here, we first isolated, purified and characterized a novel Vitenegu acid from V. negundo L. herb that specifically inhibits NLRP3 inflammasome activation, without affecting NLRC4 or AIM2 inflammasomes. Vitenegu acid blocks the oligomerization of NLRP3, thus inhibiting NLRP3 inflammasome assembly and activation. In vivo data show that Vitenegu acid exerts therapeutic effects on NLRP3 inflammasome-dependent inflammation. Taken together, our results suggest that Vitenegu acid is a candidate therapeutic agent for treating NLRP3 inflammasome related diseases.

A spiro ent-clerodane homodimer with a rare 6/6/6/6/6-fused pentacyclic scaffold, spiroarborin (1), together with four new monomeric analogues (2-5), were isolated from Callicarpa arborea. Their structures were elucidated by comprehensive spectroscopic data analysis, quantum-chemical calculations, and X-ray diffraction. A plausible biosynthetic pathway of 1 was proposed, and a biomimetic synthesis of its derivative was accomplished. Compound 1 showed a potent inhibitory effect by directly binding to the YEATS domain of the 11-19 leukemia (ENL) protein with an IC50 value of 7.3 μM. This gave a KD value of 5.0 μM, as recorded by a surface plasmon resonance binding assay.

•66 ent-clerodane diterpenoids, including 52 new compounds, were isolated from Callicarpa arborea.•Their bioactivity against pyroptosis were evaluated, and the typical α,β-unsaturated-γ-hemiacetal lactone ring was a key active segments from SAR analysis.•Compound 1 showed potent inhibitory activity against pyroptosis by blocking NLRP3 inflammasome activation.•Compound 1 treatment markedly reduced infiltration of CD11b+F4/80+ macrophages into lung and protected lung injury in LPS- induced septic mice.

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 Callicarpaarborea and 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 6-8 showed potent inhibitory effects against the NLRP3 inflammasome with IC50 values from 1.4 to 5.3 μM, and 2 significantly blocked NLRP3 inflammasome-induced pyroptosis by inhibiting Casp-1 activation and IL-1β secretion in J774A.1 cells.

LTR-retrotransposable elements are major components of diploid (Gossypium arboreum) and tetraploid (Gossypium hirsutum) cotton genomes that have undergone dramatic increases in copy number during the course of evolution. However, little is known about the biological functions of LTR-retrotransposable elements in cotton. Here, we show that a copia-like LTR-retrotransposable element has maintained considerable activity in both G. arboreum and G. hirsutum. We identified two functional domains of the retrotransposon and analyzed their expression levels in various cotton tissues, including leaves, ovules, and germinating seeds. ChIP-qPCR (chromatin immunoprecipitation followed by quantitative PCR), using a copia-specific antibody, established that copia-like proteins primarily bind to the first exons of several protein-coding genes in cotton cells. This finding suggests that retrotransposons play a novel, important role in regulating the transcriptional activities of protein-coding genes with various biological activities.

Fungal drug resistance is a major health threat, and reports of clinical resistance worldwide are becoming increasingly common. In a research program to discover new molecules to help overcome this problem, 14 new lanostane-type triterpenoids, gibbosicolids A-G (2-8) and gibbosic acids I-O (9-15), were isolated from the fruiting bodies of Ganoderma gibbosum, along with seven known triterpenoid derivatives. These compounds featured high levels of oxidation, epimerization, and γ-lactonization. Structures were elucidated by comprehensive spectroscopic analyses and HRMS data. Absolute configurations were assigned based on quantum chemical calculations, including calculated chemical shift with DP4+ analysis, coupling constants, and electronic circular dichroism (ECD) methods. Results show that the calculated NMR with DP4+ analysis could not reliably establish the overall spatial configuration of molecules possessing independent and free-rotational stereoclusters. All these compounds significantly increased the sensitivity of fluconazole (FLC)-resistant C. albicans to FLC. Compounds 2, 5, 9, 12, 16, 17, and 21 exhibited strong antifungal activity against FLC-resistant C. albicans when combined with FLC, with MIC50 values ranging from 3.8 to 8.8 μg/mL.

Phytochemical investigation of the leaves and twigs of Callicarpa cathayana led to the isolation of six new clerodane diterpenoids, cathayanalactones A-F (1-6), together with seven analogues (7-13). Their structures were established by extensive NMR analyses together with experimental and calculated ECD spectra analyses. Compounds 1, 2, 3, 7 and 11 showed inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.

Natural products (NPs) are a promising source of anti-inflammatory molecules for the development of drugs. Despite there being an abundance of reports of large numbers of NPs having bioactivity in preliminary cell-based assays of anti-inflammatory potential, their further optimization and exploration are limited by the lack of a comprehensive understanding of their effective scaffold structure or biological targets. To facilitate target-based studies of anti-inflammatory NPs, the details of 665 NPs reported to have anti-inflammatory activity were extracted from the literature and compiled into a data set we termed InflamNat. The physicochemical properties of the NPs were analyzed, and the distribution of their structures and scaffolds is presented. A compound-target network was constructed from data in the PubChem Bioassay database. The results demonstrated that, compared to natural anticancer compounds in the NPACT database, compounds from the InflamNat data set contained a comparable distribution of compound types but with a higher proportion satisfying Lipinski's rule. The all-atom structures and scaffold of the compounds were diverse and barely convergent, with flavonoids and triterpenoids being the groups with the greatest abundance. The biological targets of the InflamNat compounds were identified as belonging to a variety of protein families that had varied function. Seventy-two percent of InflamNat compounds involved in the network were identified as having more than one biological target, highlighting the potential for multitarget anti-inflammatory drug development. In conclusion, anti-inflammatory NPs provide a good library for the screening of target-based leads or fragment-based drug design. Thus, elucidation of their biological targets is fundamental for either a specific single-target or multitarget drug development strategy. Meanwhile, a large proportion of the chemical space of anti-inflammatory NPs is still unexplored, with novel active scaffolds remaining to be discovered.

Due to the economic value of natural textile fiber, cotton has attracted much research attention, which has led to the publication of two diploid genomes and two tetraploid genomes. These big data facilitate functional genomic study in cotton, and allow researchers to investigate cotton genome structure, gene expression, and protein function on the global scale using high-throughput methods. In this review, we summarized recent studies of cotton genomes. Population genomic analyses revealed the domestication history of cultivated upland cotton and the roles of transposable elements in cotton genome evolution. Alternative splicing of cotton transcriptomes was evaluated genome-widely. Several important gene families like MYC, NAC, Sus and GhPLDα1 were systematically identified and classified based on genetic structure and biological function. High-throughput proteomics also unraveled the key functional proteins correlated with fiber development. Functional genomic studies have provided unprecedented insights into global-scale methods for cotton research.