Zedoary turmeric oil injection ameliorates lung inflammation via platelet factor 4 and regulates gut microbiota disorder in respiratory syncytial virus-infected young mice.

BACKGROUND: Respiratory syncytial virus (RSV)-induced lung inflammation is one of the main causes of hospitalization and easily causes disruption of intestinal homeostasis in infants, thereby resulting in a negative impact on their development. However, the current clinical drugs are not satisfactory. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM), has been used for clinical management of inflammatory diseases. However, its in vivo efficacy against RSV-induced lung inflammation and the underlying mechanism remain unclear. PURPOSE: The present study was designed to confirm the in vivo efficacy of ZTOI against lung inflammation and intestinal disorders in RSV-infected young mice and to explore the potential mechanism. STUDY DESIGN AND METHODS: Lung inflammation was induced by RSV, and cytokine antibody arrays were used to clarify the effectiveness of ZTOI in RSV pneumonia. Subsequently, key therapeutic targets of ZTOI against RSV pneumonia were identified through multi-factor detection and further confirmed. The potential therapeutic material basis of ZTOI in target tissues was determined by non-target mass spectrometry. After confirming that the pharmacological substances of ZTOI can reach the intestine, we used 16S rRNA-sequencing technology to study the effect of ZTOI on the intestinal bacteria. RESULTS: In the RSV-induced mouse lung inflammation model, ZTOI significantly reduced the levels of serum myeloperoxidase, serum amyloid A, C-reactive protein, and thymic stromal lymphoprotein; inhibited the mRNA expression of IL-10 and IL-6; and decreased pathological changes in the lungs. Immunofluorescence and qPCR experiments showed that ZTOI reduced RSV load in the lungs. According to cytokine antibody arrays, platelet factor 4 (PF4), a weak chemotactic factor mainly synthesized by megakaryocytes, showed a concentration-dependent change in lung tissues affected by ZTOI, which could be the key target for ZTOI to exert anti-inflammatory effects. Additionally, sesquiterpenes were enriched in the lungs and intestines, thereby exerting anti-inflammatory and regulatory effects on gut microbiota. CONCLUSION: ZTOI can protect from lung inflammation via PF4 and regulate gut microbiota disorder in RSV-infected young mice by sesquiterpenes, which provides reference for its clinical application in RSV-induced lung diseases.

PepPre: Promote Peptide Identification Using Accurate and Comprehensive Precursors.

Accurate and comprehensive peptide precursor ions are crucial to tandem mass-spectrometry-based peptide identification. An identification engine can derive great advantages from the search space reduction enabled by credible and detailed precursors. Furthermore, by considering multiple precursors per spectrum, both the number of identifications and the spectrum explainability can be substantially improved. Here, we introduce PepPre, which detects precursors by decomposing peaks into multiple isotope clusters using linear programming methods. The detected precursors are scored and ranked, and the high-scoring ones are used for subsequent peptide identification. PepPre is evaluated both on regular and cross-linked peptide data sets and compared with 11 methods. The experimental results show that PepPre achieves a remarkable increase of 203% in PSM and 68% in peptide identifications compared to instrument software for regular peptides and 99% in PSM and 27% in peptide pair identifications for cross-linked peptides, surpassing the performance of all other evaluated methods. In addition to the increased identification numbers, further credibility evaluations evidence the reliability of the identified results. Moreover, by widening the isolation window of data acquisition from 2 to 8 Th, with PepPre, an engine is able to identify at least 64% more PSMs, thereby demonstrating the potential advantages of wide-window data acquisition. PepPre is open-source and available at http://peppre.ctarn.io.

Multiple anti-inflammatory mechanisms of Zedoary Turmeric Oil Injection against lipopolysaccharides-induced acute lung injury in rats elucidated by network pharmacology combined with transcriptomics.

BACKGROUND: Prospects for the drug treatment of acute lung injury (ALI) is unpromising. Managing inflammation can prevent ALI from progressing and minimize further deterioration. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM) that has been used against ALI, has shown significant anti-inflammatory effects. However, the mechanisms underlying these effects remain unclear. PURPOSE: Elucidate the anti-inflammatory mechanism by which ZTOI acts against ALI in rats using an ingredients-targets-pathways (I-T-P) interaction network. STUDY DESIGN AND METHODS: The key ingredients of ZTOI were characterized using UPLC-MS/MS combined with literature mining. The target profiles of each ingredient were established using drug-target databases. The anti-inflammatory activity of ZTOI against lipopolysaccharides (LPS)-induced rat ALI was validated using histopathology and inflammatory factor assessments. The therapeutic targets of ZTOI were screened by integrating transcriptomic results of lung tissues with protein-protein interaction (PPI) expansion. Using KEGG pathway enrichment, an I-T-P network was established to determine the essential interactions among ingredients, targets, and pathways of ZTOI against lung inflammation in ALI. Molecular docking and immunofluorescence staining were utilized to confirm the accuracy of the I-T-P network. RESULTS: A total of 11 sesquiterpenes, whose target profiles may characterize the potential function of ZTOI, were identified as key ingredients. In the ALI rat model, ZTOI can alleviate lung inflammation by decreasing the levels of C-reactive protein, interleukin-6, interleukin-1ß, and tumor necrosis factor α both in serum and lung tissues. Based on our biological samples, transcriptomics, PPI network expansion, and KEGG pathway enrichment, 11 ingredients, 174 targets, and 8 signaling pathways were linked in the I-T-P networks. From these results, ZTOI could be inferred to exert multiple anti-inflammatory effects against ALI through Toll-like receptor, NF-kappa B, RIG-I-like receptor, TNF, NOD-like receptor, IL-17, MAPK, and the Toll and Imd signaling pathways. In addition, two significantly regulated targets in the transcriptome, Usp18 and Map3k7, could be the essential anti-inflammatory targets of ZTOI. CONCLUSION: By integrating network pharmacology with ingredient identification and transcriptomics, we show the multiple anti-inflammatory mechanisms by which ZTOI acts against ALI on an I-T-P level. This work also provides a methodological reference for related research into TCM.

Seco and Nor-seco Isodhilarane-Type Meroterpenoids from Penicillium purpurogenum and the Configuration Revisions of Related Compounds.

Seco and nor-seco isodhilarane-type meroterpenoids (SIMs and NSIMs) are mainly found in Penicillium fungi and have been characterized by highly congested polycyclic skeletons and a broad range of bioactivities. However, the literature reports inconsistent configuration assignments for some SIMs and NSIMs, due to their complex polycyclic systems and multichiral centers. Herein, we described eight SIMs and NSIMs isolated from the EtOAc extract of Penicillium purpurogenum, which led to the configuration revisions of purpurogenolide C (1a), berkeleyacetal B (2a), chrysogenolide F (3a), and berkeleyacetal C (4a) as compounds 1-4, respectively. Furthermore, extensive re-evaluation of the experimental and computational 13C NMR chemical shifts of the reported 39 SIMs and NSIMs provided an empirical approach for determining the C-9 relative configuration, according to the 13C NMR chemical shifts of C-9, which contributed to the configuration revisions of another three SIMs (5a and 6a) and NSIMs (7a), denoted as compounds 5-7, respectively. Biological assays indicated that compound 3 exhibited cytotoxic activity against HepG2 and A549 cell lines with IC50 values of 5.58 and 6.80 µM, respectively. Compounds 2-4, 8, 9, and 32 showed moderate hepatoprotective activity at 10 µM in the APAP-induced HepG2 cell injury model.

Three new polyoxygenated bergamotanes from the endophytic fungus Penicillium purpurogenum IMM 003 and their inhibitory activity against pancreatic lipase.

Purpurolides D-F (1-3), three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system, were isolated from the endophytic fungus Penicillium purpurogenum IMM 003. Their structures were unambiguously elucidated based on extensive spectroscopic data analyses, 13C NMR chemical shifts calculations coupled with the DP4+ probability method, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 1-3 showed significant inhibitory activity against pancreatic lipase (PL). The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.

Structures and Biological Evaluation of Monoterpenoid Glycosides from the Roots of Paeonia lactiflora.

Fractionation of an aqueous extract of the air-dried roots of a traditional Chinese medicinal plant, Paeonia lactiflora, yielded the new monoterpenoid glycosides 1-10. Their structures were assigned via spectroscopic techniques, and the absolute configurations of 1, 4-6, and 8 were verified via chemical methods, specific rotation, and electronic circular dichroism data. Compounds 1-4 are rare compared to the reported cage-like paeoniflorin derivatives; that is, they comprised two monoterpenoidal moieties. In the in vitro assay, compounds 5, 8, and 9 showed weak inhibitions against lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages, with IC50 values of 64.8, 60.1, and 97.5 µM, respectively.

Polyketides from the fungus Penicillium decumbens.

Two new polyketides, 3,11-dihydroxy-6,8-dimethyldodecanoic acid (1) and trichopyrone B (2), together with two known polyketides, sorbicillin (3) and penicillone A (4), have been isolated from the cultures broth of the fungus Penicillium decumbens. Their structures were elucidated by extensive spectroscopic analysis. All isolated compounds were evaluated for their antibacterial and cytotoxic activities. Of these, compound 3 showed antifungal activity toward Candida albicans Y0109 with a MIC value of 50 µM. Moreover, compounds 3 and 4 exhibited selective cytotoxicity against the human hepatocellular carcinoma (QGY-7703) cell line with the IC50 values of 32.5 and 22.8 µM, respectively.

Two new terpenoid ester glycosides from the twigs of Litsea cubeba.

A new sesquiterpenoid ester glycoside (1) and a new monoterpenoid ester glycoside (2) have been isolated from an ethanol extract of the twigs of Litsea cubeba. Their structures were elucidated by extensive 1D- and 2D-NMR experiments, and the absolute configurations were determined by chemical methods, specific rotation, and a combination of experimental and theoretically calculated electronic circular dichroism spectra. Compound 1 exhibited selective cytotoxicity against A549 and HCT-8 cell lines with the IC50 values of 8.9 and 9.6 µM, respectively.

A new cytotoxic 12-membered macrolactone from the endophytic fungus Exserohilum rostratum LPC-001.

A new oxacyclododecindione-type macrolactone, (13R,14S,15R)-13-hydroxy-14-deoxyoxacyclododecindione (1), has been obtained from the solid cultures of the fungus Exserohilum rostratum, a fungal strain endophytic in Gymnadenia conopsea. Its structure, including the absolute configuration, was extensively established by 1D and 2D NMR data, the modified Mosher method, and a combination of experimental and theoretically calculated electronic circular dichroism (ECD) spectra. Compound 1 showed weak selective cytotoxicity against the A549 lung cell line with an IC50 value of 9.2 µM.

[A new styrene dimer derivative from Litsea greenmaniana].

A new styrene dimer derivative has been isolated from the branch of Litsea greenmaniana by column chromatography over silica gel and Sephadex LH-20, as well as semi-preparative HPLC. Its structure was identified by spectroscopic data analysis (MS, UV, IR, 1D and 2D NMR) as (E)-2,4-bis(p-hydroxyphenyl)-2-butenol, named as listeanol. At a concentration of 1×10-5 mol•L⁻¹, compound 1 was inactive in the assays, including cytotoxicity against human tumor cell lines (HCT-8, Bel-7402, BGC-823, A549 and A2780), antioxidant activity in Fe²âº-cystine-induced rat liver microsomal lipid peroxidation, neuroprotective activity against serum deprivation or glutamate induced neurotoxicity in cultures of PC12 cells, and the inhibitory activity against protein tyrosine phosphatase 1B (PTP1B).

Bioactive Glycosides from the Twigs of Litsea cubeba.

The air-dried twigs of Litsea cubeba, a traditional Chinese medicinal tree, afforded 10 new aromatic glycosides (1-10) and 26 known analogues. Their structures were assigned by extensive 1D and 2D NMR experiments, and the absolute configurations were resolved by chemical methods, electronic circular dichroism, specific rotation, and X-ray crystallographic analysis. Compound 4 is the first example of a naturally occurring homoneolignan glucoside. Compounds 4, 6-8, and the known neolignan glucosides (11, 12, and 14) at respective 10 µM concentrations were found to reduce acetaminophen-induced HepG2 cell injury with 30.5-46.0% inhibitions. Furthermore, compounds 12 and 15 demonstrated moderate inhibitory activities against HDAC1, with IC50 values of 3.6 and 4.6 µM, respectively.