Longistylin A from Cajanus cajan (L.) Millsp. disturbs glycerophospholipid metabolism and cytokinin biosynthesis of Nocardia seriolae.

ETHNOPHARMACOLOGICAL RELEVANCE: Nocardiosis is an uncommon infectious disease that bears certain similarities to tuberculosis, with a continuous increase in its incidence and a poor prognosis. In traditional Chinese medicine, the leaves of Cajanus cajan (L.) Millsp. are employed to treat wounds, malaria, coughs, and abdominal pain. AIM OF THE STUDY: In this study, we investigated the effects and mechanisms of longistylin A (LGA), a natural stilbene isolated from C. cajan, as a potential antibiotic against nocardiosis. MATERIALS AND METHODS: LGA was isolated from the leaves of C. cajan and assessed using a minimum bactericidal concentration (MBC) determination against Nocardia seriolae. Multi-omics analysis encompassing genes, proteins, and metabolites was conducted to investigate the impact of LGA treatment on N. seriolae. Additionally, quantitative analysis of 40 cytokinins in N. seriolae mycelium was performed to assess the specific effects of LGA treatment on cytokinin levels. Cryo-scanning electron microscopy was utilized to examine morphological changes induced by LGA treatment, particularly in the presence of exogenous trans-zeatin-O-glucoside (tZOG). The therapeutic effect of LGA was investigated by feeding N. seriolae-infected largemouth bass. RESULTS: LGA exhibited significant efficacy against N. seriolae, with MBC value of 2.56 µg/mL. Multi-omics analysis revealed that LGA disrupted glycerophospholipid metabolism and hormone biosynthesis by notably reducing the expression of glycerol-3-phosphate dehydrogenase and calmodulin-like protein. Treatment with LGA markedly disrupted 12 distinct cytokinins in N. seriolae mycelium. Additionally, the addition of exogenous tZOG counteracted the inhibitory effects of LGA on filamentous growth, resulting in mycelial elongation and branching. Furthermore, LGA treatment improved the survival rate of largemouth bass infected with N. seriolae. CONCLUSIONS: We found for the first time that LGA from C. cajan exhibited significant efficacy against N. seriolae by interfering with glycerophospholipid metabolism and cytokinin biosynthesis.

Tung Tree (Vernicia fordii) Genome Provides A Resource for Understanding Genome Evolution and Improved Oil Production.

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Biosciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree genome is 1.12 Gb, with 28,422 predicted genes and over 73% repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites; 17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effects between transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.

Effectiveness and potential mechanisms of intralipid in treating unexplained recurrent spontaneous abortion.

AIM: Abnormal natural killer (NK) cell activity has been suggested to be a high-risk factor associated with unexplained recurrent spontaneous abortion (URSA). Intralipid, like immunoglobulin, is able to lower the activity of NK cells, which has been reported to be useful for improving URSA outcomes in pregnancy. This study aimed to determine whether intralipid could be used as an alternative treatment to intravenous immunoglobulin (IVIG) which is expensive and has many side-effects. METHODS: A prospective, randomized clinical trial was conducted from December 2010 to December 2012. Eligible participants were matched and sorted randomly into the intralipid and the IVIG group. The primary outcome was the rate of successful pregnancy. In addition, comparisons of peripheral NK cell activities were accessed by flow cytometry. Moreover, the effects of intralipid on trophoblasts were investigated using a Matrigel assay with the JEG-3 cell line. RESULTS: Seventy-six patients in the intralipid group and 78 in the IVIG group completed the trial. There were no statistically significant differences in successful pregnancy rates between the two groups (92.1 vs 88.2 %, P = 0.415). The reduced NK cell concentrations revealed the cytotoxic effects of the treatments in both groups. The invasive ability of JEG-3 cells was inhibited during co-culture with patient PBMCs. However, the inhibitory effect could be alleviated if the patient PBMCs were stimulated with intralipid. CONCLUSIONS: Intralipid can be used as an alternative treatment to IVIG for URSA, and its potential mechanism of action may occur by regulating NK cell function and promoting trophoblast invasion.

Pharmacokinetic study on the multi-constituents of Huangqin-Tang decoction in rats.

Using a validated high-performance liquid chromatographic (HPLC) method, the pharmacokinetics of multi-constituents in Huangqin-Tang decoction were simultaneously studied both in the compound prescription and in each single herb decoction. At different intervals (0, 1, 2, 4, 8, 12, 24, 36, 48 h) after oral administration of the Huangqin-Tang decoction or a single herb decoction at a dose of 10 g x kg(-1), the concentrations of the constituents and their metabolites: baicalin (BG), wogonoside (WG), oroxylin-A-glucuronide (OG), baicalein (B), wogonin (W), oroxylin-A (O), paeoniflorin (PF), paeonimetabolin-I (PM-I), liquiritin (LG), liquiritigenin (L), glycyrrhizic acid (GL) and glycyrrhetinic acid (GA), were detected in the rat plasma. A new metabolite-3,5,7,2',6'-penta hydroxy flavone (visidulin I, VD-I) was found in rat plasma after oral administration of Huangqin-Tang or a single herb Huangqin decoction, and the quality was identified by HPLC and LC/MS. The pharmacokinetic parameters of the constituents and metabolites in the compound prescription and single herb decoctions were compared. All concentration-time curves corresponded to the one-compartment model. The constituents of BG, WG, OG, VD-I and LG had higher C(max) and AUC(0-lim) in the compound prescription than in the single herb decoction, and WG had significant difference. The constituents of PF, W and O only had a higher AUC(0-lim) in the compound prescription, and O had a significant difference. It was concluded, in brief, that there were obvious differences in the pharmacokinetic parameters of most constituents (especially constituent WG) between the compound prescription and single herb decoction. The constituents in the compound prescription had delayed absorption and elimination, a longer residence time in the body, and higher C(max) and AUC(0-lim), than those in the single herb decoction. Therefore, they were more efficient and durable, making them promising to exerting pharmacological effects in vivo.

Metabolism of constituents in Huangqin-Tang, a prescription in traditional Chinese medicine, by human intestinal flora.

In the course of studies on the metabolism of active components of Huangqin-Tang by human intestinal flora (HIF), Huangqin-Tang and all individual herbs in the decoctions were incubated with a human fecal suspension separately. By using a high-performance liquid chromatographic (HPLC) method which was previously established in our laboratory, the metabolites in both the compound prescription and all the single herb decoctions were identified and determined both qualitatively and quantitatively. We found that the constituents of Huangqin-Tang, incluing baicalin (baicalein 7-glucuronide; BG), wogonoside (wogoninoglucuronide; WG), oroxylin-A-glucuronide (OG) from Scutellariae Radix, paeoniflorin (PF) from Paeoniae Radix, liquiritin (liquiritigenin 4'-O-glucoside; LG), isoliquirtin (isoliquiritigenin 4-glucoside; ILG) and glycyrrhizic acid (GL) from Glycyhhizea Radix, were converted to their metabolites baicalein (B), wogonin (W), oroxylin-A (O), paeonimetabolin-I (PM-I), liquiritigenin (L), isoliquiritigenin (IL) and glycyrrhetinic acid (GA) by HIF. The contents of the metabolites in Huangqin-Tang and in each single herb decoction increased significantly after incubation with intestinal flora. Comparing with single herb decoctions, the transformation of BG, WG, OG, LG and ILG in the compound prescription was promoted, however, that of PF and GL was inhibited. All the results suggested that the glycosides of many medicinal herbs could be converted to aglycones by HIF, and the metabolism of most glycosides was improved in the compound prescription.