Rapid determination of the relative configuration of diverse 8,4'-oxyneolignans by NMR analysis: Retrospective studies, improvement and structural revision.

The characteristic 1H NMR signals (H-7 and H2-9) are significant parameters that have been widely used to assess the relative configuration of H-7 and H-8 of 8,4'-oxyneolignans. However, many usual 8,4'-oxyneolignans cannot be accurately determined by existing NMR methods and no research considering their limitations was performed until now. In this study, the application scope of NMR methods was comprehensively studied and the ΔδH9a-H9b methods have been extended to solve the majority of configuration determination difficulties. The accuracy of extended NMR methods was verified by anisotropic NMR (RCSA measurements), NMR calculation and diverse statistical analysis (MAEΔΔδ, CP3 and DP4+). Furthermore, the theoretical conformational analysis was performed to investigate the inherent limitations of existing NMR methods. This study could provide a valuable reference for determining the relative configuration of H-7 and H-8 in 8,4'-oxyneolignans and the relative configuration of 23 recently reported 8,4'-oxyneolignan derivatives should be reassigned as well.

Insight into tetrahydrofuran lignans from Isatis indigotica fortune with neuroprotective and acetylcholinesterase inhibitor activity.

Nine tetrahydrofuran lignans, including three undescribed spiro-lignans, were isolated from Isatis indigotica Fortune (Brassicaceae). Extensive spectroscopic analyses achieved the structure elucidation of these tetrahydrofuran lignans, and quantum chemical calculation combined with the MAEΔΔδ parameter. Notably, isatispironeols A-B have a unique spiro[dienone-tetrahydrofuran] molecular core. These spiro[dienone-tetrahydrofuran] lignans showed comparable neuroprotective effects as the positive control in the H2O2-induced SH-SY5Y cells model. In addition, (-)-(7R,8S,1'R,7'R,8'R)-isatispironeol A possessed more significant AChE inhibitory activity, further interact sites were also predicted by the in silico assay.

Solanoids F - I: Terpenoids from Solanum lyratum with neuroprotective effects against H2O2-induced SH-SY5Y cell injuries.

Four new terpenoids, solanoids F - I (1-4), together with eleven known compounds (5-15), were isolated from the whole herb of Solanum lyratum. The chemical structures were characterized by spectroscopic techniques, and electronic circular dichroism (ECD) data analysis was adopted to confirm the absolute configurations of 1-4. Compounds 1-6, 8 and 12-15 exhibited neuroprotective effects against H2O2-induced oxidative damage of human SH-SY5Y cells. Additionally, this study also combined Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore the potential targets and signaling pathways of active terpenoids components in intervening Alzheimer's disease (AD).

The nature compound dehydrocrenatidine exerts potent antihepatocellular carcinoma by destroying mitochondrial complexes in vitro and in vivo.

Cumulative evidence indicates that mitochondria dysfunction plays an important role in tumour treatment. Given the limited efficacy and toxicity of current mitochondria-targeted drugs, research into effective mitochondria-targeted anticancer agents remains an irresistible general trend. In this study, it was found that dehydrocrenatidine (DEC), a ß-carbolin alkaloid isolated from Picrasma quassiodes, displays a promising growth inhibitory effect in vitro and in vivo by inducing apoptosis of hepatocellular carcinoma (HCC) cells. Mechanistically, we provided that the possible target of DEC against HCC cells was determined by isobaric labels for relative and absolute quantification assay and validated them using further experiments. The results suggested that DEC can target and regulate the function of mitochondrial complexes I, III and IV, affecting oxidative phosphorylation and ultimately leading to mitochondrial dysfunction to exert its anti-HCC effects. In addition, the combination of DEC and sorafenib showed a synergistic effect and was also associated with mitochondrial dysfunction. Importantly, DEC did not show significant toxicity in mice. This study provided a new insight into underlying mechanisms in DEC-treated HCC cells, suggesting that DEC might be a mitochondrial targeting lead compound.

Discovery of alkaloids from the leaves of Isatis indigotica Fortune with neuroprotective activity.

Seven alkaloids including five undescribed ones (1a/1b, 2, 3 and 5) were obtained from the leaves of Isatis indigotica Fortune. Their structures were established by extensive spectroscopic analyses. The absolute configurations of compounds 1a, 1b, 3 and 5 were determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Subsequently, the neuroprotective effects of all the isolates against H2O2-induced injury in SH-SY5Y cells were evaluated in vitro by MTT assay. Moreover, Annexin V-FITC/PI double staining was performed, while the activities of antioxidant enzymes (SOD, CAT and GSH-Px) for compounds 1a and 1b were measured.

A new dineolignan with anti-ß-amyloid aggregation activity from the fruits of crataegus pinnatifida bge.

A new dineolignan, crataeguslignan A (1), along with one known dineolignan (2) were isolated from the fruits of Crataegus pinnatifida Bge. Its chemical structure was identified by comprehensive spectroscopic analyses. All the isolated compounds were investigated with regard to their Aß1-42 inhibition activity. Among them, 1 displayed the most potent Aß1-42 inhibitory ability with the inhibition rate of 85.2% at the concentration of 20 µM.

[Association of age distribution with the expression of angiotensin-converting enzyme 2 in lung tissues in severe acute respiratory syndrome coronavirus 2 infection: reflections from the study of RAS pathway expression in mice].

OBJECTIVE: To study the expression of angiotensin-converting enzyme 2 (ACE2) and other key molecules of the RAS pathway in normal mice at different developmental stages, and to provide ideas for understanding the infection mechanism of coronavirus disease 2019 (COVID-19) as well as the diagnosis and treatment of children with COVID-19. METHODS: The mice at different developmental stages were enrolled, including fetal mice (embryonic days 14.5 and 18.5), neonatal mice (0, 3, 7, 14, and 21 days old), young mice (28 and 42 days old), and adult mice (84 days old). The lung tissues of all fetal mice from 4 pregnant mice were collected at each time point in the fetal group. Four mice were sampled in other age groups at each time point. Whole transcriptome resequencing was used to measure the mRNA expression of AGT, ACE, ACE2, Renin, Agtr1a, Agtr1b, Agtr2, and Mas1 in mouse lung tissue. RESULTS: The expression of ACE2 in the lungs showed changes from embryonic stage to adult stage. It increased gradually after birth, reached a peak on day 3 after birth, and reached a nadir on day 14 after birth (P<0.05). The expression of AGT reached a peak on days 0 and 7 after birth and reached a nadir on day 21 after birth (P<0.05). The expression of ACE increased rapidly after birth and reached a peak on day 21 after birth (P<0.05). Agtr1a expression reached a peak on day 21 after birth (P<0.05). Agtr2 expression gradually decreased to a low level after birth. Renin, Agtr1b, and Mas1 showed low expression in lung tissues at all developmental stages. CONCLUSIONS: At different developmental stages of mice, ACE2 has dynamic expression changes, with high expression in early neonatal and adult mice. The other key molecules of the RAS pathway have their own expression patterns. These suggest that the difference in clinical features between children and adults with COVID-19 might be associated with the different expression levels of ACE2 in the different stages, and further studies are needed for the mechanism.

Allogeneic hematopoietic stem cell transplantation for Crohn disease complicated with myelodysplastic syndrome: A case report.

RATIONALE: Myelodysplastic syndrome (MDS) can be complicated with Crohn disease (CD). Irritable bowel disease (IBD) associated with MDS has already been reported in the past; however, hematopoietic stem cell transplantation (HSCT) is rarely performed. Herein, we report a case of CD with MDS for HSCT. PATIENT CONCERNS: A 41-year-old man was hospitalized due to abdominal pain and intermittent fever for 40 days. Two years later, he was readmitted due to abdominal pain and diarrhea with fever for 10 days. DIAGNOSIS: Symptoms, laboratory examinations, and imaging findings of the patient were indicative of CD complicated with MDS. INTERVENTIONS: An allogeneic HSCT was performed. OUTCOMES: He died of severe lung infection 125 days post-transplantation. LESSONS: The number of cases of CD combined with MDS remains insufficient, and no consensus opinions are available to date. Hence, HSCT is a very potential treatment method. Additional experiences are needed to determine its effectiveness.

Four pairs of alkaloid enantiomers from Isatis indigotica Fortune Ex Land with neuroprotective effects against H2O2-induced SH-SY5Y cell injury.

In the current study, four pairs of new enantiomeric alkaloids (1a/1b-4a/4b) were obtained from the leaves of Isatis indigotica Fortune Ex Land. Their structures were elucidated through spectroscopic methods and quantum mechanical calculations. Biologically, all isolates were evaluated for their neuroprotective effects against H2O2-induced SH-SY5Y cell injury. As a result, 1a and 1b exhibited enantioselective neuroprotective effects, further Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 20.93% and 17.87%, respectively.

Alkaloid Enantiomers from Isatis tinctoria with Neuroprotective Effects against H2O2-Induced SH-SY5Y Cell Injury.

Six pairs of alkaloid enantiomers including 11 new alkaloids (1A: /1B: -5A: /5B, 6A: ) were isolated from the leaves of Isatis tinctoria. Their structures were established by extensive spectroscopic analyses. Enantiomers were separated successfully by chiral chromatographic column and the absolute configurations of all isolates were determined by comparison of experimental and calculated electronic circular dichroism spectra. The isolated alkaloids were evaluated for their neuroprotective activities against H2O2-induced cell injury in human neuroblastoma SH-SY5Y cells. The results showed that 5A/5B: and 6A/6B: exhibited potent neuroprotective activities at 50 µM compared with the H2O2-treated group.

Diverse metabolites from corn silk with anti-Aß1-42 aggregation activity.

Five pairs of enantiomeric compounds (1a/1b-5a/5b) including seven undescribed compounds (1a/1b-3a/3b, 4b) along with two known ones (. and .) have been isolated from corn silk (Stigma maydis). Racemic mixtures of these enantiomers were separated by HPLC with different types of chiral columns. Their structures were elucidated based on comprehensive spectroscopic analyses together with quantum chemical calculations of 13C NMR data and electronic circular dichroism (ECD) curves. All the isolates were evaluated for their inhibition ability of self-induced Aß1-42 aggregation. Among them, compounds 4a (88.36%), 4b (74.66%) and . (85.65%) showed stronger inhibitory activity than the positive control curcumin (61.90%). The different inhibition profiles of enantiomers 4a and 4b were explained by docking simulation studies.

Discovery of cycloneolignan enantiomers from Isatis indigotica Fortune with neuroprotective effects against MPP+-induced SH-SY5Y cell injury.

A pair of new cycloneolignan enantiomers (1a and 1b) were isolated from the leaves of Isatis indigotica Fortune. Their structures were elucidated by extensive spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, MS/MS analysis, together with theoretical electronic circular dichroism (ECD) calculations. Compounds 1a and 1b were then evaluated for their neuroprotective effects against MPP+-induced SH-SY5Y cell injury. As a result, compounds 1a (77.64%) and 1b (78.62%) exhibited moderate neuroprotective activity at the concentration of 12.5 µM compared with that of MPP+ treated group (62.00% at 1 mM) by MTT assay. Furthermore, Annexin V-FITC/PI analysis showed that apoptosis ratios of 1a and 1b were reduced to 10.99% and 9.31%, respectively.

Solitary nasopharynx metastasis from hepatocellular carcinoma after liver transplantation: A case report.

RATIONALE: Hepatocellular carcinoma (HCC) is the fifth most common cancer and third leading cause of cancer-related deaths worldwide. Nasopharyngeal metastasis of hepatocellular carcinoma is very rare. This is the first report of posttransplantation nasopharyngeal metastasis. PATIENT CONCERNS: A 45-year-old man with a history of hepatitis B related hepatocellular carcinoma (HCC) in the right segment of the liver received an orthotopic liver transplant. Two year after the transplantation, he suffered from severe headache, and head contrast enhanced CT scans did not show clues for brain or skull metastasis. Then he developed hoarseness and dysphagia. DIAGNOSIS: The nasopharyngeal cancer was confirmed to be metastatic tumor from liver histologically according to biopsy. INTERVENTIONS: This patient underwent radiotherapy (RT) of the metastatic nasopharyngeal tumor, and there was significant symptomatic relief. OUTCOMES: The patient died 3 months after nasopharyngeal metastasis was diagnosed. LESSONS: Recurrence of hepatocellular carcinoma with metastasis of nasopharyngeal carcinoma after liver transplantation is rare, but the prognosis is very poor. Close follow-up of patients should be paid attention to prevent the occurrence of such diseases.

Correction: Bioactive spiropyrrolizidine oxindole alkaloid enantiomers from Isatis indigotica fortune.

Correction for 'Bioactive spiropyrrolizidine oxindole alkaloid enantiomers from Isatis indigotica fortune' by Si-Fan Liu et al., Org. Biomol. Chem., 2018, 16, 9430-9439.

Seven new neuroprotective sesquineolignans isolated from the seeds of Crataegus pinnatifida.

The investigation of the ethanol extract of the seeds of Crataegus pinnatifida led to the isolation of seven new 8-O-4' type sesquineolignans crasesquineolignan A-G (1-7), along with a reported analogue, leptolepisol B (8). The chemical structures of these compounds were elucidated based on complex analysis of their MS, 1D and 2D NMR data. All the isolated compounds were tested for their neuroprotective effects against the damage of human neuroblastoma SH-SY5Y cells induced by H2O2, and most of them showed significant neuroprotective activity. Among them, compound 4 (77.58%) showed the best protective effect, even better than the positive control (69.26%) at 25 µM.

Alkaloids from Juglans Mandshurica maxim induce distinctive cell death in hepatocellular carcinoma cells.

The aim of this work was to further investigate the anticancer potential of Juglans mandshurica Maxim, including the separation of active constituents and their anti-proliferative effects with underlying mechanism of action. Five alkaloids (1-5) were isolated from the bark of J. mandshurica. Among them, 1 showed the highest cytotoxic activities against Hep3B and HepG2 cells with an IC50 values of 61.80 and 56.24 µM, respectively. Therefore, the cellular mechanism involved 1 was subsequently studied. Our results showed that 1 markedly caused apoptosis and autophagy, but without cell cycle arrest in HepG2 cells. Interestingly, only autophagic cell death was induced in 1-treated Hep3B cells. It is concluded that the isolated alkaloids exerted a certain anti-hepatoma potential, and our results may provide a basis for the further investigation of the alkaloids extracted from J. mandshurica.

A new coumarin from Juglans mandshurica Maxim induce apoptosis in hepatocarcinoma cells.

In this study, a new coumarin, juglansoside C (1) was isolated from the bark of Juglans mandshurica. Its chemical structure was identified by comprehensive spectroscopic analyses. The in vitro cytotoxicity assay showed that 1 exhibited moderate cytotoxicity against human hepatocellular carcinoma Hep3B cells with an IC50 value of 70.9 µM. Furthermore, Annexin V-FITC/PI staining assay indicated that 1 markedly induced apoptosis in Hep3B cells.

Bioactive spiropyrrolizidine oxindole alkaloid enantiomers from Isatis indigotica Fortune.

Four pairs of new spiropyrrolizidine oxindole enantiomers (1a/1b-4a/4b) were isolated from the leaves of Isatis indigotica Fortune. Their structures and absolute configurations were elucidated by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD) and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Notably, all the isolated spiropyrrolizidine oxindoles are reported as natural products for the first time. The biosynthetic pathway of these unique structures was proposed to be formed by cycloaddition reaction. In addition, all the compounds were evaluated for their inhibitory effects on ß-amyloid aggregation by ThT assay, and the optically pure compounds 1a/1b and 2a/2b exhibited better Aß1-42 aggregation inhibition potency (85.8% and 73.6%, 71.5% and 75.8%, respectively) at a concentration of 20 µM, compared with the positive control curcumin (57.0%). The difference of the inhibitory pattern caused by chirality was also explained by molecular docking studies.

Stereoisomeric guaiacylglycerol-ß-coniferyl aldehyde ether induces distinctive apoptosis by downregulation of MEK/ERK pathway in hepatocellular carcinoma cells.

Two 8-O-4'-type neolignan epimers erythro-guaiacylglycerol-ß-coniferyl aldehyde ether (1) and threo-guaiacylglycerol-ß-coniferyl aldehyde ether (2) were isolated from the stems of Picrasma quassioides. Further chiral separation gave two pairs of enantiomers 1a/1b and 2a/2b. The cytotoxicity assay against hepatocellular carcinoma Hep3B and HepG2 cells was evaluated by MTT assay. The results showed that 1b (IC50 = 45.56 µM) and 2b (IC50 = 39.02 µM) had more cytotoxic effect than its enantiomers 1a (IC50 = 82.66 µM) and 2a (IC50 = 67.97 µM) in Hep3B cells, respectively. Moreover, 1b and 2b could induce more apoptotic cells as well as higher reactive oxygen species (ROS) generation than 1a and 2a at 50 µM. In addition, a further study on the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways was investigated. The results revealed that all compounds had no significant effect on PI3K/AKT pathway, however, 1b and 2b attenuated the relative levels of p-MEK and p-ERK when compared with 1a and 2a. Taken together, the absolute configurations of guaiacylglycerol-ß-coniferyl aldehyde ether had an impact on the inhibitory effect on Hep3B cells. The inactivation of MEK/ERK signaling pathway might contribute to apoptosis induction and ROS generation in 1b- and 2b-treated cells.