Sucrosephenylpropanoid esters and isoflavonoids isolated from Belamcanda chinensis roots and their potential anti-osteoclastogenic activity.

Repeated chromatography of the CH2Cl2 and EtOAc soluble fractions from the methanol extract of Belamcanda chinensis root yielded six new sucrosephenylpropanoid esters (1-6) and twenty-one known compounds (7-27). The structures of 1-6 were elucidated using diverse nuclear magnetic resonance (NMR) techniques and high-resolution mass spectrometry (HRMS) data analysis, together with chemical methods. All the twenty-seven isolated compounds were evaluated for their anti-osteoclastogenic activities. Preliminary screening results revealed that compounds 1 and 19 exhibited strong effects against RANKL-induced osteoclast formation in RAW264.7 cells. In addition, the treatment of mouse bone marrow macrophages (BMMs) with compounds 1 and 19 significantly decreased RANKL-induced TRAP-positive multinucleated osteoclast formation in a concentration-dependent manner without affecting cell viability. Further bioassay investigation showed that compounds 1 and 19 inhibited the expression of some osteoclast-specific marker genes and the transcription factor nuclear factor of activated T cells cytoplasmic 1 (NFATc1) in response to RANKL. To the best of our knowledge, this is the first investigation of anti-osteoclastogenic activity for compounds isolated from B. chinensis.

Model of implementing proficiency testing in Vietnam, a developing country.

Backgrounds and aims: The aim of this study is to provide a good approach for a quantitative EQA scheme assigned value with limited resources. Materials and methods: Twelve lyophilized EQA items were distributed to participants in 2021 from North to Southeast Vietnam to measure the concentration of nine parameters, including glucose, urea, creatinine, cholesterol, triglyceride, uric acid, AST, ALT, and GGT. The consensus value of the expert group and all participants were calculated and statistically compared to choose the most appropriate consensus value. Results: Fifty-nine laboratories attended the EQA scheme, including an expert group using automatic biochemistry analyzers (AAs) and all participants with auto and semi-auto biochemistry (SAA) analyzers. Consensus values of six per nine parameters were different between the two groups for at least two EQA items, including glucose, creatinine, cholesterol, uric acid, AST, and ALT. The coefficients of variation of glucose, urea, creatinine, triglycerides, uric acid, and GGT in the expert group were significantly lower than those in all the participants. Conclusion: Using the consensus values of expert groups as the assigned values of the EQA program is a relevant strategy to increase testing quality in developing countries with limited resources, such as Vietnam.

Effect of body mass index on N-terminal pro-brain natriuretic peptide values in patients with heart failure.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker used for the diagnosis of heart failure. There is a relationship between NT-proBNP levels and body mass index (BMI). The study aimed to explore the impact of BMI on NT-proBNP concentrations and to examine whether other factors independent of or combined with BMI affect NT-proBNP values in patients with heart failure. RESULTS: A total of 293 participants were recruited. The mean age was 68.9 ± 13.2 years, males accounted for 46.4% of the total cohort, the mean BMI was 23.1 ± 4.0 kg/m2, and the median NT-proBNP level was 3776 (1672-8806) pg/ml. There was an inverse relationship between BMI and log NT-proBNP (r = - 0.29; p < 0.001, Spearman correlation). Each standard deviation increase in BMI (4 kg/m2) was associated with a 7% decrease in NT-proBNP values in the total cohort. The independent inverse determinants of NT-proBNP other than BMI were male gender and eGFR, while the variables directly correlated to NT-proBNP were LVEF ≤ 40% and NYHA class III-IV heart failure. CONCLUSIONS: There is an inverse association between BMI and NT-proBNP levels. However, the correlation is weak, and there are other variables that have a significant impact on the NT-proBNP values as well. The NT-proBNP levels are still valuable in the diagnosis of heart failure regardless of BMI status.

1,5-Anhydro-d-glucitol derivative and galloylated flavonoids isolated from the leaves of Acer ginnala Maxim. as dual inhibitors of PTP1B and α-glucosidase enzymes: In vitro and in silico studies.

Four undescribed compounds (two 1,5-anhydro-d-glucitol derivatives and two galloyl derivatives) and fourteen known compounds were isolated and structurally identified from leaves of Acer ginnala Maxim. (Amur maple). Structures and absolute configurations of the four undescribed compounds were determined using extensive analysis of NMR spectroscopic, HRESI-MS, modified Mosher ester method, and comparison with spectroscopic data of known compounds. Bioactivity evaluation revealed that the isolated 1,5-anhydro-d-glucitol derivative, galloylated flavonol rhamnosides, and galloylated flavanols had inhibitory effects on both protein tyrosine phosphatase-1B (PTP1B, IC50 values ranging of 3.46-12.65 µM) and α-glucosidase (IC50 values ranging of 0.88-6.06 µM) in comparison with a positive control for PTP1B (ursolic acid, IC50 = 5.10 µM) or α-glucosidase (acarbose, IC50 = 141.62 µM). A combination of enzyme kinetic analysis and molecular docking provided additional evidence in favor of their inhibitory activities and mechanism. These data demonstrate that A. ginnala Maxim. together with its constituents are promising sources of potent candidates for developing novel anti-diabetic medications.

Structures and antiosteoclastogenic activity of compounds isolated from edible lotus (Nelumbo nucifera Gaertn.) leaves and stems.

One new 1,4-bis-phenyl-1,4-butanedione glycoside (14), one new eudesmane-type sesquiterpenoid (16), and 16 known compounds were isolated from the leaves and stems of Nelumbo nucifera Gaertn. The structures of the isolated compounds were elucidated by interpretation of their 1D and 2D NMR spectroscopic and HRESIMS data. Time-dependent density functional theory calculations and Electronic Circular Dichroism (ECD) spectroscopy was used to determine absolute configurations of the new eudesmane-type sesquiterpenoid (16). All the isolated compounds were examined for their antiosteoclastogenic activity. Preliminarily results of the TRAP staining on RAW 264.7 cells indicated that compounds 1 and 11 possess potential inhibitory effects on RANKL-induced osteoclast formation. Further bioassay investigation was carried out to reveal that compounds 1 and 11 suppressed RANKL-induced osteoclast formation in a concentration-dependent manner with the inhibition up to 55% and 78% at the concentration of 10 µM, respectively. In addition, the structure-activity relationship analysis showed that the 1,3-dioxole substitute and the double bond at C-6a/C-7 in the aporphine skeleton may be responsible for the antiosteoclastogenic activity. The findings provided valuable insights for the discovery and structural modification of aporphine alkaloids as the antiosteoclastogenic lead compounds.

PTP1B and α-glucosidase inhibitory activities of the chemical constituents from Hedera rhombea fruits: Kinetic analysis and molecular docking simulation.

In this study, we present the first investigation of Hedera rhombea Bean fruit, which led to the isolation of six undescribed compounds including two megastigmane glucosides, two rare 1,4-dioxane neolignanes, and two quinic acid derivatives, together with 26 known compounds. Their structures and absolute configurations were elucidated by extensive analysis of NMR spectroscopic data, HRMS, and ECD calculations. This is the first report on the isolation of methyl 3-O-caffeoyl-5-O-p-coumaroylquinate from a natural source. Among the isolated compounds, falcarindiol and caffeoyltryptophan showed significant PTP1B inhibition with IC50 values of 7.32 and 16.99 µM, respectively, compared to those of the positive controls [sodium orthovanadate (IC50 = 17.96 µM) and ursolic acid (IC50 = 4.53 µM)]. These two compounds along with several other compounds displayed significant α-glucosidase inhibitions with IC50 values ranging from 12.88 to 91.89 µM, stronger than that of the positive control (acarbose, IC50 = 298.07 µM). Enzyme kinetic analysis indicated that caffeoyltryptophan and falcarindiol displayed competitive and mixed-type PTP1B inhibition, respectively, whereas the α-glucosidase inhibition type was mixed-type for caffeoyltryptophan and uncompetitive (rarely reported for a-glucosidase inhibitors) for falcarindiol. In addition, molecular docking results showed that these active compounds exhibited good binding affinities toward both PTP1B and α-glucosidase with negative binding energies. The results of the present study demonstrate that these active compounds might be beneficial in the treatment of type 2 diabetes.

Anti-osteoclastogenic Effects of Indole Alkaloids Isolated from Barley (Hordeum vulgare Var. Hexastichon) Grass.

As part of our continuous program to identify new potential candidates for controlling osteolytic bone diseases from natural products, the alkaloid fraction of barley (Hordeum vulgare var. hexastichon) grass (HVA) significantly inhibited RANKL-induced osteoclast formation and protected mice from LPS-induced bone loss. A phytochemical investigation of HVA afforded nine indole alkaloids, including one new compound [hordeumin A (1)] and eight known analogues (2-9). Of them, four (1, 2, 4, and 5) were anti-osteoclastogenic compounds. Of these four, compound 5 significantly suppressed RANKL-induced osteoclast formation, actin ring formation, and bone resorption in a concentration-dependent manner. It also suppressed the RANKL-induced NF-κB and MAPK signaling pathways and the activation of c-Fos and NFATc1. Compound 5 also reduced the expression levels of osteoclast-specific marker genes, including TRAP, CtsK, DC-STAMP, OSCAR, and MMP9. Our findings suggest that HVA and its alkaloid constituents could be valuable candidates for the prevention and treatment of osteolytic bone diseases.

Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children.

The evolution of influenza viruses is fundamentally shaped by within-host processes. However, the within-host evolutionary dynamics of influenza viruses remain incompletely understood, in part because most studies have focused on infections in healthy adults based on single timepoint data. Here, we analyzed the within-host evolution of 82 longitudinally sampled individuals, mostly young children, infected with A/H1N1pdm09 or A/H3N2 viruses between 2007 and 2009. For A/H1N1pdm09 infections during the 2009 pandemic, nonsynonymous minority variants were more prevalent than synonymous ones. For A/H3N2 viruses in young children, early infection was dominated by purifying selection. As these infections progressed, nonsynonymous variants typically increased in frequency even when within-host virus titers decreased. Unlike the short-lived infections of adults where de novo within-host variants are rare, longer infections in young children allow for the maintenance of virus diversity via mutation-selection balance creating potentially important opportunities for within-host virus evolution.

Structural characterization of prenylated compounds from Broussonetia kazinoki and their antiosteoclastogenic activity.

An undescribed 1,3-diphenylpropane derivative, kazinol V and six undescribed prenylated flavonoids, broussonols F-H and broussonols K-M were isolated from the roots of Broussonetia kazinoki Siebold, together with 12 known compounds. This is the first report of the isolation and structure determination of broussonol I from a natural source. The chemical structure of the undescribed compounds was determined using conventional NMR and HRMS data. Absolute configurations were assigned using time-dependent density functional theory calculations and Electronic Circular Dichroism (ECD) spectroscopy. The isolated compounds were screened for their effects on RANKL-induced osteoclast formation using RAW264.7 cells. Among them, broussonols F, G, and K showed strong, dose-dependent antiosteoclastogenic activities. Broussonol K exhibited the most potent inhibitory activity and possessed bone resorption suppressive activity.

Garcinoxanthones SV, new xanthone derivatives from the pericarps of Garcinia mangostana together with their cytotoxic and antioxidant activities.

Xanthones (9H-xanthene-9-ones) are considered to be very promising compounds due to a variety of interesting biological and pharmacological activities. In this study, column chromatography of the methanol extract of the Garcinia mangostana L. pericarps resulted in the isolation of four new xanthones (garcinoxanthones SV, 1-4) and five known analogs including garcinone E (5), 11-hydroxy-1-isomangostin (6) mangostenone E (7), 1,3,6,7-tetrahydroxyxanthone (8), and α-mangostin (9). The structures of the new compounds were elucidated by NMR, HRESIMS, and ECD spectra. Compound 8 (1,3,6,7-tetrahydroxyxanthone) was found from the G. mangostana pericarps for the first time. All the isolated compounds (1-8) were evaluated for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and cytotoxicity in vitro against three human cancer cell lines including SK-LU-1, MCF7, and HT-29 cell lines. Compounds 3, 5, and 8 exhibited significant DPPH scavenging capacity with IC50 values of 68.55, 63.05, and 28.45 µM, respectively, in comparison with ascorbic acid (IC50 = 48.03 µM). Compounds 5 and 8 showed moderate cytotoxic effects against the three human cancer cell lines with IC50 value ranges of 19.86-27.38 µM.

Albanol B from Mulberries Exerts Anti-Cancer Effect through Mitochondria ROS Production in Lung Cancer Cells and Suppresses In Vivo Tumor Growth.

Albanol B (ABN-B), an arylbenzofuran derivative isolated from mulberries, has been shown to have anti-Alzheimer's disease, anti-bacterial and antioxidant activities. The aim of this study was to investigate the anti-cancer effect of this compound against lung cancer cells. The results show that ABN-B inhibited the proliferation of four human lung cancer cell lines (A549, BZR, H1975, and H226) and induced apoptosis, based on the cleavage of caspase-7 and PARP (poly (ADP-ribose) polymerase), as well as the downregulation of Bcl-2. ABN-B also induced cell cycle arrest at G2/M by down-regulating the expression of CKD1 (cyclin-dependent kinase 1) and cyclin B1, but up-regulating p21 (cyclin-dependent kinase inhibitor 1) expression. Notably, ABN-B increased the production of mitochondrial reactive oxygen species (ROS); however, treatment with mito-TEMPO (a specific mitochondrial antioxidant) blocked ABN-B-induced cell cycle arrest at G2/M and apoptosis, as well as the up-regulation of p21 and down-regulation of CDK1 and cyclin B1 induced by ABN-B. At the molecular level, ABN-B-induced mitochondrial ROS production increased the phosphorylation levels of AKT (protein kinase B) and ERK1/2 (extracellular signal-regulated kinase 1/2), while the inhibition of these kinases blocked the ABN-B-induced up-regulation of p21 and down-regulation of CDK1 and cyclin B1. Moreover, ABN-B significantly suppressed tumor growth in Ex-3LL (Lewis lung carcinoma) tumor-bearing mice. Taken together, these results suggest that ABN-B can exert an anti-cancer effect by inducing apoptosis and cell cycle arrest at G2/M through mitochondrial ROS production in lung cancer cells.

Phytochemical and pharmacological properties of Myristica fragrans Houtt.: an updated review.

Myristica fragrans Houtt. (Myristicaceae), an aromatic evergreen tree, is well known as a commercial source of mace (aril) and nutmeg (seed), which have long been widely used as spices in the culinary field. In addition, various parts of M. fragrans have been used in folk medicine for treating several diseases. Since its extensive uses in the culinary sector and folk medicine, M. fragrans has long attracted a great deal of attention from pharmacologists and chemists. Numerous studies have indicated that M. fragrans contains diverse phytochemicals such as lignans, neolignans, diphenylalkanes, phenylpropanoids, and terpenoids, which exhibit many of pharmacological activities. Among them, macelignan (1), meso-dihydroguaiaretic acid (2), myristicin (111), and malabaricone C (Mal C, 104) are the most active compounds. The aim of this review is to comprehensively summarize the phytochemical and pharmacological properties of M. fragrans that have reported to date.

Inhibition of PTP1B by farnesylated 2-arylbenzofurans isolated from Morus alba root bark: unraveling the mechanism of inhibition based on in vitro and in silico studies.

Among the 2-arylbenzofuran derivatives isolated from Morus alba, the farnesylated 2-arylbenzofuran is a rarer constituent. The derivative has been reported to exert anti-obesity effect; however, its inhibitory effect on protein tyrosine phosphatase 1B (PTP1B) has not been investigated. In the previous study, the presence of the farnesyl group in the structure of 2-arylbenzofurans was found to have positive influences on their pancreatic lipase inhibitory activity. In the present study, we have confirmed the authenticity of the notation based on the PTP1B inhibitory activity of farnesylated 2-arylbenzofurans. Specifically, two farnesylated 2-arylbenzofurans [morusalfurans B (2) and C (3)] showed strong inhibitory effects on PTP1B with IC50 values of 8.92 and 7.26 µM, respectively, which was significantly higher than that of the positive controls [sodium orthovanadate (IC50 = 15.10 µM) and ursolic acid (IC50 = 11.34 µM)]. Besides, two 2-arylbenzofurans [morusalfurans A (1) and F (6)], one flavonoid [morusalnol B (9)], and one geranylated stilbene [morusibene A (11)] exhibited PTP1B inhibition with IC50 values ranging from 11.02 to 26.56 µM. Kinetic studies revealed compounds 2, 3, 6, and 11 as mixed type PTP1B inhibitors, while 1 and 9 are known as noncompetitive. Molecular docking simulations demonstrated that these active compounds can bind with the respective catalytic or/and allosteric sites of PTP1B with negative binding energies and the results are in accordance with that of the kinetic studies. To the best of our knowledge, this is the first time, the PTP1B inhibitory activity of eleven compounds (1-11), as well as the mechanism of action underlying the effects on PTP1B enzyme of the active compounds, were investigated. In vitro and in silico results suggest that the farnesylated 2-arylbenzofurans from M. alba may potentially be utilized as an effective treatment therapy for type 2 diabetes mellitus and its associated complications.

A Diketopiperazine, Cyclo-(L-Pro-L-Ile), Derived From Bacillus thuringiensis JCK-1233 Controls Pine Wilt Disease by Elicitation of Moderate Hypersensitive Reaction.

Pine wilt disease (PWD) caused by the pine wood nematode (PWN) Bursaphelenchus xylophilus is one of the devastating diseases affecting pine forests worldwide. Although effective control measurements are still missing, induction of resistance could represent a possible eco-friendly alternative. In this study, induced resistance-based in vitro and in vivo screening tests were carried out for selection of bacteria with the ability to suppress PWD. Out of 504 isolated bacteria, Bacillus thuringiensis JCK-1233 was selected for its ability to boost pathogenesis-related 1 (PR1) gene expression, a marker of systemic acquired resistance. Moreover, treatment of pine seedlings with B. thuringiensis JCK-1233 resulted in increased expression of other defense-related genes, and significantly inhibited PWD development under greenhouse conditions. However, B. thuringiensis JCK-1233 showed no direct nematicidal activity against B. xylophilus. To identify the effective compound responsible for the induction of resistance in B. thuringiensis JCK-1233, several diketopiperazines (DPKs) including cyclo-(D-Pro-L-Val), cyclo-(L-Pro-L-Ile), cyclo-(L-Pro-L-Phe), and cyclo-(L-Leu-L-Val) were isolated and tested. Foliar treatment of pine seedlings with Cyclo-(L-Pro-L-Ile) resulted in suppression of PWD severity and increased the expression of defense-related genes similarly to B. thuringiensis JCK-1233 treatment. Interestingly, treatment with B. thuringiensis JCK-1233 or cyclo-(L-Pro-L-Ile) showed moderately enhanced expression of PR-1, PR-2, PR-3, PR-4, PR-5, and PR-9 genes following inoculation with PWN compared to that in the untreated control, indicating that they mitigated the burst of hypersensitive reaction in susceptible pine seedlings. In contrast, they significantly increased the expression levels of PR-6 and PR-10 before PWN inoculation. In conclusion, foliar spraying with either B. thuringiensis JCK-1233 culture suspension or DPKs could induce resistance in pine seedlings, thereby alleviating the serious damage by PWD. Taken together, this study supports aerial spraying with eco-friendly biotic or abiotic agents as a valuable strategy that may mark an epoch for the control of PWD in pine forests.

Antioxidant and Antidiabetic Activities of Flavonoid Derivatives from the Outer Skins of Allium cepa L.

The onion, known as the bulb onion or common onion, is not only a key ingredient in many tasty and healthy vegetarian meals but also many traditional medicines. Nine new flavonoids [cepaflavas A, B (5, 6), cepadials A-D (7-9 and 14), and cepabiflas A-C (10-12)] and six known compounds (1-4, 13, 15) were obtained from the outer skins of Allium cepa L. Among them, compounds 5, 6, and 9 might be artificial products formed during extraction and isolation. New compounds were structurally elucidated using various spectroscopy/spectrometry techniques, including NMR and HRMS, and computational methods. Their absolute configurations were determined using time-dependent density functional theory calculations, combined with ECD spectroscopy, optical rotation calculation, and statistical procedures (CP3 and DP4 analysis). The free radical scavenging assays revealed that the new compounds 10-12 possessed considerable antioxidant activities with IC50 values of 4.25-8.88 and 7.12-8.14 µM against DPPH and ABTS•+, respectively. Compounds 13-15 showed substantial inhibitory activities against both α-glucosidase and protein tyrosine phosphatase 1B (PTP1B), with IC50 values of 0.89-6.80 and 1.13-6.82 µM, respectively. On the basis of molecular docking studies, 13 and 15 were predicted to have high binding capacity and strong affinity toward the active site of PTP1B.

Tetra-aryl cyclobutane and stilbenes from the rhizomes of Rheum undulatum and their α-glucosidase inhibitory activity: Biological evaluation, kinetic analysis, and molecular docking simulation.

One achiral tetra-aryl cyclobutane [rheundulin A (1)] and three stilbene glycosides [rheundulins B-D (2-4)] were isolated from the methanol extract of Rheum undulatum L., along with eight known compounds (5-12). Structural determination of the new compounds (1-4) was accomplished using comprehensive spectroscopic methods. Compound 1 represents the first example of a dimeric stilbene linked via a cyclobutane ring from the Rheum genus. All isolates were screened for their inhibition against α-glucosidase. Among them, stilbene derivatives (5 and 6) showed strong inhibitory effects on α-glucosidase with IC50 values of 0.5 and 15.4 µM, respectively, which were significantly higher than that of the positive control, acarbose (IC50 = 126.8 µM). Rheundulin A (1) showed moderate α-glucosidase inhibition with an IC50 value of 80.1 µM. In addition, kinetic analysis and molecular docking simulation of the most active compound (5) with α-glucosidase were performed for the first time. Kinetic studies revealed that compound 5 competitively inhibited the active site of α-glucosidase (Ki = 0.40 µM), while 6 had a mixed-type inhibitory effect against α-glucosidase (Ki = 15.34 µM). Molecular docking simulations of 5 and 6 demonstrated negative-binding energies, indicating high proximity to the active site and tight binding to α-glucosidase enzyme.

Stilbenes with Potent Protein Tyrosine Phosphatase-1B Inhibitory Activity from the Roots of Polygonum multiflorum.

Seven new stilbene glycosides including three dimers (1-3) and four monomers (4-7) were isolated from the roots of Polygonum multiflorum along with nine previously identified stilbenes (8-16). In addition, two deglucosylated stilbenes, 2a and 3a, were also obtained as new dimeric stilbenes. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (NMR, HRMS, and ECD). To the best of our knowledge, this represents the first isolation of a phenylpropanoid (C6-C3) substituted with a stilbene unit (7) from the Polygonaceae family. In an in vitro enzyme assay with human recombinant protein tyrosine phosphatase-1B (PTP1B), compounds 2-5 showed weak PTP1B inhibition with an IC50 value range of 27.4-37.6 µM, while three deglucosylated stilbenes 2a, 3a, and 8a exhibited IC50 values of 2.1, 1.9, and 12.1 µM, respectively. The inhibition modes and binding mechanism of selected inhibitors (2a and 3a) were investigated using kinetic methods and molecular docking simulations.

Arylbenzofurans from the Root Bark of Morus alba as Triple Inhibitors of Cholinesterase, ß-Site Amyloid Precursor Protein Cleaving Enzyme 1, and Glycogen Synthase Kinase-3ß: Relevance to Alzheimer's Disease.

Cholinesterase, ß-site amyloid precursor protein cleaving enzyme 1 (BACE1), and glycogen synthase kinase-3ß (GSK-3ß) are the three main enzymes responsible for the early onset of Alzheimer's disease (AD). The main aim of the present study was to delineate and accentuate the triple-inhibitory potential of arylbenzofurans from Morus alba against these enzymes. Overall, the enzyme inhibition assays demonstrated the prominence of mulberrofuran D2 as an inhibitor of AChE, BChE, BACE1, and GSK-3ß enzymes with IC50 values of 4.61, 1.51, 0.73, and 6.36 µM, respectively. Enzyme kinetics revealed different modes of inhibition, and in silico modeling suggested that mulberrofuran D2 inhibited these enzymes with low binding energy through hydrophilic, hydrophobic, and π-cation interactions in the active site cavities. Similarly, in Aß-aggregation assays, mulberrofuran D2 inhibited self-induced and AChE-induced Aß aggregation in a concentration-dependent manner that was superior to reference drugs. These results suggest that arylbenzofurans from M. alba, especially mulberrofuran D2, are triple inhibitors of cholinesterase, BACE1, and GSK-3ß and may represent a novel class of anti-AD drugs.

Lignans from Saururus chinensis exhibit anti-inflammatory activity by influencing the Nrf2/HO-1 activation pathway.

As part of our ongoing program to develop anti-inflammatory agents, an extract derived from Saururus chinensis collected in Korea was found to inhibit nitric oxide (NO) production in RAW264.7 cells. Bioassay-guided fractionation led to the isolation two new (1 and 2) and six known dineolignans (3-8). To the best of our knowledge, manassatin B1 (3) was isolated from S. chinensis for the first time. All structures were elucidated using extensive spectroscopic analysis. Of these compounds, 2 and 8 inhibited lipopolysaccharide (LPS)-induced production of NO and showed IC50 values of 5.80 and 1.52 µM, respectively. LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) was also significantly suppressed by the administration of 2 and 8. In addition, these lignans induced the expression of heme oxygenase-1 (HO-1) in a concentration-dependent manner. Nuclear translocation of nuclear-E2-related factor 2 (Nrf2), a key regulator of HO-1 protein expression, was also induced in RAW264.7 cells treated with 2 and 8. These findings suggested that these lignans exerted anti-inflammatory effects in RAW264.7 cells through modulation of the Nrf2/HO-1 pathway and that they were potential HO-1 inducers for preventing or treating inflammation.

Trichosanhemiketal A and B: Two 13,14-seco-13,14-epoxyporiferastanes from the root of Trichosanthes kirilowii Maxim.

Of the 32 Trichosanthes species in China, T. kirilowii Maxim. is the most renowned species used in traditional Chinese medicine and has diverse pharmacological properties. However, most of the phytochemical studies of T. kirilowii have focused on the fruits and seeds. In our investigation of the chemical constituents of T. kirilowii roots, two previously undescribed sterols [trichosanhemiketal A and B (1 and 2)], together with 13 known compounds, were isolated and their structures were elucidated. To the best of our knowledge, this represents the first isolation of compounds with a 13,14-seco-13,14-epoxyporiferastane (1-2) skeleton from the Cucurbitaceae family. The anti-inflammatory activity of the isolated compounds was determined through an analysis of their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells. Of the compounds, 4, 5, 6, and 8 showed significant inhibitory activities, with IC50 values of 8.5, 15.1, 25.4, and 28.5 µM, respectively. In addition, compound 4 inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression in a concentration-dependent manner.