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Compounds derived from Curcuma longa L. (C. longa) have been extensively studied and reported to be effective and safe for the prevention and treatment of various diseases, but most research has been focused on curcuminoids derived from C. longa. As neurodegenerative diseases are associated with oxidation and inflammation, the present study aimed to isolate and identify active compounds other than curcuminoids from C. longa to develop substances to treat these diseases. Seventeen known compounds, including curcuminoids, were chromatographically isolated from the methanol extracts of C. longa, and their chemical structures were identified using 1D and 2D NMR spectroscopy. Among the isolated compounds, intermedin B exhibited the best antioxidant effect in the hippocampus and anti-inflammatory effect in microglia. Furthermore, intermedin B was confirmed to inhibit the nuclear translocation of NF-κB p-65 and IκBα, exerting anti-inflammatory effects and inhibiting the generation of reactive oxygen species, exerting neuroprotective effects. These results highlight the research value of active components other than curcuminoids in C. longa-derived compounds and suggest that intermedin B may be a promising candidate for the prevention of neurodegenerative diseases.

Lindera erythrocarpa contains various constituents such as cyclopentenedione-, flavonoid-, and chalcone-type components. In this study, a novel bi-linderone derivative and 17 known compounds were isolated from the leaves of L. erythrocarpa by using various chromatographic methods. The structures of the components were determined from nuclear magnetic resonance and mass spectrometry data. All isolated compounds were tested for anti-inflammatory and anti-neuroinflammatory activities in lipopolysaccharide (LPS)-induced BV2 and RAW264.7 cells. Some of these compounds showed anti-inflammatory effects by inhibiting the nitric oxide (NO) produced by LPS. In particular, linderaspirone A (16), bi-linderone (17) and novel compound demethoxy-bi-linderone (18) showed significant inhibitory effects on the production of prostaglandin E2 (PGE2), tumor necrosis factor-α, and interleukin-6. The three compounds also inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), which are pro-inflammatory proteins, and the activation of nuclear factor κB (NF-κB). Therefore, linderaspirone A (16), bi-linderone (17), and demethoxy-bi-linderone (18) isolated from the leaves of L. erythrocarpa have therapeutic potential in neuroinflammatory diseases.

SummaryOver the course of an individual’s lifetime, genomic alterations accumulate in somatic cells. However, the mutational landscape by retrotranspositions of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome, is poorly understood in normal cells. Here, we explored the whole-genome sequences of 892 single-cell clones established from various tissues collected from 28 individuals. Remarkably, 88% of colorectal epithelial cells acquired somatic L1 retrotranspositions (soL1Rs), carrying ∼3 events per cell on average with substantial intra- and inter-individual variances, which was accelerated at least 10-fold during tumourigenesis. Breakpoints of soL1Rs suggested that a few variant mechanisms can be involved in the L1 retrotransposition processes. Fingerprinting of donor L1s using source-specific unique sequences revealed 34 hot L1s, 44% of which were newly discovered in this study, and many ultra-rare hot L1s in the human population showed higher retrotransposition potential in somatic lineages than common sources. Multi-dimensional analysis of soL1Rs with early embryonic developmental relationships, genome-wide methylation, and gene expression profiles of the clones demonstrated that (1) soL1Rs occur from early embryogenesis at a substantial rate, (2) epigenetic activation of hot L1s is stochastically acquired during the wave of early global epigenomic reprogramming, rather than by the sporadic loss-of-methylation at the late stage, and (3) most L1 transcripts in the cytoplasm do not generate soL1Rs in somatic lineages. In summary, this study provides insights into the retrotransposition dynamics of L1s in the human genome and the resultant somatic mosaicism in normal human cells.

Morus alba fruits (MAF) belong to the Moraceae family, which are known to be effective in treating diabetic, autoimmune, and hormonal diseases owing to its low toxicity. MAF, as excerpted from Donguibogam, a representative Korean medical encyclopedia protected by UNESCO, has been widely used to treat lumbago, arthritis, and diabetes. Based on these effects, MAF is investigated for unidentified effects of atopic dermatitis, characterized by complex etiology of skin barrier dysfunction, inflammation, and chronic pruritus.The antioxidant, inflammatory, and immunomodulatory properties of MAF and its bioactive compounds have been widely reported. According to an examination of 1-chloro-2,4-dinitrobenzene-induced AD-like skin lesions in NC/Nga mice, AD symptoms, such as increased dermatitis score, scratching frequency, immunoglobulin E, trans-epidermal water loss, epidermal thickness, and infiltration of mast cells, were relieved by topical MAF administration. They effectively attenuated cytokines and chemokines, such as interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, IL-17A, IL-22, IL-1β, tumor necrosis factor-α, thymic stromal lymphopoietin (TSLP), thymic- and activation-regulated chemokine, normal T cell expression, and macrophage-derived chemokine secretion at the mRNA level in TNF-α/IFN-γ induced HaCaT (human immortalized keratinocyte) cells.Both in vivo and in vitro models, MAF increased the expression of filaggrin, involucrin, and loricrin, as well as inhibited the activation of Janus kinase 2, signal transducer and activator of transcription proteins 1, and mitogen-activated protein kinase pathways, including extracellular signal-regulated kinase, c-jun N-terminal kinase, and p38. Moreover, MAF reduced the expression of TSLP and periostin, which play important roles in skin pruritus as chronic pruritogenic factors.These data indicate that MAF could be used as a potential treatment for AD-like skin lesions by regulating the inflammatory response, improving physical skin barriers, and relieving symptomatic pruritus.

Meretrix lusoria (M. lusoria) is an economically important shellfish which is widely distributed in South Eastern Asia that contains bioactive peptides, proteins, and enzymes. In the present study, the extracted meat content of M. lusoria was enzymatic hydrolyzed using four different commercial proteases (neutrase, protamex, alcalase, and flavourzyme). Among the enzymatic hydrolysates, M. lusoria protamex hydrolysate (MLPH) fraction with MW ≤ 1 kDa exhibited the highest free radical scavenging ability. The MLPH fraction was further purified and an amino acid sequence (KDLEL, 617.35 Da) was identified by LC-MS/MS analysis. The purpose of this study was to investigate the anti-obesity and anti-hyperglycemic effects of MLPH containing antioxidant peptides using ob/ob mice. Treatment with MLPH for 6 weeks reduced body and organ weight and ameliorated the effects of hepatic steatosis and epididymal fat, including a constructive effect on hepatic and serum marker parameters. Moreover, hepatic antioxidant enzyme activities were upregulated and impaired glucose tolerance was improved in obese control mice. In addition, MLPH treatment markedly suppressed mRNA expression related to lipogenesis and hyperglycemia through activation of AMPK phosphorylation. These findings suggest that MLPH has anti-obesity and anti-hyperglycemic potential and could be effectively applied as a functional food ingredient or pharmaceutical.

본 연구는 황기와 지치 복합물인 ALM16이 lipopolysaccharide 처리에 의해 자극된 RAW264.7 대식세포의 염증반응에 미치는 영향에 대하여 조사하였다. ALM16은 RAW264.7 대식세포에 대하여 최대 200 μg/mL의 농도까지 독성은 보이지 않았다. 항염증 활성을 검정하기 위해 nitric oxide (NO), prostaglandin E2 (PGE2) 및 pro-inflammatory cytokines 생성량을 측정한 결과, ALM16은 각각의 생성량을 농도의존적으로 감소시켰다. 또한 ALM16은 NO와 PGE2 생성에 관여하는 inducible nitric oxide synthase (iNOS)와 cyclooxygenase-2 (COX-2)의 단백질 발현을 억제하였다. 한편, 항염증 활성 조절 기전을 확인하기 위하여 NK-kB의 핵으로의 이동과 DNA-binding activity 및 MAPK 신호전달 경로에 대한 ALM16의 영향을 확인한 결과, ALM16은 NF-κB의 핵으로 이동과 DNA-binding activity를 유의적으로 억제하였으며, JNK와 ERK 특이적으로 인산화를 억제함으로써 MAPK 신호전달 경로 활성을 억제하였다. 이러한 결과를 종합하여 볼 때 ALM16이 MAPK와 NF-κB의 신호전달 경로 억제를 통한 iNOS와 COX-2의 발현을 조절하고, 이로 인하여 NO, PGE2 및 pro-inflammatory cytokines의 생성이 감소하여 염증 반응을 조절하는 능력이 있는 것으로 판단된다.

Breast cancer is the most common cancer in women, and metastasis is the leading cause of death in breast cancer patients. Although chemoprevention is widely employed to treat breast cancer, anticancer drugs can cause significant adverse effects. Lysimachia christinae Hance (LH) is a traditional Chinese medicinal plant with diverse therapeutic effects. However, its potential anticancer activity has not been fully investigated in breast cancers to date. Using high‐performance liquid chromatography–mass spectrometry, we found that the main constituent of LH extract (LHE) was rutin. Our results indicated that LHE or rutin markedly decreased the proliferation and viability of estrogen receptor (ER)‐positive MCF‐7 and ER‐negative HCC38 human breast cancer cells. LHE treatment induced morphological changes in apoptotic nuclei using 4′,6‐diamidino‐2‐phenylindole (DAPI) staining. Annexin V–fluorescein isothiocyanate (FITC) propidium iodide (PI) staining assay revealed that apoptosis significantly increased in both breast cancer cell types after LHE treatment. Additionally, the expression of poly (ADP‐ribose) polymerase (PARP), Bcl‐2, and phospho‐Akt decreased, while that of cleaved PARP and p53 increased, in both cell types. Furthermore, LHE treatment inhibited epithelial–mesenchymal transition (EMT). LHE treatment significantly upregulated E‐cadherin level in MCF‐7 and HCC38 cells, while vimentin level was downregulated in HCC38 cells. In addition, transwell and wound‐healing assays revealed that LHE or rutin inhibited breast cancer cell migration. Overall, these findings demonstrate that LHE is a promising therapeutic agent that acts by promoting apoptosis and reducing cell proliferation, EMT, and cell migration in ER‐positive and ER‐negative breast cancer cells., Lysimachia christinae Hance extract (LHE) effectively showed anticancer effects by inhibiting cancer cell proliferation and inducing apoptosis in estrogen receptor (ER)‐positive MCF‐7 and ER‐negative HCC38 human breast cancer cells. Moreover, LHE negatively regulated epithelial–mesenchymal transition (EMT) and decreased breast cancer cell migration.

Repeated column chromatography of Syringa dilatata flowers, a native shrub to Korea, led to the isolation of eight new oleoside-type secoiridoids, syringoleosides A–H (1–8), as well as five known s...

As a long-established medicinal and edible homologous plant, Taraxacum officinale Wigg. is widely distributed in Asia, Europe, and other parts of the world. T. officinale is reported to exert a variety of biological and pharmacological activities, including anticancer, hepatoprotective, and anti-obesity effects. In this study, we evaluated the anti-inflammatory effects of ethanol extracts of T. officinale (A-TOW) by examining the suppression of proinflammatory mediators in LPS-stimulated BV2 and mouse hippocampus. Furthermore, A-TOW also inhibited the nuclear translocation of nuclear factor [Formula: see text]B p65 caused by stimulation with LPS. In addition, A-TOW regulates heme oxygenase (HO)-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in BV2 cells. The effects of A-TOW on the over-expression of proinflammatory mediators were partially reversed by transfection of the cells with HO-1 siRNA. These findings suggest that the potent anti-inflammatory activity of T. officinale, possibly through the regulation of Nrf2/HO-1 and NF-[Formula: see text]B signaling pathway.

Malus toringoides (Rehd.) Hughes (Rosaceae) is used as a traditional folk medicine in the Tibet autonomous region of China to treat hypertension, hyperglycemia, and hyperlipidemia. However, few modern pharmacological data on the use of this plant against diabetic syndrome are available. In this study, we examined the vascular protection provided by a 70% ethanol extract of

Atopic dermatitis (AD) is a kind of inflammation on the skin following with swollen, itchy, dryness and cracked skin. Though the exact cause of AD is unknown, there are evidence that people with AD have a compromised skin barrier along with inflammation. Eclipta prostrata Linné is a traditional herbal medicinal plant, has been used for the diabetes, obesity, jaundice, and inflammation. We supposed E. prostrata L. has an anti-inflammatory effect on the skin.We aimed to assess the effect of E. prostrata L. EtOH extract (EP) and elucidate the associated molecular mechanisms.The effect of EP and the molecular mechanisms were eluciated in house dust mite (HDM)-induced AD mice model and TNF-α/IFN-γ-stimulated HaCaT keratinocytes by histological analysis, enzyme-linked immunosorbent assay, quantitative real time polymerase chain reaction, and Western blot.The results revealed that EP improved the progression of AD symptoms, decreasing epidermis/dermis thickness, infiltrated immune cells, and restored the skin barrier dysfunction and imbalanced immune response. EP suppressed the expressions of T helper (Th)1, Th2, Th17 cytokines, phosphorylation of extracellular signal-regulated kinase/signal transducer and activator of transcription 1 in skin of HDM-induced AD mice as well as inhibition the translocation of nuclear factor-κB in HaCaT keratinocytes.Collectively, EP improved the allergic inflammation of the skin through recovery the skin barrier, and regulation the immune balance. These results suggest EP may have therapeutic potential as an anti-atopic agent.

Using combined chromatographic separation techniques, three new triterpenoids named lycomclavatols A-C (

Objective The prenylated xanthones compounds, macluraxanthone B (MCXB) was isolated from the MeOH extracts of Cudrania tricuspidata. In this study, we investigated the effect of MCXB on inflammatory response. Materials and methods Anti-inflammatory effects of MCXB were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 and BV2 cells. We observed their anti-inflammatory effects by ELISA, western blot analysis, and immunofluorescence. Results MCXB significantly inhibited the LPS-stimulated production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α in RAW264.7 and BV2 cells. MCXB also reduced the LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 proteins. Incubating cells with MCXB prevented subsequent activation of the nuclear factor kappa B (NF-κB) signaling pathway by inhibiting the nuclear localization and DNA-binding activity of the p65 subunit induced by LPS. MCXB inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinases (MAPKs) in RAW264.7 and BV2 cells. MCXB induced the expression of heme oxygenase (HO)-1 protein, and the inhibitory effect of MCXB on nitric oxide production was partially reversed by a selective HO-1 inhibitor. Discussion and conclusions Our results suggested that the anti-inflammatory effect of MCXB is partly regulated by HO-1 induction. In conclusion, MCXB could be a useful candidate for the development of therapeutic and preventive agents to treat inflammatory diseases.

Chemical investigation of the Antarctic fungi Pleosporales sp. SF-7343 revealed four known secondary fungal metabolites: alternate C (1), altenusin (2), alternariol (3), and altenuene (4). The compound structures were identified primarily by NMR and MS analyses. Atopic dermatitis, an inflammatory disease, is driven by the abnormal activation of T helper (Th) 2 cells and barrier dysfunction. We attempted to identify the anti-inflammatory components of SF-7343. Initial screening showed that compounds 1 and 3 inhibited the secretion of interleukin-8 and -6 in tumor necrosis factor-α/interferon-γ-treated HaCaT cells, and these compounds also showed inhibitory effects on CCL5 and CCL22. Compounds 1 and 3 also downregulated the protein expression levels of intercellular adhesion molecule-1 and upregulated the expression of filaggrin and involcurin. The mechanism study results showed that compounds 1 and 3 inhibited nuclear translocation of nuclear factor-kappa B p65 and the phosphorylation of STAT1 and STAT3. Compound 1, but not compound 3, significantly promoted the expression of heme oxygenase (HO)-1. The effects of compound 1 were partly reversed by co-treatment with a HO-1 inhibitor, tin protoporphyrin IX. Taken together, this study demonstrates the potential value of Antarctic fungal strain SF-7343 isolates as a bioresource for bioactive compounds to prevent skin inflammation.

Chemical investigation of the Antarctic fungi Pleosporales sp. SF-7343 revealed four known secondary fungal metabolites: alternate C (1), altenusin (2), alternariol (3), and altenuene (4). The compound structures were identified primarily by NMR and MS analyses. Atopic dermatitis, an inflammatory disease, is driven by the abnormal activation of T helper (Th) 2 cells and barrier dysfunction. We attempted to identify the anti-inflammatory components of SF-7343. Initial screening showed that compounds 1 and 3 inhibited the secretion of interleukin-8 and -6 in tumor necrosis factor-α/interferon-γ-treated HaCaT cells, and these compounds also showed inhibitory effects on CCL5 and CCL22. Compounds 1 and 3 also downregulated the protein expression levels of intercellular adhesion molecule-1 and upregulated the expression of filaggrin and involcurin. The mechanism study results showed that compounds 1 and 3 inhibited nuclear translocation of nuclear factor-kappa B p65 and the phosphorylation of STAT1 and STAT3. Compound 1, but not compound 3, significantly promoted the expression of heme oxygenase (HO)-1. The effects of compound 1 were partly reversed by co-treatment with a HO-1 inhibitor, tin protoporphyrin IX. Taken together, this study demonstrates the potential value of Antarctic fungal strain SF-7343 isolates as a bioresource for bioactive compounds to prevent skin inflammation.

Aging is associated with immune disregulation and oxidative stress which lead to inflammation and neurodegenerative diseases. We have tried to identify the anti-neuroinflammatory and anti-inflammatory components of Coreopsis lanceolata L. The dried flowers of C. lanceolata were extracted with 70% EtOH, and the obtained extract was divided into CH2Cl2, EtOAc, n-BuOH, and H2O fractions. The CH2Cl2 fraction was separated using silica gel and C-18 column chromatography to yield phenylheptatriyne (1), 2′-hydroxy-3,4,4′-trimethoxychalcone (2), and 4′,7-dimethoxyflavanone (3). Additionally, the EtOAc fraction was subjected to silica gel, C-18, and Sephadex LH-20 column chromatography to yield 8-methoxybutin (4) and leptosidin (5). All the compounds isolated from C. lanceolata inhibited the production of nitric oxide (NO) in LPS-induced BV2 and RAW264.7 cells. In addition, phenylheptatriyne and 4′,7-dimethoxyflavanone reduced the secretion of inflammatory cytokines, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6. Among them, phenylheptatriyne was significantly downregulated in the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Subsequently, phenylheptatriyne also effectively inhibited nuclear factor-kappa B (NF-κB) activation in LPS-stimulated BV2 and RAW264.7 cells. Based on these results, the anti-neuroinflammatory effect of phenylheptatriyne isolated from C. lanceolata was confirmed, which may exert a therapeutic effect in treatment of neuroinflammation-related diseases.

Begonia semperflorens Link et Otto has been broadly raised up for ornamental purpose as well comestible blossom. As the reproductive structures of phanerogams, flowers contain various secondary metabolites and have many biological activities. Accordingly, we began the contrivance for isolation and analysis of flavonoids contained in B. semperflorens flowers. MeOH extraction of B. semperflorens followed solvent fractionation was prosecuted. Column chromatography of non-polar fraction gave four flavonoids using several resins. Identification of the flavonols were established as quercetin (1), kaempferol (2), astragalin (3), and isoquercetin (4) by interpreting a variety of spectral information. Quercetin (1) and kaempferol (2) inhibited NO production and protected against t-BHP-induced oxidative stress. Kaempferol (2) also protected cell death of glutamate-treated HT22. Quantitative analysis of flavonoid content in B. semperflorens flowers was also performed using HPLC experiment.

Higher-order chromatin structure is important for the regulation of genes by distal regulatory sequences

Aims: Our aim was to investigate the effects of peripheral arterial stiffness on the risk of progression of renal disease in patients with type 2 diabetes (T2D). Methods: This was a single center, retrospective cohort study. Brachial-ankle pulse wave velocity (baPWV) tests were performed on T2D patients in 2015. Increased arterial stiffness was defined as baPWV of ≥ 1800 cm/s. We applied criteria for progression of renal disease according to EMPA-REG OUTCOME trial. Results: In total, 186 patients were enrolled in the final study. The mean age was 59.1 years and male:female ratio was 1.73:1. Thirteen (7%) patients progressed to renal disease during the average follow-up time of 35.3 months. In particular, the risk of progression to macroalbuminuria was significantly higher in the baPWV ≥ 1800 cm/s group (HR 6.216, p = 0.020). Individuals with a baPWV of ≥ 1800 cm/s (when comparisons were adjusted for age, sex, blood pressure, diabetes duration, eGFR, and use of renin-angiotensin system inhibitors) had a significantly higher risk of the progression of renal disease (HR = 8.480, p = 0.014). Conclusion: These results suggest that peripheral arterial stiffness (baPWV ≥ 1800 cm/s) may be a risk factor for the progression of renal disease in T2D patients.

A prenylated flavonoid, cudraflavanone B, is isolated from Cudrania tricuspidata. In this study, we investigated its anti-inflammatory and anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced RAW264.7 and BV2 cells. In our initial study of the anti-inflammatory effects of cudraflavanone B the production of nitric oxide and prostaglandin E2 was attenuated in LPS-stimulated RAW264.7 and BV2 cells. These inhibitory effects were related to the downregulation of inducible nitric oxide synthase and cyclooxygenase-2. In addition, cudraflavanone B suppressed the production of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α in LPS-induced RAW264.7 and BV2 cells. Moreover, the evaluation of the molecular mechanisms underlying the anti-inflammatory effects of cudraflavanone B revealed that the compound attenuated the nuclear factor-kappa B signaling pathway in LPS-induced RAW264.7 and BV2 cells. In addition, cudraflavanone B inhibited the phosphorylation of extracellular signal-regulated kinase mitogen-activated protein kinase signaling pathways in these LPS-stimulated cells. Thus, cudraflavanone B suppressed nuclear factor-κB, and extracellular signal-regulated kinase mitogen-activated protein kinase mediated inflammatory pathways, demonstrating its potential in the treatment of neuroinflammatory conditions.

A hypernomic reaction or an abnormal inflammatory process could cause a series of diseases, such as cardiovascular disease, neurodegeneration, and cancer. Additionally, oxidative stress has been identified to induce severe tissue injury and inflammation. Carpesium cernuum L. (C. cernuum) is a Chinese folk medicine used for its anti-inflammatory, analgesic, and detoxifying properties. However, the underlying molecular mechanism of C. cernuum in inflammatory and oxidative stress conditions remains largely unknown. The aim of this study was to examine the effects of a methanolic extract of C. cernuum (CLME) on lipopolysaccharide- (LPS-) induced RAW 264.7 mouse macrophages and a sepsis mouse model. The data presented in this study indicated that CLME inhibited LPS-induced production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264.7 cells. CLME treatment also reduced reactive oxygen species (ROS) generation and enhanced the expression of heme oxygenase-1 (HO-1) protein in a dose-dependent manner in the LPS-stimulated RAW 264.7 cells. Moreover, CLME treatment abolished the nuclear translocation of nuclear factor-κB (NF-κB), enhanced the activation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), and reduced the expression of extracellular signal-related kinase (ERK) and ERK kinase (MEK) phosphorylation in LPS-stimulated RAW 264.7 cells. These outcomes implied that CLME could be a potential antioxidant and anti-inflammatory agent.

Heme oxygenase (HO)-1 is a detoxifying phase II enzyme that plays a role in both inflammatory and oxidative stress responses. Curdrania tricuspidata is widespread throughout East Asia and is used as a therapeutic agent in traditional medicine. We investigated whether treatment with sixteen flavonoid or xanthone compounds from C. tricuspidata could induce HO-1 expression in HT22 hippocampal cells, RAW264.7 macrophage, and BV2 microglia. In these compounds, kuwanon C showed the most remarkable HO-1 expression effects. In addition, treatment with kuwanon C reduced cytoplasmic nuclear erythroid 2-related factor (Nrf2) expression and increased Nrf2 expression in the nucleus. Significant inhibition of glutamate-induced oxidative injury and induction of reactive oxygen species (ROS) occurred when HT22 hippocampal cells were pretreated with kuwanon C. The levels of inflammatory mediator and cytokine, which increased following lipopolysaccharide (LPS) stimulation, were suppressed in RAW264.7 macrophage and BV2 microglia after kuwanon C pretreatment. Kuwanon C also attenuated p65 DNA binding and translocation into the nucleus in LPS-induced RAW264.7 and BV2 cells. The anti-inflammatory, anti-neuroinflammatory, and neuroprotective effects of kuwanon C were reversed when co-treatment with HO-1 inhibitor of tin protoporphyrin-IX (SnPP). These results suggest that the neuroprotective and anti-inflammatory effects of kuwanon C are regulated by HO-1 expression.

The extracellular matrix components laminin and elastin serve key roles in stem cell therapy. Elastin-like polypeptides (ELPs), derived from a soluble form of elastin, affect the proliferation and differentiation of various types of cells. In the present study, a novel protein was designed containing globular domains 1-3 of laminin α5 (Lα5LG1-3) fused to ELPs (Lα5LG1-3/ELP). Lα5LG1-3/ELP was expressed in Escherichia coli and displayed a molecular size of ~70 kDa on 12% SDS-polyacrylamide gels. The cellular activities, such as cellular adhesion (adhesion assay) and proliferation (MTT cytotoxicity assay), of human mesenchymal stem cells (hMSCs) treated with 1 µg/ml of Lα5LG1-3/ELP were enhanced compared with those of untreated cells. Additionally, the number of undifferentiated hMSCs and their degree of stemness were assessed based on the gene expression levels of the stem cell markers cluster differentiation 90 (CD90), endoglin (CD105) and CD73. The expression levels of these markers were upregulated by 2.42-, 2.29- and 1.92-fold, respectively, in the hMSCs treated with Lα5LG1-3/ELP compared with the levels in untreated controls. Thus, Lα5LG1-3/ELP may be used to enhance the viability of hMSCs and preserve their undifferentiated state, whereby the clinical applications of hMSCs may be improved.

Mecasin, a traditional medicine, contains nine herbal constituents: Curcuma longa, Salvia miltio rhiza, Gastrodia elata, Chaenomeles sinensis, Polygala tenuifolia, Paeonia japonica, Glycyrrhiza uralensis, Atractylodes japonica and processed Aconitum carmichaeli. Several biological effects of mecasin have been described both in vivo and in vitro. Previous studies have demonstrated that mecasin has anti-inflammatory effects. The purpose of the present study was to determine anti-inflammatory effects of mecasin and its natural product constituents on lipopolysaccharide (LPS)-stimulated BV2 cells by measuring nitrite and nitric oxide contents. Nitrite production levels in LPS-stimulated BV2 cells incubated with mecasin and each individual constituent of mecasin were measured. The results suggested that C. longa, P. tenuifolia and P. japonica inhibited nitrite production in a pattern similar to that of mecasin. The effect of mecasin was likely a result of synergistic effects of its natural herb constituents.

The global obesity epidemic has nearly doubled since 1980, and this increasing prevalence is threatening public health. It has been reported that natural products could contain potential functional ingredients that may assist in preventing obesity. Bojungchiseub-tang (BJT), mentioned in the Donguibogam as an herbal medication for the treatment of edema, a symptom of obesity, consists of eleven medicinal herbs. However, the pharmacological activity of BJT has not been investigated. The present study was designed to investigate the putative effect of BJT on the adipogenesis of 3T3-L1 cells and the weight gain of high-fat diet (HFD-) fed C57BL/6 mice. Oil Red O staining was conducted to examine the amount of lipids in 3T3-L1 adipocytes. Male C57BL/6 mice were divided into three groups: standard diet group (control, CON), 45% HFD group (HFD), and HFD supplemented with 10% of BJT (BJT). The expression levels of genes and proteins related to adipogenesis in cells, WAT, and liver were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. We found that BJT treatment significantly decreased the protein and mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) in a dose-dependent manner in differentiated 3T3-L1 cells. Similar to the results of the in vitro experiment, BJT suppressed HFD-induced weight gain in an obese mouse model. In addition, BJT effectively reduced the HFD-induced epididymal adipose tissue weight/body weight index. BJT also downregulated the mRNA levels of PPARγ, C/EBPα, and SREBP1 in the epididymal adipose and liver tissue of HFD-fed obese mice. These findings suggest that BJT induces weight loss by affecting adipogenic transcription factors.

A repeated column chromatography for Forsythia koreana Nakai. flowers afforded a phenylethane glycoside, which was identified as 8′-(3,4-dihydroxyphenyl)ethyl-O-α-l-rhamnopyranosyl-(1 → 4)-2-O-(E)-caffeoyl-α-l-arabinopyranoside based on spectroscopic analyses of 1D NMR (1H-NMR, 13C-NMR, DEPT), 2D NMR (gCOSY, gHSQC, gHMBC), FAB/MS, specific rotation, and IR spectrometry. This compound was isolated from F. koreana flower for the first time in this study. The compound showed scavenge activities in ORAC and DPPH radicals with the values of 0.83 ± 0.01 and 84.66 ± 0.75% (at the concentration of 500 ppm), respectively. It also inhibited production of NO for RAW 264.7 stimulated by LPS and protected oxidative stress induced by glutamate in HT22-immortalized hippocampal. The IC50 on inhibition of NO production and EC50 value on protective efficacy of oxidative stress were 78.72 ± 1.43 μM and 176.25 ± 7.23 μM, respectively. These results demonstrate that the phenylethanoid glycoside might be useful as a neuroprotective agent because of their antioxidant, anti-inflammatory, and neuroprotective effects.

Dalbergia odorifera T. Chen (Leguminosae) grows in Central and South America, Africa, Madagascar, and Southern Asia. D. odorifera possesses many useful pharmacological properties, such as antioxidative and anti-inflammatory activities in various cell types. 4-Methoxydalbergione (MTD) and 4'-hydroxy-4-methoxydalbergione (HMTD) were isolated from the EtOH extract of D. odorifera by several chromatography methods. The chemical structures were elucidated by nuclear magnetic resonance (NMR) and mass spectrum (MS). Anti-inflammatory and cytoprotective effects were examined using BV2 microglial cells and murine hippocampus. MTD and HMTD were demonstrated to induce heme oxygenase (HO)-1 protein levels through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in BV2 microglial cells, while only MTD upregulated HO-1 in HT22 cells. MTD and HMTD induced HO-1 expression through JNK MAPK pathway in BV2 cells, whereas only MTD activated the ERK and p38 pathways in HT22 cells. MTD was also shown to activated MTD and HMTD suppressed lipopolysaccharide-stimulated nitric oxide (NO) and prostaglandin E2 production by inhibiting inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in a dose-dependent manner. Furthermore, MTD and HMTD attenuated pro-inflammatory cytokine productions. These anti-inflammatory effects were found to be mediated through the nuclear factor-kappa B (NF-κB) pathway. MTD exhibited neuroprotective effects on glutamate-induced neurotoxicity by promoting HO-1 in HT22 cells. The anti-inflammatory and cytoprotective effects of MTD and HMTD were partially reversed by an HO inhibitor tin protoporphyrin IX. In addition, MTD and HMTD inhibited pro-inflammatory cytokines and NF-κB pathway in primary rat microglia. These findings suggest that MTD and HMTD have therapeutic potential against neurodegenerative diseases accompanied by microglial activation and/or oxidative cellular injury.

Oxidative stress contributes to neuronal death in the brain, and neuronal death can cause aging or neurodegenerative disease. Heme oxygenase 1 (HO-1) serves a vital role in the regulation of biological reactions, including oxidative stress associated with reactive oxygen species. In the present study, acerogenin C isolated from the Aceraceae plant Acer nikoense, which is used as a Japanese folk medicine for hepatic disorders and eye diseases. However, there have been no studies on the mechanisms underlying the antineurodegenerative biological activities of acerogenin C. In the present study, acerogenin C demonstrated neuroprotective action against glutamate‑induced cell death in hippocampal HT22 cells through the upregulation of HO‑1 expression. These effects were also associated with nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the activation of phosphoinositide 3‑kinase/protein kinase B. Taken together of the efficacy researches, this study determines that the Nrf2/HO‑1 pathways denotes a biological mark and that acerogenin C might contribute to prevention of neurodegenerative disorders.

Previous phytochemical investigations of Akebiae Caulis resulted in the isolation of triterpenes, triterpene glycosides, phenylethanoid glycosides and megastigmane glycoside. Amyloid beta (Aβ), the main component of the senile plaques detected in Alzheimer's disease, induces cell death. However, only a limited number of studies have addressed the biological and pharmacological effects of Akebiae Caulis. In particular, the inhibitory activity of Akebiae Caulis against Aβ42 fibrillogenesis remains unclear. Herein, a new triterpene glycoside, akequintoside F (1), along with nine known compounds pulsatilla saponin A (2), collinsonidin (3), akebonic acid (4), hederagenin (5), 1-(3',4'-dihydroxycinnamoyl) cyclopentane-2,3-diol (6), asperosaponin C (7), leontoside A (8), quinatic acid (9), and quinatoside A (10) were isolated from Akebiae Caulis using repeated column chromatography with silica gel, LiChroprep RP-18, and MCI gel. The chemical structures of compounds 1-10 were illustrated based on 1D and 2D NMR spectroscopy, including 1H-1H COSY, HSQC, HMBC and NOESY spectroscopic analyses. Compound 1 a novel compound and known compounds 6 and 7 were isolated for the first time from this plant. Among these compounds, 1, 3, 4, 5 and 7 displayed significant inhibitory effects on Aβ42 induced fibrillogenesis. We present the first report of new compound 1 and the inhibitory effects of components from Akebiae Caulis on Aβ42 fibrillogenesis.

Ethnopharmacological relevance As an important medicinal material constituting a variety of traditional Chinese medicine prescriptions, Nepeta angustifolia C. Y. Wu was used as a folk medicine to treat various vascular-related diseases including apoplexia, and cerebral haemorrhage in Tibet, China. Our previous studies have shown that this plant had a significant protective effect on vascular dysfunction of the intracerebral haemorrhage and diabetic rats. In present study, we aimed to investigate the protective effects and underlying mechanisms of Nepeta angustifolia on diabetic nephropathy (DN), a microvascular complication. Aim of the study This study is aim to evaluate the protective effect of ethanol extracts of N. angustifolia (NA) on DN, and explore mechanism of action to provide basis for its pharmacological action against DN. Materials and methods High-fat diet and low-dose streptozotocin administration (HFD/STZ) induced diabetic rats were randomly divided into 5 groups (n = 8): the diabetic model group, metformin group, and three dose groups of NA (60 mg/kg, 120 mg/kg, 240 mg/kg). After administration of NA for 8 weeks, the blood, urine and renal tissue were collected for subsequent experiments. Biochemical markers (urine protein, Cr, BUN), oxidative stress makers (SOD, GSH-px and MDA) and pro-inflammatory mediators (TNF-α, IL-1β, IL-6 and MCP-1) were evaluated by commercial kit and ELISA, respectively. The effect of NA on DN was further confirmed by evaluation of renal histopathology by using the H&E, PAS and Masson staining. The H2O2-induced HBZY-1 cells (rat glomerular mesangial cells) were also been used to evaluate the renal protective effect of NA (50 μg/mL, 100 μg/mL, 200 μg/mL). The oxidative stress makers were detected by commercial kit. The levels of apoptosis and related proteins (caspase 3, 9) were detected by TUNEL assay and western blot analysis, respectively. The depolarization of mitochondrial membrane potential was detected by JC-1 staining assay. Results The administration of NA is helpful to maintain near normal body weight, blood glucose, urine volume, urine protein, kidney index and serum levels of Cr and BUN. NA treatment significantly improve renal dysfunction by the down-regulation of renal oxidative stress and pro-inflammatory mediators in HFD/STZ induced diabetic rats. In vitro experiments, NA has a significant cellular protective effect in H2O2-induced HBZY-1 cells, as well as the regulation in increases of SOD level and the decreases of ROS and MDA levels. Furthermore, NA treatment can significantly inhibit H2O2 induced mesangial cells apoptosis by the increasing mitochondrial potential and suppressing caspases-madiated signaling pathway. Conclusions NA has obvious improvement on renal dysfunction in HFD/STZ induced diabetic rats. NA can protect mesangial cells by inhibiting oxidative stress induced apoptosis, which may be related to its regulation of mitochondrial-caspase apoptosis pathway.

Single-cell technologies enable measure of unique cellular signatures, but are typically limited to a single modality. Computational approaches allow integration of diverse single-cell datasets, but their efficacy is difficult to validate in the absence of authentic multi-omic measurements. To comprehensively assess the molecular phenotypes of single cells in tissues, we devised single-nucleus methylCytosine, Chromatin accessibility and Transcriptome sequencing (snmC2T-seq) and applied it to post-mortem human frontal cortex tissue. We developed a computational framework to validate fine-grained cell types using multi-modal information and assessed the effectiveness of computational integration methods. Correlation analysis in individual cells revealed distinct relations between methylation and gene expression. Our integrative approach enabled joint analyses of the methylome, transcriptome, chromatin accessibility and conformation for 63 human cortical cell types. We reconstructed regulatory lineages for cortical cell populations and found specific enrichment of genetic risk for neuropsychiatric traits, enabling prediction of cell types with causal roles in disease.

Brain cell damage that results from oxidative toxicity contributes to neuronal degeneration. The transcription factor nuclear factor‑E2‑related factor 2 (Nrf2) regulates the expression of heme oxygenase (HO)‑1 and glutathione (GSH), and serves a key role in the pathogenesis of neurological diseases. Brassica rapa is a turnip that is unique to Ganghwa County, and is used mainly for making kimchi, a traditional Korean food. In the current study, brassicaphenanthrene A (BrPA) from B. rapa was demonstrated to exhibit protective effects against neurotoxicity induced by glutamate via Nrf2‑mediated HO‑1 expression. Similarly, BrPA increased the expression of cellular glutathione and glutamine‑cysteine ligase genes. Furthermore, BrPA caused the nuclear translocation of Nrf2 and increased antioxidant response element (ARE) promoter activity. Nrf2 also mediated HO‑1 induction by BrPA through the PI3K/Akt and JNK regulatory pathways. The results of the present study indicated the neuroprotective effect of BrPA, a natural food component from B. rapa.

Recent advances in the development of single cell epigenomic assays have facilitated the analysis of gene regulatory landscapes in complex biological systems. Methods for detection of single-cell epigenomic variation such as DNA methylation sequencing and ATAC-seq hold tremendous promise for delineating distinct cell types and identifying their critical cis-regulatory sequences. Emerging evidence has shown that in addition to cis-regulatory sequences, dynamic regulation of 3D chromatin conformation is a critical mechanism for the modulation of gene expression during development and disease. It remains unclear whether single-cell Chromatin Conformation Capture (3C) or Hi-C profiles are suitable for cell type identification and allow the reconstruction of cell-type specific chromatin conformation maps. To address these challenges, we have developed a multi-omic method single-nucleus methyl-3C sequencing (sn-m3C-seq) to profile chromatin conformation and DNA methylation from the same cell. We have shown that bulk m3C-seq and sn-m3C-seq accurately capture chromatin organization information and robustly separate mouse cell types. We have developed a fluorescent-activated nuclei sorting strategy based on DNA content that eliminates nuclei multiplets caused by crosslinking. The sn-m3C-seq method allows high-resolution cell-type classification using two orthogonal types of epigenomic information and the reconstruction of cell-type specific chromatin conformation maps.

We want to find the anti-neuroinflammatory action of the taurine derivative Glucose-Taurine Reduced (G-T-R). The anti-neuroinflammatory action by G-T-R were investigated in lipopolysaccharide (LPS)-induced BV2 microglia. G-T-R inhibited the production of nitric oxide and prostaglandin E2, and down-regulated the protein expression of inducible NO synthase and cyclooxygenase-2. In addition, G-T-R reduced the cytokines secretion such as tumor necrosis factor (TNF-α), interleukin (IL) -1β and IL-6, in BV2 microglia treated with LPS. In addition, G-T-R dose-dependently decreased the activation of nuclear factor-kappa B. These findings confirmed the anti-neuroinflammatory activity of G-T-R, which may exert protective effects against neuroinflammatory-related diseases.

In the present study, we investigated the regulation of inflammatory effects by glucose-taurine reduced (G-T-R), a taurine-carbohydrate derivative, on lipopolysaccharide (LPS)-induced RAW264.7 macrophages. The anti-inflammatory action of G-T-R revealed that this derivative markedly inhibited the nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW264.7 macrophages induced by LPS. Suppression of NO and PGE2 production was involved in the inhibitory action by G-T-R on the inducible nitric oxide synthase and cyclooxygenase-2 proteins expression. G-T-R decreased the production of a variety of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Moreover, G-T-R effectively suppressed the nuclear factor-kappa B (NF-κB) activation in LPS-stimulated RAW264.7 macrophages according to evaluation of the molecular inflammatory mechanisms. Thus, we suggest that G-T-R modulates several inflammatory pathways mediated by NF-κB activation, demonstrating its potential or preventing and treating inflammatory conditions.

In the present study, we evaluated the antioxidant and anti-stress activities of taurine in electric foot-shock stress model rats. Taurine supplementation markedly increased the hepatic glutathione (GSH) levels, compared to the levels in the stress group. In addition, activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were improved in the taurine-treated group. Plasma cortisol and dehydroepiandrosterone-sulfate (DHEA-S) levels were significantly reduced in the taurine-supplemented group compared to those in the stress group. In contrast, the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were markedly increased in the taurine or betaine-treated group compared to those in the stress group. It may be concluded that taurine produces beneficial effects in the form of antioxidant status and biochemical alterations in foot-shock-induced acute stress in rats.

Ribose-taurine (Rib-T) suppressed the generation of inflammatory mediators and cytokines, such as nitric oxide (NO) and prostaglandin E2 (PGE2) through the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β induced by LPS was effectively blocked by Rib-T. Moreover, the anti-inflammatory actions of Rib-T were involved in its inhibitory effects against the nuclear translocation of nuclear factor-kappa B (NF-κB) p65, and NF-κB DNA-binding activity. These results suggest that the anti-inflammatory action of Rib-T is associated with NF-κB regulation.

The dried flowers of Chionanthus retusus were extracted with 80% MeOH, and the concentrate was divided into EtOAc, n-BuOH, and H2O fractions. Repeated SiO2, octadecyl SiO2 (ODS), and Sephadex LH-20 column chromatography of the EtOAc fraction led to the isolation of four flavonols (1&ndash, 4), three flavones (5&ndash, 7), four flavanonols (8&ndash, 11), and one flavanone (12), which were identified based on extensive analysis of various spectroscopic data. Flavonoids 4&ndash, 6 and 8&ndash, 11 were isolated from the flowers of C. retusus for the first time in this study. Flavonoids 1, 2, 5, 6, 8, and 10&ndash, 12 significantly inhibited NO production in RAW 264.7 cells stimulated by lipopolysaccharide (LPS) and glutamate-induced cell toxicity and effectively increased HO-1 protein expression in mouse hippocampal HT22 cells. Flavonoids with significant neuroprotective activity were also found to recover oxidative-stress-induced cell damage by increasing HO-1 protein expression. This article demonstrates that flavonoids from C. retusus flowers have significant potential as therapeutic materials in inflammation and neurodisease.

The dried flowers of Chionanthus retusus were extracted with 80% MeOH, and the concentrate was divided into EtOAc, n-BuOH, and H2O fractions. Repeated SiO2, octadecyl SiO2 (ODS), and Sephadex LH-20 column chromatography of the EtOAc fraction led to the isolation of four flavonols (1–4), three flavones (5–7), four flavanonols (8–11), and one flavanone (12), which were identified based on extensive analysis of various spectroscopic data. Flavonoids 4–6 and 8–11 were isolated from the flowers of C. retusus for the first time in this study. Flavonoids 1, 2, 5, 6, 8, and 10–12 significantly inhibited NO production in RAW 264.7 cells stimulated by lipopolysaccharide (LPS) and glutamate-induced cell toxicity and effectively increased HO-1 protein expression in mouse hippocampal HT22 cells. Flavonoids with significant neuroprotective activity were also found to recover oxidative-stress-induced cell damage by increasing HO-1 protein expression. This article demonstrates that flavonoids from C. retusus flowers have significant potential as therapeutic materials in inflammation and neurodisease.

In the present study, we evaluated the antioxidant and anti-stress activities of taurine in electric foot-shock stress model rats. Taurine supplementation markedly increased the hepatic glutathione (GSH) levels, compared to the levels in the stress group. In addition, activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were improved in the taurine-treated group. Plasma cortisol and dehydroepiandrosterone-sulfate (DHEA-S) levels were significantly reduced in the taurine-supplemented group compared to those in the stress group. In contrast, the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were markedly increased in the taurine or betaine-treated group compared to those in the stress group. It may be concluded that taurine produces beneficial effects in the form of antioxidant status and biochemical alterations in foot-shock-induced acute stress in rats.

In the present study, we investigated the laxative effects of taurine in a rat model of loperamide-induced constipation. Rats were divided into six groups of six animals each: normal (NOR), control (CON), loperamide + Dulcolax (5.5 mg/kg, p.o.), and loperamide + various doses of taurine (7.5, 15, and 30 mg/kg, p.o.). Laxative activity was determined based on body weight, feeding characteristics, fecal properties, gastrointestinal transit (GIT) ratio, and the levels of serum gastrointestinal hormones. Taurine supplementation significantly increased the number, wet weight, and water content of fecal pellets in rats with loperamide-induced constipation. GIT ratio and loperamide-induced serum metabolic parameters, such as gastrin (GAS), motilin (MTL), and somatostatin (SS) significantly changed after supplementation with taurine in loperamide-induced constipated rats. We suggest that taurine had a potent effect against loperamide-induced constipation in part by increasing gastrointestinal motility.