Inhibitory effects of catalpol on DNCB-induced atopic dermatitis and IgE-mediated mast cells reaction.

Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation. Catalpol is an iridoids, possessing anti-inflammatory, antioxidant, and neuroprotective activities. It can be added to food as a dietary supplement. To evaluate the effects and mechanisms of catalpol on AD, both in vitro and in vivo studies were conducted. It was found that catalpol downregulated the phosphorylation of Lyn and Syk to inhibit various downstream pathways, including intracellular Ca2+ elevation, cytokines generation, and histamine release, which ultimately controlled mast cell (MCs) degranulation. The results showed that catalpol alleviated AD-like skin lesions and MC infiltration via regulation of pro-Th2 and Th2 cytokines in vivo. Furthermore, this compound reduced the levels of IgE in AD mice and improved allergic reactions in PCA mice. The results provided that catalpol was potentially developed as a dietary supplement to improve AD and other atopic diseases.

Vasicine alleviates 2,4-dinitrochlorobenzene-induced atopic dermatitis and passive cutaneous anaphylaxis in BALB/c mice.

Atopic dermatitis (AD), a type of skin inflammation, is associated with immune response mediated by T-helper 2 (Th2) cells, and mast cells. Vasicine is an alkaloid isolated from Adhatoda vasica, a popular Ayurvedic herbal medicine used for treating inflammatory conditions. In the present study, the anti-AD effects of vasicine were evaluated on 2,4-dinitrochlorobenzene-induced AD-like skin lesions in BALB/c mice. The potential anti-allergic effects of vasicine were also assessed using the passive cutaneous anaphylaxis (PCA) test. The results showed that the oral administration of vasicine improved the severity of AD-like lesional skin by decreasing histopathological changes and restoring epidermal thickness. Vasicine also inhibited the infiltration of mast cells in the skin and reduced the levels of pro-Th2 and Th2 cytokines as well as immunoglobulin E in the serum. Finally, vasicine inhibited the expression of pro-Th2 and Th2 cytokines in skin tissues, indicating the therapeutic potential of vasicine for AD.

Discovery of novel indole and indoline derivatives against Candida albicans as potent antifungal agents.

With the widespread use of azole antifungals in the clinic, the drug resistance has been emerging continuously. In this work, we have designed and prepared a series of novel indole and indoline derivatives, and in vitro antifungal activity against C. albicans were evaluated. The results showed that title compounds exhibited good antifungal effect on Azole-resistant C. albicans. Further mechanism study demonstrated that S18 could inhibit the biofilm formation and hyphae growth of C. albicans through the Ras-cAMP-PKA signaling pathway.

Copper(II)-catalyzed Synthesis of Benzoxazoles from Inactive 2-chloroanilides.

AIM AND OBJECTIVE: Benzoxazoles are of great importance in natural products, pharmaceutical agents as well as synthetic intermediates. Although many works on the construction of benzoxazoles by Cu-catalyzed intramolecular O-arylation of ortho-haloanilides have been reported, only a few reports about transition metal-catalyzed synthesis of benzoxazoles from inactive 2-chloroanilides so far. This work aimed to explore a green and cheap protocol for intramolecular O-arylation of inactive 2-chloroanilides to prepare 2-arylbenzoxazoles. MATERIALS AND METHODS: We found that Cu(acac)2/1,10-Phen complex was beneficial to intramolecular O-arylation of 2-chloroanilides using K2CO3 as a base in EtOH at 90 °C to prepare benzoxazoles. RESULTS: An efficient and green method was developed for Cu(II)-catalyzed intramolecular Oarylation of inactive 2-chloroanilides. CONCLUSION: In this way, many 2-arylbenzoxazoles were prepared in good yields.

Antifungal Activity and Potential Mechanism of 6,7, 4'-O-Triacetylscutellarein Combined With Fluconazole Against Drug-Resistant C. albicans.

The increased resistance of Candida albicans to conventional antifungal drugs poses a huge challenge to the clinical treatment of this infection. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. This study assessed the effect of 6,7,4'-O-triacetylscutellarein (TA) combined with fluconazole (FLC) on C. albicans in vitro and in vivo. TA combined with FLC showed good synergistic antifungal activity against drug-resistant C. albicans in vitro, with a partial inhibitory concentration index (FICI) of 0.0188-0.1800. In addition, the time-kill curve confirmed the synergistic effect of TA and FLC. TA combined with FLC showed a strong synergistic inhibitory effect on the biofilm formation of resistant C. albicans. The combined antifungal efficacy of TA and FLC was evaluated in vivo in a mouse systemic fungal infection model. TA combined with FLC prolonged the survival rate of mice infected with drug-resistant C. albicans and reduced tissue invasion. TA combined with FLC also significantly inhibited the yeast-hypha conversion of C. albicans and significantly reduced the expression of RAS-cAMP-PKA signaling pathway-related genes (RAS1 and EFG1) and hyphal-related genes (HWP1 and ECE1). Furthermore, the mycelium growth on TA combined with the FLC group recovered after adding exogenous db-cAMP. Collectively, these results show that TA combined with FLC inhibits the formation of hyphae and biofilms through the RAS-cAMP-PKA signaling pathway, resulting in reduced infectivity and resistance of C. albicans. Therefore, this study provides a basis for the treatment of drug-resistant C. albicans infections.

Activity of Compound Agrimony Enteritis Capsules against invasive candidiasis: Exploring the differences between traditional Chinese medicine prescriptions and its main components in the treatment of diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Agrimony Enteritis Capsules (FFXHC) is an ethnomedicine derived from Yi Nationality Herbal Medicine for the treatment of enteritis. We found that compared to berberine hydrochloride (BBR), a component of this medicine, FFXHC was more efficacious in the mouse model of IC mice in significantly alleviating lung and intestinal lesions. " Our study provides a novel perspective into the pharmacological mechanism of action of the ethnic compound FFXHC. AIM OF THE STUDY: To determine the underlying mechanism of the superiority of FFXHC over BBR in IC. MATERIALS AND METHODS: The susceptibility of Candida albicans to FFXHC was evaluated in vitro. The mouse model of IC was established and the survival rate, weight change, the number of organ colonies, and immune organ coefficient of the mice were determined, the effect of FFXHC on the immune function of mice, including changes in the number of immune cells, levels of the related inflammatory cytokines (INF-γ, TNF-α, MCP-1, IL-6, and IL-17A), and the antimicrobial peptide, LL-37 (CRAMP in mice), were determined. Mice feces were collected and changes in the intestinal microecology were studied. RESULTS: Our findings indicated that FFXHC was not active against Candida albicans and did not restore the sensitivity of the resistant strain in vitro; however, it had a therapeutic effect that improve survival rate on mice with IC. The number of lymphocytes and neutrophils of mice with IC treated with FFXHC increased significantly. The intestinal microecology of mice was restored and the abundance of the probiotic Bacteroides was increased, which further stimulated the production of the antimicrobial peptide, LL-37, which is required for acquired immunity. Furthermore, the levels of Th cell-related cytokines, including INF-γ, TNF-α, and IL-17A were significantly increased, whereas those of the proinflammatory cytokines, IL-6 and MCP-1, decreased. With the activation of acquired immunity, the immune function of mice was restored, the body weight and survival rate of mice improved considerably, the coefficients of the thymus and spleen increased, and the number of fungal colonies in the lung and kidney decreased. CONCLUSIONS: FFXHC could eliminate fungi by increasing the relative abundance of probiotics in Bacteroides and the number of neutrophils, thereby promoting the production of CRAMP and resulting in a fungicidal effect, leading to acquired immunity. Although BBR has an antifungal effect, we found that it was not as effective as FFXHC.

Efficient Cu-catalyzed intramolecular O-arylation for synthesis of benzoxazoles in water.

An efficient method was developed for synthesis of benzoxazoles by Cu-catalyzed intramolecular O-arylation of o-halobenzanilides in water. This strategy provides several advantages, such as high yields, water as a green solvent and functional groups tolerance.

2-Benzoylbenzofuran derivatives possessing piperazine linker as anticancer agents.

A series of novel 2-benzoylbenzofuran derivatives possessing piperazine linker have been prepared, and their in vitro anticancer activity against a panel of human tumor cell lines by MTT assay were evaluated. The results demonstrated that tertiary amine derivatives exhibited better cytotoxic activity, and SAR study revealed that electron-donating substituents on the phenyl ring of the derivatization functionality contributed to potent anticancer activities. Among them, compounds 6, 9, 11, 18, 23 and 25 displayed both better anti-tumor activity and lower cytotoxic effect on human normal liver cell L02. Further apoptosis analysis showed that compound 18 significantly induced apoptosis in A549 cell, which was considered as the most potent anticancer agent.

Synthesis and Biological Evaluation of New Piperazine Substituted 3, 5-Diarylisoxazolines.

AIM AND OBJECTIVE: Isoxazolines are an important class of nitrogen and oxygen-containing heterocycles, which have gained much importance as the potential biological agents. In order to study structureactivity relationships of isoxazolines, this work has been conducted. MATERIALS AND METHODS: A series of new piperazine substituted 3, 5-diarylisoxazoline derivatives (6-31) were designed and synthesized, and in vitro anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and anticancer effect against a panel of human tumor cell lines (Hela, A549 and SGC7901) by MTT assay were evaluated. RESULTS: The substituents of the NH group of piperazine ring had an obvious influence on biological activities. Especially, compounds 5, 7, 8, 10, 11, 13 and 27-showed good inhibitory effect on the generation of NO compared to dexamethasone. Furthermore, derivatives 5, 6, 7, 8, 9, 13 and 26 were found to be potential selectively anticancer activity on human tumor cell lines, which displayed better cytotoxic activity to positive control 5- FU. CONCLUSION: Piperazine substituted 3, 5-diarylisoxazoline derivatives could be considered as new antiinflammatory and anticancer agents.

Synthesis of Scutellarein Derivatives with a Long Aliphatic Chain and Their Biological Evaluation against Human Cancer Cells.

Scutellarin is the major active flavonoid extracted from the traditional Chinese herbal medicine Erigeron breviscapus (Vant.) Hand-Mazz., which is widely used in China. Recently, accumulating evidence has highlighted the potential role of scutellarin and its main metabolite scutellarein in the treatment of cancer. To explore novel anticancer agents with high efficiency, a series of new scutellarein derivatives with a long aliphatic chain were synthesized, and the antiproliferative activities against Jurkat, HCT-116 and MDA-MB-231 cancer cell lines were assessed. Among them, compound 6a exhibited the strongest antiproliferative effects on Jurkat (IC50 = 1.80 µM), HCT-116 (IC50 = 11.50 µM) and MDA-MB-231 (IC50 = 53.91 µM). In particular, 6a even showed stronger antiproliferative effects than the positive control NaAsO2 on Jurkat and HCT-116 cell lines. The results showed that a proper long aliphatic chain enhanced the antiproliferative activity of scutellarein.

Kudinoside-D, a triterpenoid saponin derived from Ilex kudingcha suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes.

The leaves of Ilex Kudingcha, locally named "Kudingcha" in China, has been traditionally applied for treating obesity. Studies have demonstrated that the ethanol extract of Ilex kudingcha have anti-adipogenic effects. However, the constituent which was responsible for its anti-obesity and its underlying molecular mechanism has not yet been elucidated. This research explored the anti-obesity effect of kudinoside-D which was a main natural component of triterpenoid saponin from the ethanol extract of Ilex kudingcha, on lipid accumulation and the potential mechanism of action of adipogenesis in 3T3-L1 adipocytes. The adipocytes were treated with various concentrations of kudinoside D (0 to 40µM) during differentiation. The image-based Oil Red O staining analyses revealed that KD-D, dose dependently reduced cytoplasmic lipid droplet in 3T3-L1 adipocytes with the IC50 is 59.49µM. Meanwhile, major adipogenic transcription factor peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein-α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c) were significantly repressed as well as their target genes. The phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated-acetyl CoA carboxylase (ACC) expression were also increased. In addition, the inhibitory effects of KD-D on the expressions of PPARγ and C/EBPα were weakened when cells were cotreated with AMPK inhibitor Compound C. These results indicated KD-D exerts anti-adipogenic effects through modulation of adipogenic transcription factors via AMPK signaling pathway. And the current findings demonstrated that KD-D was a potential therapeutic candidate for alleviating obesity and hyperlipidemia.

Three new C-alkylated flavonoids from Desmodium oblongum.

Three new C-alkylated flavonoids, 4'-hydroxy-8-isobutyryl-7-methoxy-6-methyl-flavone (1), 4',7-dimethoxy-8-isobutyryl-6-methyl-flavone (2), and 4',7-dimethoxy-8-isobutyryl-flavone (3), together with three know ones luteolin (4), kaemferol (5), and quercetin (6), were isolated from Desmodium oblongum. Their structures were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. Compound 1 showed cytotoxicity against NB4, SHSY5Y, and MCF7 cell lines with IC50 values of 8.5, 6.5, and 7.8 µM; compound 2 showed cytotoxicity against SHSY5Y and PC3 cell lines with IC50 values of 5.0 and 6.8 µM; compound 3 displayed cytotoxicity against SHSY5Y and MCF7 cell lines with IC50 values of 6.4 and 9.4 µM, respectively.

Simultaneous Qualitation and Quantitation of Chlorogenic Acids in Kuding Tea Using Ultra-High-Performance Liquid Chromatography-Diode Array Detection Coupled with Linear Ion Trap-Orbitrap Mass Spectrometer.

Kuding tea, the leaves of Ilex Kudingcha C.J. Tseng, has been applied for treating obesity, hypertension, cardiovascular disease, hyperlipidemia, and so on. The chlorogenic acids (CGAs) in Kuding tea have shown excellent antioxidative, antiobesity, anti-atherosclerotic and anticancer activities. Nevertheless, the chemical profiles of CGAs in Kuding tea have not been comprehensively studied yet, which hinders further quality control. In the present study, a sensitive ultra-high-performance liquid chromatography-diode array detection coupled with a linear ion trap-Orbitrap (UHPLC-DAD-LTQ-Orbitrap) method was established to screen and identify CGAs in Kuding tea. Six CGA standards were first analyzed in negative ion mode with a CID-MS/MS experiment and then the diagnostic product ions (DPIs) were summarized. According to the retention behavior in the RP-ODS column, accurate mass measurement, DPIs and relevant bibliography data, a total of 68 CGA candidates attributed to 12 categories were unambiguously or preliminarily screened and characterized within 18 min of chromatographic time. This was the first systematic report on the distribution of CGAs in Kuding tea. Meanwhile, the contents of 6 major CGAs in Kuding tea were also determined by the UHPLC-DAD method. All the results indicated that the established analytical method could be employed as an effective technique for the comprehensive and systematic characterization of CGAs and quality control of the botanic extracts or Chinese medicinal formulas that contain various CGAs.

Design, Synthesis, and Biological Evaluation of Novel Benzofuran Derivatives Bearing N-Aryl Piperazine Moiety.

A series of novel hybrid compounds between benzofuran and N-aryl piperazine have been synthesized and screened in vitro for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages and for anticancer activity against three human tumor cell lines. The results demonstrated that derivative 16 not only had inhibitory effect on the generation of NO (IC50 = 5.28 µM), but also showed satisfactory and selective cytotoxic activity against human lung cancer line (A549) and gastric cancer cell (SGC7901) (IC50 = 0.12 µM and 2.75 µM, respectively), which was identified as the most potent anti-inflammatory and anti-tumor agent in this study.

Design, synthesis and anticancer activity of novel hybrid compounds between benzofuran and N-aryl piperazine.

A series of novel hybrid compounds between benzofuran and N-aryl piperazine have been designed and prepared. These derivatives were evaluated for their in vitro anti-tumor activity against a panel of human tumor cell lines by MTT assay. The results demonstrated that amide derivatives were more bioactive than sulfonamide compounds in general, and that chloro or trifluoromethyl substituent was vital for modulating cytotoxic activity. In particular, compound 13 was found to be the most potent compound against 4 strains human tumor cell lines, and exhibited cytotoxic activity selectively against Hela (0.03µM).

Roemerine Improves the Survival Rate of Septicemic BALB/c Mice by Increasing the Cell Membrane Permeability of Staphylococcus aureus.

Staphylococcus aureus is one of the most frequently occurring hospital- and community-associated pathogenic bacteria featuring high morbidity and mortality. The occurrence of methicillin-resistant S. aureus (MRSA) has increased persistently over the years. Therefore, developing novel anti-MRSA drugs to circumvent drug resistance of S. aureus is highly important. Roemerine, an aporphine alkaloid, has previously been reported to exhibit antibacterial activity. The present study aimed to investigate whether roemerine can maintain these activities against S.aureus in vivo and further explore the underlying mechanism. We found that roemerine is effective in vitro against four S. aureus strains as well as in vivo against MRSA insepticemic BALB/c mice. Furthermore, roemerine was found to increase cell membrane permeability in a concentration-dependent manner. These findings suggest that roemerine may be developed as a promising compound for treating S. aureus, especially methicillin-resistant strains of these bacteria.

Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms.

Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 µg/mL RM inhibited biofilm formation significantly (p < 0.01) both in Spider medium and Lee's medium. In addition, RM could inhibit yeast-to-hyphae transition of C. albicans in a dose-dependent manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6, HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 µg/mL RM treatment. Furthermore, the toxicity of RM was investigated using C. elegans worms, three cancer cells and one normal cell. The date showed that RM had no significant toxicity. In conclusion, RM could inhibited the formation of C. albicans biofilm in vitro, but it had no fungicidal effect on planktonic C. albicans cells, and the anti-biofilm mechanism may be related to the cAMP pathway.

[Study on Chemical Constituents of Peanut Hull].

OBJECTIVE: To investigate the chemical constituents of peanut hull. METHODS: Several chromatography methods such as silica gel and Sephadex LH-20 combined with recrystallization were applied to isolate the compounds. Based on spectrum technologies (MS,1H-NMR and 13C-NMR) and physico-chemical methods, structures of isolated compounds were identified. RESULTS: Twelve compounds were isolated and elucidated as luteolin (1), diosmetin (2), 5,7,3',4'-tetrahydroxy-8-prenyflavone (3),5,7,3'-trihydroxy-4'- methoxy-8-prenylflavone(4), eriodicrtyol (5), racemoflavone (6), hydnocarpin (7), 5,7-dihydroxy chromone (8), 5-hydroxy-chromone- 7-O-ß-D-glucoside (9), ferulic acid (10), ß-sitosterol (11) and daucosterol(12). CONCLUSION: Except compounds 1, 5 and 8, all compounds are obtained from peanut hull for the first time.

Limonoids from the fruits of Cipadessa cinerascens.

A new limonoid, 3-de(2-methylbutanoyl)-3-propanoylcipadesin (1), along with 10 known limonoids and 1 known triterpenoid, was isolated from the fruits of Cipadessa cinerascens. Their structures were elucidated on the basis of spectroscopic analysis. All compounds were evaluated for their antimicrobial activities, and compounds 6 and 12 showed weak antimicrobial activities against MRSA 82(#) and MRSA 92(#).

[Chemical constituents from aerial part of Aconitum brachypodum].

OBJECTIVE: To study the chemical constituents from the aerial part of Aconitum brachypodum. METHODS: The constituents were isolated and purified by silica gel, activated alumina and Sephadex LH-20 column chromatography. their structures were elucidated on the basis of spectral data and physiochemical evidence. RESULTS: Eleven compounds were isolated from 80% ethanol extract and identified as secokaraconitine (1), brachyaconitines A (2), C (3), talatisamine (4), hypaconitine (5), songrine (6), bullatine A (7), 7-carbony sitosterone (8), lupeol (9), ß-sitosterol (10) and daucosterol (11). CONCLUSION: All compounds are isolated from the aerial part of Aconitum brachypodum for the first time.