Four new resin glycosides from Ipomoea muricata seeds: muricatins XIV-XVII.

Ipomoea muricata (L.) Jacq. seeds (Convolvulaceae) are used as a traditional laxative and carminative medicine. Muricatins XIV (1), XV (2), XVI (3), and XVII (4), were isolated from I. muricata seeds as four new resin glycosides, along with seven known compounds, three of which were isolated for the first time as natural products; their structures were determined using MS and NMR spectroscopy. Compounds 1-4 are macrolactones (jalapins); the sugar moieties of 1, 2, and 4 are partially acylated with 2S-methylbutyric acid, while that of 3 is esterified with 2S-methylbutyric and 2S-methyl-3S-hydroxybutyric acids. In addition, the antiviral activities of the seven compounds obtained in this study, together with five known compounds obtained in our previous study into resin glycosides from I. muricata seeds, were evaluated against herpes simplex virus type 1 (HSV-1); their cytotoxicities against HL-60 human promyelocytic leukemia cells were also investigated. All examined jalapins exhibited similar or slightly weaker anti-HSV-1 activities than acyclovir, the positive control; however, the glycosidic acid of 4 was inactive, while its methyl ester was weakly active. On the other hand, cytotoxicity testing against HL-60 cells showed similar results to those observed during anti-HSV-1 activity testing, with the exception that one jalapin was less active.

Development and Validation of a Nomogram for Predicting Obstructive Sleep Apnea Severity in Children.

Purpose: The clinical presentation of Obstructive Sleep Apnea (OSA) in children is insidious and harmful. Early identification of children with OSA, particularly those at a higher risk for severe symptoms, is essential for making informed clinical decisions and improving long-term outcomes. Therefore, we developed and validated a risk prediction model for severity in Chinese children with OSA to effectively identify children with moderate-to-severe OSA in a clinical setting. Patients and Methods: From June 2023 to September 2023, we retrospectively analyzed the medical records of 367 Children diagnosed with OSA through portable bedside polysomnography (PSG). Predictor variables were screened using the least absolute shrinkage and selection operator (LASSO) and logistic regression techniques to construct nomogram to predict the severity of OSA. Receiver operating characteristic curve (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to determine the discrimination, calibration, and clinical usefulness of the nomogram. Results: A total of 367 children with a median age of 84 months were included in this study. Neck circumference, ANB, gender, learning problem, and level of obstruction were identified as independent risk factors for moderate-severe OSA. The consistency indices of the nomogram in the training and validation cohorts were 0.841 and 0.75, respectively. The nomogram demonstrated a strong concordance between the predicted probabilities and the observed probabilities for children diagnosed with moderate-severe OSA. With threshold probabilities ranging from 0.1 to 1.0, the predictive model demonstrated strong predictive efficacy and yielded improved net benefit for clinical decision-making. ROC analysis was employed to classify the children into high and low-risk groups, utilizing the Optimal Cutoff value of 0.39. Conclusion: A predictive model using LASSO regression was developed and validated for children with varying levels of OSA. This model identifies children at risk of developing OSA at an early stage.

Ophiopogonin D ameliorates non­alcoholic fatty liver disease in high­fat diet­induced obese mice by improving lipid metabolism, oxidative stress and inflammatory response.

Lipid metabolic disorders, oxidative stress and inflammation in the liver are key steps in the progression of non-alcoholic fatty liver disease (NAFLD). Ophiopogonin D (OP-D), the main active ingredient of Ophiopogon japonicus, exhibits several pharmacological activities such as antioxidant and anti-inflammatory activities. Therefore, the current study aimed to explore the role of OP-D in NAFLD in a high-fat diet (HFD)-induced obesity mouse model. To investigate the effect of OP-D on NAFLD in vivo, a NAFLD mouse model was established following feeding mice with HFD, then the mice were randomly treated with HFD or HFD + OP-D for 4 weeks. Subsequently, primary mouse hepatocytes were isolated, and enzyme-linked immunosorbent assay, reverse transcription-quantitative PCR western blotting and immunofluorescence analysis were used for assessment to explore the direct effect of OP-D in vitro. The results of the present study indicated that OP-D could ameliorate NAFLD in HFD-induced obese mice by regulating lipid metabolism and antioxidant and anti-inflammatory responses. Additionally, OP-D treatment decreased lipogenesis and inflammation levels in vitro, suggesting that the NF-κB signaling pathway may be involved in the beneficial effects of OP-D on NAFLD.

Inhibition of suplatast tosilate on EPSC in the single paratracheal ganglion neurons attached with presynaptic boutons.

Using single neurons of rat paratracheal ganglia (PTG) attached with presynaptic boutons, the effects of suplatast tosilate on excitatory postsynaptic currents (EPSCs) were investigated with nystatin-perforated patch-clamp recording technique. We found that suplatast concentration dependently inhibited the EPSC amplitude and its frequency in single PTG neurons attached with presynaptic boutons. EPSC frequency was higher sensitive to suplatast than EPSC amplitude. IC50 for EPSC frequency was 1.1 × 10-5 M, being similar to that for the effect on histamine release from mast cells and lower than that for the inhibitory effect on cytokine production. Suplatast also inhibited the EPSCs potentiated by bradykinin (BK), but it did not affect the potentiation itself by BK. Thus suplatast inhibited the EPSC of PTG neurons attached with presynaptic boutons at both the presynaptic and postsynaptic sites.NEW & NOTEWORTHY In this study, using single neurons of rat paratracheal ganglia (PTG) attached with presynaptic boutons, the effects of suplatast tosilate on excitatory postsynaptic currents (EPSCs) were investigated with patch-clamp recording technique. We found that suplatast concentration dependently inhibited the EPSC amplitude and its frequency in single PTG neurons attached with presynaptic boutons. Thus suplatast inhibited the function of PTG neurons at both of presynaptic and postsynaptic sites.

The Effects of Orofacial Myofunctional Therapy on Children with OSAHS's Craniomaxillofacial Growth: A Systematic Review.

Orofacial myofunctional therapy (OMT) is one of the therapeutic methods for neuromuscular re-education and has been considered as one of the auxiliary methods for obstructive sleep apnea hypopnea syndrome (OSAHS) and orthodontic treatment. There is a dearth of comprehensive analysis of OMT's effects on muscle morphology and function. This systematic review examines the literature on the craniomaxillofacial effects of OMT in children with OSAHS. This systematic analysis was carried out using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards, and the research was scanned using PICO principles. A total of 1776 articles were retrieved within a limited time, with 146 papers accepted for full-text perusing following preliminary inspection and 9 of those ultimately included in the qualitative analysis. Three studies were rated as having a severe bias risk, and five studies were rated as having a moderate bias risk. Improvement in craniofacial function or morphology was observed in most of the 693 children. OMT can improve the function or morphology of the craniofacial surface of children with OSAHS, and its effect becomes more significant as the duration of the intervention increases and compliance improves. In the majority of the 693 infants, improvements in craniofacial function or morphology were seen. The function or morphology of a kid's craniofacial surface can be improved with OMT, and as the duration of the intervention lengthens and compliance rises, the impact becomes more pronounced.

Garlicnin B1, an Active Cyclic Sulfide from Garlic, Exhibits Potent Anti-Inflammatory and Anti-Tumor Activities.

This study aimed to investigate the pharmacological activities of garlicnin B1, a cyclic sulfide compound found abundantly in garlic and structurally similar to onionin A1, which has been shown to possess strong anti-tumor effects. In vitro studies demonstrated that garlicnin B1 significantly reduced intracellular reactive oxygen species triggered by hydrogen peroxide in colon cancer cells. In a mouse colitis model induced by dextran sulfate sodium, garlicnin B1 at a low dose (5 mg/kg) remarkably ameliorated the symptoms and pathological progression. Additionally, garlicnin B1 exhibited considerable tumoricidal activity with an IC50 value of ~20 µM, as observed in cytotoxicity assays. In vivo experiments using the mouse sarcoma S180 transplanted model and the azoxymethane (AOM) or DSS-induced colon cancer model showed that garlicnin B1 effectively suppressed tumor growth in a dose-dependent manner, with marked inhibition at 80 mg/kg. These results suggest that garlicnin B1 has diverse functions that could be achieved by carefully manipulating the dosing regimen. We anticipate that garlicnin B1 has the potential to be used beneficially in the future for the treatment of cancer and inflammatory diseases, although further studies are warranted to elucidate its mechanisms of action.

HPMA copolymer conjugated 5-aminolevulinic acid exhibits superior efficacy for photodynamic therapy with tumor-responsive and targeting properties.

In this study, we developed a nanoformulation of 5-aminolevulinic acid (5-ALA) for tumor-targeted photodynamic therapy, in which 5-ALA was conjugated with a biocompatible polymer N-(2-hydroxypropyl)methacrylamide (HPMA) through the hydrazone bond, i.e., P-ALA. P-ALA behaves as the nano-sized molecule with an average size of 5.5 nm in aqueous solution. P-ALA shows a largely increased release rate in acidic pH than physiological pH, suggesting the rapid release profile in acidic tumor environment. P-ALA did not show apparent cytotoxicity up to 0.1 mg/ml, however, under light irradiation, remarkable cell death was induced with the IC50 of 20-30 µg/ml. More importantly, we found significantly higher tumor accumulation of P-ALA than 5-ALA which benefit from its nano-size by taking advantage of the enhanced permeability and retention (EPR) effect. Consequently, P-ALA exhibited much improved in vivo antitumor efficacy without any apparent side effects. We thus anticipate the application of P-ALA as a nano-designed photosensitizer for anticancer photodynamic therapy.

Ripe Tomato Saponin Esculeoside A and Sapogenol Esculeogenin A Suppress CD4+ T Lymphocyte Activation by Modulation of Th2/Th1/Treg Differentiation.

We report that esculeoside A (EsA), a glycoside and a major component in ripe tomato fruit, ameliorated experimental dermatitis in mice. However, the underlying immunologic molecular mechanisms are unknown. The present study examined its underlying immune nutrition mechanism using concanavalin A (ConA)-blast mouse splenocyte primary culture. We found that EsA and its sapogenol esculeogenin A (Esg-A) concentration-dependently suppressed T-lymphoproliferation using CFSE-labeled flow-cytometry and water-soluble tetrazolium (WST) assay. Using ELISA and q-PCR methods, EsA/Esg-A showed profound decreases in T helper 2 (Th2)-relevant interleukin-4 (IL-4) secretion and mRNA expression, and GATA3 expression. Moreover, EsA/Esg-A suppressed CD4+ T-lymphocyte activation by decreasing IL-2 secretion and mRNA expression and CD25+ cell proportion. Further, EsA/Esg-A alleviated Treg suppressive activity by reducing IL-10 secretion, Foxp3 mRNA expression, and cell numbers. We suggest the immune nutrition function by tomato component, and highlight that EsA/Esg-A are capable of reducing CD4+ T-lymphocyte activation via a reduction in Th2-lymphocyte activity by modulation of Th2/Th1/Treg subunit differentiation.

Tumor Stimulus-Responsive Biodegradable Diblock Copolymer Conjugates as Efficient Anti-Cancer Nanomedicines.

Biodegradable nanomedicines are widely studied as candidates for the effective treatment of various cancerous diseases. Here, we present the design, synthesis and evaluation of biodegradable polymer-based nanomedicines tailored for tumor-associated stimuli-sensitive drug release and polymer system degradation. Diblock polymer systems were developed, which enabled the release of the carrier drug, pirarubicin, via a pH-sensitive spacer allowing for the restoration of the drug cytotoxicity solely in the tumor tissue. Moreover, the tailored design enables the matrix-metalloproteinases- or reduction-driven degradation of the polymer system into the polymer chains excretable from the body by glomerular filtration. Diblock nanomedicines take advantage of an enhanced EPR effect during the initial phase of nanomedicine pharmacokinetics and should be easily removed from the body after tumor microenvironment-associated biodegradation after fulfilling their role as a drug carrier. In parallel with the similar release profiles of diblock nanomedicine to linear polymer conjugates, these diblock polymer conjugates showed a comparable in vitro cytotoxicity, intracellular uptake, and intratumor penetration properties. More importantly, the diblock nanomedicines showed a remarkable in vivo anti-tumor efficacy, which was far more superior than conventional linear polymer conjugates. These findings suggested the advanced potential of diblock polymer conjugates for anticancer polymer therapeutics.

Decrease of Hyaluronidase Activity and Suppression of Mouse CD4+ T Lymphocyte Activation by Tomato Juice Saponin Esculeoside B, and Its Sapogenol Esculeogenin B.

(1) Background: A naturally occurring glycoside, esculeoside B (EsB), has been identified as a major component in juice or canned tomato. We reported how EsB ameliorated mice experimental atopic dermatitis by a decrease in serum IgE levels. However, the underlying immunologic molecular mechanisms are unknown. (2) Methods: The present study tested the effects of EsB on hyaluronidase activity and CD4+ T lymphocyte activation using concanavalin A (ConA)-blast mouse splenocyte primary culture. (3) Results: We found that EsB and its sapogenol esculeogenin B (Esg-B) decreased hyaluronidase activity by a modified Morgan-Elson method. We demonstrated that EsB/Esg-B dose-dependently suppressed T-lymphoproliferation using CFSE-labeled flow-cytometry and water-soluble tetrazolium (WST) assay. Using ELISA and q-PCR methods, EsB/Esg-B suppressed the cytokine secretion and mRNA expression of Th2-relevant IL-4 and Th1-relevant IFN-γ. Moreover, both EsB/Esg-B showed a reduction in IL-10 secretion, but only Esg-B decreased IL-2 secretion. (4) Conclusions: Our study is the first to demonstrate how EsB/Esg-B inhibit hyaluronidase activity and reduce CD4+ T-lymphocyte activation via a reduction in Th2-lymphocyte activity by modulation of Th2/Th1/Treg subunits differentiation.

Different effects on the tonus of colon and ileum isolated from mouse by resin glycoside (pharbitin) of Pharbitidis Semen.

BACKGROUND: Pharbitidis Semen (the seeds of Pharbitis nil), traditionally used as a purgative in Japan, China and Korea, contains a resin glycoside fraction named pharbitin, which is known as a purgative ingredient. Due to the complex nature of pharbitin, little is known about either the action on intestinal tension caused by resin glycoside itself or by its components. METHODS: In this study, we investigated the effects of pharbitin, the glycosidic acid fraction (pharbitic acid) and the aglycone fraction (phar-genin) generated from pharbitin on peristalsis of colon and ileum isolated from mice with the Magnus method. RESULTS: We demonstrated that pharbitin (3-30 µg/mL) concentration-dependently increased tonus of mice colon via acetylcholine receptors, its components phar-genin (1.27-12.7 µg/mL) and pharbitic acid (10-1000 µg/mL) also had the increment on colon tonus. On the other hand, ileum tension decreased in the presence of pharbitin. CONCLUSIONS: The effects of resin glycoside of Pharbitidis Semen on colon tonus are different with those on ileum tonus isolated from mice. In the next step it is necessary to investigate details of its pharmacological mechanism.

Expression Dynamics of Heme Oxygenase-1 in Tumor Cells and the Host Contributes to the Progression of Tumors.

Heme oxygenase (HO-1) plays an important role in cellular protection against various stresses. The induction of HO-1 is an effective strategy for reactive oxygen species-related diseases, inflammatory diseases, as well as suppressing carcinogenesis. On the other hand, the high expression of HO-1 is now well known in many tumors. In this study, we investigated the dynamics of HO-1 expression in the host and the tumor. In the mouse sarcoma S180 solid tumor model and the rat hepatoma AH136B ascitic tumor model, HO-1 expression in the tumor, as indicated by the end product of HO-1 activation, i.e., carbon monoxide, gradually increased along with tumor growth. Over-expression of HO-1 expression in mouse colon cancer C26 tumor cells significantly promoted tumor growth as well as lung metastasis, whereas opposite results were found when the HO-1 expression was reduced in the cells. On the other hand, upregulating HO-1 levels in the host by using an HO-1 inducer protected the progression of the xenograft tumor in mice, whereas lowering HO-1 expression in the host with an HO-1 inhibitor showed accelerated tumor growth and lung metastasis after subcutaneous tumor xenograft inoculation. These findings strongly suggest that the balance of HO-1 levels in the host and the tumor cells is essential for the occurrence, progression, and prognosis of cancer. Maintenance of appropriately high HO-1 levels in the host is favorable for cancer prevention, whereas suppression of HO-1 in the tumor cells may thus become a therapeutic strategy for cancer.

Styrene Maleic Acid Copolymer-Based Micellar Formation of Temoporfin (SMA@ mTHPC) Behaves as A Nanoprobe for Tumor-Targeted Photodynamic Therapy with A Superior Safety.

Tumor-targeted photodynamic therapy (PDT) using polymeric photosensitizers is a promising anticancer therapeutic strategy. Previously, we developed several polymeric nanoprobes for PDT using different polymers and PDT agents. In the study, we synthesized a styrene maleic acid copolymer (SMA) micelle encapsulating temoporfin (mTHPC) that is a clinically used PDT drug, SMA@mTHPC, with a hydrodynamic size of 98 nm, which showed high water solubility. SMA@mTHPC maintained stable micelle formation in physiological aqueous solutions including serum; however, the micelles could be disrupted in the presence of detergent (e.g., Tween 20) as well as lecithin, the major component of cell membrane, suggesting micelles will be destroyed and free mTHPC will be released during intracellular uptake. SMA@mTHPC showed a pH-dependent release profile, for which a constant release of ≈20% per day was found at pH 7.4, and much more release occurred at acidic pH (e.g., 6.5, 5.5), suggesting extensive release of free mTHPC could occur in the weak acidic environment of a tumor and further during internalization into tumor cells. In vitro cytotoxicity assay showed a lower cytotoxicity of SMA@mTHPC than free mTHPC; however, similar in vivo antitumor effects were observed by both SMA@mTHPC and free THPC. More importantly, severe side effects (e.g., body weight loss, death of the mice) were found during free mTHPC treatment, whereas no apparent side effects were observed for SMA@mTHPC. The superior safety profile of SMA@mTHPC was mostly due to its micelle formation and the enhanced permeability and retention (EPR) effect-based tumor accumulation, as well as the tumor environment-responsive release properties. These findings suggested SMA@mTHPC may become a good candidate drug for targeted PDT with high safety.

Calyhedins I-VI: Resin glycosides from the rhizomes of Calystegia hederacea.

Six previously undescribed resin glycosides, calyhedins I-VI, were isolated from the rhizomes of Calystegia hederacea Wall., which are the first genuine resin glycosides isolated from C. hederacea. The structures of calyhedins I-VI were determined based on spectroscopic data and chemical evidence. All the compounds have macrolactone structures (jalapins), and their sugar moieties were partially acylated by five organic acids. Calyhedins I, II-V, and VI have 27-, 28-, and 23-membered rings, respectively, and calyhedins IV-VI are the first jalapins with a sugar chain consisting of seven monosaccharides. Additionally, the cytotoxic activity of calyhedins II and III toward HL-60 human promyelocytic leukemia cells was evaluated. Both compounds demonstrated almost the same activity as the positive control, cisplatin.

Unraveling the role of Intralipid in suppressing off-target delivery and augmenting the therapeutic effects of anticancer nanomedicines.

Intralipid, a clinically used lipid emulsion, was reportedly utilized as one strategy to suppress off-target delivery of anticancer nanomedicines; Intralipid also effectively improved drug delivery to tumors and produced better therapeutic effects. However, the mechanisms involved-the why and how-in Intralipid's facilitation of delivery of nanomedicines to tumors have not yet been reported in detail. In this study, we investigated Intralipid and discovered the beneficial effects of Intralipid pretreatment when using three anticancer nanomedicines, including the clinically approved drug doxorubicin (Doxil). Intralipid pretreatment induced a 40% reduction in liver uptake of a polymeric nanoprobe used in photodynamic therapy as well as a 1.5-fold-increased nanomedicine accumulation in tumors. This increased accumulation consequently led to significantly better therapeutic effects, and this finding was validated by using Doxil. As an interesting result, Intralipid pretreatment significantly prolonged the plasma half-life of nanomedicines in normal healthy mice but not in tumor-bearing mice, which suggests that tumors become an alternative route of nanomedicine delivery when liver delivery is suppressed. Also, we found markedly increased tumor blood flow, as measured by fluorescence angiography, and significantly lower blood viscosity after Intralipid pretreatment. All our results together indicate that Intralipid treatment not only suppressed off-target nanomedicine delivery by the reticuloendothelial system, but more important, it enhanced nanomedicine delivery to tumors by improving tumor blood flow, which is key to satisfactory drug delivery via the enhanced permeability and retention effect. Significantly better therapeutic outcomes were thus achieved by the strategy of combining utilization of nanomedicines and Intralipid pretreatment. STATEMENT OF SIGNIFICANCE: Off-target delivery to organs such as the liver and obstructed tumor blood flow as is often seen in advanced cancers are major barriers to the therapeutic efficacy of anticancer nanomedicines. Intralipid has been shown effective for suppressing nanomedicine accumulation in the liver, resulting in improved anticancer effects. Unraveling the mechanisms involved in this process will be greatly helpful for the clinical application of anticancer nanomedicines. We reported here that Intralipid could also significantly increase tumor delivery of nanomedicine, which is beneficial for improving tumor blood flow and lowering blood viscosity. To our knowledge, this is the first study to investigate the role of Intralipid in this regard. This knowledge provides a solid rationale for the use of Intralipid in combination with anticancer nanomedicines.

Anti-proliferative Activities of Some Bivalent Symmetrical 5-Substituted Hydantoin Derivatives towards Human Brain Glioma U251 Cells (U251) and Human Carcinoma Cells (KB3-1).

Novel bivalent twin-drug type hydantoin derivatives were evaluated in vitro using a human brain glioma cell line (U251) and a human carcinoma cell line (KB3-1). Among the 5-substituted hydantoin derivatives (1a-b and 2a-d) examined in this study, bivalent symmetrical 5-substituted hydantoin derivative 1b showed the highest anti-proliferative activity towards both U251 and KB3-1 cells. The values of anti-proliferative activity (IC50) of this hydantoin derivative against the two cell lines (U251 and KB3-1) were 0.46 and 5.21 µM, respectively. The anti-proliferative activity of all of the compounds except for compounds 2a and 2d against U251 cells was higher than that of cisplatin. Bivalent symmetrical compound 1b had a biphenylmethane linker in the molecule. All of the tested bivalent hydantoin derivatives showed higher activity against U251 cells than against KB3-1 cells. For twin-drug type hydantoin derivatives 2a-d, which have a linear methylene linker in the molecules, it was found that methylene linker length in these molecules have an effect on the anti-proliferative activity against U251 and KB3-1 cells.

Anti-proliferative Activities towards Human Brain Glioma U251 Cells and Human Carcinoma Cells (KB3-1) of Some Twin-Drug Type Bivalent C2-Symmetrical Phenylboronic Acid Derivatives.

Derivatives of C2-symmetrical bivalent phenylboronic acid exhibit several remarkable biological activities such as anti-herpes simplex virus (HSV)-1 and cytotoxic activities against Vero cells and they can reverse the effect of anticancer drugs. Novel symmetrical bivalent molecules were synthesized and their biological activities were evaluated in vitro using a human brain glioma cell line (U251) and a human carcinoma cell line (KB3-1). Among the tested compounds (1a-i), bivalent C2-symmetrical phenylboronic acid derivative 1g showed the highest anti-proliferative activity towards both U251 and KB3-1 cells. The values of 50% anti-proliferative activity (IC50) of this compound against the two cell lines (U251 and KB3-1) were 19.0 and 3.78 µM, respectively. The anti-proliferative activity of compound 1g towards KB3-1 cells was higher than that of cisplatin. The bivalent C2-symmetrical compound 1g had a linear methylene linker in the molecule.

Preparation and Antiviral Activity of Some New C3- and CS-Symmetrical Tri-Substituted Triazine Derivatives Having Benzylamine Substituents.

We report the preparation of new C3- and CS-symmetrical molecules constructed on a triazine (TAZ) template. Anti-herpes simplex virus type 1 (anti-HSV-1) and cytotoxic activities against Vero cells of synthesized TAZ derivatives were evaluated. The results suggested that the presence of an electron-donating group(s) on the benzene ring in benzylamine groups on the TAZ template is an important structural factor for expressing a high level of anti-HSV-1 activity and low cytotoxicity for these C3 types of TAZ derivatives. Among the tested TAZ derivatives, compounds 4f and 7h showed the highest anti HSV-1 activities (EC50=0.98 and 1.23 µM, respectively) and low cytotoxic activities to Vero cells (50% cytotoxic concentration (CC50)=292.2 and >200 µM, respectively).

Direct Potentiation of Capsaicin Current by Histamine and Its Effect by Suplatast on Rat Trigeminal Ganglia Neurons.

In this study, we investigated the effect of histamine on capsaicin-induced current and its influence by suplatast in rat trigeminal ganglia neurons using a patch-clamp technique. We found that histamine directly potentiated capsaicin-induced currents in rat sensory neurons, and suplatast had little effect on this potentiation. Since it has been known that suplatast suppresses histamine release from mast cells, it is possible that suplatast inhibits the activation of nociceptive fibers in the pathological condition via prevention of histamine-induced potentiation of the transient receptor potential vanilloid 1 receptor-mediated currents.

Antiviral Activity and Molecular Geometry of Some New Symmetrical Tris(aminoalkyl)amine Derivatives.

We report the preparation of new tripodal receptor-type C3- and CS-symmetrical molecules constructed on a tris(2-aminoethyl)amine (TAEA) template. Both the anti-herpes simplex virus type 1 (anti-HSV-1) activity and cytotoxic activity of synthesized receptor-type derivatives were evaluated in order to find a characteristic structural feature for these bioactivities of compounds. Among the compounds of synthesized symmetrical TAEA-related derivatives, compound 13k showed high anti-HSV-1 activity (50% effective concentration (EC50)=16.7 µM) and low cytotoxicity (50% cytotoxic concentration (CC50)=>200 µM). The presence of a hydrogen bond donor proton in the molecule is thought to be an important structural factor for expressing potential anti-HSV-1 activities.