Inhibitory effects of Jasminum grandiflorum L. essential oil on lipopolysaccharide-induced microglia activation-integrated characteristic analysis of volatile compounds, network pharmacology, and BV-2 cell.

Neuroinflammation is considered to have a prominent role in the pathogenesis of Alzheimer's disease (AD). Microglia are the resident macrophages of the central nervous system, and modulating microglia activation is a promising strategy to prevent AD. Essential oil of Jasminum grandiflorum L. flowers is commonly used in folk medicine for the relief of mental pressure and disorders, and analyzing the volatile compound profiles and evaluating the inhibitory effects of J. grandiflorum L. essential oil (JGEO) on the excessive activation of microglia are valuable for its application. This study aims to explore the potential active compounds in JGEO for treating AD by inhibiting microglia activation-integrated network pharmacology, molecular docking, and the microglia model. A headspace solid-phase microextraction combined with the gas chromatography-mass spectrometry procedure was used to analyze the volatile characteristics of the compounds in J. grandiflorum L. flowers at 50°C, 70°C, 90°C, and 100°C for 50 min, respectively. A network pharmacological analysis and molecular docking were used to predict the key compounds, key targets, and binding energies based on the detected compounds in JGEO. In the lipopolysaccharide (LPS)-induced BV-2 cell model, the cells were treated with 100 ng/mL of LPS and JGEO at 7.5, 15.0, and 30 µg/mL, and then, the morphological changes, the production of nitric oxide (NO) and reactive oxygen species, and the expressions of tumor necrosis factor-α, interleukin-1ß, and ionized calcium-binding adapter molecule 1 of BV-2 cells were analyzed. A total of 34 compounds with significantly different volatilities were identified. α-Hexylcinnamaldehyde, nerolidol, hexahydrofarnesyl acetone, dodecanal, and decanal were predicted as the top five key compounds, and SRC, EGFR, VEGFA, HSP90AA1, and ESR1 were the top five key targets. In addition, the binding energies between them were less than -3.9 kcal/mol. BV-2 cells were activated by LPS with morphological changes, and JGEO not only could clearly reverse the changes but also significantly inhibited the production of NO and reactive oxygen species and suppressed the expressions of tumor necrosis factor-α, interleukin-1ß, and ionized calcium-binding adapter molecule 1. The findings indicate that JGEO could inhibit the overactivation of microglia characterized by decreasing the neuroinflammatory and oxidative stress responses through the multi-compound and multi-target action modes, which support the traditional use of JGEO in treating neuroinflammation-related disorders.

The Aggregates of Near-Infrared Cyanine Dyes in Phototherapy.

Cyanines in the near-infrared region are a typical example of a classic fluorescent dye that has garnered significant attention and widespread use in the life sciences and biotechnology. Their character to form assemblies or aggregates has inspired the development of various functional cyanine dye aggregates in phototherapy. This article provides a brief summary of the strategies used to prepare these cyanine dye aggregates. The reports in this concept suggest that the self-assembly of cyanine dyes can enhance their photostability, opening up new possibilities for their application in phototherapy. This concept may encourage researchers to explore the development of functional fluorescent dye aggregates further.

Aconitine Induces TRPV2-Mediated Ca2+ Influx through the p38 MAPK Signal and Promotes Cardiomyocyte Apoptosis.

Aconitine is the main effective component of traditional Chinese medicine Aconitum, which has been proved to have severe cardiovascular toxicity. The toxic effect of aconitine on cardiomyocytes is related to intracellular calcium overload, but the mechanism remains unclear. The aim of this study was to explore the mechanism of aconitine inducing intracellular Ca2+ overload and promoting H9c2 cardiomyocyte apoptosis through transient receptor potential cation channel subfamily V member 2 (TRPV2). After treated with different concentrations of aconitine, the level of cell apoptosis, intracellular Ca2+, and expression of p-p38 MAPK and TRPV2 of H9c2 cardiomyocytes were detected. The results showed that aconitine induced Ca2+ influx and H9c2 cardiomyocyte apoptosis in a dose-dependent manner and promoted p38 MAPK activation as well as TRPV2 expression and plasma membrane (PM) metastasis. siTRPV2, tranilast, and SB202190 reversed intracellular Ca2+ overload and H9c2 cardiomyocyte apoptosis induced by aconitine. These results suggested that aconitine promoted TRPV2 expression and PM metastasis through p38 MAPK signaling, thus inducing intracellular Ca2+ overload and cardiomyocyte apoptosis. Furthermore, TRPV2 is a potential molecular target for the treatment of aconitine poisoning.

The effects of aloe emodin-mediated antimicrobial photodynamic therapy on drug-sensitive and resistant Candida albicans.

The extensive and repetitive use of antifungal drugs has led to the development of drug-resistant Candida albicans. Antimicrobial photodynamic therapy (aPDT) has received considerable attention as an emerging and promising approach to combat drug-resistant microbes. This study evaluated the photodynamic effects mediated by aloe emodin (AE), a natural compound isolated from Aloe vera and Rheum palmatum, on azole-sensitive and azole-resistant C. albicans in vitro. AE exhibited no significant dark toxicity, but in the presence of light, effectively inactivated C. albicans cells in a concentration-dependent manner. The uptake of AE by fungal cells was investigated by confocal laser scanning microscopy (CLSM), and the results showed that AE possessed stronger ability to enter into C. albicans cells following light irradiation. Transmission electron microscopy analysis suggested that AE-mediated aPDT could induce damage to the cell wall, cytoplasm, and nucleus. Damage to the surface of C. albicans was observed by scanning electron microscopy. These results suggest that AE is a potential PS for use in aPDT of drug-resistant C. albicans strains, and AE-mediated aPDT shows promise as an antifungal treatment.

Antimicrobial photodynamic therapy against multidrug-resistant Acinetobacter baumannii clinical isolates mediated by aloe-emodin: An in vitro study.

BACKGROUND AND AIM: Antimicrobial photodynamic therapy (aPDT) has received considerable attention as an emerging and promising approach for treating superficial infections. The aim of this study was to investigate aPDT mediated by aloe emodin (AE), a natural compound isolated from Aloe vera and Rheum palmatum, against multidrug-resistant (MDR) Acinetobacter baumannii clinical isolates in vitro. METHODS: The photodynamic inactivation (PDI) efficacies of AE on three MDR A. baumannii isolates were assessed by colony forming units (CFU) assay. The aPDT effects mediated by AE on the genomic DNA, membrane integrity, and cellular structure of MDR A. baumannii were also investigated. RESULTS: AE showed no obvious dark toxicity, but inactivated the MDR A. baumannii isolates in an AE concentration and light energy dose-dependent manner. Agarose gel electrophoresis and LIVE/DEAD BacLight Bacterial Viability kit assay indicated that the genomic DNA and membrane integrity of MDR A. baumannii were damaged after AE-mediated aPDT treatment. Transmission electron microscopy (TEM) images demonstrated that AE-mediated aPDT could induce rupture of bacterial cell wall and membrane, and condensation of ribosomes in the cytoplasm. CONCLUSIONS: The results obtained in this study suggested that AE could serve as a potential antibacterial photosensitizer in the treatment of superficial infections caused by MDR A. baumannii.

Pharmacokinetic/pharmacodynamic evaluation of linezolid for the treatment of staphylococcal infections in critically ill patients.

Several studies have demonstrated that the ideal therapeutic effect of linezolid cannot be achieved in critically ill patients with the recommended standard dosing regimen of 600 mg every 12 h (q12h). Moreover, the optimal strategy for successful treatment is still lacking. This study analysed factors influencing the efficacy of linezolid treatment and determined the target for successful treatment by logistic regression in 27 critically ill patients with staphylococcal infection who received linezolid 600 mg q12h. The results showed that only the 24-h area under the concentration-time curve to minimum inhibitory concentration (AUC24/MIC) ratio was significantly associated with staphylococcal eradication. Reaching 80% bacterial eradication required an AUC24/MIC of 120.5, defining the therapeutic target. Different dosing regimens were evaluated using Monte Carlo simulation to determine the optimal dosage strategy for linezolid. Although the probability of target attainment (PTA) was high (>99.9%) for the standard dosing regimen at MIC ≤ 1 mg/L, the PTA was almost 0 at MIC = 2 mg/L, thus the dosing regimen required adjustment. In addition, if the dosing regimen was adjusted to 600 mg every 8 h or 600 mg every 6 h, the major staphylococci (except for MRSA and MSSA) exhibited a cumulative fraction of response of >80%, showing a higher treatment success. These findings indicate that a strategy of high linezolid dosage may be needed to increase the probability of successful treatment at MIC > 1 mg/L. The role of therapeutic drug monitoring should be encouraged for optimising linezolid exposure in critically ill patients.

Efficacy of thymosin α1 and interferon α for the treatment of severe acute pancreatitis in a rat model.

The present study aimed to investigate the effects of treatment with thymosin α1 (TA1) or interferon α (IFNα) following the establishment of severe acute pancreatitis (SAP) in rats. A total of 144 Sprague­Dawley rats were randomly divided into four groups. The rats in all four groups were celiotomized, and the rats in the control group were administered with an intravenous injection of saline. The three other groups were administered with 5% 1 ml/kg sodium taurocholate via the cholangiopancreatic duct. SAP group rats were administered with an intravenous injection of saline; TA1 group rats received 26.7 µg/kg TA1; and interferon α (INFα) group rats received 4.0x105 U/kg IFNα. The rats were anesthetized and blood samples were collected from the animals 3, 12 and 24 h after surgery. The levels of T cell subsets, serum enzyme indicators, cytokines and procalcitonin (PCT) were measured. The general conditions of the rats were observed until sacrifice, and pancreatic and lung tissue samples were sampled for hematoxylin and eosin staining and histological scoring. The expression levels of aspartate transaminase, lactate dehydrogenase, α­amylase (AMY), P­type­amylase, lipase, PCT, tumor­necrosis factor α, interleukin (IL)­4, IL­5, and IL­18 in the TA1 and IFNα­treated rats were significantly lower, compared with those of the SAP rats within the first 24 h of model establishment (P<0.05). The TA1 and IFNα­treated rats exhibited significantly increased levels of CD3+, CD4+ and CD8+ T cells, and an increased ratio of CD4+/CD8+ cells, compared with SAP rats. Histological analysis revealed that the TA1 and IFNα­treated rats exhibited significantly ameliorated pancreas and lung damage, and mortality rates were reduced from 50.0% (6/12) to 25.0% (3/12) and 33.3% (4/12), respectively. The immunomodulatory agents TA1 and IFNα reduced acute inflammation, decreasing cell damage and enhancing immune function and survival rates in the SAP rats.

Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines.

Conifer somatic embryogenesis: improvements by supplementation of medium with oxidation-reduction agents.

A major barrier to the commercialization of somatic embryogenesis technology in loblolly pine (Pinus taeda L.) is recalcitrance of some high-value crosses to initiate embryogenic tissue (ET) and continue early-stage somatic embryo growth. Developing initiation and multiplication media that resemble the seed environment has been shown to decrease this recalcitrance. Glutathione (GSH), glutathione disulfide (GSSG), ascorbic acid and dehydroascorbate analyses were performed weekly throughout the sequence of seed development for female gametophyte and zygotic embryo tissues to determine physiological concentrations. Major differences in stage-specific oxidation-reduction (redox) agents were observed. A simple bioassay was used to evaluate potential growth-promotion of natural and inorganic redox agents added to early-stage somatic embryo growth medium. Compounds showing statistically significant increases in early-stage embryo growth were then tested for the ability to increase initiation of loblolly pine. Low-cost reducing agents sodium dithionite and sodium thiosulfate increased ET initiation for loblolly pine and Douglas fir (Mirb) Franco. Germination medium supplementation with GSSG increased somatic embryo germination. Early-stage somatic embryos grown on medium with or without sodium thiosulfate did not differ in GSH or GSSG content, suggesting that sodium thiosulfate-mediated growth stimulation does not involve GSH or GSSG. We have developed information demonstrating that alteration of the redox environment in vitro can improve ET initiation, early-stage embryo development and somatic embryo germination in loblolly pine.

Authentication of Polygonati Odorati Rhizoma and other two Chinese Materia Medica of the Liliaceae family by pharmacognosy technique with GC-MS analysis.

Yuzhu (Polygonati Odorati Rhizoma), Kangdingyuzhu (Polygonati Prattii Rhizoma), and zhugenqiyuzhu (Disporopsis Fuscopictae Rhizoma) are of the same family, but of different genera. They have all often used in Chinese Materia Medica (CMM) as Polygonati Odorati Rhizoma in China market. Three species of CMM are confused. For better application, we need to identify these plants accurately. This study use pharmacognosy technique and GC-MS analysis, three species of CMM were authenticated. In macroscopic characteristics, the fruit of Polygonati Odorati Rhizoma is blue-black, while the other two are maroon and dark purple orderly. Nodes of Polygonati Odorati Rhizoma are upward and light uplift, about 1 cm spacing, while the other are not. As for microscopic characteristics, the cortex of Polygonati Odorati Rhizoma only occupies about 1/5 of the radius of the transverse section with inconspicuous endodermis, which is much smaller than others. The type of vascular bundles of Polygonati Odorati Rhizoma is closed collateral, but the other is amphivasal. Raphides of calcium oxalate are scattered, but Raphides of the other two are like brooms and neat rows. GC-MS analysis of essential oil could provide different characteristics to distinguish three species. Twenty-three compounds were identified from essential oil of Polygonati Odorati Rhizoma and the main components were n-hexadecanoic acid (49.45%), while n-hexadecanoic acid of the other two are 23.92% and 9.45%. The content of n-hexadecanoic is strongly different. This research was aimed to establish a method by pharmacognosy and GC-MS analysis to identify three CMM and for providing scientifical data to ensure accuracy of origin of three species.

[Determination of forsythiaside B and poliumoside in different origin and parts from Callicarpa kwangtungensis].

The RP-HPLC method was used to determinate the contents of forsythiaside B and poliumoside in different origin and parts from Callicarpa kwangtungensis. The linear ranges of forsythiaside B and poliumoside were 0. 106-3. 18 and 0. 105 2-3. 156 microg, respectively. The average recoveries of forythiaside B and poliumoside were 99. 01% ( RSD 1. 2%) and 100. 13% (RSD 0. 90% ), respectively. The contents of forsythiaside B and poliumoside were changed in different origin and parts from C. kwangtungensis. The sample from the area of Luxi, Pingxiang City, Jiangxi Province has the highest contents of forsythiaside B and poliumoside. The contents of forsythiaside B and poliumoside in different parts from C. kwangtungensis in Luxi are: leaf > stem > fruit. This result will provide a scientific basis for quality control and reasonable utilzation of C. kwangtungensis.

[Study on the extraction of indirubin from Isatis indigotica Fort].

OBJECTIVE: To study the optimal process of the extraction of indirubin from Isatis indigotica Fort. METHODS: The process was studied by supersonic extraction, refluxing and orthogonal design with the content of indirubin as the detective marker. Then the extraction of indirubin with supersonic extraction and other methods were compared basing on the yield of extracts. RESULTS: Among them, the supersonic extraction was the simplest and the most rapid and the most complete in extraction. And the optimal conditions were A1 B1 C2 D3: supersonic extraction with 60% ethanol, 1 hour, 10-fold solvent and 3 times. CONCLUSION: The supersonic extraction can extract more indirubin from Isatis indigotica Fort in shorter time with less energy. It also shows a promising prospect for leaching the effective constituents from Chinese herbal medicine by supersonic extraction.