Molecular mechanism underlying coencapsulating chrysophanol and hesperidin in octenylsuccinated ß-glucan aggregates for improving their corelease and bioaccessibility.

Chrysophanol and hesperidin are natural nutraceuticals that exhibit synergistic bioactivities, but their hydrophobicity limits their applications, and it is unclear whether coencapsulation can improve their solubility and release behaviors. The objective of this work was to coencapsulate chrysophanol and hesperidin by octenylsuccinated ß-glucan aggregates (OSßG-Agg) and to reveal how coencapsulation improves their release and bioaccessibility. Mechanisms underlying the hypothesis of beneficial effects in coloading, corelease and bioaccessibility were revealed. The solubilization of OSßG-Agg was due to hydrogen-bonding among ß-glucan moieties of OSßG and hydroxyl groups of chrysophanol and hesperidin and hydrophobic interactions among octenyl chains of OSßG and hydrophobic moieties of chrysophanol and hesperidin. Structural analyses confirmed the hypothesis that chrysophanol molecules were nearly embedded deeper into the interior of hydrophobic domains, and most of hesperidin molecules were incorporated into the exterior of the hydrophobic domains of OSßG-Agg due to the strength of these interactions, but they interacted in OSßG-Agg with a dense and compact structure rather than existing in isolation. The combined effects delayed their release and enhanced their bioaccessibility because of dynamic equilibrium between the favorable interactions and unfavorable structural erosion and relaxation of OSßG-Agg. Overall, OSßG-Agg is effective at codelivering hydrophobic phenolics for functional foods and pharmaceuticals.

Preparation of Rehmanniae Radix Praeparata Polysaccharide Iron(III) Complex and Evaluation of Its Biological Activity.

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron (III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×104 Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties.

Mechanism underlying joint loading and controlled release of ß-carotene and curcumin by octenylsuccinated Gastrodia elata starch aggregates.

This study aimed to fabricate a novel codelivery system to simultaneously load ß-carotene and curcumin in a controlled and synergistic manner. We hypothesized that the aggregates of octenylsuccinated Gastrodia elata starch (OSGES) could efficiently load and control the release of ß-carotene and curcumin in combination. Mechanisms underlying the self-assembly of OSGES, coloading, and corelease of ß-carotene and curcumin by relevant aggregates were studied. The OSGES could form aggregates with a size of 120.2 nm containing hydrophobic domains surrounded by hydrophilic domains. For coloading, the increased solubilities were attributed to favorable interactions between ß-carotene and curcumin as well as interactions with octenyl and starch moieties via hydrophobic and hydrogen-bond interactions, respectively. The ß-carotene and curcumin molecules occupied the interior and periphery of hydrophobic domains of OSGES aggregates, respectively, and they did not exist in isolation but interacted with each other. The ß-carotene and curcumin combination-loaded OSGES aggregates with a size of 310.5 nm presented a more compact structure than ß-carotene-only and curcumin-only loaded OSGES aggregates with sizes of 463.5 and 202.9 nm respectively, suggesting that a transition from a loose cluster to a compact cluster was accompanied by coloading. During in vitro digestion, the joint effect of ß-carotene and curcumin prolonged their release and increased their bioaccessibility due to competition between favorable hydrophobic and hydrogen-bond interactions and the unfavorable structure erosion and relaxation of the loaded aggregates. Therefore, OSGES aggregates were designed for the codelivery of ß-carotene and curcumin, indicating their potential to be applied in functional foods and dietary supplements.

Purification and structural analysis of a novel polysaccharide from Rehmannia Radix Praeparata.

In this paper, the purification, structure, and antioxidant activity of Rehmannia Radix Praeparata polysaccharide (RRPP) were studied. The RRPP was separated using DEAE-52 cellulose and Sephadex G-100. The RRPP consisted of xylose, glucose, rhamnose, galactose, and mannose in ratios of 10.64:5.58:3.52:1.39:1.0. No protein was detected in the RRPP fraction, and the molecular weight of RRPP was about 1.75 × 106 Da. The basic skeleton information was obtained using periodic acid oxidation-Smith degradation, and RRPP contained 1→, 1 → 2, 1 → 3, 1 → 4, 1 → 2,6, 1 → 4,6 or 1 → 6, 1 → 2,3, 1 → 2,3,4, and other glycosidic bonds. Fourier transform infrared spectroscopy also showed that RRPP has both α- and ß-glycosidic bonds. The in vitro antioxidant activity test showed that RRPP could potentialize scavenging effect on ABTS+· and its scavenging rate was 91.3%.

New antifungal strategies: Drug combination and co-delivery.

The growing occurrence of invasive fungal infections and the mounting rates of drug resistance constitute a significant menace to human health. Antifungal drug combinations have garnered substantial interest for their potential to improve therapeutic efficacy, reduce drug doses, reverse, or ameliorate drug resistance. A thorough understanding of the molecular mechanisms underlying antifungal drug resistance and drug combination is key to developing new drug combinations. Here we discuss the mechanisms of antifungal drug resistance and elucidate how to discover potent drug combinations to surmount resistance. We also examine the challenges encountered in developing such combinations and discuss prospects, including advanced drug delivery strategies.

A distinction between Fritillaria Cirrhosa Bulbus and Fritillaria Pallidiflora Bulbus via LC-MS/MS in conjunction with principal component analysis and hierarchical cluster analysis.

Fritillaria Cirrhosa Bulbus (known as chuanbeimu in Chinese, FCB) is one of the most used Chinese medicines for lung disease. However, a variety of substitutes have entered the market, with Fritillaria Pallidiflora Bulbus (FPB) being the most common. Due to their similarity in appearance, morphology, and chemical composition but a large price difference, the FCB has frequently been adulterated with the FPB, posing a serious challenge to the distinction and quality of the FCB. Therefore, we aimed to distinguish FCB and FPB based on their main nine isosteroidal alkaloid contents and test the potential of chemometrics as a discrimination approach for evaluating quality. The nine major isosteroidal alkaloids were measured using a liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach in 41 batches of FCB and 17 batches of FPB. Additionally, they were categorized and distinguished using the methods of hierarchical cluster analysis (HCA) and principal component analysis (PCA). Quantitative analysis revealed that the nine alkaloids were present in different amounts in the two types of Fritillariae bulbus. In FCB, the highest amount was peimisine (17.92-123.53 µg/g) and the lowest was delavine (0.42-29.18 µg/g), while in FPB, imperialine was higher (78.05-344.09 µg/g), but verticinone and verticine were less than the other seven alkaloids. The FCB and FPB were successfully classified and distinguished by the HCA and PCA. Taken together, the method has a good linear relationship (R2 > 0.9975). The LOD and LOQ of the nine alkaloids were in the range of 0.0651-0.6510 and 0.1953-1.9531 ng/mL, respectively. The intra- and inter-day precision were shown to be excellent, with relative standard deviations (RSDs) below 1.63% and 2.39%, respectively. The LC-MS/MS method in conjunction with HCA and PCA can effectively differentiate FCB and FPB. It may be a promising strategy for quality evaluation and control at the FCB.

[Synthesis, characterization, and immunological activity of Rehmannia glutinosa seleno-polysaccharides].

The present study explored the optimum synthesis process of Rehmannia glutinosa seleno-polysaccharides with acetic acid as a catalyst, characterized the structure of R. glutinosa seleno-polysaccharides by Fourier transform infrared spectroscopy(FT-IR), scanning electron microscopy(SEM), thermogravimetry(TG), and atomic force microscopy(AFM), and preliminarily investigated the immunological activity of R. glutinosa seleno-polysaccharides. The results showed that the optimal conditions for the synthesis of R. glutinosa seleno-polysaccharides included m(acetic acid)∶m(R. glutinosa polysaccharides)=0.80, m(Na_2SeO_3)∶m(R. glutinosa polysaccharides)=1.25, reaction temperature of 80.0 ℃, and reaction time of 7.0 h. Under these conditions, the selenium content of R. glutinosa seleno-polysaccharides was 2.239 mg·g~(-1). The acetic acid catalysis method was milder than the nitric acid method, without affecting the structure of polysaccharides. The results of IR, SEM, TG, and AFM showed that R. glutinosa seleno-polysaccharides were properly prepared. The results of immunological activity showed that compared with the control group, R. glutinosa seleno-polysaccharides could significantly promote the phagocytic capacity of mouse monocyte macrophages and improve the spleen index and thymus index of mice. In the concentration range of 15-240 µg·mL~(-1), the proliferation of spleen lymphocytes of mice was strengthened, and the IL-2 and IFN-γ secretion by Th1 cytokines was promoted. This study can provide references for the further development and application of R. glutinosa polysaccharides.

Isosteroid alkaloids with different chemical structures from Fritillariae cirrhosae bulbus alleviate LPS-induced inflammatory response in RAW 264.7 cells by MAPK signaling pathway.

Isosteroid alkaloids, natural products from Fritillariae Cirrhosae Bulbus, are well known for its antitussive, expectorant, anti-asthmatic and anti-inflammatory properties. However, the anti-inflammatory effect and its mechanism have not been fully explored. In this study, the anti-inflammatory activitives and the potential mechanisms of five isosteroid alkaloids from F. Cirrhosae Bulbus were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. The pro-inflammatory mediators and cytokines were measured by Griess reagent, ELISA and qRT-PCR. The expression of MAPKs was investigated by western blotting. Treatment with the five isosteroid alkaloids in appropriate concentrations could reduce the production of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in supernatant, and suppressed the mRNA expressions of TNF-α and IL-6. Meanwhile, the five isosteroid alkaloids significantly inhibited the phosphorylated activation of mitogen activated protein kinase (MAPK) signaling pathways, including extracellular signal-regulated kinase (ERK1/2), p38 MAPK and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK). These results demonstrated that isosteroid alkaloids from F. Cirrhosae Bulbus exert anti-inflammatory effects by down-regulating the level of inflammatory mediators via mediation of MAPK phosphorylation in LPS-induced RAW264.7 macrophages, thus could be candidates for the prevention and treatment of inflammatory diseases.

Isosteroid alkaloids from Fritillaria cirrhosa bulbus as inhibitors of cigarette smoke-induced oxidative stress.

Fritillaria cirrhosa bulbus is a Chinese folk herb famous for its antitussive, expectorant, anti-asthma and anti-inflammatory properties, and is widely used to treat respiratory diseases. However, the impacts of F. cirrhosa bulbus on oxidative stress are still unkown. In the present study, we investigated the potential effect and mechanism of six isosteroid alkaloids with different chemical structures from F. cirrhosa bulbus on protection against cigarette smoke-induced oxidative stress in RAW264.7 macrophages. The results showed that six isosteroid alkaloids reduced reactive oxygen species (ROS) production, elevated glutathione (GSH) level and promoted heme oxygenase (HO-1) expression, which is in association with induction of NF-E2-related factor 2 (Nrf2) nuclear translocation and up-regulation of Nrf2 expression. Among these alkaloids, verticinone, verticine, imperialine-3-ß-D-glucoside, delavine and peimisine exhibited more potent effect against CSE-induced oxidative stress than that of imperialine. These findings for the first time demonstrated that F. cirrhosa bulbus may play a protective role in cellular oxidative stress by activating Nrf2-mediated antioxidant pathway. Furthermore, the differences in antioxidant effects of these alkaloids were compared, as well as the corresponding structure-activity relationships were preliminarily elucidated. This suggested that F. cirrhosa bulbus might be a promising therapeutic treatment for the prevent of oxidative stress-related diseases.

Antitumor Activity of Isosteroidal Alkaloids from the Plants in the Genus Veratrum and Fritillaria.

Isosteroidal alkaloids are a category of promising bioactive compounds which mostly exist in plants of genus Veratrum and Fritillaria. The pharmacological activities of isosteroidal alkaloids include antihypertensive, antitussive, anti-inflammatory, antithrombosis, among others. Recently, some studies show that this kind of alkaloids exhibited significant antitumor activity. To the best of our knowledge, there is no review focusing on their antitumor activity and mechanism of their antitumor activity. To fill the gap, in this review, we summarized antitumor effects of the isosteroidal alkaloids from genus Veratrum and Fritillaria on different tumors and the mechanisms of their antitumor activity. In conclusion, this kind of alkaloids has extensive antitumor activity, and there are several main mechanisms of their antitumor activity, including the Hedgehog signaling pathway, caspase-3 dependent apoptosis, cell cycle, and autophagy.

Optimization of extraction and enrichment of steroidal alkaloids from bulbs of cultivated Fritillaria cirrhosa.

The bulbs of cultivated Fritillaria cirrhosa (BCFC) are used in China both for food and folk medicine due to its powerful biological activities. The aim of this study is to optimize the extraction and enrichment conditions of alkaloids from BCFC. Firstly, the orthogonal experimental design was used to optimize and evaluate four variables (ethanol concentration, solid-liquid ratio, extraction time, and temperature). Thereafter, resin adsorption was as a means to enrich alkaloids. Among 16 tested resins, H-103 resin presented higher adsorption capacity and desorption ratio. The equilibrium experimental data of the adsorption of total alkaloids, imperialine, and peimisine were well-fitted to the pseudo-first-order kinetics model, Langmuir and Freundlich isotherms models. Finally, in order to optimize the parameters for purifying alkaloids, dynamic adsorption and desorption tests were carried out. After one run treatment with H-103 resin, the contents of total alkaloids, imperialine, and peimisine in the product were 21.40-, 18.31-, and 22.88-fold increased with recovery yields of 94.43%, 90.57%, and 96.16%, respectively.

Air quality impact of the coal-fired power plants in the northern passageway of the China West-East Power Transmission Project.

This paper analyzes the air quality impacts of coal-fired power plants in the northern passageway of the West-East Power Transmission Project in China. A three-layer Lagrangian model called ATMOS, was used to simulate the spatial distribution of incremental sulfur dioxide (SO2) and coarse particulate matter (PM10) concentrations under different emission control scenarios. In the year 2005, the emissions from planned power plants mainly affected the air quality of Shanxi, Shaanxi, the common boundary of Inner Mongolia and Shanxi, and the area around the boundary between Inner Mongolia and Ningxia. In these areas, the annually averaged incremental SO2 and PM10 concentrations exceed 2 and 2.5 microg/m3, respectively. The maximum increases of the annually averaged SO2 and PM10 concentrations are 8.3 and 7.2 microg/m3, respectively, which occur around Hancheng city, near the boundary of the Shaanxi and Shanxi provinces. After integrated control measures are considered, the maximum increases of annually averaged SO2 and PM10 concentrations fall to 4.9 and 4 microg/m3, respectively. In the year 2010, the areas affected by planned power plants are mainly North Shaanxi, North Ningxia, and Northwest Shanxi. The maximum increases of the annually averaged SO2 and PM10, concentrations are, respectively, 6.3 and 5.6 microg/m3, occurring in Northwest Shanxi, which decline to 4.4 and 4.1 microg/m3 after the control measures are implemented. The results showed that the proposed power plants mainly affect the air quality of the region where the power plants are built, with little impact on East China where the electricity will be used. The influences of planned power plants on air quality will be decreased greatly by implementing integrated control measures.