Stereoselective Synthesis of Xylodonin A and 22-Hydroxyxylodonin A and Discovery of Analogues with Cytotoxic Activity.

The first and stereoselective synthesis of xylodonin A and 22-hydroxyxylodonin A, two drimane-type sesquiterpenoid natural products, was developed from the readily available (+)-sclareolide. This route features an allylic oxidation and acid-promoted dehydration for construction of the key intermediate 6-hydroxyisodrimenin. Representative analogues were synthesized, and their previously unknown bioactivities were revealed after biological evaluation. The analogue 19a exhibited cytotoxic activity against liver cancer HepG2 cells (IC50: 8.8 vs 5.9 µM) that was comparable to that of the clinical anticancer drug etoposide with lower toxicity to normal liver HL7702 cells (IC50 > 100 µM).

Molecular and cellular pruritus mechanisms in the host skin.

Pruritus, also known as itching, is a complex sensation that involves the activation of specific physiological and cellular receptors. The skin is innervated with sensory nerves as well as some receptors for various sensations, and its immune system has prominent neurological connections. Sensory neurons have a considerable impact on the sensation of itching. However, immune cells also play a role in this process, as they release pruritogens. Disruption of the dermal barrier activates an immune response, initiating a series of chemical, physical, and cellular reactions. These reactions involve various cell types, including keratinocytes, as well as immune cells involved in innate and adaptive immunity. Collective activation of these immune responses confers protection against potential pathogens. Thus, understanding the molecular and cellular mechanisms that contribute to pruritus in host skin is crucial for the advancement of effective treatment approaches. This review provides a comprehensive analysis of the present knowledge concerning the molecular and cellular mechanisms underlying itching signaling in the skin. Additionally, this review explored the integration of these mechanisms with the broader context of itch mediators and the expression of their receptors in the skin.

Chemical constituents from Uncaria laevigata and their anti-inflammatory activities and action mechanism.

A new alkaloid 1* (scandine Z) and fourteen known natural products were isolated from 95% ethanol extract of Uncaria laevigata for the first time. Besides compound 1*, these fourteen compounds were firstly isolated from Uncaria laevigata. Excitedly, compound 4 exhibited strong anti-inflammatory activity (IC50 = 8.12 µmol/L), which wasn't described before. Moreover, compound 1* also de--monstrated certain anti-inflammatory activity (IC50 = 10.34 µmol/L). Network pharmacology suggested that compound 4 was involved in the IL-17 signalling pathway and the regulation of inflammation pathway. Molecular docking confirmed that it showed strong binding activity with the target protein (peroxisome proliferator-activated receptor γ, PPAR). Overall, compounds 1* and 4 exhibited strong anti-inflammatory activity and served as lead compounds and anti-inflammatory molecules for further study in vivo.

Recent development of carrier materials in anthocyanins encapsulation applications: A comprehensive literature review.

Anthocyanins are natural polyphenols belonging to the flavonoid family that possess a variety of putative health benefits when consumed in a balanced diet. However, applications of anthocyanins in, for example, functional foods are limited due to poor stability, degradation, and low transmembrane efficiency. To maintain bioactivities of anthocyanins and optimize their use, various carrier materials have been developed. Here, we reviewed the uses of the different carrier materials (organic/inorganic, micro/nano) for anthocyanin encapsulation and delivery over the past five years. The performance of different materials and interactions between anthocyanins and these materials are described. Lastly, we give our perspective on the future development trend of anthocyanin encapsulation strategies.

Antifouling and Self-Healing Performance of Marine Coatings Based on Hydrogen-Bond Interactions.

Biofouling is an urgent problem that has to be solved in marine industries. As the traditional antifouling coating loses its antifouling ability after being damaged, the introduction of self-healing performance into the antifouling coating becomes a high priority. Accordingly, we report here a self-healing and antifouling polyurethane composite coating (PCL/MPU-Si/M) with the use of its carbonyl groups as multiple hydrogen bond acceptors. Its fabrication is carried out under mild and solvent-free conditions, forming a "cross-linking" network structure composed of alternately strong and weak bonds based on multiple carbonyl groups. The self-healing efficiency of PCL/MPU-Si/M in tensile strength is 85% after 48 h at room temperature, and higher temperatures can accelerate this self-healing process. Lubricant polydimethylsiloxane and antifoulant medetomidine endow the material with antifouling properties. The maximum antibacterial ability and algae inhibition coverage ability are 91.7 and 90.9%, respectively. This work provides a possible perspective for the design of antifouling and self-healing marine coatings.

Co-encapsulation of curcumin and anthocyanins in bovine serum album-fucoidan nanocomplex with a two-step pH-driven method.

BACKGROUND: Curcumin (CUR) and anthocyanins (ACN) are recommended due to their bioactivities. However, their nutritional values and health benefits are limited by their low oral bioavailability. The incorporation of bioactive substances into polysaccharide-protein composite nanoparticles is an effective way to enhance their bioavailability. Accordingly, this study explored the fabrication of bovine serum albumin (BSA)-fucoidan (FUC) hybrid nanoparticles using a two-step pH-driven method for the delivery of CUR and ACN. RESULTS: Under a 1:1 weight ratio of BSA to FUC, the point of zero charge moved from pH ⁓ 4.7 for BSA to around 2.5 for FUC-coated BSA, and the formation of BSA-FUC nanocomplex was pH-dependent by showing the maximum CUR emission wavelength shifting from 546 nm (CUR-loaded BSA-FUC at pH 4.7) and 544 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 4.7) to 540 nm (CUR-loaded BSA-FUC at pH 6.0) and 539 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 6.0). Elevated concentrations of NaCl from 0 to 2.5 mol L-1 caused particle size increase from about 250 to about 800 nm, but showing no effect on the encapsulation efficiency of CUR. The CUR and ACN entrapped, respectively, in the inner and outer regions of the BSA-FUC nanocomplex were released at different rates. After incubation for 10 h, more than 80% of ACN was released, while less than 25% of CUR diffused into the receiving medium, which fitted well to Logistic and Weibull models. CONCLUSION: In summary, the BSA-FUC nanocomposites produced by a two-step pH-driven method could be used for the co-delivery of hydrophilic and hydrophobic nutraceuticals. © 2023 Society of Chemical Industry.

Divergent and Stereoselective Synthesis of Ustusal A, (-)-Albrassitriol, and Elegansin D.

The first synthesis of ustusal A as well as expeditious access to (-)-albrassitriol is described as featuring a singlet oxygen [4 + 2] cycloaddition, achieving the desired stereoselectivity for the 1,4-cis-hydroxyl groups. Transformation of (+)-sclareolide to III followed by a key Horner-Wadsworth-Emmons (HWE) reaction and stereospecific allylic oxidation facilitated the first synthesis of elegansin D. The biological evaluation of these natural products together with seven elegansin D analogues was performed, among which several elegansin D analogues exhibited potential anticancer activity against liver cancer HepG2 cells (IC50 = 11.99-25.58 µM) with low cytotoxicity on normal liver HL7702 cells (IC50 > 100 µM).

Comprehensive analysis of different types of ginsenosides in the different parts of American ginseng by targeted and nontargeted MS/MS scanning.

To comprehensively study the ginsenosides distribution in the various tissues of American ginseng, the qualitative and quantitative-targeted and nontargeted mass spectroscopic methods were established using the high-performance liquid chromatography coupled with Qtrap triple quadrupole mass spectrometry (HPLC-QtrapQQQ-MS). The total ginsenosides of the root, stem, and leaf of American ginseng were determined by a colorimetric method, and the contents showed the order from high to low root, stem, and leaf. Eighty-two kinds of ginsenosides were detected in the different parts of American ginseng by enhanced mass scan-information-dependent data acquisition (IDA)-enhanced product ion (EPI) scan mode, including 69 from the root, 62 from the stem, and 48 from the leaf. An HPLC-multiple reaction monitoring (MRM) method was established, and 28 representative ginsenosides were further quantified in the three parts. Nearly all ginsenosides had the highest contents in the root and the lowest content in the leaf. Three types of ginsenosides (protopanaxadiol [PPD]-, protopanaxatiol [PPT]-, and oleanolic acid [OA]-types) were analyzed by precursor ion-IDA-EPI and MRM-IDA-EPI scan modes. Root had the most abundant ginsenosides in PPD- and PPT-type ginsenosides. Meanwhile, the OA-type ginsenosides are significantly enriched in the stem and leaf of American ginseng. The results provided a supplement to the quality assessment of American ginseng. PRACTICAL APPLICATION: The distribution profile of ginsenosides in the parts of American ginseng is different. Except for the root, the stem, and leaf of American ginseng have the most abundant ginsenosides in oleanolic acid type. The results reported herein can help the manufacturers choose appropriate materials to extract the ginsenosides.

Comprehensive evaluation of corrosion inhibition performance and ecotoxicological effect of cinchona IIa as a green corrosion inhibitor for pickling of Q235 steel.

Here, to prevent the corrosion of Q235 steel in the pickling and discover novel green corrosion inhibitors, the corrosion inhibition performance and eco-toxicity of cinchonain IIa were evaluated. Electrochemical experiments confirms that 200 mg/L cinchonain IIa reveals good corrosion inhibition performance with 94.08% on Q235 steel in HCl for 48 h. Scanning electron microscope (SEM) and atomic force microscope (AFM) observations suggest that cinchonain IIa can be firmly attached to the metal surface by forming a barrier film. The X-ray photoelectron spectroscopy (XPS) results further verify the bonding interaction between the functional groups and the steel matrix, and indicate the existence of protective film on the steel. Meanwhile, the inhibition mechanism at the molecular/atomic level is revealed through molecular dynamics simulation. Additionally, acute toxicity test shows that cinchonain IIa is a low toxic corrosion inhibitor. Moreover, the antioxidant enzyme activity experiments confirm that cinchonain IIa discloses no obvious damage to the antioxidant system of zebrafish. Overall, cinchonain IIa exhibits low potential risks to the healthy development of aquatic organisms and ecosystems. As a proven green and low toxic corrosion inhibitor, cinchonain IIa has a sustainable application in the anti-corrosion industry.

Co-encapsulation of curcumin and resveratrol in zein-bovine serum albumin nanoparticles using a pH-driven method.

In the present study, zein-bovine serum albumin (BSA) composite nanoparticles (NPs) are produced with the use of a pH-driven method. The mass ratio of BSA to zein has a significant impact on the particle size, but exhibits a limited effect on the surface charge. With an optimal zein/BSA weight ratio of 1 : 2, zein-BSA core-shell NPs are fabricated for the single/co-loading of curcumin and resveratrol. The incorporation of curcumin or/and resveratrol into zein-BSA NPs changes the configuration of the proteins (zein and BSA), and zein NPs transform resveratrol and curcumin from the crystalline structure to the amorphous state. Compared with resveratrol, curcumin has higher binding strength with zein BSA NPs, showing higher encapsulation efficiency and storage stability. The co-encapsulation of curcumin is found to be an effective method to improve the encapsulation efficiency and shelf-stability of resveratrol. Through this co-encapsulation technology, curcumin and resveratrol are retained in different NP regions via polarity mediation and released at different rates. The hybrid NPs formed from zein and BSA through a pH-driven method exhibit the potential of co-delivery of resveratrol and curcumin.

Concise synthesis of marine natural products smenodiol and (-)-pelorol.

A facile synthesis of marine natural product smenodiol has been achieved in 23.2% overall yield within 8 steps from readily available starting materials, which facilitates a concise synthesis of the marine natural product (-)-pelorol by employing a TMSOTf-mediated Friedel-Crafts reaction with a methyl ester in the aryl as the key step.

A concise synthesis of marine natural product (-)-15-oxopuupehenol from (+)-sclarelide.

A step-economical synthesis of (-)-15-oxopuupehenol from cheap and readily available (+)-sclarelide is achieved with 20.3% overall yield in 9 steps. The key features of this synthetic mythology include a palladium catalyzed tandem carbine migratory insertion reaction to construct the key skeleton, a DDQ-mediated isomerization/oxidation of allyl alcohol to afford α, ß-unsaturated ketone, and a NaOH-induced intramolecular Michael addition followed by acetonide deprotection to give (-)-15-oxopuupehenol.

Fabrication of foxtail millet prolamin/caseinate/chitosan hydrochloride composite nanoparticles using antisolvent and pH-driven methods for curcumin delivery.

Co-assembled foxtail millet (FP)-sodium casein (NaCas) nanocomplex and NaCas coated FP nanoparticles (NPs) were produced by using pH-cycle and anti-solvent methods, respectively. Subsequently, the effects of chitosan hydrochloride (CHC) coating on the particle size, surface charge and physicochemical stability of the two different FP/NaCas nanoparticles (NPs) were evaluated. With the addition of CHC, the particle size of NaCas coated FP NPs and co-assembled FP-NaCas nanocomplex significantly increased from 128.3 nm and 69.5 nm to 183.5 nm and 113.8 nm, respectively. The stability of the two kinds of CHC coated FP-based NPs to different pH values and varying ionic strengths was different due to their different NP structures. Using different fabrication formulations, co-assembled FP-NaCas NPs entrapped curcumin in relatively hydrophilic microenvironment and showed higher curcumin retention rate in comparison with NaCas coated FP NPs in terms of long-term storage stability. The results revealed that the produced CHC coated FP/NaCas nanocomplexes could be very beneficial in entrapping and delivering bioactive substances.

Processing technologies, phytochemistry, bioactivities and applications of black ginseng-a novel manufactured ginseng product: A comprehensive review.

Black ginseng is a novel manufactured ginseng product, and the application of black ginseng products in market is increasing in recent years. Black ginseng is prepared by steaming and fermentation, but not as mature as processing red ginseng. Therefore, complete proposals for preparation techniques are firstly presented. Additionally, there are also abundant chemical components in black ginseng, including ginsenosides, polysaccharides, amino acids, polyphenols, flavonoids, etc. Among them, ginsenosides, polysaccharides and phenolic compounds are the main ingredients, making health benefits of black ginseng stronger than other ginseng products. Therefore, black ginseng as a functional food has come to the market in various forms, such as candies, tea, porridge, soup, etc. The improvement in nutrition, flavor, and safety has exhibited a broad prospect for black ginseng products in food industry. Accordingly, preparation technologies, phytochemistry, health benefits and application of black ginseng are comprehensively evaluated.

Total Synthesis of Marine Natural Products (+)-Strongylin A and Corallidictyal D by Regio- and Stereoselective Cyclization of Alkenyl Benzenes.

An expeditious access to marine natural products (+)-strongylin A and corallidictyal D is described. A TFA/Et3SiH-induced reductive isomerization of enols I to alkenyl benzenes II followed by a selectivity-controlled cyclization in the presence of HCl and BF3·Et2O affords benzofuran III and benzopyran IV, respectively. The applicability of this HCl-induced cyclization is showcased by a regio- and stereoselective synthesis of corallidictyal D, while BF3·Et2O-promoted cyclization posterior to rearrangement of an alkenyl benzene provides a regioselectively different benzopyran, (+)-strongylin A.

Environmentally benign cinchonain IIa from Uncaria laevigata for corrosion inhibition of Q235 steel in HCl corrosive medium: Experimental and theoretical investigation.

Traditional corrosion inhibitors make great contribution to metal protection, but also cause environmental pollution. To solve the problem, plant extracts as green corrosion inhibitors have attracted much attention in recent years. Plants are good raw materials for corrosion inhibitors and also meet the requirements of industry. However, they have not been successfully applied in industry due to the unknown composition of the effective corrosion inhibitors and large dosage thereof. Therefore, cinchonain IIa was separated from Uncaria laevigata with abundant sources and low cost from nature in this work. Here we hypothesized that cinchonain IIa could show good corrosion inhibition performance for Q235 steel in the acidic medium. Through experiments and theoretical calculation, we studied the corrosion inhibition effect of cinchonain IIa on Q235 in 1 M HCl solution at 298 K for 48 h. Electrochemical experiments revealed that the inhibition efficiency of 200 mg/L cinchonain IIa in 1 M HCl for Q235 steel was 94.08% for 48 h. It even showed over 93% corrosion inhibition efficiency and durable protection performance to 28 d. Surface observations indicated that cinchonain IIa were firmly attached to the steel surface by forming a protective film. Moreover, quantum chemical calculation and molecular dynamics simulation revealed the inhibition mechanism at molecular and atomic level. Compared with some plant extracts, here we demonstrate that the outstanding advantages of cinchonain IIa include sustained protective effect, small dosage, and low toxicity. Accordingly, it may be used as a green industrial corrosion inhibitor with great potential in oilfield acidification and acid pickling.

Structure and hypoglycemic effect of a neutral polysaccharide isolated from sea cucumber Stichopus japonicus.

In addition to its high nutritious value, sea cucumber has been recognized by folk medicine for a long time. This study investigated the structure and hyperglycemic activity of a neutral polysaccharide (NPsj) from sea cucumber Stichopus japonicus, whose molecular weight was determined as 301.75 kDa by HPGPC method. Monosaccharide composition analysis indicated that NPsj is a glucan. The structure of NPsj was obtained by combining the analysis of methylation analysis, FTIR, NMR, periodate oxidation, Smith degradation and ESI-MS, which is mainly composed of (1 â†’ 4)-α-d-glucoses with ß-d-glucose(1→) branches substituted at O-6 every 7-9 of 1,4 linked glucoses. An in vitro insulin resistance Hep G2 cells model and a 3 T3-L1 cells model were established, and the NPsj has significant effect to increase glucose consumption with no toxicity at 10-100 µg/mL. Furthermore, NPsj upregulates the phosphorylation of Akt1 and down-regulated GSK3ß, and then reduces the phosphorylation of GS, indicating its mechanism of ameliorating insulin resistance via Akt/GSK3ß/GS signaling pathway.

Single/co-encapsulation capacity and physicochemical stability of zein and foxtail millet prolamin nanoparticles.

In the last few decades, zein has been extensively studied owing to its wide commercial availability and the ability to self-assemble into nanosphere structure to encapsulate biologically active substances for targeted delivery. This work emphasized on comparing the encapsulation efficiency of hydrophobic active biomolecules and the physicochemical stability of composite nanoparticles (NPs) made up of zein- and foxtail millet prolamin (FP) -caseinate. Puerarin, resveratrol, diosmetin, and curcumin with various LogP values were selected as model drugs to study the single/co-encapsulation capacity, storage stability, and in vitro release profiles. Both LogP values (polarity) and specific structure are the main factors affecting the encapsulation efficiency. FP-based NPs could entrap more resveratrol, which may be related to the lower hydrophobic amino acid content of FP in comparison with that of zein. Co-encapsulation, in vitro release and long-term storage stability experiments confirmed that the model drugs were encapsulated in different NP regions mediated by polarity. Moreover, co-encapsulation changed the environment of curcumin from relatively polar microenvironment to hydrophobic regions. These hydrophobic regions retained significantly more curcumin during long-term storage stability. Overall, our results suggest that the hydrophobic amino acid composition of prolamin affects the encapsulation capacity. Various bioactives were encapsulated in the prolamin-based NPs via polarity mediation, and co-encapsulation could effectively retain the active molecules during storage.

Mesoporous crosslinked chitosan-activated clinoptilolite biocomposite for the removal of anionic and cationic dyes.

A mesoporous crosslinked chitosan-activated clinoptilolite biocomposite (CS-GA/ACP) was prepared with chitosan (CS) as the substrate and glutaraldehyde (GA) as the crosslinking agent. Structural analysis of the CS-GA/ACP composite beads was performed using FTIR, SEM, and BET techniques. The adsorption properties of the CS-GA/ACP for Congo red (CR) and methylene blue (MB) removal were examined using a batch method. The effects of CS loading, CS-GA/ACP dosages (0.005-0.25 g), pH values (3-11), initial concentrations (30-300 mg/L), contact time (5-120 min), ionic strength, and temperatures (25-65 â„ƒ) on the adsorption of CR and MB on the CS-GA/ACP composite beads were investigated. The pseudo-second-order kinetics could better describe the adsorption process than the pseudo-first-order kinetics, and the Langmuir isotherms model agreed well with the experimental data. The maximum adsorption capacities of the CS-GA/ACP for CR and MB were 180.59 mg/g and 143.67 mg/g at 25 â„ƒ, respectively. The proposed mechanism studies showed that the possible interaction between the adsorbent and dye molecules were Yoshida H-bonding, dipole-dipole H-bonding, electrostatic interaction and n-π interaction. The CS-GA/ACP can be recycled to remove dyes without significant loss of efficacy, and the adsorption of dyes on the CS-GA/ACP is spontaneous endothermic adsorption. Overall, the CS-GA/ACP showed an excellent performance for dyes removal in aqueous solution and could be a practical candidate for industrial applications.

Chondroitin sulfate deposited on foxtail millet prolamin/caseinate nanoparticles to improve physicochemical properties and enhance cancer therapeutic effects.

In this study, curcumin (Cur)-loaded chondroitin sulfate (CS)-sodium caseinate (NaCas)-stabilized foxtail millet prolamin (FP) composite nanoparticles (NPs) were fabricated via a one-pot process. FP is capable of self-assembly via liquid antisolvent precipitation under neutral and alkaline conditions (pH 7.0-11.0). Under this condition, the microstructures of hydrophobic FP cores, amphiphilic NaCas and hydrophilic CS shells were fabricated readily by a one-pot method. With an optimal FP/NaCas/CS weight ratio of 3 : 2 : 4, FP-NaCas-CS NPs shared globular microstructures at about 145 nm, and hydrophobic interactions, electrostatic forces, and hydrogen bonds were the main driving forces for the formation and maintenance of stable FP-NaCas-CS NPs. CS coating enhanced the pH stability but reduced the ionic strength stability. The formed NPs were stable over a wide pH range from 2.0 to 8.0 and elevated salt concentrations from 0 to 3 mol L-1 NaCl. FP-NaCas-CS NPs exhibited a higher Cur encapsulation efficiency of 93.4% and re-dispersion capability after lyophilization. Moreover, CS coating promoted selective accumulation in CD44-overexpressing HepG2 cells, resulting in higher inhibition of tumor growth compared to free Cur and FP-NaCas NP-encapsulated Cur. As for comparison, encapsulated Cur exhibited reduced cytotoxicity on normal liver cells L-O2. This preclinical study suggests that FP-NaCas-CS NPs could be very beneficial in terms of encapsulating hydrophobic drugs, improving the effectiveness of cancer therapies and reducing side effects on normal tissues.