Multi-layered effects of Panax notoginseng on immune system.

Recent research has demonstrated the immunomodulatory potential of Panax notoginseng in the treatment of chronic inflammatory diseases and cerebral hemorrhage, suggesting its significance in clinical practice. Nevertheless, the complex immune activity of various components has hindered a comprehensive understanding of the immune-regulating properties of Panax notoginseng, impeding its broader utilization. This review evaluates the effect of Panax notoginseng to various types of white blood cells, elucidates the underlying mechanisms, and compares the immunomodulatory effects of different Panax notoginseng active fractions, aiming to provide the theory basis for future immunomodulatory investigation.

Stretchable, Programmable and Magnet-Insensitive Protonic Display Based on Integrated Ionic Circuit.

As a new approach to "More than Moore", integrated ionic circuits serve as a possible alternative to traditional electronic circuits, yet the integrated ionic circuit composed of functional ionic elements and ionic connections is still challenging. Herein, a stretchable and transparent ionic display module of the integrated ionic circuit has been successfully prepared and demonstrated by pixelating a proton-responsive hydrogel. It is programmed to excite the hydrogel color change by a Faraday process occurring at the electrode at the specific pixel points, which enables the display of digital information and even color information. Importantly, the display module exhibits stable performance under strong magnetic field conditions (1.7 T). The transparent and stretchable nature of such ionic modules also allows them to be utilized in a broad range of scenarios, which paves the way for integrated ionic circuits.

Uniformly Hybrid Surface Containing Adjustable Hydrophobic/Hydrophilic Components Obtained by Programmed Strain for Synergistic Anti-Icing.

Sufficient efforts have been put into the design of anti-icing materials to eliminate the icing hazard. Among the currently approved anti-icing concepts, hydrophilic/hydrophobic hybrid anti-icing materials inspired by antifreeze proteins show excellent properties in inhibiting ice nucleation, inhibiting ice crystal growth, and reducing ice adhesion. However, it is still a great challenge to accurately regulate the hydrophilic and hydrophobic hybrid components of the coating surface to clarify the synergistic mechanism. This work proposes a strain-manipulated surface modification strategy, and an anti-icing coating with adjustable hydrophilic/hydrophobic hybrid components prepared by combining chemical vapor deposition and siloxane chemistry is obtained. According to the ice resistance experiment at -15 °C, the performance of anti-icing is closely related to the proportion of hydrophilic and hydrophobic hybrids. The icing delay time and ice adhesion strength of the material with the optimal hydrophilic/hydrophobic components are 280 s and 18.6 kPa, respectively. These unique properties can be attributed to the synergistic effect of hydrophilic and hydrophobic structures on the regulation of interfacial water.

A Programmable Actuator as Synthetic Earthworm.

Natural earthworm with the ability to loosen soils that favors sustainable agriculture has inspired worldwide interest in the design of intelligent actuators. Given the inability to carry heavy loads and uncontrolled deformation, the vast majority of actuators can only perform simple tasks by bending, contraction, or elongation. Herein, a degradable actuator with the ability to deform in desired ways is presented, which successfully mimics the burrowing activities of earthworms to loosen soils with increased soil porosity by digging, grabbing, and lifting the soil when it receives rains. Such a scarifying actuator is made of degradable cellulose acetate and uncrosslinked polyacrylamide via the swelling-photopolymerizing method. The water absorption of polyacrylamide in moisture conditions causes rapid and remarkable bending. Such mechanical bending can be controlled in specific areas of the cellulose acetate film if polyacrylamide is polymerized in a patterned way, so as to generate complicated deformations of the whole cellulose acetate. Patterning polyacrylamide within cellulose acetate is achieved based on reversible surface protection by means of pen writing, rather than the traditional masking techniques. The water-induced deformation of programmable cellulose-based actuators is well preserved in soil, which is appropriate for promoting rain diffusion as well as root breath.

Antifreezing, Adhesive, and Ultra-Stretchable Ionogel for AI-Enabled Motion Tracking and Recognition in Winter Sports.

Motion tracking and recognition are gaining increasing attention in athletes' training for winter sports due to their importance in posture correction and injury prevention. Electronic skin serves as a better candidate compared to vision-based methods. However, the challenges of its application include sensing materials with good stretchability, softness, anti-freeze, non-volatility, and adhesion, and data processing techniques of high intelligence and efficiency. Here, we propose an antifreezing, adhesive, and ultra-stretchable organic ionogel (OIG). Maximum elongation of over 6500% has been obtained for the OIG of the double network, and the mechanical stretchability is retained at temperatures ranging from -50 to 50 °C. Importantly, the multi-sensor system could realize motion "recognition" rather than "perception" with the help of a convolutional neural network.

Self-Shaping Microemulsion Gels for Cultural Relic Cleaning.

Cleaning is a foundational and essential operation of protection and restoration of cultural relics, which is also the key step of follow-up works. To overcome the problems of uncontrollable diffusion of cleaning solvents and poor coverage of the cleaning solvent carriers on rough surfaces, here, we propose a strategy of using a self-shaping microemulsion gel that is prepared via emulsifying oleophilic solvents into the specific shear-thinning hydrogel structures. The gel can adaptively cover rough surfaces during the cleaning process coupled with avoidance of unnecessary diffusion of the cleaning solvents, and the mechanical reinforcement of in situ polymerized double-network gels enables its easy peeling off from the surfaces without leaving determinable residues. As a representative demonstration, Paraloid B72, a widely used material for the repair and reinforcement of cultural relics, is employed as a model discolored coating, which can be effectively removed from the rough surface of simulated cultural relics after treatment with the resulting gels. Convincingly, the strategy of constructing agarose/polyacrylamide hybrid double-network gels with shear-thinning and self-shaping performances for the cleaning of cultural relics not only improves the convenience and accuracy of operation but also exhibits an efficient cleaning effect, which will greatly expand the application of microemulsion gels in the cleaning of rough surfaces of cultural relics.

Renatured hydrogel painting.

Hydrogel coatings pave an avenue for improving the lubricity, biocompatibility, and flexibility of solid surfaces. From the viewpoint of practical applications, this work establishes a scalable method to firmly adhere hydrogel layers to diverse solid surfaces. The strategy, termed as renatured hydrogel painting (RHP), refers to adhering dehydrated xerogel to a surface with appropriate glues, followed by the formation of a hydrogel layer after rehydration of the xerogel. With the benefits of simplicity and generality, this strategy can be readily applied to different hydrogel systems, no matter what the substrate is. Hydrogel adhesion is demonstrated by its tolerance against mechanical impact with hydrodynamic shearing at 14 m/s. This method affords powerful supplements to renew the surface chemistry and physical properties of solid substrates. In addition, we show that the RHP technique can be applied to living tissue, with potential for clinical applications such as the protection of bone tissue.

A Comprehensive Characterization of a 10 at.% Yb:YSAG Laser Ceramic Sample.

We report a comprehensive characterization of a 10 at.% Yb3+-doped YSAG (Yb:Y3ScxAl(5-x)O12, x = 1.5) ceramic, including microstructural, spectroscopic and laser properties. Moreover, we illustrate and discuss the fabrication technique. Yb3+ in YSAG features a broader absorption and emission band than in traditional YAG, which is advantageous for laser applications (i.e., tunable laser sources, ultrafast pulse generation). Pumping in a quasi continuous wave regime at 936 nm, the ceramic has shown good laser performance as the maximum output power was 6.3 W with a corresponding slope efficiency (ηs) of 67.8%. In continuous wave regime instead, the maximum output power was 5 W with ηs = 52.7%. The laser emission wavelengths in free running were λL = 1051 nm and λL = 1031 nm, depending on the output coupler transmission. Finally, by a tunable cavity we obtained laser emission spanning from 991.5 to 1073 nm, i.e., 81.5 nm, which is the broadest tuning range ever reported for this material, to the best of our knowledge.

Gastrodin Inhibits Store-Operated Ca2+ Entry and Alleviates Cardiac Hypertrophy.

Cardiac hypertrophy is a major risk factor for heart failure, which are among the leading causes of human death. Gastrodin is a small molecule that has been used clinically to treat neurological and vascular diseases for many years without safety issues. In the present study, we examined protective effect of gastrodin against cardiac hypertrophy and explored the underlying mechanism. Phenylephrine and angiotensin II were used to induce cardiac hypertrophy in a mouse model and a cultured cardiomyocyte model. Gastrodin was found to alleviate the cardiac hypertrophy in both models. Mechanistically, gastrodin attenuated the store-operated Ca2+ entry (SOCE) by reducing the expression of STIM1 and Orai1, two key proteins in SOCE, in animal models as well as in cultured cardiomyocyte model. Furthermore, suppressing SOCE by RO2959, Orai1-siRNAs or STIM1-siRNAs markedly attenuated the phenylephrine-induced hypertrophy in cultured cardiomyocyte model. Together, these results showed that gastrodin inhibited cardiac hypertrophy and it also reduced the SOCE via its action on the expression of STIM1 and Orai1. Furthermore, suppression of SOCE could reduce the phenylephrine-induced cardiomyocyte hypertrophy, suggesting that SOCE-STIM1-Orai1 is located upstream of hypertrophy.

In Vitro and In Vivo Effects of Norathyriol and Mangiferin on α-Glucosidase.

Norathyriol is a metabolite of mangiferin. Mangiferin has been reported to inhibit α-glucosidase. To the best of our knowledge, no study has been conducted to determine or compare those two compounds on inhibiting α-glucosidase in vitro and in vivo by far. In this study, we determined the inhibitory activity of norathyriol and mangiferin on α-glucosidase in vitro and evaluated their antidiabetic effect in diabetic mice. The results showed that norathyriol inhibited α-glucosidase in a noncompetitive manner with an IC50 value of 3.12 µM, which is more potent than mangiferin (IC50 = 358.54 µM) and positive drug acarbose (IC50 = 479.2 µM) in the zymological experiment. Both of norathyriol and mangiferin caused significant (p < 0.05) reduction in fasting blood glucose and the blood glucose levels at two hours after carbohydrate loading and it was interesting that mangiferin and norathyriol can make the decline of the blood glucose earlier than other groups ever including normal group in the starch tolerance test. However, norathyriol and mangiferin did not significantly influence carbohydrate absorption in the glucose tolerance test. Therefore, the antidiabetic effects of norathyriol and mangiferin might be associated with α-glucosidase, and norathyriol was more potent than mangiferin.

Comparative analysis of the neuroprotective effects of ginsenosides Rg1 and Rb1 extracted from Panax notoginseng against cerebral ischemia.

Panax notoginseng, a traditional Chinese medicine, has been used for thousands of years to treat ischemic patients. More than 20 saponin components have been isolated from P. notoginseng root and identified chemically. However, these different chemical components have different roles. In this study we compared the neuroprotective mechanisms of ginsenosides Rg1, Rb1, Rg1/Rb1, and panax notoginsenoside (PNS) against injuries caused by cerebral ischemia-reperfusion (I/R). Our results show that all of these treatments significantly reduced infarction volume and alleviated neurological deficits caused by cerebral I/R. The increase in malondialdehyde (MDA) concentration was inhibited by these treatments in the hippocampus. The decreased expressions of thioredoxin-1 (Trx-1), copper-zinc superoxide dismutase (SOD-1), protein kinase B (PKB/Akt), and nuclear factor-kappa B (NF-κB) caused by cerebral I/R were restored by these treatments. The expression of heat shock protein 70 (HSP70) was enhanced in the middle cerebral artery occlusion (MCAO) group, as well as in all of the treatment groups. These results suggest that Rg1 and Rb1 have similar roles in protecting the brain from ischemic damage; however, neither Rg1/Rb1 nor PNS have synergistic effects, thus either Rg1 or the Rb1 monomer should be considered as a pharmacological neuroprotective strategy for use in the case of ischemic stroke.

Preparation and evaluation of sustained-release solid dispersions co-loading gastrodin with borneol as an oral brain-targeting enhancer.

Borneol is a traditional Chinese medicine that can promote drug absorption from the gastrointestinal tract and distribution to the brain. However, stomach irritation may occur when high doses of borneol are used. In the present work, gastrodin, the main bioactive ingredient of the traditional Chinese drug "Tianma" (Rhizoma Gastrodiae) was used as a model drug to explore reasonable application of borneol. Sustained-release solid dispersions (SRSDs) for co-loading gastrodin and borneol were prepared using ethylcellulose as a sustained release matrix and hydroxy-propyl methylcellulose as a retarder. The dispersion state of drug within the SRSDs was analyzed by using scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffractometry. The results indicated that both gastrodin and borneol were molecularly dispersed in an amorphous form. Assay of in vitro drug release demonstrated that the dissolution profiles of gastrodin and borneol from the SRSDs both fitted the Higuchi model. Subsequently, gastric mucosa irritation and the brain targeting of the SRSDs were evaluated. Compared with the free mixture of gastrodin and borneol, brain targeting of SRSDs was slightly weaker (brain targeting index: 1.83 vs. 2.09), but stomach irritation obviously reduced. Sustained-release technology can be used to reduce stomach irritation caused by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery.

Role of glucose transporters in the intestinal absorption of gastrodin, a highly water-soluble drug with good oral bioavailability.

Gastrodin, a sedative drug, is a highly water-soluble phenolic glucoside with poor liposolubility but exhibits good oral bioavailability. The current study aims to investigate whether glucose transporters (GLTs) are involved in the intestinal absorption of gastrodin. The intestinal absorption kinetics of gastrodin was determined using the rat everted gut sac model, the Caco-2 cell culture model and the perfused rat intestinal model. In vivo pharmacokinetic studies using diabetic rats with high GLT expression were performed. Saturable intestinal absorption of gastrodin was observed in rat everted gut sacs. The apparent permeability (Papp) of gastrodin from the apical (A) to basolateral (B) side in Caco-2 cells was two-fold higher than that from B to A. Glucose or phlorizin, a sodium-dependent GLT (SGLT) inhibitor, reduced the absorption rates of gastrodin from perfused rat intestines. In vivo pharmacokinetic studies showed that the time of maximum plasma gastrodin concentration (Tmax) was prolonged from 28 to 72 min when orally co-administered with four times higher dose of glucose. However, the Tmax of gastrodin in diabetic rats was significantly lowered to 20 min because of the high intestinal SGLT1 level. In conclusion, our findings indicate that SGLT1 can facilitate the intestinal absorption of gastrodin.

Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation.

UNLABELLED: Ginsenoside Rb1 and Rg1 are major components of Panax notoginseng (P.N.), an herb with known clinical efficacy in hypertension and myocardial ischemia in Eastern countries. This investigation is to elicit the mechanism of these components in hypertension via their effect on vascular reaction. To assess the ability of P.N. in hypertension, P.N. extracts were injected in spontaneously hypertensive rats (SHR) via the vena caudalis; Low dosages of P.N. extracts significantly lowered blood pressure in SHR. Examination with Rb1 and Rg1 revealed significant vasodilatation using mouse coronary arteries in a dose-dependent manner. Rb1- and Rg1-induced vasodilatation was blocked by pre-incubation with eNOS and PI3K inhibitors. Coronaries of eNOS-/- mice showed attenuated vasodilatation with Rb1 and Rg1. In addition, both Rb1 and Rg1 induce nitric oxide (NO) generation through increasing the phosphorylation of eNOS, activating Na+-independent l-arginine transport, and stimulating cationic amino acid transport (CAT)-1 mRNA expression in cultured endothelial cells. CONCLUSION: Ginsenoside Rb1 and Rg1 increased endothelial-dependent vessel dilatation through the activation of NO by modulating the PI3K/Akt/eNOS pathway and l-arginine transport in endothelial cells. These findings may have important implications for understanding the mechanisms of clinical efficacy of the herb P.N. when used in the regulation of blood pressure.

Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin.

Gastrodin is the major bioactive constituent of the traditional Chinese drug "Tianma." It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.

[Study on drug release of gastrodin ion-activated nasal in situ gel in vitro].

OBJECTIVE: To study on the drug release characteristics and mechanism of gastrodin ion-activated nasal in situ gel in vitro. METHOD: Regularity and mechanism of the drug release of gastrodin nasal in situ gel were studied by using the diffusion cell model and the membrane-less dissolution model, respectively. A novel kinesis diffusion cell model was designed according to the characteristics of release environment of nasal cavity. It was used to investigate the effect of adhesiveness on the release of the in situ gel. RESULT: Drug release of gastrodin nasal in situ gel followed the one order release model. Erosion rate of the gel was low and not linearly correlated with the release rate. Compared with gastrodin solution, the nasal in situ gel could increase release time and release amount. CONCLUSION: Gastrodin in the nasal in situ gel is released mainly by diffusion rather than erosion. Release amount of the in situ gel in nasal cavity may be obviously increased because of its adhesiveness.

[Brain targeting of gastrodin nasal in situ gel].

OBJECTIVE: To investigate the biodistribution of gastrodin ion-activated nasal in situ gel in rat blood and brain tissues and to evaluate its brain targeting. METHODS: Intravenous administration of gastrodin solution or intranasal administration of gastrodin nasal in situ gel were given to 32 rats, respectively. The concentrations of gastrodin in the plasma and gastrodigenin in the brain tissues of the rats were determined by HPLC. RESULTS: The intranasal administration of the in situ gel of gastrodin produced more significant brain targeting effect than the intravencus administration of gstrodin solution (P < 0.01). The area under curve (AUC) of cerebrum, cerebellum and olfactory bulb increased by 1.16, 0.77 and 3.34 times, with 2.66. 2.18 and 5.34 brain targeting indexes (BTI), respectively. The mean residence time (MRT) increased by nearly four-folds. CONCLUSION: Gastrodin nasal in situ gel can improve the brain targeting of gastrodin and slow its release.

Effect of borneol on the distribution of gastrodin to the brain in mice via oral administration.

Both borneol and gastrodin are bioactive substances derived from traditional Chinese medicine. In this paper, the effect of borneol on the distribution of gastrodin to the brain in mice via oral administration was investigated. Gastrodin concentrations in plasma and gastrodigenin (active metabolite of gastrodin) concentrations in the brain of mice were determined by reversed-phase high-performance liquid chromatography, after intragastric administration of gastrodin (200 mg kg(-1)) alone or combined with different doses (200, 400 and 600 mg kg(-1)) of borneol simultaneously or the same dose (400 mg kg(-1)) of borneol given 20 and 40 min beforehand, respectively. Compared with the administration of gastrodin alone, gastrodin coadministrated with borneol could have been rapidly absorbed from the gastrointestinal tract; the peak time of gastrodin in the plasma became shorter (5-15 vs. 30 min); the bioavailability of gastrodigenin in the brain was increased by 33.6-108.8%; and obvious brain-targeting effect was observed. The enhancing effect was attenuated when the dose of borneol was too high (600 mg kg(-1)), or the time interval between the administration of borneol and gastrodin was longer than 40 min. The results indicate that borneol can accelerate the absorption of gastrodin in the gastrointestinal tract and promote its distribution to the brain. Therefore, borneol is a promising promoter for oral brain-targeting drug delivery.