Chelerythrine induces apoptosis and ferroptosis through Nrf2 in ovarian cancer cells.

Ovarian cancer is a prevalent malignancy in the female reproductive system, representing a significantly fatal and incurable tumor. Chelerythrine (CHE), a natural benzopyridine alkaloid, has demonstrated a broad spectrum of anticancer activities. Nevertheless, the ovarian cancer inhibitory impact of CHE remains unclear. In this study, we investigated the cytotoxic mechanism and potential targets of CHE on in vitro cultures of A2780 and SKOV3 cells derived from ovarian cancer. Additionally, in vivo experiments were conducted to confirm the suppressive impact of CHE on tumor growth in nude mice. The findings revealed that CHE impeded the growth of A2780 and SKOV3 cells in a concentration-time-dependent manner and significantly suppressed the development of tumors in nude mice. CHE elevated the level of oxidative stress in tumor cells, prompted cell cycle halt in the S phase, and increased their mitochondrial membrane potential. Western blotting results demonstrated that CHE could modulate the expression of proteins associated with apoptotic and ferroptosis processes in A2780 and SKOV3 cells. Nrf2 was verified to be an upstream key target mediating the inhibitory impact of CHE on ovarian cancer cells. In summary, CHE exerts its anti-cancer effects on ovarian cancer by modulating Nrf2, inhibiting cellular proliferation, and promoting apoptosis and ferroptosis.

Ultra-high-performance liquid chromatography-mass spectrometry combined with molecular docking and molecular dynamics simulation reveals the source of bitterness in the traditional Chinese medicine formula Runchang-Tongbian.

The Runchang-Tongbian (RCTB) formula is a traditional Chinese medicine (TCM) formula consisting of four herbs, namely Cannabis Fructus (Huomaren), Rehmanniae Radix (Dihuang), Atractylodis Macrocephalae Rhizoma (Baizhu), and Aurantii Fructus (Zhiqiao). It is widely used clinically because of its beneficial effect on constipation. However, its strong bitter taste leads to poor patient compliance. The bitter components of TCM compounds are complex and numerous, and inhibiting the bitter taste of TCM has become a major clinical challenge. Here, we use ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) and high-resolution mass spectrometry to identify 59 chemical components in the TCM compound RCTB formula. Next, four bitter taste receptors, TAS2R39, TAS2R14, TAS2R7, and TAS2R5, which are tightly bound to the compounds in RCTB, were screened as molecular docking receptors using the BitterX database. The top-three-scoring receptor-small-molecule complexes for each of the four receptors were selected for molecular dynamics simulation. Finally, seven bitter components were identified, namely six flavonoids (rhoifolin, naringin, poncirin, diosmin, didymin, and narirutin) and one phenylpropanoid (purpureaside C). Thus, we proposed a new method for identifying the bitter components in TCM compounds, which provides a theoretical reference for bitter taste inhibition in TCM compounds.

A Metabolomics Study of the Effects of Eleutheroside B on Glucose and Lipid Metabolism in a Zebrafish Diabetes Model.

(1) Background: Diabetes is a common metabolic disease that seriously endangers human health. In the present study, we investigated the therapeutic effects of the active ingredient Eleutheroside B (EB) from the traditional Chinese medicine Eleutheroside on diabetes mellitus in a zebrafish model. Concomitant hepatic injury was also analysed, along with the study of possible molecular mechanisms using metabolomics technology. This work should provide some theoretical references for future experimental studies. (2) Methods: A zebrafish diabetes model was constructed by soaking in a 1.75% glucose solution and feeding a high-fat diet. The intervention drug groups were metformin (100 µg∙mL-1) and EB (50, 100, and 150 µg∙mL-1) via water-soluble exposure for 30 days. Glucose, TG, TC, LDL-C, and HDL-C were evaluated in different treatment groups. GLUT4 protein expression was also evaluated in each group, and liver injury was observed by HE staining. Metabolomics techniques were used to investigate the mechanism by which EB regulates endogenous markers and metabolic pathways during the development of diabetes. (3) Results: All EB treatment groups in diabetic zebrafish showed significantly reduced body mass index (BMI) and improved blood glucose and lipid profiles. EB was found to upregulate GLUT4 protein expression and ameliorate the liver injury caused by diabetes. Metabolomics studies showed that EB causes changes in the metabolic profile of diabetic zebrafish. These were related to the regulation of purine metabolism, cytochrome P450, caffeine metabolism, arginine and proline metabolism, the mTOR signalling pathway, insulin resistance, and glycerophospholipid metabolism. (4) Conclusions: EB has a hypoglycaemic effect in diabetic zebrafish as well as significantly improving disorders of glycolipid metabolism. The mechanism of action of EB may involve regulation of the mTOR signalling pathway, purine metabolism, caffeine metabolism, and glycerophospholipid metabolism.

Intracerebral Fluorescence-Photoacoustic Dual-Mode Imaging for Precise Diagnosis and Drug Intervention Tracing in Depression.

Unravelling the pathophysiology of depression is a unique challenge. Depression is closely associated with reduced norepinephrine (NE) levels; therefore, developing bioimaging probes to visualize NE levels in the brain is a key to elucidating the pathophysiological process of depression. However, because NE is similar in structure and chemical properties to two other catecholamine neurotransmitters, epinephrine and dopamine, designing an NE-specific multimodal bioimaging probe is a difficult task. In this work, we designed and synthesized the first near-infrared fluorescent-photoacoustic (PA) dual-modality imaging probe for NE (FPNE). The ß-hydroxyethylamine of NE was shown to react via nucleophilic substitution and intramolecular nucleophilic cyclization, resulting in the cleavage of a carbonic ester bond in the probe molecule and release of a merocyanine molecule (IR-720). This process changed the color of the reaction solution from blue-purple to green, and the absorption peak was red-shifted from 585 to 720 nm. Under light excitation at 720 nm, linear relationships between the concentration of NE and both the PA response and the fluorescence signal intensity were observed. Thus, the use of intracerebral in situ visualization for diagnosis of depression and monitoring of drug interventions was achieved in a mouse model by fluorescence and PA imaging of brain regions after administration of FPNE by tail-vein injection.

Bioconversion of Ginsenoside Rf into Its Hydrated Derivative with Elevated Anti-inflammatory Effect by a Highly Specific Biocatalytic System of Cordyceps Sinensis.

The presence of 25-OH moiety has been proved to enhance the bioactivity of dammarane saponins in many cases. However, such modification by previous strategies had compromised yield and purity of target products. Herein ginsenoside Rf was specifically transformed into 25-OH-(20S)-Rf with a conversion rate of 88.03 % by a Cordyceps Sinensis-mediated biocatalytic system. The formulation of 25-OH-(20S)-Rf was calculated by HRMS, whilst its structure was validated by 1 H-NMR, 13 C-NMR, HSQC, and HMBC analysis. Time-course experiments unveiled straightforward hydration of the double bond on Rf with undetectable side reactions and maximum production of 25-OH-(20S)-Rf on the 6th day, which collectively suggested the suitable timing of harvesting this target compound. In vitro bioassay of (20S)-Rf and 25-OH-(20S)-Rf against lipopolysaccharide-induced macrophages indicated a significant boost of anti-inflammatory effects after the C24-C25 double bond was hydrated. Therefore, the biocatalytic system in this article could be leveraged to deal with macrophage-mediated inflammation under defined circumstances.

Butanol Extract of Acanthopanax senticosus (Rupr. et Maxim.) Harms Alleviates Atherosclerosis in Apolipoprotein E-Deficient Mice Fed a High-Fat Diet.

This study investigated the effect of butanol extract of AS (ASBUE) on atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. The mice were administered ASBUE (390 or 130 mg/kg/day) or rosuvastatin (RSV) via oral gavage for eight weeks. In ApoE-/- mice, ASBUE suppressed the abnormal body weight gain and improved serum and liver biochemical indicators. ASBUE remarkably reduced the aortic plaque area, improved liver pathological conditions, and lipid metabolism abnormalities, and altered the intestinal microbiota structure in ApoE-/- mice. In the vascular tissue of ASBUE-treated mice, P-IKKß, P-NFκB, and P-IκBα levels tended to decrease, while IκB-α increased in high fat-diet-fed atherosclerotic mice. These findings demonstrated the anti-atherosclerotic potential of ASBUE, which is mediated by the interaction between the gut microbiota and lipid metabolism and regulated via the Nuclear Factor-kappa B (NF-κB) pathway. This work paves the groundwork for subsequent studies to develop innovative drugs to treat atherosclerosis.

G-Quadruplexes in Repeat Expansion Disorders.

The repeat expansions are the main genetic cause of various neurodegeneration diseases. More than ten kinds of repeat sequences with different lengths, locations, and structures have been confirmed in the past two decades. G-rich repeat sequences, such as CGG and GGGGCC, are reported to form functional G-quadruplexes, participating in many important bioprocesses. In this review, we conducted an overview concerning the contribution of G-quadruplex in repeat expansion disorders and summarized related mechanisms in current pathological studies, including the increasing genetic instabilities in replication and transcription, the toxic RNA foci formed in neurons, and the loss/gain function of proteins and peptides. Furthermore, novel strategies targeting G-quadruplex repeats were developed based on the understanding of disease mechanism. Small molecules and proteins binding to G-quadruplex in repeat expansions were investigated to protect neurons from dysfunction and delay the progression of neurodegeneration. In addition, the effects of environment on the stability of G-quadruplex were discussed, which might be critical factors in the pathological study of repeat expansion disorders.

Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity.

Type 2 diabetes (T2D) is characterized by insulin resistance (IR), often accompanied by inflammation. Macrophage activation acts as an inflammatory response, which is characterized by macrophage recruitment in the initial stage. Ginsenoside Rb1 (Rb1) is a main active ingredient, which is known for its fat-reducing, anti-inflammatory effects. To clarify that Rb1 regulates macrophage activation in adipose tissue and improves tissue inflammation, network pharmacology and molecular docking were used for target prediction and preliminary validation. By constructing the co-culture model of adipose-derived stem cells (ADSC) and primary macrophage (PM), the body adipose tissue microenvironment was simulated to observe the adipogenesis degree of adipocytes under the effect of Rb1. The levels of cytokines, macrophage polarization, and protein or RNA expression in the inflammatory signaling pathway were finally detected. The results showed that 89 common targets of T2D-Rb1 were obtained after their intersection. Furthermore, according to the results of the KEGG pathway and PPI analysis, PTGS2 (COX-2) is the downstream protein of PPARγ-NF-κB. The molecular binding energy of PPARγ-Rb1 is -6.8 kcal/mol. Rb1 significantly inhibited the increase in MCP-1, TNF-α, and IL-1ß induced by hypertrophic adipocytes supernatant and promoted the expression of IL-10. Rb1 inhibited the activation of inflammatory macrophages and PM migration and upregulated PPARγ expression with the blocking of NF-κB activation. Additionally, Rb1 promoted the expression of IRS1 and PI3K in the insulin signal pathway, which had a similar effect with ROS. Therefore, Rb1 might affect macrophage activation through PPARγ, which might alleviate obese insulin resistance in T2D early stage.

Hyperoside Nanomicelles Alleviate Atherosclerosis by Modulating the Lipid Profile and Intestinal Flora Structure in High-Fat-Diet-Fed Apolipoprotein-E-Deficient Mice.

Atherosclerosis (AS) is a serious threat to human health and the main pathological basis of cardiovascular disease. Hyperoside (Hyp), a flavonoid found mainly in traditional Chinese herbs, can exert antitumor, anti-inflammatory, antioxidant, and cardiovascular-protective effects. Herein, we prepared hybrid nanomicelles (HFT) comprising Hyp loaded into pluronic F-127 and polyethylene glycol 1000 vitamin E succinate and assessed their effects on AS. To establish an AS model, apolipoprotein-E-deficient (ApoE-/-) mice were fed a high-fat diet. We then analyzed the effects of HFT on AS-induced changes in aortic tissues and metabolic markers, simultaneously assessing changes in gut flora community structure. In mice with AS, HFT significantly reduced the aortic plaque area; decreased levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, inflammatory factors, and inducible nitric oxide synthase (NOS); increased high-density lipoprotein cholesterol, endothelial NOS, superoxide dismutase, catalase, and glutathione levels; and promoted the proliferation of beneficial gut bacteria. HFT could regulate intestinal flora structure and lipid metabolism and inhibit inflammatory responses. These beneficial effects may be mediated by inhibiting nuclear factor kappa B signal activation, reducing inflammatory factor expression and improving gut microflora structure and dyslipidemia. The present study provides an empirical basis for the development and clinical application of new dosage forms of Hyp.

Mitochondria-Targeted Fluorescence/Photoacoustic Dual-Modality Imaging Probe Tailored for Visual Precise Diagnosis of Drug-Induced Liver Injury.

The multispectral optoacoustic tomography (MSOT) technique can be used to perform high-resolution molecular imaging under deep tissues, which gives the technology significant prospective for clinical application. Here, we developed a superoxide anion (O2•-)-activated MSOT and fluorescence dual-modality imaging probe (APSA) for early diagnosis of drug-induced liver injury (DILI). APSA can respond quickly to O2•-, resulting in an absorption peak blueshift from 845 to 690 nm, which also leads to the photoacoustic (PA) signal at 690 nm and the fluorescence signal at 748 nm increases linearly with increasing O2•- concentration, which can be utilized to assess the extent of liver damage. The developed MSOT imaging method can eliminate background interference from hematopoietic tissue by collecting the PA signals excited at 680, 690, 740, 760, 800, 845, and 900 nm wavelengths to achieve noninvasive in situ visual diagnosis of DILI. The developed fluorescence imaging method can be used for the imaging of endogenous O2•- in living cells and anatomic diagnosis of liver injury. The developed probe has broad application prospects in the early diagnosis of DILI.

Proteomic analysis of small extracellular vesicles from the plasma of patients with hepatocellular carcinoma.

PURPOSE: Liver cancer is one of the most common tumors with the seventh-highest incidence and the third-highest mortality. Many studies have shown that small extracellular vesicles (sEVs) play an important role in liver cancer. Here, we report comprehensive signatures for sEV proteins from plasma obtained from patients with hepatocellular carcinoma (HCC), which might be valuable for the evaluation and diagnosis of HCC. METHODS: We extracted sEVs from the plasma of controls and patients with HCC. Differentially expressed proteins in the sEVs were analyzed using label-free quantification and bioinformatic analyses. Western blotting (WB) was used to validate the abovementioned sEV proteins. RESULTS: Proteomic analysis was performed for plasma sEVs from 21 patients with HCC and 15 controls. Among the 335 identified proteins in our study, 27 were significantly dysregulated, including 13 upregulated proteins that were involved predominantly in the complement cascade (complement C1Q subcomponent subunit B (C1QB), complement C1Q subcomponent subunit C (C1QC), C4B-binding protein alpha chain (C4BPA), and C4B-binding protein beta chain (C4BPB)) and the coagulation cascade (F13B, fibrinogen alpha chain (FGA), fibrinogen beta chain (FGB), and fibrinogen gamma chain (FGG)). We verified increased levels of the C1QB, C1QC, C4BPA, and C4BPB proteins in the plasma sEVs from patients with HCC in both the discovery cohort and validation cohort. CONCLUSIONS: The complement cascade in sEVs was significantly involved in HCC progression. C1QB, C1QC, C4BPA, and C4BPB were highly abundant in the plasma sEVs from patients with HCC and might represent molecular signatures.

[Optimization of preparation technology for Acanthopanax senticosus total saponins microemulsion by D-optimal mixture design and intestinal absorption characteristics].

Following the preparation of Acanthopanax senticosus total saponins microemulsion, the formulation and preparation technology were optimized and the quality was evaluated. The absorption characteristics of A. senticosus total saponins microemulsion by the self-microemulsifying drug delivery system(SMEDDS) were investigated in the unidirectional intestinal perfusion model in vivo. The oil phase, mass ratio(K_m), number of revolutions, and drug concentration were subjected to single-factor investigation with the area of pseudo-ternary phase diagram as the index. The process was optimized by D-optimal mixture design with the particle size as the index, and then the appearance, morphology, and particle size were investigated. The mass concentrations of eleutherosides B and E in the microemulsion were determined. The results showed that the optimum formulation of A. senticosus total saponins microemulsion was determined as follows: 20.8% of water phase, 31.2% of isopropyl palmitate, and 48.0% of soybean phospholipid and absolute ethanol(K_m=1∶1). As revealed by the observation under a transmission electron microscope, the microemulsion exhibited homogeneous dispersion and was a spherical emulsion droplet in the water-in-oil type. At room temperature, the pH value was 5.19, the refractive index 1.416 5, the average particle size(26.47±0.04)nm, and the polydispersity index(PDI) 0.118±0.03. The content of the eleutherosides B and E was 0.038 9 and 0.166 4 mg·mL~(-1), respectively. The preliminary stability study showed that the solution was clear and transparent within 30 d, without stratification or content change, indicating good stability. The absorption of microemulsion in each intestinal segment was significantly improved as compared with that of the A. senticosus total saponins, with the best absorption effect detected in the ileum, which has laid a foundation for further development and utilization of A. senticosus.

Ginsenoside CK inhibits obese insulin resistance by activating PPARγ to interfere with macrophage activation.

Obesity is often accompanied by chronic low-grade inflammation, which aggravates the disorder of lipid metabolism and leads to insulin resistance (IR). Macrophage activation plays an important role in inflammation. Ginsenoside Compound K (CK) is an active metabolite of ginsenoside Rb1, which is adopting to an anti-inflammatory effective substance. In order to clarify the mechanism of ginsenoside CK on the regulation of macrophage activation in adipose tissue, the macrophage model was incubated with the supernatant of hypertrophic adipocytes, and the co-culture models of Raw264.7 and 3T3-L1 were established. The levels of related cytokines, macrophage polarization and protein expression in inflammatory signaling pathway were measured. The results showed that ginsenoside CK significantly inhibited the increase of MCP-1 and TNF-α induced by the supernatant of hypertrophic adipocytes, promoted the expression of IL-10, inhibited the activation of inflammatory macrophages and increased the expression of anti-inflammatory macrophages. Similarly, ginsenoside CK inhibited the migration of Raw264.7, blocked the activation of NF-κB, and up-regulated the expression of PPARγ. In addition, ginsenoside CK also promotes the expression of IRS-1 in insulin signal pathway. The experimental results proved that ginsenoside CK plays a crucial role in alleviating inflammation and insulin resistance in obesity, and inhibits macrophage activation through the key protein PPARγ.

Ginsenoside Compound K Assisted G-Quadruplex Folding and Regulated G-Quadruplex-Containing Transcription.

Ginsenoside compound K (CK) is one of the major metabolites of the bioactive ingredients in Panax ginseng, which presents excellent bioactivity and regulates the expression of important proteins. In this work, the effects of CK on G-quadruplexes (G4s) were quantitatively analyzed in the presence and absence of their complementary sequences. CK was demonstrated to facilitate the formation of G4s, and increase the quantity of G4s in the competition with duplex. Thermodynamic experiments suggested that the electrostatic interactions were important for G4 stabilization by CK. CK was further found to regulate the transcription of G4-containing templates, reduce full-length transcripts, and decrease the transcription efficiency. Our results provide new evidence for the pharmacological study of ginsenosides at the gene level.

Human alkaline ceramidase 2 promotes the growth, invasion, and migration of hepatocellular carcinoma cells via sphingomyelin phosphodiesterase acid-like 3B.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. It has a poor prognosis because it is often diagnosed at the advanced stage when treatments are limited. In addition, HCC pathogenesis is not fully understood, and this has affected early diagnosis and treatment of this disease. Human alkaline ceramidase 2 (ACER2), a key enzyme that regulates hydrolysis of cellular ceramides, affects cancer cell survival, however its role in HCC has not been well characterized. Our results showed that ACER2 is overexpressed in HCC tissues and cell lines. In addition, high ACER2 protein expression was associated with tumor growth; ACER2 knockdown resulted in decreased cell growth and migration. Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) promoted HCC cell growth, invasion, and migration; SMPDL3B knockdown had a significant inhibitory effect on HCC tumor growth in vivo. Moreover, ACER2 positively regulated the protein level of SMPDL3B. Of note, ACER2/SMPDL3B promoted ceramide hydrolysis and S1P production. This axis induced HCC survival and could be blocked by inhibition of S1P formation. In conclusion, ACER2 promoted HCC cell survival and migration, possibly via SMPDL3B. Thus, inhibition of ACER2/SMPDL3B may be a novel therapeutic target for HCC treatment.

Highly regioselective biotransformation of ginsenoside Rg1 to 25-OH derivatives of 20(S/R)-Rh1 by Cordyceps Sinensis.

25-OH ginsenosides are potent and rare prodrugs in natural sources. However current strategies for such modification always end up in undesirable side products and unsatisfied yield that hinders them from further applications. Herein, ginsenoside Rg1 was thoroughly converted into 20(S/R)-Rh1 and 25-OH-20(S/R)-Rh1 by Cordyceps Sinensis in an optimum medium. The chemical correctness of either 25-OH-20(S/R)-Rh1 epimers was validated by LC-IT-TOF-MSn and 13C NMR spectrometry. The biocatalytic pathway was established as Rg1 â†’ 20(S/R)-Rh1 â†’ 25-OH-20(S/R)-Rh1. The molar bioconversion rate for total 25-OH-20(S/R)-Rh1 was calculated to be 82.5%, of which S-configuration accounted for 43.2% while R-configuration 39.3%. These two 25-OH derivatives are direct hydration products from 20(S/R)-Rh1 without other side metabolites, suggesting this is a highly regioselective process. In conclusion, this biocatalytic system could be harnessed to facilitate the preparation of diversified 25-OH ginsenosides with high yields of the target compound and simple chemical background in the reaction mixture.

Expression of MACC1 protein in gastric cancer and its effect on proliferation and invasion of gastric cancer cells.

To detect the expression of metastasis-associated colon cancer gene 1 (MACC1) protein in gastric cancer tissues, and analyze its relationship with clinicopathological parameters of gastric cancer and its effect on proliferation and invasion of gastric cancer cells. METHODS: 71 patients with gastric cancer in Fifth Hospital in Wuhan from June 2014 to March 2018 were selected as research subjects. Western blot was used to detect the expression of MACC1 in gastric cancer tissue and normal gastric mucosa tissue, and gastric cancer cell SGC7901 was transfected. Transfection group (transfected with MACC1-siRNA), negative control group (transfected with siRNA-NC) and blank control group (untreated cells) were set up. After transfection, the expressions of MACC1 protein and mRNA in the 3 groups were detected by Western blot and qRT-PCR methods, the cell proliferation was detected by MTT method, and the invasion ability of cells in vitro was detected by Transwell chamber. RESULTS: The expression of MACC1 protein in gastric cancer tissue was higher than the control group (P< 0.05). The expression of MACC1 protein in gastric cancer was related to the differentiation degree, infiltration depth, lymph node metastasis and different stages of gastric cancer (P< 0.05). After transfection, the expressions of MACC1 protein and mRNA in the transfection group was significantly lower than the negative control group and blank group (P< 0.05). There was no significant difference in cell viability between the blank group and negative control group at each time point (P> 0.05). CONCLUSION: MACC1 was highly expressed in gastric cancer tissues. The expression of MACC1 was related to the differentiation degree, infiltration depth, lymph node metastasis and staging of gastric cancer. Down-regulation of MACC1 could inhibit the proliferation and invasion of gastric cancer cells. This study provided a certain biological basis for early clinical prediction, diagnosis and treatment of gastric cancer.

Adsorption and desorption characteristics of ginsenosides from Panax ginseng C. A. Meyer on middle-pressure chromatogram isolated gels.

Four types of middle-pressure chromatogram isolated gels are evaluated for adsorption or desorption characteristics of ginsenosides from Panax ginseng. Among them, SP207SS and SP2MGS were selected for dynamic investigations based on their static adsorption or desorption capacity of total ginsenoside. Their adsorption kinetics was better explained by pseudosecond-order model and isotherms were preferably fitted to Langmuir model. Dynamic breakthrough experiments indicated an optimum sample loading speed of 4 bed volume/h for either SP207SS or SP2MGS. Desorption speed was determined to be 2 bed volume/h according to desorption amount of total ginsenoside in their effluents. Eight ginsenosides were identified and quantified by high performance liquid chromatography-triple quadropole-mass spectrometry in total ginsenoside extract and different fractions during stepwise dynamic elution. For SP207SS, 27.62% of loaded ginsenosides was detected in 40% ethanol fraction, while 59.12% of them were found in 60% ethanol fraction. As on SP2MGS, the number went to 53.71 and 44.43%, respectively. Recovery rate of ginsenosides were calculated to 78.65% for SP207SS and 89.53% for SP2MGS, respectively. Intriguingly, content of Rg1 and Re in 40% ethanol fraction from SP207SS became 20.1 and 18.6 times higher than that in total ginsenoside extract by one-step elution, which could be leveraged for the facile enrichment of these two ginsenosides from natural sources.

A Liposomal Formulation for Improving Solubility and Oral Bioavailability of Nifedipine.

Proliposomes were used to improve the solubility and oral bioavailability of nifedipine. Nifedipine proliposomes were prepared by methanol injection-spray drying method. The response surface method was used to optimize formulation to enhance the encapsulation efficiency (EE%) of nifedipine. The particle size of nifedipine proliposomes after rehydration was 114 nm. Surface morphology of nifedipine proliposomes was observed by a scanning electron microscope (SEM) and interaction of formulation ingredients was assessed by differential scanning calorimetry (DSC). The solubility of nifedipine is improved 24.8 times after forming proliposomes. In vitro release experiment, nifedipine proliposomes had a control release effect, especially in simulated gastric fluid. In vivo, nifedipine proliposomes significantly improved the bioavailability of nifedipine. The area under the concentration-time curve (AUC0-∞) of nifedipine proliposomes was about 10 times than nifedipine after oral administration. The elimination half-life (T1/2ß) of nifedipine was increased from 1.6 h to 6.6 h. In conclusion, proliposomes was a promising system to deliver nifedipine through oral route and warranted further investigation.

Study on the Structure of Ginseng Glycopeptides with Anti-Inflammatory and Analgesic Activity.

Panax ginseng is well known for its medicinal functions. As a class of important compound of ginseng, ginsenoside is widely studied around the world. In addition, ginseng glycopeptides also showed good biological activity, but researches in this field are rarely reported. In this study, ginseng glycopeptides (Gg) were first prepared from Panax ginseng by reflux extracted with 85% ethanol and the following purification with Sephadex G-15 column. Then, the inflammatory pain models induced by carrageenan and the rat pain models induced by Faure Marin were established for research on mechanism of analgesic activities. It is showed that Gg had an obvious inhibiting effect on inflammation and a significant reduction on the Malondialdehyde (MDA) of inflammatory foot tissue. And there were significant differences between moderate to high dose of Gg and model group in Interleukin 1ß (IL-1ß), Interleukin 2 (IL-2), Interleukin 4 (IL-4), Tumor necrosis factor α (TNF-α) and Histamine. The two models can be preliminarily determined that the analgesic effect of Gg may be peripheral, which mechanism may be related to the dynamic balance between proinflammatory cytokines (TNF-α, IL-1ß) and anti-inflammatory cytokines (IL-2, IL-4, and Interleukin 10 (IL-10)). A series of methods were used to study Gg in physical-chemical properties and linking mode of glycoside. The high-resolution mass spectrometry was used for identification of the structure of Gg. Moreover, the structure of 20 major Gg were investigated and identified. The structural analysis of Gg was benefit for the next study on structure-activity relationship.