Elucidation of the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus on rats fed a western-style diet via a multi-omics approach.

Long-term consumption of Western-style diet (WSD) can lead to metabolic disorders and dysbiosis of gut microbiota, presenting a critical risk factor for various chronic conditions such as fatty liver disease. In the present study, we investigated the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus kisonensis on rats fed a WSD. Male Sprague-Dawley (SD) rats, aged six weeks and weighing 180 ± 10 g, were randomly assigned to one of three groups: the normal control group (NC, n = 7), the WSD group (HF, n = 7), and the WSD supplemented with a co-fermented whole grain quinoa with black barley (FQB) intervention group (HFF, n = 7). The findings indicated that FQB was effective in suppressing body weight gain, mitigating hepatic steatosis, reducing perirenal fat accumulation, and ameliorating pathological damage in the livers and testicular tissues of rats. Additionally, FQB intervention led to decreased levels of serum uric acid (UA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). These advantageous effects can be ascribed to the regulation of FQB on gut microbiota dysbiosis, which includes the restoration of intestinal flora diversity, reduction of the F/B ratio, and promotion of probiotics abundance, such as Akkermansia and [Ruminococcus] at the genus level. The study employed the UPLC-Q-TOF-MSE technique to analyze metabolites in fecal and hepatic samples. The findings revealed that FQB intervention led to a regression in the levels of specific metabolites in feces, including oxoadipic acid and 20a, 22b-dihydroxycholesterol, as well as in the liver, such as pyridoxamine, xanthine and xanthosine. The transcriptome sequencing of liver tissues revealed that FQB intervention modulated the mRNA expression of specific genes, including Cxcl12, Cidea, and Gck, known for their roles in anti-inflammatory and anti-insulin resistance mechanisms in the context of WSD. Our findings indicate that co-fermented whole-grain quinoa with black barley has the potential to alleviate metabolic disorders and chronic inflammation resulting from the consumption of WSD.

One-pot synthesis and enzyme-responsiveness of amphiphilic doxorubicin prodrug nanomicelles for cancer therapeutics.

In this study, we report a one-pot synthesis and enzyme-responsiveness of polyethylene glycol (PEG) and glutamic acid (Glu)-based amphiphilic doxorubicin (DOX) prodrug nanomicelles for cancer therapeutics. The nanomicelles were accomplished by esterification and amidation reactions. The nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) data confirmed the structure of nanomicelles. The DOX-loaded nanomicelles showed a DLS-measured average size of 107 nm and excellent stability in phosphate-buffered saline (PBS) for 7 days. The drug loading and cumulative release rates were measured by ultraviolet-visible (UV-vis) spectrophotometry at 481 nm. The cumulative release rate could reach 100% in an enzyme-rich environment. Further, the therapeutic efficiency of nanomicelles to cancer cells was determined by cell viability and cellular uptake and distribution using HeLa cells. The cell viability study showed that the DOX-loaded nanomicelles could effectively inhibit the HeLa cell proliferation. The cellular uptake study confirmed that the nanomicelles could be effectively ingested by HeLa cells and distributed into cell nuclei. Based on the collective experimental data, this study demonstrated that the synthesized nanomicellar prodrug of DOX is a potential candidate for cancer therapeutics.

Beneficial effects of Lactobacillus-fermented black barley on high fat diet-induced fatty liver in rats.

A long-term high-fat (HF) diet can cause metabolic disorders, which might induce visceral obesity and ectopic triglyceride storage (e.g., hepatic steatosis), and increase hepatic oxidative stress. Oxidative stress plays a significant role in the development of complications associated with obesity. Fermented whole cereal foods exhibit healthy potential due to their unique phytochemical composition and the presence of probiotics. In the present study, the regular nutrients and phytochemicals of Lactobacillus-fermented black barley (Hordeum distichum L.) were analyzed. Further, the black barley fermentation broth (1 mL per 100 g BW per d, equivalent to 1 mL per kg BW of daily human intake) was administered orally to the rats fed on a high fat diet (HF). The anti-oxidative activity and hepatic metabolic profile of Lactobacillus-fermented black barley were investigated. The results showed that the fermentation processing significantly increased the contents of polyphenols (e.g., ferulic acid, etc.), flavonoids (e.g., flavone, etc.), vitamin B1 and B2, partial mineral elements (e.g., Ca, etc.), and thymine. Furthermore, compared to the HF-fed only rats, fermented black barley treatment significantly increased the activities of SOD (superoxide dismutase) and GSH-PX (glutathione peroxidase), and decreased the level of TBARS (thiobarbituric acid reactive substances) in serum, the levels of TG (triglyceride), TC (total cholesterol), NEFA (non-esterified fatty acid) in the liver, and the levels of TC, NEFA in the adipose tissue. This suggested the beneficial effects of fermented black barley on ameliorating oxidative stress and hepatic steatosis, which could be attributed to its regulatory role in the hepatic metabolism of glycerophospholipids, nicotinate and nicotinamide, glutathione, and nucleotide, and on the expression of genes related to oxidative stress (Heat shock protein 90 and reactive oxygen species modulator 1).

miR-515-5p suppresses HCC migration and invasion via targeting IL6/JAK/STAT3 pathway.

MicroRNAs (miRNAs) have been identified as critical modulators of cell migration and invasion, which are the major causes of cancer progression including hepatocellular carcinoma (HCC). However, the accurate role of miR-515-5p in HCC is still uncertain. Here, we report that miR-515-5p expression is down-regulated in HCC tissues and cell lines, and associated with absence of capsule formation (p = 0.015)﹑microvascular invasion(p = 0.003)﹑and advantange TNM stage (II-III) (p = 0.014) in HCC patients. Overexpression of miR-515-5p inhibited migration and invasion of HCC cells in vitro and in vivo, while miR-515-5p knockdown has the inverse effect. Moreover, using miRNA databases and dual-luciferase report assay, we find miR-515-5p directly binds to the 3'-untranslated region (3'-UTR) of interleukin 6 (IL6). In addition, the regulatory association between miR-515-5p and the IL-6/Janus kinase (JNK)/signal transducer and activator of transcription-3 (STAT3) signaling pathway was explored. Furthermore, overexpression of miR-515-5p inhibited the activation of the JAK/STAT3 signaling pathway, which was rescued by overexpression of IL-6. The results of the current study indicate that miR-515-5p overexpression may serve an important role in inhibiting migration and invasion of HCC cells via suppression of IL-6/JAK/STAT3 signaling pathway activation. MiR-515-5p may serve as a potential therapeutic target for HCC.

Hsa_circ_0003998 promotes epithelial to mesenchymal transition of hepatocellular carcinoma by sponging miR-143-3p and PCBP1.

BACKGROUND: Circular RNAs (circRNAs) play a critical regulatory role in cancer progression. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) metastasis remain mostly unknown. METHODS: Has_circ_0003998 (circ0003998) was identified by RNAs sequencing in HCC patients with /without portal vein tumor thrombus (PVTT) metastasis. The expression level of circ0003998 was further detected by in situ hybridization on tissues microarray (ISH-TMA) and qRT-PCR in 25 HCC patients with PVTT metastasis. Moreover, the 25 HCC patients with PVTT metastasis and 50 HCC patients without PVTT metastasis were recruited together to analyze the correlation between circ0003998 expression and HCC clinical characteristics. Transwell, migration and CCK8 assays, as well as nude mice model of lung or liver metastasis were used to evaluate the role of circ0003998 in epithelial to mesenchymal transition (EMT) in HCC. The regulatory mechanisms of circ0003998 in miR-143-3p and PCBP1 were determined by dual-luciferase reporter assay, nuclear-cytoplasmic fractionation, fluorescent in situ hybridization, RNA pull- down, microRNA sequence, western blot and RNA immunoprecipitation. RESULTS: Compared with adjacent normal liver tissues (ANL), circ0003998 expression was significantly upregulated in PVTT tissues and HCC tissues, and its expression correlates with the aggressive characteristics of HCC patients. Further assays suggested that circ0003998 promoted EMT of HCC both in vitro and in vivo. Mechanistically, our data indicated that circ0003998 may act as a ceRNA (competing endogenous RNA) of microRNA-143-3p to relieve the repressive effect on EMT-related stimulator, FOSL2; meanwhile, circ0003998 could bind with PCBP1-poly(rC) binding protein 1 (PCBP1) to increase the expression level of EMT-related genes, CD44v6. CONCLUSION: Circ0003998 promotes EMT of HCC by circ0003998/miR-143-3p/FOSL2 axis and circ0003998 /PCBP1/CD44v6 axis.

Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model.

BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 µmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 µmol/L. The viral RNA yield in cells treated with 10 µmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ±â€Š0.02] × 10vs. 1.00 ±â€Š0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 µmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ±â€Š0.12, vs.1.00 ±â€Š0.37, t = 2.42, P < 0.05) and viral replication ([6.18 ±â€Š0.95] × 10vs. 1.00 ±â€Š0.43, t = 3.98, P < 0.05). CONCLUSIONS: Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.

Downregulation of miR-196-5p Induced by Hypoxia Drives Tumorigenesis and Metastasis in Hepatocellular Carcinoma.

In hepatocellular carcinoma (HCC), the hypoxic tumor microenvironment can drive enhance tumor malignancy and recurrence. The microRNA (miRNA) miR-196-5p has been shown to modulate the progression of several cancer types, but its roles in HCC remain uncertain. In the present report we observed significant miR-196-5p downregulation in HCC tissues and cells, and we found that the expression of this miRNA significantly impaired the proliferation and metastatic potential of HCC in vitro and in vivo. We identified high-mobility group AT-hook 2 (HMGA2) as a miR-196-5p target gene that was associated with the ability of miR-196-5p to modulate the progression of HCC. Expression of miR-196-5p and HMGA2 were correlated with the clinical characteristics and poor outcomes in patients with HCC. Finally, we found that hypoxic conditions were linked with reduced miR-196-5p expression in the context of HCC. Together these results highlight the role for miR-196-5p as an inhibitor of the proliferation and metastasis of HCC via the targeting of HMGA2, with this novel hypoxia/miR-196-5p/HMGA2 pathway serving as a potential target for future therapeutic intervention.

Effects of hydrogen-rich water on the nutrient composition and antioxidative characteristics of sprouted black barley.

Hydrogen gas (H2), a multifunctional signaling molecule, has received increasing attention in recent years. In the present study, hydrogen-rich water (HRW) (2 ppm) was used for the processing of sprouted black barley (Hordeum distichum L.), and the results showed that the HRW treatment could significantly increase the germination rate and growth rate of black barley (P < 0.05). A chemical component analysis showed that in sprouted black barley, the HRW treatment could change the distribution of phytochemicals (e.g., the ionic strength of guanosine), increase the concentrations of free vanillic acid, coumaric acid, sinapic acid, conjugated sinapic acid, Ca and Fe and the hydroxyl radical scavenging rate, and decrease the protein, fat, starch and dietary fibre contents compared with the results obtained after treatment with ultra-pure water (P < 0.05). HRW can be used for the processing of sprouted grains to effectively increase their germination efficiency and concentrations of bioactive phytochemicals.

Natural small molecule bigelovin suppresses orthotopic colorectal tumor growth and inhibits colorectal cancer metastasis via IL6/STAT3 pathway.

Bigelovin, a sesquiterpene lactone, has been demonstrated to induce apoptosis, inhibit inflammation and angiogenesis in vitro, but its potential anti-metastatic activity remains unclear. In the present study, two colon cancer mouse models, orthotopic tumor allografts and experimental metastatic models were utilized to investigate the progression and metastatic spread of colorectal cancer after bigelovin treatments. Results showed that bigelovin (intravenous injection; 0.3-3 mg/kg) significantly suppressed tumor growth and inhibited liver/lung metastasis with modulation of tumor microenvironment (e.g. increased populations of T lymphocytes and macrophages) in orthotopic colon tumor allograft-bearing mice. Furthermore, the inhibitory activities were also validated in the experimental human colon cancer metastatic mouse model. The underlying mechanisms involved in the anti-metastatic effects of bigelovin were then revealed in murine colon tumor cells colon 26-M01 and human colon cancer cells HCT116. Results showed that bigelovin induced cytotoxicity, inhibition of cell proliferation, motility and migration in both cell lines, which were through interfering IL6/STAT3 and cofilin pathways. Alternations of the key molecules including Rock, FAK, RhoA, Rac1/2/3 and N-cadherin, which were detected in bigelovin-treated cancer cells, were also observed in the tumor allografts of bigelovin-treated mice. These findings strongly indicated that bigelovin has potential to be developed as anti-tumor and anti-metastatic agent for colorectal cancer.

Effects of various additives on the pyrolysis characteristics of municipal solid waste.

Additives can have a significant impact on the pyrolysis process. The effects of three additives (CaO, MSW char and biomass) on the pyrolysis characteristics of municipal solid waste (MSW) were investigated using a fixed-bed reactor. In addition, the effects of additives and temperature on the MSW pyrolysis product yield, the composition of MSW pyrolysis gases, and the composition of MSW pyrolysis tar were investigated using fixed bed reactor, GC-MS and FTIR, respectively. The results showed that the maximum tar yield of the MSW reached 28.73% at 600 °C and the tar yield decreased with increasing amounts of CaO and MSW. The tar yield began to decrease when the additive amount of CaO was 5% and decreased to 23.05% when the additive amount of MSW char (C) was 30%. Synergistic pyrolysis of the biomass and MSW was observed when the additive amount of the pine increased to 75% (with a tar yield of 37.91%). Regarding gas composition, with increasing additives content, the CO2 yield decreased, while the CO yield increased. According to the FTIR analysis of the tar, CaO enhanced the condensation of the aromatic rings and converted the aliphatic hydrocarbons, while C reduced the oxygenic groups of the tar. The GC-MS results revealed that the additives decreased the yield of carboxylic acid and ethanol, and increased the ester yield. The additives were also found to have a deoxidation effect that decreased the acid content, potentially improving the quality and stability of the tar.

Bigelovin triggered apoptosis in colorectal cancer in vitro and in vivo via upregulating death receptor 5 and reactive oxidative species.

Colorectal cancer (CRC) is the third most prevalent cancer and the third highest cancer-related mortality in the United States. Bigelovin, a sesquiterpene lactone isolated from Inula helianthus aquatica, has been proven to induce apoptosis and exhibit anti-inflammatory and anti-angiogenic activities. However, the effects of bigelovin on CRC and underlying mechanisms have not been explored. The present study demonstrated that bigelovin exhibited potent anti-tumor activities against CRC in vitro and in vivo. Bigelovin suppressed cell proliferation and colony formation and induced apoptosis in human colorectal cancer HT-29 and HCT 116 cells in vitro. Results also revealed that bigelovin activated caspases, caused the G2/M cell cycle arrest and induced DNA damage through up-regulation of death receptor (DR) 5 and increase of ROS. In HCT 116 xenograft model, bigelovin treatment resulted in suppression of tumor growth. Bigelovin at 20 mg/kg showed more significant tumor suppression and less side effects than conventional FOLFOX (containing folinic acid, 5-fluorouracil and oxaliplatin) treatment. In addition, in vivo data confirmed that anti-tumor activity of bigelovin in CRC was through induction of apoptosis by up-regulating DR5 and increasing ROS. In conclusion, these results strongly suggested that bigelovin has potential to be developed as therapeutic agent for CRC patients.

Lazaroid U83836E protects the heart against ischemia reperfusion injury via inhibition of oxidative stress and activation of PKC.

Oxidative stress has been demonstrated to be important during myocardial ischemia/reperfusion injury (MIRI). The lazaroid U83836E, which combines the amino functionalities of the 21­aminosteroids with the antioxidant ring portion of vitamin E, is a reactive oxygen species scavenger. The aim of the current study was to investigate the effect of U83836E on MIRI and its mechanisms of action. Rat hearts were subjected to 30 min ligation of the left anterior descending coronary artery, followed by 2 h reperfusion. The results demonstrated that at 5 mg/kg, U83836E markedly protected cardiac function in ischemia/reperfusion rat models, decreased the malondialdehyde content and creatinine kinase activity, while increasing superoxide dismutase and glutathione peroxidase activity. Additionally, U83836E significantly decreased the histological damage to the myocardium, reduced the area of myocardial infarction in the left ventricle and modified the mitochondrial dysfunction. Furthermore, U83836E enhanced the translocation of protein kinase Cε (PKCε) from the cytoplasm to the membrane. However, the cardioprotective effects of U83836E were reduced in the presence of the PKC inhibitor, chelerythrine (1 mg/kg). Therefore, the results of the present study suggest that U83836E has a potent protective effect against MIRI in rat models through the direct anti­oxidative stress mechanisms and the activation of PKC signaling.

Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement.

Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem-ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic.

Multiple-fingerprint analysis for investigating quality control of Flammulina velutipes fruiting body polysaccharides.

Quality control issues overshadow potential health benefits of the edible mushroom Flammulina velutipes, with the detection and isolation of polysaccharides posing particular problems. In this study, multiple-fingerprint analysis was performed using chemometrics to assess polysaccharide quality and antioxidant activity of F. velutipes fruiting bodies from different sources. The authentic source exhibited differences in both oxygen radical absorbance capacity and ferric reducing antioxidant power from foreign sources. IR spectroscopic/HPLC fingerprints of polysaccharide extracts from the authentic source were established and applied to assess the polysaccharide quality of foreign sources. Analysis of IR fingerprints using Pearson correlation coefficient gave correlation coefficient r values of 0.788 and 0.828 for two foreign sources, respectively, indicating distinctness from the authentic source. Analysis of HPLC fingerprints using the supervised method by Traditional Chinese Medicine could not discriminate between sources (r > 0.9), but principal component analysis of IR and HPLC fingerprints distinguished the foreign sources.

Characterization of phytochemicals and antioxidant activities of red radish brines during lactic acid fermentation.

Red radish (Raphanus L.) pickles are popular appetizers or spices in Asian-style cuisine. However, tons of radish brines are generated as wastes from industrial radish pickle production. In this study, we evaluated the dynamic changes in colour properties, phenolics, anthocyanin profiles, phenolic acid composition, flavonoids, and antioxidant properties in radish brines during lactic acid fermentation. The results showed that five flavonoids detected were four anthocyanins and one kaempferol derivative, including pelargonidin-3-digluoside-5-glucoside derivatives acylated with p-coumaric acid, ferulic acid, p-coumaric and manolic acids, or ferulic and malonic acids. Amounts ranged from 15.5-19.3 µg/mL in total monomeric anthocyanins, and kaempferol-3,7-diglycoside (15-30 µg/mL). 4-Hydroxy-benzoic, gentisic, vanillic, syringic, p-coumaric, ferulic, sinapic and salicylic acids were detected in amounts that varied from 70.2-92.2 µg/mL, whereas the total phenolic content was 206-220 µg/mL. The change in colour of the brine was associated with the accumulation of lactic acid and anthocyanins. The ORAC and Fe2+ chelation capacity of radish brines generally decreased, whereas the reducing power measured as FRAP values was increased during the fermentation from day 5 to day 14. This study provided information on the phytochemicals and the antioxidative activities of red radish fermentation waste that might lead to further utilization as nutraceuticals or natural colorants.

Total glucosides of paeony inhibit the proliferation of fibroblast-like synoviocytes through the regulation of G proteins in rats with collagen-induced arthritis.

The aim of this study was to investigate the expression of G proteins in fibroblast-like synoviocytes (FLSs) from rats with collagen-induced arthritis (CIA) and to determine the effect of total glucosides of paeony (TGP). CIA rats were induced with chicken type II collagen (CCII) in Freund's complete adjuvant. The rats with experimental arthritis were randomly separated into five groups and then treated with TGP (25, 50, and 100mg/kg) from days 14 to 35 after immunization. The secondary inflammatory reactions were evaluated through the polyarthritis index and histopathological changes. The level of cyclic adenosine monophosphate (cAMP) was measured by radioimmunoassay. The FLS proliferation response was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The toxin-catalyzed ADP-ribosylation of G proteins was performed through autoradiography. The results show that TGP (25, 50, and 100mg/kg) significantly decreased the arthritis scores of CIA rats and improved the histopathological changes. TGP inhibited the proliferation of FLSs and increased the level of cAMP. Moreover, the FLS proliferation and the level of Gαi expression were significantly increased, but the level of Gαs expression was decreased after stimulation with IL-1ß (10ng/ml) in vitro. TGP (12.5 and 62.5µg/ml) significantly inhibited the FLS proliferation and regulated the balance between Gαi and Gαs. These results demonstrate that TGP may exert its anti-inflammatory effects through the suppression of FLS proliferation, which may be associated with its ability to regulate the balance of G proteins. Thus, TGP may have potential as a therapeutic agent for the treatment of rheumatoid arthritis.

[Study on in vitro release and percutaneous absorption of Huoxue Zhitong gel].

To evaluate in vitro release and transdermal behaviors of Huoxue Zhitong gel, modified Franz diffusion cell methods was applied to investigate in vitro transdermal absorption of Huoxue Zhitong gel and the content of paeonolan in receptor fluid composed of PEG400%-95% ethanol-water (l:3:6)were determined by HPLC. The results were processed and different equations were fitted. The release law were in accordance with Weibull equation and the fitting equation was In[-1/(1 - Q)] = -0.790 51nt - 1.7012 (r = 0.9809). In 8 hours, cumulative release of paeonol was 85. 18% and the release rate was 2.827 µg . cm-2 h-1. Transdermal actions were consistent with zero-level model fit and the fitting equation was Q(t) = 1.7579t + 0. 7213 (r = 0.9991). In 8 hours, cumulative transdermal rate and transmission rate of paeonol was 54. 85%, 1. 820 µg . cm-2 h-1. So the Huoxue Zhitong gel had a good release and transdermal properties.

[Study on in vitro release and percutaneous absorption for Zhitong cataplasm].

To evaluate in vitro release and transdermal behaviors of Zhitong cataplasm, modified Franz diffusion cell method was applied to investigate in vitro transdermal absorption of Zhitong cataplasm and the content of tetrahydropalmatine was determined by HPLC. In 24 hours, accumulative release rate of tetrahydropalmatine was 81. 9%, transmission rate was 2.26 microg x cm(-2) x h(-1). In 48 hours, accumulative transdermal rate and transmission rate of tetrahydropalmatine were 20.31%, 0.22 pg x cm(-2) x h(-1). So Zhitong cataplasm had a good release and transdermal properties and transdermal actions were consistent with zero-order kinetics process.