Accelerating the Phase Formation Kinetics of Alluaudite Sodium Iron Sulfate Cathodes via Ultrafast Thermal Shock.

Alluaudite sodium iron sulfate (NFS) exhibits great potential for use in sodium-ion battery cathodes due to its elevated operating potential and abundant element reserves. However, conventional solid-state methods demonstrate a low heating/cooling rate and sluggish reaction kinetics, requiring a long thermal treatment to effectively fabricate NFS cathodes. Herein, we propose a thermal shock (TS) strategy to synthesize alluaudite sodium iron sulfate cathodes using either hydrous or anhydrous raw materials. The analysis of the phase formation process reveals that TS treatment can significantly facilitate the removal of crystal water and decomposition of the intermediate phase Na2Fe(SO4)2 in the hydrous precursor. In the case of the anhydrous precursor, the kinetics of the combination reaction between Na2SO4 and FeSO4 can be also accelerated by TS treatment. Consequently, pure NFS phase formation can be completed after a substantially shorter time of post-sintering, thereby saving significant time and energy. The TS-treated NFS cathode derived from hydrous precursor exhibits higher retention after 200 cycles at 1C and better rate capability than the counterpart prepared by conventional long-term tube furnace sintering, demonstrating the great potential of this novel strategy.

Exploring the effect of polyamines on NK cell function in colorectal cancer process based on glycolysis.

Natural killer (NK) cells are lymphocytes with important anti-tumour functions. Cellular metabolism is dynamically regulated in NK cells and strongly influences their responses. Myc is a key regulator of immune cell activity and function, but little is known about how Myc controls NK cell activation and function. In this study, we found that c-Myc is involved in the regulation of NK cell immune activity. In the development of colon cancer, the energy generation disorder of tumor cells promotes the plunder of polyamines of NK cells by tumor cells, resulting in the inhibition of NK cell c-Myc. After inhibition of c-Myc, glycolysis of NK cells was impaired, resulting in decreased killing activity. There are three main types of polyamines: putrescine (Put), spermidine (Spd) and spermine (Spm). We found that the NK cells could reverse the inhibition state of c-Myc and glycolysis energy supply disorder and recover the killing activity of NK cells after giving certain spermidine. These results suggest that polyamine content and glycolysis supply under the regulation of c-Myc play a crucial role in the immune activity of NK cells.

Targeting erythrocyte-mediated hypoxia to alleviate lung injury induced by pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PAs) are widely distributed natural toxins and have been extensively studied for their hepatotoxicity. However, PA-induced pulmonary toxicity remains less studied regarding the initiating mechanism and treatment approaches. Our previous study demonstrated the formation of pyrrole-hemoglobin adducts after PA exposure in vivo, which is suspected to affect the oxygen-carrying capacity of erythrocytes [red blood cells (RBCs)] consequently. The present study aimed to investigate the effects of PAs on the oxygen-carrying capacity of RBCs and the potential of targeting RBC-mediated hypoxia to alleviate PA-induced lung injury. First, rats were treated with retrorsine (RTS) or monocrotaline (MCT) intravenously at 0.2 mmol/kg. The results of Raman spectrometry analysis on blood samples revealed both RTS and MCT significantly reduced the oxygen-carrying capacity of RBCs. Further, MCT (0.2 mmol/kg) was orally given to the rats with or without pretreatment with two doses of erythropoietin (Epo, 500 IU/kg/dose every other day), an RBC-stimulating agent. Biochemical and histological results showed pretreatment with Epo effectively reduced the cardiopulmonary toxicity induced by MCT. These findings provide the first evidence that adduction on hemoglobin, and the resulting RBC damage and impaired oxygen-carrying capacity, are the major initiating mechanism underlying PA-induced pulmonary arterial hypertension (PAH), while targeting the RBC damage is a potential therapeutic approach for PA-induced lung injury.

Designing narratives and data visuals in comic form for social influence in climate action.

Climate change is difficult to connect with personally, because people only regard the phenomenon as important if it becomes a perceived threat to themselves. Arguments like statistics and policy debates are extrinsic motivators, which do not necessarily align people's own intrinsic motives with those of climate action. Instead, narratives and visual communication can influence viewers implicitly by the way they show and reinforce actions and thoughts that align with climate action. In this design study, we used comics created for human-level climate change influence to promote ideas like future-based thinking, sharing of responsibility, and caring for each other. We also created data visuals that illustrate future consequences of climate change for the purpose of averting negative alternative realities. To see whether our design can affect audience perception of climate change on the human level of goals and desires, we showed the comics to readers unfamiliar with the themes of the stories, presenting them as manga about characters and situations. The survey showed that data stories can affect the way naive readers interpret narratives to align with pro-climate attitudes such as sharing and future-vision, and that readers are focused on the human-level of the data and story as opposed to the physical resource level. Speculative fiction and data visuals provide a potentially effective way to influence individuals' climate change attitudes by showing alternative realities and attributes of collective responsibility and planning-for-the-future as data stories.

Effects of glycolysis and polyamine predation on intestinal epithelial barrier in colorectal cancer.

Colorectal cancer (CRC) is the second most lethal cancer and the third most common cancer in the world, and its prognosis is severely affected by high intestinal mucosal permeability and increasing tumor burden. Studies have shown that the expression of hypoxia induce factor 1α (HIF1α) is up-regulated in a variety of tumor tissues, which is related to multiple metabolic reprogramming of tumor cells. However, the role of HIF1α in CRC tumor growth, tumor polyamine metabolism and intestinal mucosal barrier damage has not been studied. Here, we constructed different types of CRC tumor-bearing mice models by inoculating HCT116 cells with different levels of HIF1α expression (knockdown, wild type, overexpression) in the armpits of mice to explore the upstream and downstream regulators of HIF1α, the effects of HIF1α on the growth of CRC, and the CRC polyamine metabolism and its effect on the intestinal mucosal barrier. We found that with the increase of HIF1 gene expression, tumor growth was promoted and intestinal mucosal permeability was increased. The expression of glycolysis-related proteins was up-regulated, the rate-limiting enzyme ODC of polyamine synthesis was decreased, and the transfer protein of polyamine was increased. HPLC showed that the polyamine content in the tumor tissue of the overexpression group HIF1α OE was higher than that of the wild group HIF1α (+/+), and higher than that of the knockdown group HIF1α (-/-), but the content of polyamines in intestinal mucosa was the opposite. After supplementation of exogenous polyamines, the content of polyamines in intestinal mucosa and tumor tissue increased, and the damage of intestinal mucosa was alleviated. In conclusion, upon activation of the MYC/HIF1 pathway, tumor glycolysis is enhanced, tumors require more energy and endogenous polyamine synthesis is reduced. Therefore, in order to meet its growth needs, tumor will rob polyamines in the intestinal mucosa, resulting in intestinal mucosal epithelial barrier dysfunction.

The prevalence and characteristics of MCCB cognitive impairment in unmedicated patients with bipolar II depression and major depressive disorder.

BACKGROUND: Cognitive impairment has been acknowledged as a core clinical manifestation of bipolar disorder (BD) as well as major depressive disorder (MDD). Determining the prevalence and characteristics of cognitive impairment is important for clinical interventions. This study investigated the prevalence and characteristics of cognitive impairment based on the Measurement and Treatment Research to Improve Cognition Schizophrenia Consensus Cognitive Battery (MCCB) in both BD and MDD. METHOD: One hundred and forty-nine BD II depression, 147 MDD, and 124 demographically matched healthy controls (HC) underwent MCCB cognitive assessment. The prevalence of MCCB cognitive impairment and group difference comparisons were performed. Additionally, association analysis was performed to investigate the relationship between cognitive performance and clinical variables. RESULTS: Compared to the HC group, both BD II depression and MDD groups had a significantly reduced performance for all MCCB cognitive domains (all p < 0.05). The numerical scores for visual learning were lower in the BD II depression group compared to the MDD group. 32.89% of the BD II depression patients had clinically significant impairment (>1.5 SD below the normal mean) in two or more MCCB domains compared to 23.13% for MDD patients. CONCLUSIONS: A high percent of patients in the BD II depression and MDD group exhibited MCCB cognitive impairments with clinical significance. Cognitive impairments were more common in BD II depression patients compared to MDD patients, particularly for visual learning. These findings suggest that clinicians should be aware of the severe cognitive impairment in mood disorders and establish effective cognitive screening and intervention strategies.

Characterization of liver injury induced by a pyrrolizidine alkaloid in rats.

BACKGROUND: Pyrrolizidine alkaloids (PAs) are common phytotoxins. PA intoxication is reported to cause severe acute liver damage, typically known as hepatic sinusoidal obstruction syndrome (HSOS), but it remains obscure whether the acute liver damage may progress into chronic liver disease characterized by hepatic fibrosis. PURPOSE: This study aims to characterize the biochemical markers of liver injury and histological features of regressive and progressive liver fibrosis, and to examine changes in hepatic gene expression that may underpin mechanisms of fibrogenesis in rats induced by retrorsine (RTS), a representative toxic PA. STUDY DESIGN/METHODS: Rats were gavaged with RTS via two dosing regimens, i.e. a single dose of 40 mg/kg (Group 1) and two doses of 40 mg/kg and 20 mg/kg on day 0 and day 7 (Group 2), respectively. Rats receiving one (Group 3) or two (Group 4) doses of vehicle served as negative controls. The animals were followed for up to 16 weeks by serum biochemical analyses and histological examination, and gene expression assays of liver tissues. RESULTS: Acute liver injury on day 2 manifested as HSOS, characterized by sinusoidal dilation, endothelial cell damage, and elevated serum alanine aminotransferase activity and bilirubin levels. In Group 1, mild liver fibrosis developed at sinusoids and perisinusoidal space surrounding the central veins at week 1 and 2, and thereafter, all liver injury resolved gradually. In Group 2, liver fibrosis progressed within the 16-week observation period. No apparent liver injury was observed in Groups 3 and 4. Compared with negative control groups, RTS induced myofibroblastic activation, TGF-ß1 signaling, and changes in expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). These dynamic changes differed in Groups 1 and 2, corresponding with the regression and progression of liver fibrosis, respectively, in these groups. CONCLUSION: This study has provided in-vivo proof of concept that "one hit" and "two hits" of RTS lead to acute resolving liver injury and chronic progressive liver fibrosis, respectively. These animal models may serve as powerful tools for studying RTS toxicology and related preventive and therapeutic strategies and as positive controls for studying other PA- and non-PA-induced liver injury.

Pulmonary toxicity is a common phenomenon of toxic pyrrolizidine alkaloids.

The hepatotoxic pyrrolizidine alkaloids (PAs) are metabolically activated in the liver to form reactive dehydro-PAs, which generate pyrrole-protein adducts leading to hepatotoxicity. Monocrotaline, but not other PAs, is also pneumotoxic, supposedly due to the migration of the liver-generated corresponding dehydro-PA into the lung to form pyrrole-protein adducts to induce pneumotoxicity. The present study investigated whether other PAs are also pneumotoxic. Metabolic activation of four representative hepatotoxic PAs, monocrotaline, retrorsine, riddelliine and clivorine, was investigated using rat liver or lung S9 incubation. All PAs produced pyrrole-protein adducts significantly in rat liver S9 but negligible in lung S9 fraction, revealing that liver is the key organ responsible for metabolic activation generating dehydro-PAs. Furthermore, these four PAs and another two PAs present in the alkaloid extract of Gynura segetum, a widely used PA-producing herb responsible for human PA poisonings in China, were orally administered to rats using the same hepatotoxic dose of 0.2 mmol/kg. All six PAs induced pneumotoxicity in rats within 48 h. The results demonstrated that pneumotoxicity could be a common phenomenon of PAs and the liver-derived dehydro-PAs might move to the lung and form pyrrole-protein adducts, leading to pulmonary toxicity.

The role of formation of pyrrole-ATP synthase subunit beta adduct in pyrrolizidine alkaloid-induced hepatotoxicity.

Pyrrolizidine alkaloids (PAs) are one of the most significant groups of hepatotoxic phytotoxins. It is well-studied that metabolic activation of PAs generates reactive pyrrolic metabolites that rapidly bind to cellular proteins to form pyrrole-protein adducts leading to hepatotoxicity. Pyrrole-protein adducts all contain an identical core pyrrole moiety regardless of structures of the different PAs; however, the proteins forming pyrrole-protein adducts are largely unknown. The present study revealed that ATP synthase subunit beta (ATP5B), a critical subunit of mitochondrial ATP synthase, was a protein bound to the reactive pyrrolic metabolites forming pyrrole-ATP5B adduct. Using both anti-ATP5B antibody and our prepared anti-pyrrole-protein antibody, pyrrole-ATP5B adduct was identified in the liver of rats, hepatic sinusoidal endothelial cells, and HepaRG hepatocytes treated with retrorsine, a well-studied representative hepatotoxic PA. HepaRG cells were then used to further explore the consequence of pyrrole-ATP5B adduct formation. After treatment with retrorsine, significant amounts of pyrrole-ATP5B adduct were formed in HepaRG cells, resulting in remarkably reduced ATP synthase activity and intracellular ATP level. Subsequently, mitochondrial membrane potential and respiration were reduced, leading to mitochondria-mediated apoptotic cell death. Moreover, pre-treatment of HepaRG cells with a mitochondrial membrane permeability transition pore inhibitor significantly reduced retrorsine-induced toxicity, further revealing that mitochondrial dysfunction caused by pyrrole-ATP5B adduct formation significantly contributed to PA intoxication. Our findings for the first time identified ATP5B as a protein covalently bound to the reactive pyrrolic metabolites of PAs to form pyrrole-ATP5B adduct, which impairs mitochondrial function and significantly contributes to PA-induced hepatotoxicity.

Absorption Properties of Luteolin and Apigenin in Genkwa Flos Using In Situ Single-Pass Intestinal Perfusion System in the Rat.

The flower bud of Daphne genkwa (Genkwa Flos) is a commonly used herbal medicine in Asian countries. Luteolin and apigenin are two recognized active flavonoids in Genkwa Flos. The aim of this study was to investigate the intestinal absorption mechanisms of Genkwa Flos flavonoids using in situ single-pass intestinal perfusion rat model. Using HPLC, we determined its major effective flavonoids luteolin, apigenin, as well as, hydroxygenkwanin and genkwanin in biological samples. The intestinal absorption mechanisms of the total flavonoids in Genkwa Flos (TFG) were investigated using in situ single-pass intestinal perfusion rat model. Comparing the TFG absorption rate in different intestinal segments, data showed that the small intestine absorption was significantly higher than that of the colon ([Formula: see text]). Compared with duodenum and ileum, the jejunum was the best small intestinal site for TFG absorption. The high TFG concentration (61.48[Formula: see text][Formula: see text]g/ml) yielded the highest permeability ([Formula: see text]). Subsequently, three membrane protein inhibitors (verapamil, pantoprazole and probenecid) were used to explore the TFG absorption pathways. Data showed probenecid, a multidrug resistance protein (or MRP) inhibitor, effectively enhanced the TFG absorption ([Formula: see text]). Furthermore, by comparing commonly used natural absorption enhancers on TFG, it was observed that camphor was the most effective. In Situ single-pass intestinal perfusion experiment shows that TFG absorption is much higher in the small intestine than in the colon, and the TFG is absorbed mainly via an active transport pathway with MRP-mediated efflux mechanism. Camphor obviously enhanced the TFG absorption, and this could be an effective TFG formulation preparation method to increase clinical effectiveness after Genkwa Flos administration. Our study elucidated the TFG absorption mechanisms, and provided new information for its formulation preparation.

The enhancement mechanism of wine-processed Radix Scutellaria on NTG-induced migraine rats.

To elucidate the increasing dissolution and enhancement mechanism of wine-processed Radix Scutellaria (RS) by fractal theory in nitroglycerin (NTG)-induced migraine rats. We prepared three RS from the process with 10% (S1), 15% (S2), 20% (S3) (v/m) rice wine. Mercury intrusion porosimetry and scanning electron microscope were employed to explore the internal structure of RS and the components dissolution of RS was analyzed by HPLC. Rats were randomly allocated into following groups and orally given different solutions for 10days: normal group (NOR, normal saline), model group (MOD, normal saline), Tianshu capsule group (TSC, 0.425mg/kg), ibuprofen group (IBU, 0.0821mg/kg), crude RS group (CRU, 1.04mg/kg) and wine-processed RS group (WP, 1.04mg/kg) followed by bolus subcutaneously injection of NTG (10mg/kg) to induce migraine model except NOR. Biochemical indexes (nitric oxide-NO, calcitonin-gene-related peptide-CGRP, and endothelin-ET) and c-fos positive cells were measured with commercial kits and immunohistochemical method, separately. Total surface area significantly increased in wine-processed RS (p<0.05) while fractal dimension markedly decreased (p<0.05) compared with crude RS. Additionally, S3 owned the highest increase of dissolution including the percentage increase of total extract, total flavonoids and main compounds (all p<0.05 vs S1 and S2). Pharmacodynamic data showed c-fos positive cells significantly decreased (p<0.05) in WP compared with MOD and the level of NO, CGRP, ET in WP was better than that of CRU. Wine-processed RS could be a promising candidate medicine for migraine treatment due to its increased component dissolution.

Gastroprotective effect of palmatine against acetic acid-induced gastric ulcers in rats.

Gastric ulcers are one of the most common gastrointestinal disorders. The aim of this study was to investigate the gastroprotective activity and possible underlying mechanisms of palmatine against acetic acid-induced gastric ulcers in rats. Palmatine was administered orally for 7 consecutive days to treat ulcers. The ulcer area, ulcer inhibition rate, histological section, platelet-activating factor (PAF) level in serum, prostaglandin E2 (PGE2) level in gastric tissue, 5-hydroxytryptamine (5-HT) level in the brain and norepinephrine (NE) level in the adrenal glands were analyzed. Histological results showed that the ulcer areas were significantly decreased by both doses of palmatine (10 and 20 mg/kg/day) compared with the model group, and the ulcer inhibition rates were 51.42% and 60.92%, respectively. Palmatine treatment markedly increased the level of PGE2 and decreased PAF, compared with the model group; however, it had no significant effect on 5-HT and NE levels. The results indicated that palmatine may exert a gastroprotective effect against gastric ulcers, and the mechanisms might be associated with the anti-inflammatory status and the protection of gastric mucosa via increasing PGE2 and decreasing PAF rather than neurohumoral regulation through 5-HT and NE. Thus, palmatine is a potential drug for treatment of gastric ulcers.

Monocyclic monoterpenes as penetration enhancers of ligustrazine hydrochloride for dermal delivery.

The purpose of this study was to explore the enhancing effects and the mechanism of monocyclic monoterpene penetration enhancers (menthol and menthone) on the transdermal absorption of ligustrazine hydrochloride (LH). Franz-type diffusion cells were used to determine percutaneous parameters of LH in vitro and surface changes of porcine skin were studied by a scanning electron microscope (SEM). The effects of promoters on the biophysical natures of stratum corneum (SC) were researched by Fourier transform-infrared (FT-IR). Penetration parameters of menthol (p < 0.01) and menthone groups (p < 0.05) were greater than those of the control; morphological changes of skin monitored by SEM demonstrated that the menthone group had the most disruption and desquamation of SC flakes, which resulted from extracted lipids. FT-IR measurements showed menthone had the greatest changes in peak shift and peak area, which resulted from C-H stretching vibrations of SC lipids. The results suggest that the penetration mechanism might include disturbing and extracting SC lipids and the hydrogen bond connection.

Hypocholesterolemic effect of emodin by simultaneous determination of in vitro and in vivo bile salts binding.

Emodin is an active anthraquinone derivative from Rheum palmatum and some other Chinese herbs and it is traditionally used for treating a variety of diseases. In this study, we investigated the hypocholesterolemic effects and mechanism of emodin on hypercholesterolemia rats. In vitro, capability of emodin binding to sodium deoxycholate which is one kind of bile salts (BAs) was evaluated by detection of surplus content of sodium deoxycholate. In vivo, hypocholesterolemic effects were assessed by determining total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) level of serum and TC, TG level of the liver. Oil red O staining was employed to determine lipid droplet of the liver. The mechanism was explored by BAs in feces, the liver and small intestine. Furthermore, cholesterol 7α-hydroxylase (CYP7A1) activity was measured to evaluate cholesterol's transforming to BAs. The results indicated that TC level of emodin group apparently decreased comparing with model group (p<0.05). Emodin could bind to BAs both in vivo (p<0.05) and in vitro. CYP7A1 activity in emodin group apparently increased comparing with model group (p<0.05). Data suggested that emodin had the potential value for treatment of hypercholesterolemia. The underlying mechanism is probably associated with binding capability to BAs and subsequent increasing expression of CYP7A1.

Antitumor Activity of Total Flavonoids from Daphne genkwa in Colorectal Cancer.

Daphne genkwa Sieb.et Zucc. is a well-known medicinal plant. This study was designed to investigate the anticancer effects of total flavonoids in D. genkwa (TFDG) in vitro and in vivo. HT-29 and SW-480 human colorectal cancer cells were cultured to investigate the anticancer activity of TFDG. In addition, the Apc(Min/+) mouse model was applied in the in vivo experiment. Results of the cell experiment revealed that TFDG possessed significant inhibitory effects on HT-29 and SW-480 human colorectal cancer cells (both p < 0.01). Furthermore, our in vivo data showed that after treatment with TFDG, there was a significant increase in life span (both p < 0.01) and tumor numbers were reduced in the colon (both p < 0.01), which was supported by the data of tumor distribution, body weight changes and organ index. Our results also indicated that expressions of interleukin (IL)-1α, IL-1ß, IL-6, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in gut tissue were downregulated by treatments of TFDG, and immunity cytokine secretions in the serum were regulated after oral administration of TFDG. Taken together, these findings suggested that TFDG has a potential clinical utility in colorectal cancer therapeutics, and TFDG's action is likely linked to its ability to regulate immune function and inhibit the production of inflammatory cytokines.

Antitumor and immunomodulatory activity of genkwanin on colorectal cancer in the APC(Min/+) mice.

Colorectal cancer is the third most common malignant tumor with high morbidity and mortality. To evaluate the antitumor effect of genkwanin on colorectal cancer enhanced by western high-fat diet, we investigated the activity of genkwanin on HT-29 and SW-480 human colorectal cancer lines in vitro and on the APC(Min/+) mice in vivo. In a cell culture system, six different inflammatory cytokines obviously stimulated two cancer cells growth in a concentration-dependent manner, while genkwanin significantly inhibited HT-29 and SW-480 human colorectal cancer cells proliferation and inflammatory cytokine IL-8 secretion. In the APC(Min/+) mice, the body weights, spleen and thymus indexes and immunity cytokine secretions were significantly improved after oral administration 12.5 and 25mg/kg/day of genkwanin. Besides, the tumor multiplicity changes and inflammatory cytokine levels were markedly reduced in two genkwanin-treated groups. The dysplastic adenomatous changes were also obviously ameliorated in gut histopathology. Taken together, our results indicated that genkwanin had a better antitumor activity partly via enhancing host immunity and decreasing the inflammatory cytokine levels. Genkwanin may be an effective chemotherapeutic agent for the treatment of colorectal cancer.

Antioxidative Activity of Flavonoids from Abrus cantoniensis against Ethanol-Induced Gastric Ulcer in Mice.

The present study investigated the flavonoids from Abrus cantoniensis against ethanol-induced gastric ulcers in mice. The flavonoids from A. cantoniensis were extracted with ethanol and purified by macroporous resin and polyamide. The 2,2-diphenyl-1-picrylhydrazyl assay was used to measure the antioxidative activities in vitro. The ethanol-induced ulcer mouse model was used to evaluate the gastroprotective activities of the flavonoids from A. cantoniensis. In addition, a method was established to ensure accuracy for animal ulcer evaluation. The flavonoids from A. cantoniensis showed a strong free radical scavenging capacity with an IC50 of 43.83 µg/mL in the 2,2-diphenyl-1-picrylhydrazyl assay. At doses between 28.16-112.67 mg/kg, the flavonoids conspicuously reduced the ulcer index in ethanol-induced mice (p<0.001). Significant differences were found in the levels of superoxide dismutase, catalase, glutathione, and myeloperoxidase in the stomach tissues between the flavonoids from the A. cantoniensis groups and the ethanol control group. The gastroprotective effect of the flavonoids from A. cantoniensis could be due to its antioxidative activity of the defensive mechanism. The data revealed that the flavonoids from A. cantoniensis could be a potential therapeutic agent for gastric ulcer prevention and treatment.

Absorption characteristics of the total alkaloids from Mahonia bealei in an in situ single-pass intestinal perfusion assay.

AIM: To investigate the absorption characteristics of the total alkaloids from Mahoniae Caulis (TAMC) through the administration of monterpene absorption enhancers or protein inhibitors. METHOD: The absorption behavior was investigated in an in situ single-pass intestinal perfusion (SPIP) assay in rats. RESULTS: The intestinal absorption of TAMC was much more than that of a single compound or a mixture of compounds (jatrorrhizine, palmatine, and berberine). Promotion of absorption by the bicyclic monoterpenoids (borneol or camphor) was higher than by the monocyclic monoterpenes (menthol or menthone), and promotion by compounds with a hydroxyl group (borneol or menthol) was higher than those with a carbonyl group (camphor or menthone). The apparent permeability coefficient (Papp) of TAMC was increased to 1.8-fold by verapamil, while it was reduced to one half by thiamine. The absorption rate constant (Ka) and Papp of TAMC were unchanged by probenecid and pantoprazole. CONCLUSION: The intestinal absorption characteristics of TAMC might be passive transport, and the intestinum tenue was the best absorptive site. In addition, TAMC might be likely a substrate of P-glycoprotein (P-gp) and organic cation transporters (OCT), rather than multidrug resistance protein (MRP) and breast cancer resistance protein (BCRP). Compared with a single compound and a mixture of compounds, TAMC was able to be absorbed in the blood circulation effectively.

Intestinal absorptive transport of Genkwanin from Flos genkwa using a single-pass intestinal perfusion rat model.

To investigate the absorptive transport behavior of genkwanin and the beneficial effects of monoterpene enhancers with different functional groups, the single-pass intestinal perfusion (SPIP) of rats was used. The results showed that genkwanin was segmentally-dependent and the best absorptive site was the duodenum. The effective permeability coefficient (P eff ) was 1.97 × 10(-4) cm/s and the absorption rate constant (Ka) was 0.62 × 10(-2) s(-1). Transepithelial transportation descended with increasing concentrations of genkwanin. This was a 1.4-fold increase in P eff by probenecid, whereas a 1.4-fold or 1.6-fold decrease was observed by verapamil and pantoprazole, respectively. Furthermore, among the absorption enhancers, the enhancement with carbonyl (camphor and menthone) was higher than that with hydroxyl (borneol and menthol). The concentration-independent permeability and enhancement by coperfusion of probenecid indicated that genkwanin was transported by both passive diffusion and multidrug resistance protein (MDR)-mediated efflux mechanisms.

Anti-rheumatoid arthritic activity of flavonoids from Daphne genkwa.

The aim of the study was to investigate the anti-rheumatoid arthritic activity of four flavonoids from Daphne genkwa (FFD) in vivo and in vitro. Flavonoids of D. genkwa were extracted by refluxing with ethanol and purified by polyamide resin. An in vivo carrageenan-induced paw edema model, tampon-granuloma model and Freund's complete adjuvant (FCA)-induced arthritis mouse model were used to evaluate the anti-rheumatoid arthritic activities of FFD. Moreover, nitric oxide (NO) release and neutral red uptake (NRU) in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were used to evaluate the anti-inflammatory effect in vitro. In addition, antioxidant effect of FFD was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A high dose of FFD significantly reduced the degree of acute inflammatory paw edema in mice as a response to carrageenan administration (p<0.01). FFD displayed a dose-dependent inhibition of granuloma formation in mice (p<0.05). FFD also inhibited chronic inflammation in adjuvant-induced arthritis rats when administered orally at the dose of 50mg/kg/day (p<0.001). In addition, FFD suppressed the production of NO and exhibited immunoregulatory function in LPS-activated RAW264.7 cells in a dose-related manner. Simultaneously, FFD revealed conspicuous antioxidant activity with IC50 values of 18.20µg/ml. FFD possesses significant anti-inflammatory and antioxidant activity, which could be a potential therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis.