[Development of Sample Size Formulas for Least Square Regression-Based Consistency Evaluation of Quantitative Indicators].

Objective To develop and verify the sample size formulas for quantitative data consistency evaluation based on the least square regression method. Methods According to the principle of least square regression-based quantitative consistency evaluation,statistical inference,and formula derivation,we developed the formulas for calculating sample size based on regression constant and regression coefficient.Furthermore,the accuracy of the formulas was verified by the data of three examples,and the results were compared with those of the sample size formula established based on the Bland-Altman(BA)method. Results The sample size formulas for regression-based quantitative consistency evaluation were deduced,and the accuracy of the formulas was verified by three examples.In addition,the results obtained with this formula had differences compared with those of the sample size formula established based on the BA method.Furthermore,consistent conclusions could be obtained by regression analysis and BA analysis with the sample size calculated with the regression method.However,with the sample size calculated based on the BA method,the consistency conclusion of regression analysis and BA analysis was sometimes not valid. Conclusion A sample size formula for quantitative consistency evaluation based on the regression method was proposed for the first time,which provided methodological support for the research in this field.

Atrachinenins D-S, novel meroterpenoids with geranyl hydroquinone moiety from Atractylodes chinensis by the LC/MS-based molecular decoy and targeted isolation.

To mine fascinating molecules from the rhizomes of Atractylodes chinensis, the known molecular formula of atrachinenin A was used as a bait to search LC-HRMS data in different subfractions. Sixteen new meroterpenoids, atrachinenins D-S (1-16) including three unprecedented carbon skeletons (1-5) and eleven new oxygen-bridged hybrids (6-16) were obtained by the targeted isolation. Their structures and absolute configurations were elucidated by the spectroscopic data and electronic circular dichroism (ECD) calculations. The isolated compounds were evaluated for their inhibitory activity of NO production and compounds 1, 4, 8, and 13 showed moderate anti-inflammatory activity. The proposed biosynthetic pathways of 1-5 were also discussed.

Coptidis Rhizoma processed with Evodia Rutaecarpa improves the effect on ulcerative colitis by increasing intestinal energy metabolites alpha-ketoglutarate and Lactobacillus reuteri.

BACKGROUND: Evodia Rutaecarpa-processed Coptidis Rhizoma (ECR) is a traditional Chinese medicine for the treatment of ulcerative colitis (UC) in China. However, the mechanisms underlying the ECR processing are not elucidated. PURPOSE: Coptidis Rhizoma (CR) regulates the gut microbiota in the treatment of gastrointestinal diseases. This study explored the mechanism of action of ECR before and after processing in UC in view of the regulation of gut microecology. STUDY DESIGN: A preclinical experimental investigation was performed using a mouse model of UC to examine the regulatory effect of ECR and its mechanisms through gut microbiota analysis and metabolomic assays. METHODS: Mice received 4% dextran sulfate sodium to establish a UC model and treated with ECR and CR. Colonic histopathology and inflammatory changes were observed. Gut microbiota was analyzed using 16 s rRNA sequencing. Transplants of Lactobacillus reuteri were used to explore the correlation between ECR processing and the gut microbiota. The expression of mucin-2, Lgr5, and PCNA in colonic epithelial cells was measured using immunofluorescence. Wnt3a and ß-catenin levels were detected by western blotting. The metabolites in the colon tissue were analyzed using a targeted energy metabolomic assay. The effect of energy metabolite α-ketoglutarate (α-KG) on L. reuteri growth and UC were verified in mice. RESULTS: ECR improved the effects on UC in mice compared to CR, including alleviating colonic injury and inflammation, and modulating gut microbiota by increasing L. reuteri level. L. reuteri dose-dependently alleviated colonic injury, increased mucin-2 level, and promoted colonic epithelial regeneration by increasing Lgr5 and PCNA expression. This was consistent with the results before and after ECR processing. L. reuteri promoted epithelial regeneration by upregulating Wnt/ß-catenin pathway. Moreover, ECR increased metabolites levels (especially α-KG) to promote energy metabolism in the colon tissue compared to CR. α-KG treatment increased L. reuteri level and alleviated mucosal damage in UC mice. It promoted L. reuteri growth by increasing the energy metabolic status by enhancing α-KG dehydrogenase activity. CONCLUSION: ECR processing improves the therapeutic effects of UC via the α-KG-L. reuteri-epithelial regeneration axis.

[Recent research on machine learning in the diagnosis and treatment of necrotizing enterocolitis in neonates]. / æœºå™¨å­¦ä¹ åœ¨æ–°ç”Ÿå„¿åæ­»æ€§å°è‚ ç»“è‚ ç‚Žè¯Šç–—ä¸­çš„ç ”ç©¶è¿›å±•.

Necrotizing enterocolitis (NEC), with the main manifestations of bloody stool, abdominal distension, and vomiting, is one of the leading causes of death in neonates, and early identification and diagnosis are crucial for the prognosis of NEC. The emergence and development of machine learning has provided the potential for early, rapid, and accurate identification of this disease. This article summarizes the algorithms of machine learning recently used in NEC, analyzes the high-risk predictive factors revealed by these algorithms, evaluates the ability and characteristics of machine learning in the etiology, definition, and diagnosis of NEC, and discusses the challenges and prospects for the future application of machine learning in NEC.

Sesquiterpenoids from the roots of Aucklandia costus and their anti-inflammatory activities.

Five undescribed sesquiterpenoid dimers, aucklandiolides A-E (1-5), one new sesquiterpenoid glycoside, ß-cyclocostunolide-15-ß-D-glucopyranoside (6), and seventeen known analogues (7-23) were isolated from the roots of Aucklandia costus. Their structures were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, and their configurations were confirmed by the computational calculations of ECD and NMR chemical shifts. Aucklandiolides A and B are the first examples of dimeric sesquiterpenoids with a unique 6/6/6/5/6/6 ring system originated from a proposed Diels-Alder cycloaddition between two eudesmane sesquiterpenoids. Besides, compounds 9-11, 20, and 22 showed significant inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells at a concentration of 20 µM.

Xianglian pill modulates gut microbial production of succinate and induces regulatory T cells to alleviate ulcerative colitis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglian pill (XLP), a traditional Chinese formula, is widely used as treatment for ulcerative colitis (UC) in China. However, the mechanism of its therapeutic effect is still unclear. AIM OF THE STUDY: Our previous studies showed a low oral bioavailability and a predominant distribution of major XLP ingredients in the gut. In the present study, we aimed to explore the mechanism of action of XLP on UC with respect to the regulation of gut microecology. MATERIALS AND METHODS: UC model rats established using 5% dextran sulfate sodium were treated with XLP. After the treatment period, bodyweight, colon length, histopathology, and inflammatory changes were evaluated. Further, changes in gut microbiota structure were detected via 16S rRNA sequencing, and microbial metabolites in feces were analyzed via a metabolomic assay. Antibiotic intervention and fecal microbiota transplantation were also employed to explore the involvement of gut microbiota, while the level of regulatory T cells (Tregs) in mesenteric lymph nodes was determined via flow cytometry. Transcriptome sequencing was also performed to determine colonic gene changes. RESULTS: XLP alleviated colonic injury, inflammation, and gut microbial dysbiosis in UC model rats and also changed microbial metabolite levels. Particularly, it significantly decreased succinate level in the tyrosine pathway. We also observed that fecal microbiota derived from XLP-treated rats conferred resilience to UC model rats. However, this therapeutic effect of XLP on UC was inhibited by succinate. Moreover, XLP increased the level of anti-inflammatory cellular Tregs via gut microbiota. However, this beneficial effect was counteracted by succinate supplementation. Further, XLP induced the differentiation of Treg possibly by the regulation of the PHD2/HIF-1α pathway via decreasing microbial succinate production. CONCLUSIONS: Our findings indicated that XLP exerts its therapeutic effects on UC mainly via the gut microbiota-succinate-Treg differentiation axis.

[Excretion of three alkaloids from Simiao Pills in urine, feces, and bile between normal and type 2 diabetic rats].

This study investigated the differences in excretion kinetics of three alkaloids and their four metabolites from Simiao Pills in normal and type 2 diabetic rats. The diabetes model was established in rats by injection of streptozotocin, and the alkaloids in urine, feces, and bile of normal and diabetic rats were detected by LC-MS/MS to explore the effect of diabetes on alkaloid excretion of Simiao Pills. The results showed that 72 h after intragastric administration of the extract of Simiao Pills, feces were the main excretion route of alkaloids from Simiao Pills. The total excretion rates of magnoflorine and berberine in normal rats were 4.87% and 56.54%, which decreased to 2.35% and 35.53% in diabetic rats, which had statistical significance(P<0.05). The total excretion rates of phellodendrine, magnoflorine, and berberine in the urine of diabetic rats decreased significantly, which were 53.57%, 60.84%, and 52.78% of those in normal rats, respectively. After 12 h of intragastric administration, the excretion rate of berberine in the bile of diabetic rats increased significantly, which was 253.33% of that of normal rats. In the condition of diabetes, the excretion rate of berberine metabolite, thalifendine significantly decreased in urine and feces, but significantly increased in bile. The total excretion rates of jateorrhizine and palmatine in the urine increased significantly, and t_(1/2) and K_e changed significantly. The results showed that diabetes affected the in vivo process of alkaloids from Simiao Pills, reducing their excretion in the form of prototype drug, affecting the biotransformation of berberine, and ultimately increasing the exposure of alkaloids in vivo, which would be conducive to the hypoglycemic effect of alkaloids. This study provides references for the clinical application and drug development of Simiao Pills in diabetes.

Chlorfortunones A and B, Two Sesquiterpenoid Dimers, Possessing Dispiro[4,2,5,2]pentadecane-6,10,14-tren Moiety from Chloranthus fortunei.

Chlorfortunones A (1) and B (2), two novel sesquiterpenoid dimers, were isolated from the roots of Chloranthus fortunei. Their structures were elucidated by spectroscopic analysis and X-ray diffraction analysis. Compounds 1 and 2 represent a new type of sesquiterpenoid dimer possessing an unprecedented 3/5/6/6/6/5 hexacyclic system with a unique dispiro[4,2,5,2]pentadecane-6,10,14-trien moiety. A plausible biosynthetic pathway of 1 and 2 was proposed. Compound 1 showed transforming growth factor (TGF)-ß inhibitory activity in MDA-MB-231 cells.

New Monoterpene-Conjugated Phenolic Constituents from Nutmeg and Their Autophagy Modulating Activities.

The seed of Myristica fragrans Houtt (nutmeg) is one of the important spices that have been extensively used in the culinary, food, beverage, and also in medicinal products industry. Previous phytochemical studies on nutmeg were mainly focused on lignans and neolignans. However, the other constituents have been poorly studied. In this study, 11 new monoterpene-conjugated phenolic derivatives, named myrifratins A-K (1-11), and five known compounds were isolated from nutmeg. The novel neolignan-diarylnonanoid-monoterpene conjugates (1 and 2) were first isolated in nature. Compounds 3-7 were rarely monoterpene-diarylnonanoid-conjugated derivatives, and 8-11 were the first examples of monoterpene-neolignan conjugates. Compounds 4-6, 12, and 13 showed potent autophagy inhibitory activities in a concentration-dependent manner. Our findings showed an uncommon class of monoterpene-conjugated phenolic derivatives in nature and reported their autophagy inhibition activities for the first time, which may give a new insight into the benefits or safety of nutmeg in foods.

Network pharmacology integrated with experimental validation reveals the regulatory mechanism of action of Hehuan Yin decoction in polycystic ovary syndrome with insulin resistance.

ETHNOPHARMACOLOGICAL RELEVANCE: Hehuan Yin decoction (HHY), first recorded in the Jingyue Quanshu (published in 1624 A.D.), is composed of Albizia julibrissin Durazz. and Ampelopsis japonica (Thunb.) Makino. AIM OF THE STUDY: This study aimed to investigate the mechanism of action of HHY in treating polycystic ovary syndrome with insulin resistance (PCOS-IR). MATERIALS AND METHODS: Network pharmacology and molecular docking were used to predict active compounds, potential targets, and pathways for PCOS-IR treatment using HHY. Female Sprague-Dawley rats were administered letrozole (1 mg/kg) with a high-fat diet to establish a PCOS-IR model. Thereafter, symptoms, ovarian pathology, serum insulin resistance, and sex hormone levels were determined. Western blotting was used to determine the levels of PI3Kp85α, AKT, phospho (p)-AKT, and GSK3ß in the ovaries of rats. RESULTS: Network pharmacology revealed 58 components in HHY and 182 potential targets that were shared between HHY and PCOS-IR. HHY could potentially treat PCOS-IR via the insulin resistance, PI3K/AKT, HIF-1, and steroid hormone biosynthesis pathways. Molecular docking revealed that PI3K, AKT1, GSK3ß, IRS1, and EGFR had high affinities to HHY compounds. In the PCOS-IR rats, HHY significantly normalised the symptoms and ovarian pathology, increased follicle-stimulating hormone (FSH) and oestradiol levels in the serum, and decreased the levels of fasting plasma glucose and fasting insulin, as well as the insulin resistance index. HHY also decreased the luteinising hormone (LH) and testosterone levels and the LH/FSH ratio in the PCOS-IR rats and increased the levels of PI3K, p-AKT, and GSK3ß in ovary tissue, which indicated the activation of the PI3K/AKT pathway. CONCLUSIONS: HHY can improve PCOS-IR symptoms via multiple pharmacological pathways and may be a potential alternative therapy for the treatment of PCOS-IR.

Comparative pharmacokinetics, intestinal absorption and urinary excretion of six alkaloids from herb pair Phellodendri Chinensis cortex-Atractylodis Rhizoma.

Phellodendri Chinensis Cortex (PCC) and Atractylodis Rhizoma (AR) are frequently used as herb pair to treat eczema and gout owing to their synergistic effects. Alkaloids are the major ingredients from PCC and the effect of their combination on the in vivo processing of alkaloids remains unclear. In this study, a simple and reliable UPLC-MS/MS method for simultaneous determination of six alkaloids in rat plasma was developed. This method was applied to a comparative pharmacokinetic study between PCC and PCC-AR in rats. Effect of AR on absorption of alkaloids was investigated by a single-pass intestinal perfusion study. The effect of AR on urinary excretion of alkaloids was studied. Pharmacokinetic studies showed that the values of rea under the concentration-time curve of phellodendrine, magnoflorine and palmatine were greater in the PCC-AR group than in the PCC group. The intestinal absorptive parameters absorption rate constant and effective permeability of phellodendrine and jatrorrhizine in PCC-AR groups were higher than those in the PCC group. Urinary excretion studies revealed that the excreted amount of alkaloids in the PCC-AR group was lower than that in the PCC group. The results revealed that the combination of PCC and AR improves intestinal absorption of alkaloids and reduces their urinary excretion, which enhances their systemic exposure. This study may explain the synergetic effects of PCC and AR in clinical applications.

Coix seed polysaccharides alleviate type 2 diabetes mellitus via gut microbiota-derived short-chain fatty acids activation of IGF1/PI3K/AKT signaling.

Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years. Coix seed (CS) as a homologous substance of traditional Chinese medicine and food, its polysaccharides can improve the symptoms of patients with metabolic disorders. Since most plant polysaccharides are difficult to digest and absorb, we hypothesized that Coix seed polysaccharides (CSP) exert hypoglycemic effects through the gut. In this study, the underlying mechanisms regulating hypoglycemic effects of CSP on a T2DM mouse model were investigated. After treatment with CSP, serum insulin and high-density lipoprotein cholesterol levels were increased, while total cholesterol, triglycerides and low-density lipoprotein cholesterol levels were decreased in T2DM mice. In addition, CSP treatment helped repair the intestinal barrier and modulated the gut microbial composition in T2DM mice, mainly facilitating the growth of short-chain fatty acid (SCFA)-producing bacteria, Spearman's analysis revealed these bacteria were positively related with the hypoglycemic efficacy of CSP. Colonic transcriptome analysis indicated the hypoglycemic effect of CSP was associated with the activation of the IGF1/PI3K/AKT signaling pathway. Correlative analysis revealed that this activation may result from the increase of SCFAs-producing bacteria by CSP. GC-MS detection verified that CSP treatment increased fecal SCFAs levels. Molecular docking revealed that SCFAs could bind with IGF1, PI3K, and AKT. Our findings demonstrated that CSP treatment modulates gut microbial composition, especially of the SCFAs-producing bacteria, activates the IGF1/PI3K/AKT signaling pathways, and exhibits hypoglycemic efficacy.

Network pharmacology and pharmacokinetics integrated strategy to investigate the pharmacological mechanism of Xianglian pill on ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with high morbidity, which leads to poor quality of life. The Xianglian pill (XLP) is a classical Chinese patent medicine and has been clinically proven to be an effective treatment for UC. PURPOSE: The pharmacological mechanism of the key bioactive ingredients of XLP for the treatment of UC was investigated by a network pharmacology and pharmacokinetics integrated strategy. STUDY DESIGN AND METHODS: Network pharmacology was used to analyze the treatment effect of nine quantified XLP ingredients on UC. Key pathways were enriched and analyzed by protein-protein interaction and Kyoto Encyclopedia of Genes and Genomes analyses. The effect of XLP on Th17 cell differentiation was validated using a mouse model of UC. The binding of nine compounds with JAk2, STAT3, HIF-1α, and HSP90AB1 was assessed using molecular docking. A simple and reliable ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous quantification of nine ingredients from XLP in plasma and applied to a pharmacokinetic study following oral administration. RESULTS: Nine compounds of XLP, including coptisine, berberine, magnoflorine,berberrubine, jatrorrhizine, palmatine, evodiamine, rutaecarpine, and dehydrocostus lactone, were detected. Network pharmacology revealed 50 crossover genes between the nine compoundsand UC. XLP treats UC mainly by regulating key pathways of the immune system, including Th17 cell differentiation, Jak-Stat, and PI3K-Akt signaling pathways. An in vivo validation in mice found that XLP inhibits Th17 cell differentiation by suppressing the Jak2-Stat3 pathway, which alleviates mucosal inflammation in UC. Molecular docking confirmed that eight compounds are capable of binding with JAk2, HIF-1α, and HSP90AB1, further confirming the inhibitory effect of XLP on the Jak2-Stat3 pathway. Moreover, apharmacokinetic study revealed that the nine ingredients of XLP are exposed in the plasma and colon tissue, which demonstrates its pharmacological effect on UC. CONCLUSION: This study evaluates the clinical treatment efficacy of XLP for UC. The network pharmacology and pharmacokinetics integrated strategy evaluation paradigm is efficient in discovering the key pharmacological mechanism of herbal formulae.

Mahuang Fuzi Xixin Decoction Ameliorates Allergic Rhinitis in Rats by Regulating the Gut Microbiota and Th17/Treg Balance.

Mahuang Fuzi Xixin Decoction (MFXD), a Chinese traditional herbal formulation, has been used to treat allergic rhinitis (AR) in China for centuries. However, the mechanism underlying its effect on AR is unclear. This study investigated the mechanism underlying the therapeutic effects of MFXD on AR. Ovalbumin-induced AR rat models were established, which were then treated with MFXD for 14 days. Symptom scores of AR were calculated. The structure of the gut microbiota was analyzed by 16S rRNA gene sequencing and qPCR. Short-chain fatty acid (SCFA) content in rat stool and serum was determined by GC-MS. Inflammatory and immunological responses were assessed by histopathology, ELISA, flow cytometry, and western blotting. Our study demonstrated that MFXD reduced the symptom scores of AR and serum IgE and histamine levels. MFXD treatment restored the diversity of the gut microbiota: it increased the abundance of Firmicutes and Bacteroidetes and decreased the abundance of Proteobacteria and Cyanobacteria. MFXD treatment also increased SCFA content, including that of acetate, propionate, and butyrate. Additionally, MFXD administration downregulated the number of Th17 cells and the levels of the Th17-related cytokines IL-17 and RORγt. By contrast, there was an increase in the number of Treg cells and the levels of the Treg-related cytokines IL-10 and Foxp3. MFXD and butyrate increased the levels of ZO-1 in the colon. This study indicated MFXD exerts therapeutic effects against AR, possibly by regulating the gut microbial composition and Th17/Treg balance.

Gegen Qinlian Decoction Treats Diarrhea in Piglets by Modulating Gut Microbiota and Short-Chain Fatty Acids.

Gut microbiota and its metabolites, short-chain fatty acids (SCFAs), play important roles in diarrheal diseases. Gegen Qinlian decoction (GQD), a Chinese herb formula, has been widely used to treat infectious diarrhea for centuries. However, little is known about the mechanism underlying its efficacy and whether it is mediated by gut microbiota and SCFAs. In this study, the composition of gut microbiota from bacterial diarrheal piglets was assessed using 16S rRNA analysis. The concentrations of fecal SCFAs were determined using a gas chromatography-mass spectrometer (GC-MS). The expression of mucosal pro-inflammatory cytokines in the colon was ascertained. Results showed that GQD reverses the reduction in the richness of gut microbiota, changes its structure, and significantly increases the relative abundances of SCFA-producing bacteria, including Akkermansia, Bacteroides, Clostridium, Ruminococcus, and Phascolarctobacterium. Moreover, GQD increased the levels of fecal SCFAs, including acetic acid, propionic acid, and butyric acid. GQD thus attenuates diarrhea in piglets. Further, our results suggest that the SCFAs could help to attenuate mucosal pro-inflammatory responses following GQD treatment by inhibiting histone deacetylase and the NF-κB pathway. We thus suggseted that gut microbiota play an important role during diarrhea treatment, an effect may be promoted by the GQD-induced structural changes of the gut microbial community and production of SCFAs. The increased levels of SCFAs probably provide further help to attenuate mucosal inflammation and diarrhea. In conclusion, our study might provide evidence that GQD treats diarrhea maybe involved in modulating gut microbiota and increasing SCFA levels.

Comparative metabolism of the eight main bioactive ingredients of gegen qinlian decoction by the intestinal flora of diarrhoeal and healthy piglets.

Diarrhoeal diseases alter the composition of intestinal flora, thereby affecting the efficacy of herbal medicinal formulations. Gegen Qinlian decoction (GQD), a Chinese traditional herbal formulation, is widely used to treat infectious diarrhoea. However, little is known about the microbial disposition of GQD in the diarrhoeal state. In this study, the comparative metabolism of components of GQD by diarrhoeal and normal intestinal flora was investigated in vitro. UPLC-MS/MS was performed for simultaneous analysis of eight ingredients of GQD in bacterial solution. The type, activities, and sources of microbial enzymes were also investigated. Microbial metabolism of daidzin, genistin and liquiritin (metabolized by ß-glucosidase); baicalin, wogonoside and glycyrrhizin (metabolized by ß-glucuronidase); and berberine and coptisine (metabolized via nitroreductase) was faster in the diarrhoeal group than in the normal group. Moreover, the activities of these enzymes in the diarrhoeal group were higher than those in the normal group. This difference might be associated with the increase in Escherichia spp. Thus, a change in the metabolism of components by diarrhoeal intestinal flora is associated with a preponderance of Escherichia spp., which might improve the efficacy of GQD. These findings have implications for understanding the action mechanism of GQD for diarrhoea treatment in terms of the microbial milieu.

Comparative pharmacokinetics of major bioactive components from Puerariae Radix-Gastrodiae Rhizome extracts and their intestinal absorption in rats.

Puerariae Radix (PR) and Gastrodiae Rhizome (GR) is frequently used in traditional herbal formulas to treat cardio-cerebral vascular diseases due to their synergistic effects. In this study, to elucidate the action mechanism of PR-GR in vivo, a simple and reliable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of nine bioactive ingredients from PR-GR in plasma was developed and applied to a comparative pharmacokinetic study following oral administration of PR, GR, and PR-GR aqueous extracts in rats. The effect of GR on the absorption of components of PR was also investigated by single-pass intestinal perfusion study. Results showed that comparing to the single herbs, PR-GR extract significantly increased the systemic exposure of puerarin, 3'-hydroxypuerarin, 3'-methoxypuerarin, 6″-O-xylosylpuerarin, daidzin, genistein, and gastrodin. Moreover, the intestinal absorption of puerarin and daidzin could be improved by GR extract and inhibitors of P-glycoprotein and multidrug resistanceassociated protein 2, respectively. These results indicate that the combination of PR and GR increases the levels of their bioactive ingredients exposed in the blood, and GR increases the absorption of ingredients of PR may by inhibition of the efflux mediated by P-glycoprotein and multidrug resistanceassociated protein 2. This is the first report for the pharmacokinetics and intestinal absorption of PR-GR, which may explain their synergetic effects in the treatment of circulatory systematic diseases and provide a meaningful insight for their clinical applications.

Comparative pharmacokinetics of three phenylpropanoids in rat plasma after oral administration of Ramulus Cinnamomi and Ramulus Cinnamomi-Ephedrae Herba herb-couple extract.

OBJECTIVE: To investigate the pharmacokinetic characteristics of three phenylpropanoids (cinnamic acid, cinnamic alcohol and coumarin) in Ramulus Cinnamomi (GZ) and Ramulus Cinnamomi-Ephedrae Herba (MH) herb-couple (GZMH). METHODS: Twelve male Sprague-Dawley rats were randomly and equally divided into the GZ and GZMH herb-couple groups. Blood samples were collected at 0, 0.08, 0.25, 0.5, 0.75, 1.5, 3, 4, 6, 8, 12, 24, 36 and 48 h after oral administration. The three phenylpropanoids in rat plasma were quantified using an ultra-performance liquid-chromatography with tandem mass spectrometry (UPLC-MS/MS) method for pharmacokinetic study. RESULTS: In GZMH group, the area under the curve (AUC), mean retention time (MRT) of cinnamic acid and coumarin were increased significantly (P<0.01, respectively), and biological half-life (t1/2z) was obviously shorter (P<0.05) compared with the GZ group. There were no significant differences in the mean retention time from 0 to ∞ (MRT0-∞), the peak concentration (Cmax), the time to peak (Tmax) and t1/2z, except for AUC and MRT0-t (the mean retention time from 0 to t) of cinnamic alcohol in the GZMH group by comparison to the GZ group (P<0.01, respectively). The AUC, MRT (both P<0.01) and t1/2z (P<0.05) of coumarin were increased significantly, while Cmax, and Tmax were decreased slightly by comparison to the GZ group (P>0.05). CONCLUSIONS: There were statistically significant differences in some pharmacokinetic parameters of the three compounds between GZ and GZMH groups, which meant that MH could affect the absorption and elimination of the three compounds.

Antipyretic and anti-asthmatic activities of traditional Chinese herb-pairs, Ephedra and Gypsum.

OBJECTIVE: Mahuang-Shigao herb-pair is a famous formula composed of Ephedra and Gypsum. The herb-pair is frequently used for treating cold symptoms and bronchial asthma in the clinical practice of Chinese medicine (CM). In the present study, we evaluated evidence for the benefit of combined use of Ephedra and Gypsum by analyzing the antipyretic and anti-asthmatic activities of Ephedra-Gypsum. METHODS: The antipyretic effects of Ephedra-Gypsum were evaluated in yeast-induced hyperthermia test. Thirty male Wistar rats were randomly divided into 5 groups, including control group, standard aspirin group, and 3 Ephedra- Gypsum groups of different doses (6, 12, 24 g/kg). Ephedra-Gypsum extract and asprin were administered orally 6 h after the injection of yeast solution and body temperature was measured every 1 h for 8 h. The antiasthmatic effects of Ephedra-Gypsum were evaluated using an ovalbumin (OVA)-induced asthmatic rat model. Thirty-six male SD rats were randomly divided into 6 groups. Rats were alternately sensitized and OVA+Al(OH) challenged by exposure to mists of ovalbumin. Ephedra-Gypsum extracts (6, 12, 24 g/kg) or dexamethasone were administered 45 min prior to the allergen challenge for 8 days. Latent period and the weight of wet to dry ratio of lung were determined. In addition, the eosinophils in blood and white blood cell (WBC) were counted by an YZ-Hemavet Analyzer. RESULTS: The Ephedra-Gypsum extracts at test dose (6, 12, 24 g/kg) significantly and dose-dependently attenuated yeast-induced fever in rats. The Ephedra-Gypsum extracts also prolonged the latent period, reduced OVA-induced increases in eosinophils and WBC, and decreased the wet and dry weight ratio of the lungs in the anti-asthmatic test. CONCLUSIONS: These findings indicate that the Ephedra-Gypsum extract has antipyretic and anti-asthmatic properties. Hence, the results support additional scientific evidence in prescriptions.

[Study on material basis of Mahuang Fuzi Xixin decoction for anti-inflammation and immune suppression based on combined method of serum pharmacochemistry and serum pharmacology].

To investigate me material basis of Mahuang Fuzi Xixin decoction (MFXD) for anti-inflammation and immune-suppression based on the combined method of serum chemical and serum pharmacological. The LC-MS/MS fingerprints of MFXD, drug-containing serum and blank serum were compared to define the components in plasma. Histamine, ß-hexosaminidase released from RBL-2H3 cell infulenced by drug-containing serum at different time points were measured by ELISA. The effect of drug-containing serum on lipopolysaccharide-induced splenocyte proliferation at different time points were determined by MTT. A correlation analysis was made on components of MFXD and pharmacological indexes based the stepwise regression method. After the intragastrical administration with MFXD, 32 components were discovered in rat serum, including 27 prototype components (10 from Mahuang, 13 from Fuzi and four from Xixin) and five unknown components. Compared with blank serum, drug-containing serum could reduce the release of histamine from RBL-2H3 induced by antigen at different time points (P < 0.05); except the 4-hour drug-containing serum, all of the remaining drug-containing serums could inhibit the RBL-2H3 mastocyte degranulation induced by antigen at different time points (P < 0.05). Drug-containing serum could significantly lipopolysaccharide-induced mouse splenocyte proliferation at 15 and 30 min (P < 0.05). A regression analysis was made on the chemical data of components absorbed into blood and pharmacological indexes, i. e. release rate of histamine, release rate of ß-hexosaminidase and inhibition rate of splenocyte. This suggested the close correlations among methyl pseudo-ephedrine, pseudoephedrine and histamine released from RBL-2H3 induced by antigen; pseudoephedrine, hypaconine, methyl pseudoephedrine and ß-hexosaminidase released from RBL-2H3 induced by antigen; as well as benzoyl hypaconine, benzoylaconine, 14-benzoyl-10-OH-mesaconine, mesaconine and lipopolysaccharide-induced mouse splenocyte proliferation. Methylpseudoephedrine, pseudoephedrine, benzoyl hypaconine, benzoylaconine and mesaconine may be part of material basis of MFXD on anti-inflammation and immune suppression.