Polymethoxyflavones in citrus extract has a beneficial effect on hypercholesterolemia rats by promoting liver cholesterol metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia is characterized by the disorder of lipid metabolism accompanied by oxidative stress damage, and low-grade inflammation, with the pathway of cholesterol and bile acid metabolic are an important triggering mechanism. Polymethoxyflavones (PMFs) are the active constituents of Aurantii Fructus Immaturus, which have many biological effects, including anti-inflammatory, antioxidant activities, anti-obesity, suppressing adipogenesis in adipocytes, and ameliorate type 2 diabetes, with potential roles for regulation of lipid metabolism. However, its associated mechanisms on hyperlipidemia remain unclear. AIM OF THE STUDY: This study aims to identify the anti-hypercholesterolemia effects and mechanisms of PMFs in a hypercholesterolemia model triggered by high-fat compounds in an excessive alcohol diet (HFD). MATERIALS AND METHODS: A hypercholesterolemia rat model was induced by HFD, and PMFs was intragastric administered at 125 and 250 mg/kg daily for 16 weeks. The effects of PMFs on hypercholesterolemia were assessed using serum lipids, inflammatory cytokines, and oxidative stress levels. Hematoxylin & eosin (H&E) and Oil Red O staining were performed to evaluate histopathological changes in the rat liver. The levels of total cholesterol (TC) and total bile acid (TBA) in the liver and feces were determined to evaluate lipid metabolism. RAW264.7 and BRL cells loaded with NBD-cholesterol were used to simulate the reverse cholesterol transport (RCT) process in vitro. The signaling pathway of cholesterol and bile acid metabolic was evaluated by Western Blotting (WB) and qRT-PCR. RESULTS: Lipid metabolism disorders, oxidative stress injury, and low-grade inflammation in model rats were ameliorated by PMFs administration. Numerous vacuoles and lipid droplets in hepatocytes were markedly reduced. In vitro experiments results revealed decreased NBD-cholesterol levels in RAW264.7 cells and increased NBD-cholesterol levels in BRL cells following PMFs intervention. PMFs upregulated the expression of proteins associated with the RCT pathway, such as LXRα, ABCA1, LDLR, and SR-BI, thereby promoting TC entry into the liver. Meanwhile, the expression of proteins associated with cholesterol metabolism and efflux pathways such as CYP7A1, CYP27A1, CYP7B1, ABCG5/8, ABCB1, and BSEP were regulated, thereby promoting cholesterol metabolism. Moreover, PMFs treatment regulated the expression of proteins related to the pathway of enterohepatic circulation of bile acids, such as ASBT, OSTα, NTCP, FXR, FGF15, and FGFR4, thereby maintaining lipid metabolism. CONCLUSIONS: PMFs might ameliorate hypercholesterolemia by promoting the entry of cholesterol into the liver through the RCT pathway, followed by excretion via metabolism pathways of cholesterol and bile acid. These findings provide a promising therapeutic potential for PMFs to treat hypercholesterolemia.

[Effect of Yunkang Oral Solution on pregnant mice with spleen deficiency syndrome].

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin ß(ß-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(ß-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.

[Effect of superfine powder and aqueous extract of Polygonati Rhizoma on rats with natural perimenopausal syndrome].

This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, ß-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.

The role of cytoreductive surgery and intraperitoneal chemotherapy in gastric cancer.

Gastric cancer (GC) with peritoneal carcinomatosis (PC) progresses rapidly and has historically dismal survival rates. Given the aggressive tumor biology and poor survival outcomes of patients with GC/PC, additional treatments beyond systemic chemotherapy are needed. Cytoreductive surgery and intraperitoneal chemotherapy have been effective management options for peritoneal surface malignancies, with increasing data to support their use in GC/PC. This review highlights the evolution of the surgical treatment of GC/PC, and discusses critical studies supporting the role of cytoreductive surgery, appropriate patient selection, and various methods in the delivery of intraperitoneal chemotherapy for patients with GC/PC.

The beneficial effects of Polygonatum sibiricum Red. superfine powder on metabolic hypertensive rats via gut-derived LPS/TLR4 pathway inhibition.

BACKGROUND: Metabolic hypertension (MH) is characterized by elevated blood pressure accompanied by metabolic abnormalities, with the gut-derived lipopolysaccharide/toll like receptor 4 (LPS/TLR4) pathway an important triggering mechanism. The conventional Chinese plant Polygonatum sibiricum Red. is traditionally used as a medicinal and edible food source. Currently, several studies have examined its anti-obesity and anti-diabetic actions, with potential roles for MH treatment; however, specific P. sibiricum Red. roles in MH and associated mechanisms remain unclear. OBJECTIVES: Our purpose was to identify the effects and mechanisms of P. sibiricum Red. superfine powder (PSP) in a MH rat model triggered by high sugar and high fat compounds in an excessive alcohol diet (ACHSFDs). METHODS: A MH rat model was induced by ACHSFDs, and PSP was administered daily at 0.5 and 1.0 g/kg doses, respectively. Firstly, the effects of PSP on MH were assessed using blood pressure, serum lipid, and lipid deposition assays in the liver. Changes in intestinal flora were detected by high-throughput 16S rRNA sequencing, while metabolite short-chain fatty acids (SCFAs) and LPS levels were quantified by gas chromatography (GC) and enzyme-linked immunosorbent assay (ELISA), respectively. Hematoxylin & eosin (H&E) staining and transmission electron microscopy (TEM) were performed to evaluate histopathological changes in the rat colon. d-lactic acid (d-LA) levels and tight junction proteins (TJPs) expression were also measured to assess intestinal barrier function. Also, aortic endothelial microstructures, serum endothelin 1 (ET-1), and nitric oxide (NO) levels were investigated to determine vascular endothelial function. Finally, the TLR4/MyD88 signaling pathway in the aorta and gut was evaluated by western blotting, immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Blood pressure and blood lipid metabolism disorders induced by ACHSFDs in MH rats were improved by PSP administration. Intestinal flora analyses revealed decreased SCFAs and LPS levels following PSP administration, which was accompanied by increased Streptococcus species levels and decreased Desulfobacter and Desulfovibrio species levels. PSP increased SCFAs levels, and the expression of SCFAs receptors GPCR41 and GPCR43 in the colon. Meanwhile, the expression of tight junction proteins (TJPs) such as Claudin-1, occludin were upregulated in the ileum and colon, while TLR4 and MyD88 were downregulated, thereby strengthening intestinal barrier integrity and reducing serum LPS levels. Additionally, PSP treatment improved vascular endothelial function by inhibiting the TLR4/MyD88 pathway in vessels, improving vascular endothelial cell shedding, and regulating the NO and ET-1 balance. CONCLUSIONS: We demonstrated the beneficial effects and potential mechanisms of PSP in our MH rat model. Based on gut microbiota structure modulation and intestinal barrier improvements, PSP inhibited LPS-induced vascular TLR4/MyD88 signaling activation to improve vascular endothelial function, which in turn reduced blood pressure. Our study provides valuable insights on PSP therapy for MH.

[Meta-analysis of Shenqi Jiangtang Granules combined with western medicine on adverse pregnancy outcomes in women with gestational diabetes mellitus].

The present study evaluated the effect of Shenqi Jiangtang Granules(SJG) combined with western medicine on the adverse pregnancy outcomes in women with gestational diabetes mellitus(GDM). PubMed, Web of Science, CNKI, Wanfang, and VIP were searched for clinical randomized controlled trials(RCTs) of SJG combined with western medicine against GDM. The included RCTs were assessed for risks using the assessment criteria recommended by the Cochrane handbook for systematic reviews of interventions. Meta-analysis was performed using Stata 12.0 and RevMan 5.3. Nineteen RCTs were included, with 1 647 patients involved, including 824 cases treated with western medicine alone, and 823 cases treated with SJG combined with western medicine. The course of treatment ranged from 2 to 12 weeks. As revealed by Meta-analysis results, compared with western medicine treatment alone, SJG combined with western medicine could reduce the incidence of postpartum hemorrhage(OR=0.23, 95%CI[0.10, 0.53], P=0.000 6), gestational hypertension(OR=0.24, 95%CI[0.13, 0.45], P<0.000 01), polyhydramnios(OR=0.24, 95%CI[0.12, 0.45], P<0.000 1), premature rupture of membranes(OR=0.20, 95%CI[0.09, 0.45], P<0.000 1), cesarean section(OR=0.40, 95%CI[0.29, 0.55], P<0.000 01), macrosomia(OR=0.19, 95%CI[0.08, 0.47], P<0.000 3), neonatal asphyxia(OR=0.22, 95%CI[0.12, 0.40], P<0.000 01), premature delivery(OR=0.19, 95%CI[0.12, 0.30], P<0.000 01), proteinuria(OR=0.19, 95%CI[0.06, 0.58], P=0.004) and hypoglycemia(OR=0.28, 95%CI[0.16, 0.50], P<0.000 1). The funnel plots and Egger's test showed that except macrosomia, there was no significant publication bias in the results of other indicators. Therefore, as indicated by the findings, SJG combined with western medicine can reduce the incidence of adverse pregnancy outcomes in GDM patients. However, due to the uneven quality of the included trials, the clinical application of this protocol requires caution.

[Effects of different extracts of Dendrobium officinale on rats with chronic pharyngitis induced by pepper water combined with ammonia].

Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1ß(IL-1ß), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor ß1(TGF-ß1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1ß, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.

Deep eutectic solvents as switchable solvents for highly efficient liquid-liquid microextraction of phenolic antioxidant: Easily tracking the original TBHQ in edible oils.

Synthetic antioxidant tert-butylhydroquinone (TBHQ) is easily oxidized to tert-butylquinone (TQ) during the storage of edible oils, resulting in an obvious decrease in the content of TBHQ in edible oils. Therefore, it is quite desirable to develop a simple analytical method for accurately tracking the original content of TBHQ in edible oils. In this work, deep eutectic solvents (DESs) have been successfully used in room temperature vortex-assisted liquid-liquid microextraction (VALLME) of TBHQ from edible oils. The DES composed of ethylene glycol and choline chloride (ChCl) could selectively extract TBHQ from edible oils containing both TBHQ and TQ. The DES composed of sesamol and ChCl (molar ratio of 3:1) could efficiently reduce TQ to TBHQ and extract TBHQ from edible oils. The whole VALLME process only required 5 min at room temperature. This switchable DESs-based VALLME with common RP-HPLC analysis showed high efficiency and good performance with linearity (R2 = 0.9999) in 5-500 mg/kg range, detection limit of 0.02 mg/kg, recoveries of 96.1-106.0% and intra-/inter-day precision below 2.0%. This analytical method is suitable for detecting the current content of TBHQ and tracking the original content of TBHQ during the storage of edible oils at room temperature, respectively.

[Effect of Dendrobii officinalis superfine powder on overeating greasy-induced metabolic hypertension in rats].

Dendrobii officinalis, with a definite effect of nourishing Yin and clearing heat, has been a folk habit for drinking after being mixed with water. Because its superfine powder has the advantages of high dissolution and convenient drinking, we observed the effect of D. officinalis superfine powder on metabolic hypertension model rats and its possible mechanism in this experiment, which can be used as a reference for its clinical application for hypertension. The overeating greasy-induced metabolic hypertension model was established with high-fat, high-sugar and high-purine diet. These rats were orally administered with 400 mg·kg~(-1) and 200 mg·kg~(-1) of D. officinalis superfine powder for 20 consecutive weeks. During this period, blood pressure, blood lipid, blood glucose, insulin and other related indexes of glucose and lipid metabolism were monitored; the levels of lipopolysaccharide(LPS), C-reactive protein(CRP), interleukin 6(IL-6) and other inflammatory mediators were measured; the levels of nitric oxide(NO) and endothelin-1(ET-1) were detected, and the histomorphological and ultrastructural changes of aorta were observed. In addition, the expression of LPS/TLR4 pathway-related molecules in aorta was determined. The results showed that long-term administration of D. officinalis superfine powder significantly reduced the levels of systolic blood pressure(SBP), diastolic blood pressure(DBP) and mean arterial pressure(MBP) in metabolic hypertension model rats, decreased the levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-c), glucose(Glu), and insulin(INS) levels in blood, increased the contents of high density lipoprotein cholesterol(HDL-c),decreased the LPS, CRP, IL-6 and ET-1 levels in blood and increased NO content. Furthermore, it improved the abnormality of aortic histomorphology and endothelial ultrastructure, and inhibited the protein expression of TLR4, myeloid differentiation factor(MyD88), IL-6, interleukin-1 ß(IL-1ß), and tumor necrosis factor-α(TNF-α) as well as mRNA expression of TNF-α and IL-1ß in aorta. In conclusion, D. officinalis superfine powder may improve the abnormal function and structure of blood vessels by inhibiting the activation of LPS/TLR4 pathway, thus playing a role against metabolic hypertension.

[Protective effects of Dendrobium officinale superfine powder against LPS-induced intestinal mucosal injury in mice].

This study aims to investigate the preventive effect of Dendrobium officinale in LPS-induced intestinal mucosal damage. Forty SPF-grade C57 BL/6 J male mice were randomly divided into normal group(NC), model group(LPS), and two superfine powder groups of Dendrobium officinale(DOF)(DOF-L, 0.30 g·kg~(-1)and DOF-H, 0.60 g·kg~(-1), respectively), with 10 mice in each group. DOF superfine powder suspension was given via oral administration to mice for 7 days, while the mice in NC and LPS groups received the same volume of saline for 7 days. On the eighth day, the mice in LPS group and DOF treatment groups were injected with LPS(5 mg·kg~(-1)) by intraperitoneal injection to establish the intestinal mucosal injury model, while the mice in NC group were injected with the same volume of sterile saline in the same manner. Six hours after injection with LPS or saline, plasma and the intestinal tissue were collected. The diamine oxidase(DAO) and D-lactate levels in plasma were detected with a biochemical method. The levels of proinflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma were detected by ELISA. The histomorphology and ultrastructure of mouse ileum tissues were observed by hematoxylin-eosin(HE) staining in optical microscope and transmission electron microscope(TEM). The expression and distribution of tight junction(TJ) proteins claudin-1, occludin and F4/80 were detected by immunohistochemistry while the protein expression levels of Toll-like receptor 4(TLR-4) and nuclear factor kappa B p65(NF-κB p65) in jejunum were detected by Western blot. The experimental results showed that continuous intragastric administration of D. officinale superfine powder for 7 days obviously alleviated the damage and ultrastructural changes of intestinal mucosa induced by LPS; significantly decreased DAO and D-lactate levels in plasma in model group(P<0.05); up-regulated the protein expression of claudin-1 and occludin in ileum tissues; down-regulated the protein expression of TLR-4 and NF-κB p65 in jejunum tissues(P<0.01); significantly decreased TNF-α and IL-6 levels in plasma(P<0.05); and decreased the infiltration of F4/80~+ macrophage cells. Our results suggested that D. officinale had significant protective effects on LPS-induced intestinal mucosal damage and reduced intestinal permeability. The mechanism might be related to its effects of inhibiting inflammation via TLR-4/NF-κB p65, and up-regulating the expression of tight junction proteins.

[Improvement effect and mechanism of ethanol extract from Citri Reticulatae Pericarpium on triglyceride in hyperlipidemia model rat].

The aim of this paper was to study the improvement effect of ethanol extract from Citri Reticulatae Pericarpium(CRP) on triglyceride of hyperlipidemia model rats, and to explore the possible mechanism. SD rats were randomly divided into normal group, model group, positive control group, and high, medium and low-dose CRP ethanol extract groups, with 10 rats in each group. During the experiment, except for the normal group that was fed with distilled water and ordinary feed, rats in the other groups were given different concentrations of alcohol and fed with high-sugar and fat diets. All rats were given free diets. While being modeled, each group was administered with 0.01 mL·g~(-1) by gavage once a day for six weeks. Blood samples were collected after two weeks, four weeks and six weeks of drug treatment. After the completion of the experiment, blood, liver and adipose tissue were collected. Triglyceride(TG), alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP) in serum, TG in liver tissue and TG in fecal were detected. Free fatty acid(FFA) and triglyceride-related hydrolase, such as adipose tiglyceride lipase(ATGL), lipoprotein lipase(LPL), hepatic lipase(HL), hormone-sensitive triglyceride lipase(HSL) were detected by ELISA. The mRNA expressions of peroxisome proliferators-activated receptors(PPARγ), sterol regulatory element binding protein 1 c(SREBP-1 c) and farnesoid X receptor(FXR) were determined by RT-PCR. Compared with the model group, each administration group could reduce TG levels in serum and liver to varying degrees, reduce serum ALT, AST, ALP activities, significantly reduce free fatty acid content in serum, significantly increase triglyceride metabolism-related enzymes, including fat ATGL, LPL and liver HL content, and significantly reduced the content of fat HSL. According to the study of transcriptional regulation genes relating to triglyceride metabolism, extract from CRP could significantly increase the mRNA expressions of PPARγ and FXR. In conclusion, ethanol extract from CRP could ob-viously reduce the TG level of hyperlipidemia model rats, and might reduce plasma TG content by increasing PPARγ-LPL/ATGL and FXR-HL triglyceride hydrolysis pathways.

[Effect of Wubi Shanyao Pills on sexual dysfunction in rats with adenine-induced kidney-Yang deficiency].

The aim of this paper was to study the effect of Wubi Shanyao Pills on sexual dysfunction in rats with kidney-Yang deficiency and to investigate its possible mechanism. Adenine(100 mg·kg~(-1)) was administered to male SD rats for 8 weeks to establish kidney-Yang deficiency model, and at the same time, Wubi Shanyao Pills(2, 1, 0.5 g·kg~(-1)) were administered to rats for 8 weeks. The syndrome manifestation of kidney-Yang deficiency was observed in rats and the scores of symptoms were evaluated. Sexual behavior indexes(incubation period and times of capture, straddle and ejaculation) were measured by mating experiment. The levels of serum testosterone(T), estradiol(E_2), follicle stimulating hormone(FSH), luteinizing hormone(LH), and gonadotropin releasing hormone(GnRH) were measured by radioimmunoassay. The wet weights of testis and seminal vesicle were measured. The content of fructose in seminal plasma was detected by UV spectrophotometry. The pathological changes of testis and epididymis were observed by HE staining. The expression levels of transforming growth factor(TGF-ß1) and cytochrome P450 aromatase(CYP19) in testis were detected by immunohistochemistry and Western blot. The results showed that Wubi Shanyao Pills could significantly reduce the score of kidney-Yang deficiency syndrome, improve the symptoms of kidney-Yang deficiency syndrome, shorten capture, straddle and ejaculation latency, increase capture and straddle times, increase serum T, LH, FSH, E_2 and GnRH levels, increase the wet weight of testis and seminal vesicle and fructose content in seminal plasma, improve the pathological structure of testis and epididymis, and inhibit the expression of TGF-ß1 and increase CYP19 in testis of the model rats. Therefore, Wubi Shanyao Pills can significantly improve sexual dysfunction in rats with kidney-Yang deficiency, and its mechanism may be related to regulating the low function of hypothalamus pituitary gonad(HPG) axis and improving the disorder of sex hormone secretion. In addition, it may be also related to inhibiting the expression of testicular TGF-ß1, increasing the expression of CYP19 protein, and then regulating the amount of T converted to E_2.

In Vitro-to-In Vivo Extrapolation of Transporter Inhibition Data for Drugs Approved by the US Food and Drug Administration in 2018.

A systematic analysis of the inhibition transporter data available in New Drug Applications of drugs approved by the US Food and Drug Administration (FDA) in 2018 (N = 42) was performed. In vitro-to-in vivo predictions using basic models were available for the nine transporters currently recommended for evaluation. Overall, 29 parents and 16 metabolites showed in vitro inhibition of at least one transporter, with the largest number of drugs found to be inhibitors of P-gp followed by BCRP. The most represented therapeutic areas were oncology drugs and anti-infective agents, each comprising 31%. Among drugs with prediction values greater than the FDA recommended cutoffs and further evaluated in vivo, 56% showed positive clinical interactions (area under the concentration-time curve ratio (AUCRs) ≥ 1.25). Although all the observed or simulated inhibitions were weak (AUCRs < 2), seven of the nine interactions (involving five drugs) resulted in labeling recommendations. Interestingly, more than half of the drugs with predictions greater than the cutoffs had no further evaluations, highlighting that current basic models represent a useful, simple first step to evaluate the clinical relevance of in vitro findings, but that multiple other factors are considered when deciding the need for clinical studies. Four drugs had prediction values less than the cutoffs but had clinical evaluations or physiologically-based pharmacokinetic simulations available. Consistent with the predictions, all of them were confirmed not to inhibit these transporters in vivo (AUCRs of 0.94-1.09). Overall, based on the clinical evaluations available, drugs approved in 2018 were found to have a relatively limited impact on drug transporters, with all victim AUCRs < 2.

[Effects and active substances of ethanol extract from Dendrobium officinale on metabolic hypertensive rats induced by comprehensive dietary].

Previous studies of Dendrobium officinale on anti-hypertension effect always focused only on the blood pressure,while polysaccharides of D. officinale( DOP) have been traditionally considered as one of the main effective substances. This study aimed to evaluate the effect of ethanol extract from D. officinale( DOE) on blood pressure,Glu and lipid profile in metabolic hypertensive rats induced by comprehensive dietary factors,and elucidate the composition of effective fractions from DOE. A metabolic hypertension model of rat induced by high-sugar,high-fat diet and alcohol drinking was adopted to evaluate the effect of DOE on hypertension and other metabolic disorders. Blood pressure,Glu and lipid profile were detected to find the features and differences of DOE and DOP on metabolic hypertension. Furthermore,DOE was separated with three different common solvents according to the polarity. Along with blood pressure,Glu,UA and lipid profile,hemorheology,oxidative index and aortas structure changes were adopted to evaluate the comprehensive effects of the most effective fractions on metabolic hypertension. Finally,HPLC-DAD-MS was adopted to identify the components of the most effective fraction. The SBP and Glu of models were decreased significantly after administration of DOE and DOP for 6 weeks,while TG in DOE groups also reduced dramatically. The DOE was separated with ether,n-butanol respectively and named NAF,NBF and NCF. SBP,TG,Glu,UA of model rats were decreased significantly after 4 weeks administration with NBF. The level of MDA in serum was down-regulated,while GSH-Px and T-AOC were up-regulated obviously after 12 weeks.And the blood viscosity also obviously decreased,with less collagen deposition of aortas by Masson's trichrome staining. NBF was mainly composed of phenols and flavone C-glycosides,whose aglycone was apigenin,and monosaccharide was connected to C-6 and C-8. Ethanol extract from D.officinale has an positive effect in alleviating hypertension and metabolic disorders in metabolic hypertension. Medium polarity fraction was the effective fraction of alcohol extraction from D. officinale,and mainly composed of phenols and flavone C-glycosides.

[Correlation between lipid-lowering efficacy and components of Pericarpium Citri Reticulatae].

Based on pharmacodynamics-component correlation analysis,the best effective part of hyperlipidemia of Pericarpium Citri Reticulatae( PCR) was screened out to confirm the possible constituents with the lipid regulating effect,in order to provide a basis for the development of new drugs. Hyperlipidemia rats induced by fat emulsion were used to screen out the best hypolipidemic parts of PCR with TC,LDL-c as the index. HPLC-ESI-MS were used to analyze common constituents of the different solvent extracts from PCR. The constituents were classified and identified based on the retention time,m/z and UV spectra. And the HPLC-DAD were used to determine the contents of flavonoids( narirutin,hesperidin,didymin,nobiletin,tangeretin,3,5,6,7,8,3',4'-heptemthoxyflavone).Correlation analysis was conducted on the constituents and efficacy with the method of SPSS ANOVA bivariate correlation. Five extracts could significantly decrease the content of TC,LDL-c of hyperlipemia rats induced by fat emulsion,and the best effective part were95% ethanol and ethyl acetate. There were 19 common peaks in five different solvent extracts from PCR,and 17 flavonoids were identified and classified,including 10 polymethoxyflavonoids and 7 other flavonoids. According to the raw material quantity,the order of content of flavonones arranged from high to low: n-butyl alcohol part> 95% ethanol part> water part> ethyl acetate part> petroleum ether part; and the order of PMFs arranged from high to low: n-butyl alcohol part≈95% ethanol part≈ethyl acetate part > petroleum ether part > water part. The decreased percentage of TC,LDL-c was positively correlated with 10 common PMFs constituents,which suggested that PMFs may be the effective components for reducing blood lipid.

A highly efficient microextraction technique based on deep eutectic solvent formed by choline chloride and p-cresol for simultaneous determination of lignans in sesame oils.

For simultaneous determination of lignans (i.e. sesamin, sesamolin and sesamol) in sesame oils, a highly efficient ultrasonic-assisted liquid-liquid microextraction (UALLME) technique was developed based on deep eutectic solvents (DESs) composed of choline chloride and p-cresol. Compared with the common polyols-based DESs (i.e. choline chloride-ethylene glycol), the phenolic DESs exhibited higher extraction efficiency for both polar lignans (i.e. sesamol) and non-polar lignans (i.e. sesamin and sesamolin) due to the π-π interaction between lignans and DES. After the UALLME process, DES phase was analyzed by HPLC-UV. Under optimized condition, all three lignans showed good linear calibration curves and low limit of detection. The recoveries were in the range of 97.3-120%, and the intra-day and inter-day precisions were less than 0.97%. Moreover, this method was used for simultaneous determination of lignans in 15 commercial oil samples. The results showed that the new microextraction technique achieved similar efficiency as the conventional liquid-liquid extraction method.

Developing User Personas to Aid in the Design of a User-Centered Natural Product-Drug Interaction Information Resource for Researchers.

Pharmacokinetic interactions between natural products and conventional drugs can adversely impact patient outcomes. These complex interactions present unique challenges that require clear communication to researchers. We are creating a public information portal to facilitate researchers' access to credible evidence about these interactions. As part of a user-centered design process, three types of intended researchers were surveyed: drug-drug interaction scientists, clinical pharmacists, and drug compendium editors. Of the 23 invited researchers, 17 completed the survey. The researchers suggested a number of specific requirements for a natural product-drug interaction information resource, including specific information about a given interaction, the potential to cause adverse effects, and the clinical importance. Results were used to develop user personas that provided the development team with a concise and memorable way to represent information needs of the three main researcher types and a common basis for communicating the design's rationale.

Effect of a stilbene glycoside-rich extract from Polygoni Multiflori Radix on experimental non-alcoholic fatty liver disease based on principal component and orthogonal partial least squares discriminant analysis.

Polygoni Multiflori Radix is a traditional Chinese medicine used clinically to support the functions of the liver and kidneys and to treatment hyperlipidemia. In previous studies, an effective fraction, rich in 2,3,5,4'-tetrahydroxy stilbene-2-O-ß-D-glucoside (TSG), was separated from Polygoni Multiflori Radix and demonstrated hypolipidemic activity. The present study aimed to systematically assess the effect of this fraction on non-alcoholic fatty liver disease (NAFLD). A NAFLD model was established by feeding Sprague-Dawley rats a high-fat diet with 10% fructose solution for 18 weeks. Hematoxylin and eosin staining was applied for hepatic histopathological analysis. In addition, enzyme activities, lipid metabolism, inflammatory factors and insulin resistance indices were measured using a fully automatic blood biochemistry analyser and ELISA. Furthermore, cytochrome P450 2E1 (CYP2E1) and peroxisome proliferator-activated receptor α (PPARα) mRNA and protein expression were evaluated using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Principal component analysis and orthogonal partial least squares discriminant analysis were used to analyse the data. The results revealed that the TSG-rich fraction (TSGP) significantly lowered the serum total cholesterol and triglyceride levels, and the liver free fatty acid, CYP2E1 mRNA and malondialdehyde levels, in addition to mitigating hepatic enlargement and alleviating liver steatosis. Furthermore, it upregulated PPARα mRNA expression in the liver tissue. The results indicated that TSGP exhibited a protective effect against NAFLD and the underlying mechanism may involve augmentation of anti-lipid peroxidation capacity via regulation of PPARα and CYP2E1-mediated pathways.

Gypenosides Inhibits Xanthine Oxidoreductase and Ameliorates Urate Excretion in Hyperuricemic Rats Induced by High Cholesterol and High Fat Food (Lipid Emulsion).

BACKGROUND The aim of this study was to study the effects of gypenosides (GPS) on lowering uric acid (UA) levels in hyperuricemic rats induced by lipid emulsion (LE) and the related mechanisms. GPS are natural saponins extracted from Gynostemma pentaphyllum. MATERIAL AND METHODS Forty-eight male SD rats were randomly divided into six groups: normal, model, two positive controls, and two GPS treated groups (two different doses of GPS). The normal group rats were fed a basic diet, and the other rats were orally pretreated with LE. Urine and blood were collected at regular intervals. Full automatic biochemical analyzer was used to detect the concentration levels of serum UA (SUA), serum creatinine (SCr), BUN, and urine UA (UUA), and urine creatinine (UCr) and fractional excretion of UA (FEUA). ELISA kits were used to detect enzymes activities: xanthine oxidase (XOD), adenosime deaminase (ADA), guanine deaminase (GDA), and xanthine dehydrogenase (XDH). Immunohistochemistry was used to observe kidney changes and protein (URAT1, GLUT9, and OAT1) expression levels. RT-PCR was used to detect the relevant mRNA expression levels. RESULTS Treatment with GPS significantly reduced the SUA, prevented abnormal weight loss caused by LE, and improved kidney pathomorphology. Treatment with GPS also decreased the levels of XOD, ADA, and XDH expression, increased the kidney index and FEUA, downregulated URAT1 and GLUT9 expression and upregulated OAT1 expression in the kidney. CONCLUSIONS GPS may be an effective treatment for hyperuricemia via a decrease in xanthine oxidoreductase through the XOD/XDH system; and via an increase in urate excretion through regulating URAT1, GLUT9, and OAT1 transporters.

Magnetic Mesoporous Palladium Catalyzed Selective Hydrogenation of Sunflower Oil.

In this paper, a novel magnetic mesoporous Pd catalyst is used to catalyse selective hydrogenation of sunflower oil at a mild temperature of 50°C. Effects of reaction temperature, stirring speed, time, catalyst loading and hydrogen pressure on the reaction activity, trans fatty acid (TFA) and stearic acid formation were studied. Under the condition of 3.2 mg Pd/100 g oil, 50°C, 1300 rpm stirring speed and 19.0 atm of H2, the lowest amount of TFA generated during the reaction (IV = 80) was 14.9 ± 0.4% while 11.4 ± 0.4% of stearic acid was produced. And this magnetic Pd-catalyst can be reused easily for at least six times without significant catalyst deactivation, the amount of TFA almost remained unchanged. Moreover, this Pd-catalyst shows a good magnetic separation, which provides a potential method for the facile oil modification.