Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11ß-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11ß-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11ß-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 µmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2D; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D. Circulating 8 and M2D, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11ß-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.

Complete plastome sequence of Flueggea virosa (Roxburgh ex Willdenow) Voigt (Phyllanthaceae): a medicinal plant.

Flueggea virosa is a tropical plant of the Phyllanthaceae family, which has high medicinal value. Here, we report and characterize the complete plastome of F. virosa. The complete plastome is 154,961 bp in length and contains the typical structure and gene content of angiosperm plastome, including two inverted repeat (IR) regions of 27,575 bp, a large single-copy (LSC) region of 83,397 bp and a small single-copy (SSC) region of 16,414 bp. The plastome contains 130 genes, consisting of 80 unique protein-coding genes, 30 unique tRNA gene, 4 unique rRNA genes (5S rRNA, 4.5S rRNA, 23S rRNA and 16S rRNA). The overall A/T content in the plastome of F. virosa is 63.10%. The complete plastome sequence of F. virosa will provide a useful resource for the conservation genetics of this species as well as for phylogenetic studies in Phyllanthaceae.

[Development of indel markers for molecular authentication of Panax ginseng and P. quinquefolius].

Panax ginseng and P. quinquefolius are two kinds of important medicinal herbs. They are morphologically similar but have different pharmacological effects. Therefore, botanical origin authentication of these two ginsengs is of great importance for ensuring pharmaceutical efficacy and food safety. Based on the fact that intron position in orthologous genes is highly conserved across plant species, intron length polymorphisms were exploited from unigenes of ginseng. Specific primers were respectively designed for these two species based on their insertion/deletion sequences of cytochrome P450 and glyceraldehyde 3-phosphate dehydrogenase, and multiplex PCR was conducted for molecular authentication of P.ginseng and P. quinquefolius. The results showed that the developed multiplex PCR assay was effective for molecular authentication of P.ginseng and P. quinquefolius without strict PCR condition and the optimization of reaction system.This study provides a preferred ideal marker system for molecular authentication of ginseng,and the presented method can be employed in origin authentication of other herbal preparations.

Phototherapy for treating foot ulcers in people with diabetes.

BACKGROUND: Foot ulcers are a disabling complication of diabetes that affect 15% to 25% of people with diabetes at some time in their lives. Phototherapy is a relatively new, non-invasive, and pain-free treatment method, which promotes the ulcer repair process through multiple mechanisms such as increased cell growth and vascular activity. Phototherapy may be used as an alternative approach for the treatment of foot ulcers in people with diabetes, but the evidence for its effect compared with placebo or other treatments has not yet been established. OBJECTIVES: To assess the effects of phototherapy for the treatment of foot ulcers in people with diabetes. SEARCH METHODS: We searched the Cochrane Wounds Specialised Register (11 October 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 10), Ovid MEDLINE (11 October 2016), Ovid MEDLINE (In-Process & Other Non-Indexed Citations) (11 October 2016), Ovid Embase (11 October 2016), EBSCO CINAHL Plus (11 October 2016), and China National Knowledge Infrastructure (24 June 2017). We also searched clinical trials registries for ongoing and unpublished studies on 24 June 2017, and screened reference lists to identify additional studies. We used no restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: Randomised controlled trials or cluster randomised controlled trials that 1) compared phototherapy with sham phototherapy, no phototherapy, or other physical therapy modalities, 2) compared different forms of phototherapy, or 3) compared phototherapy of different output power, wavelength, power density, or dose range, in adults with diabetes and an open foot ulcer of any severity, in any setting. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, and 'Risk of bias' assessment. We combined the study outcomes when appropriate. MAIN RESULTS: Eight trials with 316 participants met the inclusion criteria. Most of the included studies were single-centre studies that were carried out in clinics or hospitals with a sample size ranging from 14 to 84. We generally considered the included studies to be at unclear or high risk of bias, as they had one domain at high risk of bias, or three or more domains at unclear risk of bias.We did not identify any studies that reported valid data for time to complete wound healing. Meta-analysis of four studies including 116 participants indicated that participants receiving phototherapy may experience a greater proportion of wounds completely healed during follow-up compared with those receiving no phototherapy/placebo (64.5% for the phototherapy group versus 37.0% for the no phototherapy/placebo group; risk ratio 1.57, 95% confidence interval 1.08 to 2.28; low-quality evidence, downgraded for study limitations and imprecision). Two studies mentioned adverse events in the results; one study with 16 participants suggested that there were no device-related adverse events, and the other study with 14 participants suggested that there was no clear difference between phototherapy and placebo group.Four studies reported change in ulcer size, but primarily due to high heterogeneity, they were not combined. Results from individual trials (including 16 participants to 84 participants) generally suggested that after two to four weeks of treatment phototherapy may result in a greater reduction in ulcer size but the quality of the evidence was low due to unclear risk of bias in the original trial and small sample size. We based the analyses for quality of life and amputations on only one study each (28 participants and 23 participants respectively); both outcomes showed no clear difference between the phototherapy group and the no phototherapy/placebo group. AUTHORS' CONCLUSIONS: This systematic review of randomised trials suggested that phototherapy, when compared to no phototherapy/placebo, may increase the proportion of wounds completely healed during follow-up and may reduce wound size in people with diabetes, but there was no evidence that phototherapy improves quality of life. Due to the small sample size and methodological flaws in the original trials, the quality of the evidence was low, which reduces our confidence in these results. Large, well-designed randomised controlled trials are needed to confirm whether phototherapy could be an effective option for the treatment of foot ulcers in people with diabetes.

[Effect of grafting on rhizosphere soil environment and its relationship with disease resistance and yield of pepper.] / å«æŽ¥å¯¹è¾£æ¤’æ ¹é™ åœŸå£¤çŽ¯å¢ƒçš„å½±å“åŠå ¶ä¸ŽæŠ—ç— æ€§å’Œäº§é‡çš„å ³ç³».

We investigated the effect of grafting on the root rhizosphere soil microorganisms, physical properties, nutrient content, soil-borne disease and yield of pepper, using 'Weishi' (WS) and 'Buyeding' (BYD) as rootstocks, the cultivar pepper 'Xinfeng 2' (XF) as scion, and the own-root (XF/XF) pepper as the control. The results indicated that XF/WS and XF/BYD significantly increased the populations of fungi and actinomycetes and the percentage of actinomycetes. 60 days after transplanting, the activities of catalase (CAT) and peroxidase (POD) were much higher in root rhizosphere soil of grafted pepper. 90 days after transplanting, the activities of phosphatase, invertase, urease, and nitrate reductase (NR) were much higher in root rhizosphere soil of XF/WS. In addition, The XF/WS and XF/BYD also highly increased hydrocarbon compounds in soil extraction, slightly increased electric conductivity (EC) but lowered nitrogen, phosphorus and potassium contents in root rhizosphere soil. Higher pH in root rhizosphere soil was found in XF/WS but not in XF/BYD. These data indicated that grafting could optimize the rhizosphere soil environment of pepper and enhance the resistance of soil-borne diseases. The yields of XF/WS and XF/BYD were increased by 40.8% and 28.7%, respectively.

Phenolic Compounds from the Roots of Rhodiola crenulata and Their Antioxidant and Inducing IFN-γ Production Activities.

In the present study, two new phenolic compounds 1 and 11, a pair of lignan isomers 12 and 13 with their absolute configurations established for the first time, were isolated from the ethanol extract of the roots of Rhodiola crenulata, together with 13 known phenolic compounds, and their structures were elucidated via NMR, HRESIMS, UV, IR and CD analyses. All the isolated compounds were evaluated for their in vitro antioxidant activities using the 2,2-diphenyl-1-picryhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. Ten of them exhibited significant antioxidant activities compared to ascorbic acid. Furthermore, the inducibilities of the isolated compounds to IFN-γ production were also assessed. Compounds 1, 8, 9, 12, 13, 14 and 15 could moderately stimulate IFN-γ expression.

The independent role of the aortic root ganglionated plexi in the initiation of atrial fibrillation: An experimental study.

OBJECTIVE: The major atrial ganglionated plexi (GP) can initiate atrial fibrillation alone without any contribution from the extrinsic cardiac nervous system. However, if stimulation of the ventricular GP, especially the aortic root GP, can provoke atrial fibrillation (AF) alone is unknown. Our study was designed to investigate the independent role of aortic root GP activity in the initiation of AF. METHODS: In 10 Langendorff-perfused canine hearts, the atrial effective refractory period, pulmonary vein effective refractory period, and percentage of AF induced were measured at baseline and during aortic root GP stimulation. RESULTS: Stimulation of the aortic root GP shortened the atrial effective refractory period from 128 ± 10 ms at baseline to 103 ± 15 ms (P < .05) and shortened the pulmonary vein effective refractory period from 139 ± 14 ms to 114 ± 15 ms (P < .05). Furthermore, the percentage of AF induced in the 10 isolated hearts increased from 10% at baseline to 90% during aortic root GP stimulation (P < .05). CONCLUSIONS: In Langendorff-perfused canine hearts, stimulation of the aortic root GP provokes AF in the absence of any extrinsic cardiac nerve activity. The aortic root GP is an important element in the intrinsic neuronal loop that can increase the risk of AF in isolated heart models.

[Protective effect of Qihuang Mingmu capsule on retina of diabetic mice and its impact on VEGF expression].

OBJECTIVE: To investigate the protective effect of Qihuang Mingmu capsule (QHMM) on retina of diabetic mice and its impact on VEGF expression. METHOD: Forty KK/Upj-Ay mice were randomly divided into the model group and high, middle and low dose QHMM (8.32, 4.16, 2.08 g x kg(-1)) groups. Additional 10 C57BL/6 mice were selected as the control group. Mice were orally administered for three months. Their general appearance, fasting blood-glucose (FBG) and glycosylated hemoglobin (HbA1c) were observed. Pathological changes of retina were observed by light microscope and electron microscope. The expressions of vascular endothelial growth factor (VEGF), growth factor receptors-1 (Flt-1) and growth factor receptors-2 (Flk-1) were examined by Real-time PCR (qPCR) and Western blot. RESULT: QHMM could ameliorate the symptoms of diabetic mice to varying degrees, decrease FBG and HbA1c, alleviate pathological lesions of retina and decrease the expressions of VEGF, Flt-1, Flk-1 mRNA and protein. CONCLUSION: QHMM has the protective effect on diabetic retinopathy of mice by inhibiting the expressions of VEGF, Flt-1 and Flk-1 and intervening VEGF-VEGFR signal transduction pathway.

A simple and rapid technique for the authentication of the ginseng cultivar, Yunpoong, using an SNP marker in a large sample of ginseng leaves.

Yunpoong is an important Korean ginseng (Panax ginseng C. A. Meyer) cultivar, but no molecular marker has been available to identify Yunpoong from other cultivars. In this study, we developed a single nucleotide polymorphism (SNP) marker for Yunpoong based on analysis of expressed sequence tags (ESTs) in an exon region of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. This SNP marker had high specificity to authenticate Yunpoong in twelve different main ginseng cultivars. For application of the molecular marker, a rapid identification method was established based on the NaOH-Tris method and real-time polymerase chain reaction (PCR) in order to ensure more efficiency in the cultivar selection. The biggest feature of the NaOH-Tris method was that it made the extraction of DNA very simple and rapid in young leaf tissues. We only spent 1 min to extract DNA and directly used it to do PCR. In this report, the conventional DNA extraction method was used to develop molecular marker process, and the NaOH-Tris method was applied in screening large numbers of cultivars. Moreover, the greatest advantage of the real-time PCR compared with traditional PCR, is time saving and high efficiency. Thus, this strategy provides a rapid and reliable method for the specific identification of Yunpoong in a large number of samples.

[Identification of chemical constituents in qiliqiangxin capsule by UPLC-Q-TOF/MS(E)].

In order to clarify the chemical constituents in Qiliqiangxin capsule, a rapid ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometry (UPLC-Q-TOF/MS(E)) method was established. Forty peaks were identified on line using this method. The herbal sources of these peaks were assigned. The results implied that triterpenoid saponins, flavonoid glycosides, C21-steroids and phenolic acids were included in the main components of Qiliqiangxin capsule. The method is simple and rapid for elucidation of the constituents of Qiliqiangxin capsule and the results are useful for the quality control of Qiliqiangxin capsule.

[Effects of Tongxinluo on neuron ultrastructure and endothelial cell self-repairing ability in hypoxia preconditioning mice].

OBJECTIVE: To observe the ultrastructure changes of cerebral cortex neuron and endothelial cell in hypoxia preconditioning mice and the effects of Tongxinluo (TXL, Chinese traditional medilihe) on them. METHODS: Mice were randomly divided into 4 groups: control group, hypoxia group, hypoxia preconditioning (HP) group and Tongxinluo (TXL) group. The hypoxia preconditioning mice were exposed by repetitive hypoxia for 5 runs. The animal's tolerance time of each hypoxia run was recorded. The ultrastructure change of cerebral neuron and endothelial cell were studied by electron microscope. RESULTS: The hypoxic tolerance time in HP and TXL groups were significantly increased run by run. Compared with HP group, the tolerance time of TXL group were increased in every run. The ultrastructure of cerebral neuron and endothelial cell in hypoxia group changed obviously, mitochondrion and endoplasmic reticulum destroyed. However they were slighter in HP group than those in hypoxia group. The change in TXL group had no obvious differentce with control group and were slighter than those in HP group. CONCLUSION: Hypoxia preconditioning shows that organism has a strong self-repairing ability. Tongxinluo self-repairing; could increase self-repairing ability and adaptive ability of mice to hypoxia obviously.

Development of molecular markers for the determination of the new cultivar 'Chunpoong' in Panax ginseng C. A. Meyer associated with a major latex-like protein gene.

Chunpoong is one of the most valuable cultivars of Panax ginseng C. A. MEYER, and is widely grown in Korea and China. Insertion/deletion (InDel) markers and single nucleotide polymorphism (SNP) markers are useful tools for marker-assisted selections. The SNP marker for determinate Chunpoong was previously developed from the nad7 gene of mtDNA by Wang et al. (2009) but was effective only on a limited range of cultivars. In this study, we studied the reasons for this limited application and developed new useful markers for application in Chunpoong-breeding programs. The new markers of InDel and SNP were designed in the major latex-like protein (MLP-like) gene which was highly expressed in 4-year-old Chunpoong expressed sequence tags (ESTs). To validate the marker in polymerase chain reaction (PCR), we used an InDel marker for identification of Chunpoong in the 70 Panax samples based on a double-blind test, and the success rate was 100%. For rapid and reliable assay of Chunpoong in numerous samples, we utilized an EvaGreen dye and melting curve method on real-time PCR. Furthermore, we designed an SNP marker that depended on the InDel region for more efficient detection of Chunpoong in real-time PCR. Compared with PCR-based assays, our Chunpoong SNP marker and real-time PCR assay offers a significant savings of time and labor in the analysis of large numbers of Chunpoong samples.

[Protective effect of Tongxinluo Ultramicro-pulverization on experimental myocardial infarction of rats].

OBJECTIVE: To study the effects of Tongxinluo ultramicro-pulverization (TXLU) on experimental myocardial infarction and platelet aggregation of rats, investigate its mechanisms on ischemia heart disease and offer a reference to clinical usage. METHOD: Rats were separated randomly into 7 groups: sham, model, diltiazem (0.15 mg x kg(-1)), TXL(1.2 g x kg(-1)), TXLU (1.2, 0.6, 0.3 g x kg(-1)). The experimental myocardial infarction was induced with ligating the left anterior descending branch of the coronary of rats. The infarction size was determined after myocardium tissue was stained with 2,3,5-triphenyltetrazolium chloride (TTC). And the serum of rats was separated to analyze CK, LDH, SOD, MDA. Another 60 rats were separated randomly into 6 groups: control, aspirin (0.15 mg x kg(-1)), TXL (1.2 g x kg(-1)), TXLU (1.2 ,0.6,0.3 g x kg(-1)). The rat platelet aggregation was induced with adenosine diphosphate (ADP) and collagen to observe the inhibitory effects of TXLU. RESULT: TXLU could relieve the myocardial infarction size and weight stained with TTC significantly, the myocardial infarction size of the three groups of TXLU were (2.7 +/- 2.1)%, (3.4 +/- 1.2)%, (2.8 +/- 1.8)%, compared with model group (8.9 +/- 5.9)%, P < 0.05 or P < 0.01. The myocardial infarction weight of the three groups of TXLU were (8.4 +/- 3.5)%, (8.7 +/- 4.1)%, (9.7 +/- 4.1)%, compared with model group (l2.2 +/- 3.6)% P < 0.05 or P < 0. 01. And the content of MDA and the activities of CK and LDH in rats subjected with ligation of coronary artery were inhibited obviously too, compared with model group P < 0.05 or P < 0.01, then the activity of SOD increased. TXLU could inhibit the maximum percentage of rats platelet aggregation induced with ADP and collagen, the maximum percentage of platelet aggregation induced with ADP were (26.9 +/- 9.2)%, (24.4 +/- 13.4)%, (30.6 +/- 12.2)%, compared with control group (44.3 +/- 15. 7)% P < 0.05 or P < 0.01; The maximum percentage of platelet aggregation induced with collagen were (33.8 +/- 6.9)%, (32.1 +/- 8.3)%, (41.5 +/- 7.8)%, compared with control group (49.2 +/- 15.9)%, P < 0.05 or P < 0.01. CONCLUSION: The experiment results indicated that TXLU could protect myocardial tissue of rats from ischemic injury and the mechanism may be related with antioxidation and inhibiting platelet aggregation, and the results also suggested TXLU could lower clinical dosage.

[Effect of tongshenluo capsule on the components of extracellular matrix and their metabolism in kidney of rats with diabetic nephropathy].

OBJECTIVE: To investigate the effect of Tongshenluo Capsule (TSL) on the components of extracellular matrix (ECM) and their metabolism in kidney of rats with diabetic nephropathy (DN), and to explore its mechanism of kidney protecting. METHODS: The DN model rats established by one side nephrectomy and intraperitoneal injection of streptozotocin were randomly divided into 5 groups, the sham-operation group, the model group, the Valsartan group, the Gliquidon group, and the TSL group, 10 in each group. Levels of fasting blood glucose (FBG) and 24-h urinary micro-content of albumin (24 h mAlb) were determined dynamically; the serum glycosyl hemoglobin (HbA1c)was determined after the last medication; the ultrastructural changes of kidney were observed by transmission electron microscope; the expressions of collagen IV (IV-C), fibronctin (FN), laminin(LN), and the ECM metabolism influencing factors, including MMP-2, tissue inhibitor of metalloproteinase (TIMP-2), transfer growth factor-beta1 (TGF-beta1) in renal tissue were detected by immunohistological chemistry and image collecting analytical system. Results TSL could decrease the levels of FBG, HbA1c, 24 h mAlb (P < 0.05 or P < 0.01), ameliorate the thickness of glomerular basement membrane (GBM), decrease the components of ECM, down-regulate TGF-beta1 and TIMP-2 expression, and up-regulate MMP-2 expression (P < 0.05 or P < 0.01). CONCLUSION: TSL plays a role of kidney protection by decreasing the ECM components expression and regulate ECM metabolism.

[Clinical observation on isolated electroacupuncture for treatment of peripheral facial paralysis].

OBJECTIVE: To study on therapeutic effect of isolated electroacupuncture on peripheral facial paralysis. METHODS: One hundred cases were randomly divided into an observation group of 60 cases and a control group of 40 cases. The observation group were treated by isolated electroacupuncture and the control group by normal electroacupuncture. Jiache (ST 6), Yangbai (GB 14), Dicang (ST 4), Xiaguan (ST 7), Fengchi (GB 20) and Hegu (LI 4) were selected and same drugs were administrated in the two groups. Then their therapeutic effects were observed. RESULTS: Forty-five cases were cured, 11 cases were markedly effective and 4 cases improved with an effective rate of 100.0% in the observation group, and corresponding figures were 26, 2 and 10 cases, and 95.0% in the control group, the observation group being better than the control group (P < 0.01). CONCLUSION: Isolated electroacupuncture has a significant therapeutic effect on facial paralysis, being better than that of normal electroacupuncture.