Cucurbitane-type triterpenoids from the fruits of Citrullus colocynthis.

A phytochemical investigation of the fruits of Citrullus colocynthis resulted in the isolation of 21 structurally diverse cucurbitane triterpenoids, including 9 previously undescribed ones, colocynins A-I (1-9). Their absolute configurations were elucidated by means of quantum chemical electronic circular dichroism (ECD) calculations, CD exciton chirality method, and single-crystal X-ray crystallography. Colocynins A-C (1-3) represent the first examples of nonanorcucurbitane-type triterpenoids. An anti-acetylcholinesterase activity assay showed that 6, 10, 13, 18, and 20 exhibited inhibitory activities, with IC50 values ranging from 5.0 to 21.7 µM. In addition, 18 and 21 showed significant cytotoxicity against PACA, A431, and HepG2 cells, with IC50 values ranging from 0.042 to 0.60 and 3.6-14.4 µM, respectively.

Three New Xanthones from Hypericum scabrum and Their Quorum Sensing Inhibitory Activities against Chromobacterium violaceum.

Quorum sensing (QS) plays an important role in the production of virulence factors and pathogenicity in pathogenic bacteria and is, therefore, a hopeful target to fight against bacterial infections. During our search for natural QS inhibitors, two new xanthonolignoids (1 and 2), each existing as a racemic mixture, one new simple oxygenated xanthone (7), and eight known analogs (3-6, 8-11) were isolated from Hypericum scabrum Linn. Chiral separation of 1 yielded a pair of enantiomers 1a and 1b. The structures of these compounds were elucidated by spectroscopic analysis and ECD (electrostatic circular dichroism) calculations. All isolates were evaluated for their QS inhibitory activity against Chromobacterium violaceum. Both 9 and 10 exhibited the most potent QS inhibitory effects with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 31.25 and 62.5 µM, respectively. Crystal violet staining was used to further evaluate the biofilm inhibition potential of compounds 7, 9 and 10, and the formation of biofilms increased with decreasing drug concentration in a classic dose-dependent manner. The results of a cytotoxicity assay revealed that compounds 7, 9 and 10 exhibited no cytotoxic activity on PC-12 cells at the tested concentration.

Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum scabrum.

Eighteen polycyclic polyprenylated acylphloroglucinols were isolated from the whole plant of Hypericum scabrum Linn., including six new compounds (1-6). Their structures were elucidated by comprehensive spectroscopic analyses. The evaluation of their cytotoxic activities was carried out against SMMC-7721 and MGC-803 cell lines. We found that most tested compounds exhibited moderate cytotoxic activities against SMMC-7721 cell line except for 11 and 12, while compounds 1, 5-7, 13 and 16 also showed cytotoxic activities on MGC-803 cells. Besides, Bacillus subtilis, MRSA and MDPRA were also used to test inhibitory activity of these compounds. Our results showed that only compounds 12 and 13 presented weak inhibitory activity against Bacillus subtilis, while compounds 7, 13 and 14 also inhibited MRSA weakly.

Monoterpenoid Glycosides from the Leaves of Ligustrum robustum and Their Bioactivities.

The leaves of Ligustrum robustum have been applied as Ku-Ding-Cha, a functional tea to clear heat, remove toxins, and treat obesity and diabetes, in Southwest China. The phytochemical research on the leaves of L. robustum led to the isolation and identification of eight new monoterpenoid glycosides (1-8) and three known monoterpenoid glycosides (9-11). Compounds 1-11 were tested for the inhibitory activities on fatty acid synthase (FAS), α-glucosidase, α-amylase, and the antioxidant effects. Compound 2 showed stronger FAS inhibitory activity (IC50: 2.36 ± 0.10 µM) than the positive control orlistat (IC50: 4.46 ± 0.13 µM), while compounds 1, 2, 5 and 11 displayed more potent ABTS radical scavenging activity (IC50: 6.91 ± 0.10~9.41 ± 0.22 µM) than the positive control L-(+)-ascorbic acid (IC50: 10.06 ± 0.19 µM). This study provided a theoretical basis for the leaves of L. robustum as a functional tea to treat obesity.

Amicoumacins from a desert bacterium: quorum sensing inhibitor against Chromobacterium violaceum.

In our study, the anti-quorum sensing (QS) activity of fermentation broth from TRM B-02, a bacterium isolated from Taklimakan desert, was investigated using the biosensor bioassay on Chromobacterium violaceum ATCC12472. TRM B-02 was 100% similar to Bacillus subtilis subsp. Inaquosorum KCTC 13429(T) by genotypic and phenotypic analyses. Based on anti-QS activity tracking, six known amicoumacins, named as AI-77-H (1), AI-77-F (2), amicoumacin B (3), amicoumacin C (4), AI-77-C (5) and bacilosarcins D (6), were isolated and identified. Among them, compounds 1-3 exhibited a better inhibitory effect on C. violaceum ATCC12472. Further research suggested that compounds 1-3 could significantly down-regulate the expressions of violacein operon A (vioA), vioB, vioD and vioE and up-regulate vioC. Docking experiments indicated that compounds 1-3 may act as an inhibitor of violacein biosynthetic pathway competitively inhibiting the binding of flavin adenine dinucleotide (FAD) with the vioD enzyme.[Figure: see text].

Effect of Modified Shenfuwan on Lumbar Disc Herniation Due to Kidney Deficiency and Cold Coagulation / 中国实验方剂学杂志

Objective:To observe short-term and long-term effect of modified Shenfuwan on lumbar disc herniation due to kidney deficiency and cold coagulation. Method:100 cases were randomly divided into the control group and observation group，50 cases each. The control group were taken meloxicam tablets，7.5 mg each time，once a day and the observation group were given modified Shenfuwan，300 mL each time，twice a day. The treatment course was 3 months. The short form McGill pain questionnaire（SF-MPQ），oswestry disability index（ODI），and lumbar intervertebral disc herniation due to kidney deficiency and cold coagulation by traditional Chinese medicine （TCM ） syndrome were observed before and after treatment. Whole blood viscosity （high，medium，low），serum inflammatory factors ［tumor necrosis factor-alpha（TNF-<italic>α</italic>），interleukin-1<italic>β</italic>（IL-1<italic>β</italic>），interleukin-6（IL-6），pain mediators［endothelin-1（ET-1），prostaglandin E₂（PGE₂），cyclooxygenase-2（COX-2）］ were detected. The clinical efficacyand，recurrence rate followed up for 12 and 24 months was was observed. The type and time of adverse reactions were recorded during the study. Result:After treatment，the total effective rate in the observation group was 98.0%（49/50） higher than that 82.0%（41/50） in the control group（<italic>P</italic><0.05）. After 12 months of follow-up，the recurrence rate in the observation group was 23.9%（11/46） lower than that 52.5%（21/40） in the control group （<italic>χ</italic>²＝5.193，<italic>P</italic><0.05）. After 24 months of follow-up，the recurrence rate in the observation group was 43.9%（18/41） lower than that that 80.6%（29/36） in the control group（<italic>P</italic><0.05）. Compared with the control group after treatment，SF-MPQ，ODI，TCM symptoms，whole blood viscosity，TNF-<italic>α</italic>，IL-1<italic>β</italic>，IL-6，ET-1，PGE₂ and COX-2 were significantly reduced in the observation group（<italic>P</italic><0.05）. The incidence of adverse reactions in the observation group was 2.0%（1/50） lower than that 52.0%（26/50） in the control group（<italic>χ</italic>²＝6.264，<italic>P</italic><0.05）. Conclusion:Modified Shenfuwan can significantly improve the short-term and long-term clinical efficacy of patients with lumbar disc herniation due to kidney deficiency and cold coagulation syndrome，and the incidence of adverse reactions is low.

Effect of Modified Anshentang on Serum Inflammatory Factors, Immune Function, Bone Metabolism on Treatment of Patients with Ankylosing Spondylitis in Early and Middle Stages / 中国实验方剂学杂志

Objective:This study aims to investigate the clinical efficacy of modified Anshentang on the treatment of ankylosing spondylitis in early and middle stages with kidney deficiency and cold-governing syndrome and its effect on serum inflammatory factors， immune function， and bone metabolism indexes of patients. Method:In this study， 120 patients were randomly divided into control group and observation group， 60 cases in each group. On the basis of ethotrexate treatment， patients in control group took Bushen Shuji granule orally， while patients in observation group took modified Anshentang orally for 8 weeks. Before and after treatment， patients in two groups were observed for clinical symptoms ［ bath ankylosing spondylitis patient global score （BAS-G）， bath ankylosing spondylitis disease activity index （BASDAI）， spondyloarthritis research consortium of Canada （SPARCC）， traditional Chinese medicine symptoms （TCM symptoms）<italic> </italic>］， serum inflammatory factors ［ tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>）， macrophage migration inhibitory factor （MIF）， interleukin-23 （IL-23）］， immune function ［ immunoglobulin A（IgA）， immunoglobulin G（IgG）， immunoglobulin M（IgM）］， bone metabolic indicators ［osteocalcin （BGP）， bone morphogenetic protein-2 （BMP-2）， bonespecific alkaline phosphatase （BALP）］. The clinical efficacy， adverse reactions and recurrence rates of 12 months in two groups were observed. Result:During the study， 4 cases dropped out from control group and 2 cases from observation group. The total effective rate of 96.55% （56/58） in observation group was higher than 80.36% （45/56） in control group （<italic>χ</italic>²=4.827，<italic>P</italic><0.05）. The recurrence rate of 5.17% （3/58） in observation group was lower than 19.64% （11/56） in control group （<italic>χ</italic>²=5.187， <italic>P</italic><0.05）. Compare with control group after treatment， BAS-G，BASDAI， SPARCC， TCM symptoms， TNF-<italic>α</italic>， MIF and IL-23 in observation group were significantly decreased （<italic>P</italic><0.05）， while BGP， BMP-2， BALP， IgA， IgG and IgM were significantly increased （<italic>P</italic><0.05）. The incidence of adverse reactions was 12.07%（7/58） in observation group， which was lower than 32.14%（18/56） in control group （<italic>χ</italic>²=4.826，<italic>P</italic><0.05）. Conclusion:Modified Anshentang is effective in the treatment of ankylosing spondylitis in early and middle stages with kidney deficiency and cold-governing syndrome， and the incidence of adverse reactions is low.

Effect and Mechanism of Modified Si Junzitang Combined with Heat-sensitive Moxibustion on IL-17, IL-22, IL-1α and Cys-C in Serum and Exhale Breath Condensate of Patients with Chronic Obstructive Pulmonary Disease at Stable Stage / 中国实验方剂学杂志

Objective::To observe the effect and mechanism of modified Si Junzitang combined with heat-sensitive moxibustion on interleukin-17(IL-17), interleukin-22(IL-22), interleukin-1α(IL-1α) and serum cystatin C(Cys-C )in serum and exhale breath condensate(EBC) of patients with chronic obstructive pulmonary disease at stable stage(COPD, Qi deficiency of lung and spleen). Method::Totally 120 cases of COPD(Qi deficiency of lung and spleen) treated in pulmonary department and thermal moxibustion department of Affiliated Hospital of Jiangxi University of traditional Chinese medicine from January 2019 to June 2019 were included and randomly divided into traditional Chinese medicine group, heat-sensitive moxibustion group and control group. The patients in traditional Chinese medicine group were treated with Si Junzitang, the patients in heat-sensitive Moxibustion group were treated with heat-sensitive moxibustion in addition to traditional Chinese medicine group, and the patients in control group were treated with placebo. All of the 3 groups were treated with oxygen and bronchodilator according to the guidelines. All groups received 3 consecutive courses of treatment, 20 days per course. After 3 courses of treatment, the clinical efficacy of the three groups, the forced expiratory volume in one second (FEV1), the forced expiratory volume in the estimated value in one second (FEV1%), the forced vital capacity (FVC), and IL-17, IL-22, IL-1α in serum and exhale breath condensate (EBC) were measured. Result::There were no statistically significant difference in general clinical data, lung function levels (FEV1, FEV1%, FVC), serum and EBC levels of IL-17, IL-22, IL-1α and Cys-C in the first three groups. The total clinical effective rate of traditional Chinese medicine group was better than the control group (P<0.05), the heat-sensitive moxibustion group was better than the traditional Chinese medicine group (P<0.05) and significantly better than the control group (P<0.01). Compared with the patients before treatment, the level of lung function was improved, while IL-17, IL-22, IL-1α and Cys-C in serum and EBC were reduced(P<0.05). The traditional Chinese medicine group was superior to that in the control group (P<0.05), the heat-sensitive moxibustion group was superior to that in the traditional Chinese medicine group (P<0.05) and significantly superior to that in the control group (P<0.01). Conclusion::Modified Si Junzitang combined with heat-sensitive moxibustion has an anti-inflammatory effect on COPD by stimulating bullishness of human body, improving body immunity, inhibiting inflammatory cytokines, reducing levels of inflammation cytokines IL-17, IL-22, IL-1α, and chronic inflammation markers serum Cys-C and inflammatory reaction, increasing the lung capacity, improving ventilation function and pulmonary function, so as to effectively relieve chest tightness asthma and other symptoms in COPD patients, and improve the clinical efficacy.

Clinical Efficacy of Modified Bixie Shengshitang on Acute Gouty Arthritis Due to Hot and Humid Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Bixie Shengshitang on acute gouty arthritis due to hot and humid syndrome. Method:According to the random number table method， 130 cases were randomly divided into control group and observation group， with 65 cases in each group. All of the cases were given the basic non-drug therapy. The control group was given colchicine， while observation group was given modified Bixie Shengshitang + colchicine for 14 d. Before treatment and at 3， 7 and 14 d after treatment， total symptom score （TSS） and traditional Chinese medicine （TCM） syndrome were observed between the two groups， respectively. Blood uric acid （BUA）， urinary uric acid （UUA）， erythrocyte sedimentation rate （ESR）， proinflammatory factors ［tumor necrosis factor-α （TNF-α）， interleukin-1 （IL-1）， interleukin-8 （IL-8）］ and anti-inflammatory factors ［interforon gamma receptor （IFN-γ）， interleukin-4 （IL-4）， interleukin-18（IL-18）］ in serum and joint fluid were detected before and after treatment. The clinical efficacy and safety of the two groups were compared. Result:The total effective rate was 96.9% （62/64） in observation group， which was higher than 80.6% （50/62） in control group （χ2=5.713， P<0.05）. Compared with control group at 3， 7 and 14 d after treatment， TSS and TCM syndrome scores in observation group were significantly reduced （P<0.05）. Compared with control group after treatment， BUA， ESR， TNF-α， IL-1β， IL-8 and UUA， IFN-γ， IL-4 and IL-18 were significantly decreased in observation group （P<0.05）. There was no serious adverse event during the study period. The incidence of adverse reactions was 54.7% （35/64） in observation group， which was lower than 82.3% （51/62） in control group （χ2=9.326， P<0.05）. Conclusion:Modified Bixie Shengshitang can significantly alleviate the clinical symptoms of patients with acute gouty arthritis due to hot and humid syndrome， and adjust levels of uric acid and inflammatory cytokines， with a low recurrence rate.

Effectiveness of Perioperative Auricular Therapy on Postoperative Pain after Total Hip Arthroplasty: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Auricular therapy (AT) is a conventional therapy in traditional Chinese medicine. However, the effectiveness of perioperative AT in pain treatment after total hip arthroplasty (THA) is still controversial. Nine randomised controlled trials (RCTs) involving 605 patients who have undergone THA with or without AT from inception to March 2018 were collected and included in this study by searching more than 12 databases (e.g., PubMed, Excerpta Medica Database, and Cochrane Library). A random-effects model that pooled seven articles showed that the visual analogue scale (VAS) in the AT group was lower than that of the control group at each postoperative time point in patients after THA, except at the time points of 6 and 36 h. The intraoperative body mass-adjusted fentanyl amount in the AT group was also lower than that of the control group in two trials. The other outcomes (time to first analgesic request and incidence of postoperative nausea and vomiting, perioperative bradycardia, and transitory hypotension) showed insignificant difference. Then, subgroup analysis showed similar results to those of the total articles with the term "VAS". Regression analysis found that the prolonged time after the operation decreased the difference in VAS between the two groups. Although all the outcomes were assessed as very low to low in the GRADE system, evidence on the effectiveness of perioperative AT in pain treatment after total hip replacement was positive.

Lycocasuarines I-Q, new Lycopodium alkaloids isolated from Lycopodiastrum casuarinoides.

Lycocasuarines I-Q (1-9), nine new lycodine-type Lycopodium alkaloids were isolated from the aerial parts of Lycopodiastrum casuarinoides (Spring) Holub ex R.D.Dixit. Their structures were unambiguously determined via extensive spectroscopic analyses, including HRESIMS, NMR, and electronic circular dichroism (ECD). The new alkaloids were evaluated for their in vitro inhibitory activity against acetylcholinesterase (AChE). Compounds 3, 5-8 exhibited marginal or weak activities with IC50 values ranging from 97.2 to 171.9 µM.

Novel hypolipidemic conjugates of fatty acid and bile acid with lysine for linkage.

Novel fatty acid-bile acid conjugates (1a-1k) were designed and synthesized by coupling of the fatty acids to the 3-OH of bile acids using lysine for linkage. In the conjugates, the 24-COOH of the bile acids was kept intact to preserve liver-specific recognition. The ability of the newly synthesized conjugates (at 100 mg/kg dosage) to reduce total cholesterol (TC) and triglyceride (TG) levels in mice fed with high-fat diet (HFD) was evaluated. Conjugates of stearic acid with cholic acid and palmitic acid with ursodeoxycholic acid (at dosages of 50, 100, and 200 mg/kg) were further evaluated to determine their ability to reduce aspartate aminotransferase (AST), alanine aminotransferase (ALT), TC, and TG levels in mice fed with HFD. All conjugates showed potent hypolipidemic activity. Further investigation revealed that compounds 1c and 1 g not only dose-dependently reduced serum levels of TC and TG, but also inhibited the elevation of serum AST and ALT levels in mice fed with HFD. Thus, compounds 1c and 1 g are promising hypolipidemic agents with hepatocyte protective effects against HFD-induced liver damage.

Effect of Modified Bazhentang on Cerebrovascular Reserve and Hemorheology in Patients with Chronic Cerebral Circulation Insufficiency / 中国实验方剂学杂志

Objective: To observe the effect of modified Bazhentang on cerebrovascular reserve and hemorheology in patients with chronic cerebral circulation insufficiency. Method: Totally 80 patients treated at Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from January 2018 to June 2018 in line with the inclusion criteria were randomly divided into the observation group (40 cases) and the control group (40 cases) using the random sequence of Stata 13.0. Both groups received basic treatments, such as antihypertensive, hypoglycemic and lipid-lowering. In addition to the therapy of the control group, the control group was also given nimodipine tablet treatment, and the observation group was given modified Bazhentang treatment, with a total course of 30 days. Before and after treatment, transcranial doppler ultrasonography (TCD) was used to detect the cerebrovascular reserve function of the two groups, so as to evaluate the clinical efficacy, and detect the hemorheology, blood routine, hepatic and renal function. Result: The effective rate of the observation group was 92.5%, and that of the control group was 80%. The clinical efficacy of the observation group was better than that of the control group (PPPPPConclusion: Modified Bazhentang can effectively treat chronic cerebral circulation insufficiency. By improving the function of cerebrovascular reserve and cerebral blood flow, it can alleviate clinical symptoms without safety problems, so as to provide a theoretical basis for the treatment of chronic cerebral circulation insufficiency with traditional Chinese medicine.

Effect and Mechanism of Modified Buzhong Yiqi Tang and Pursed-lips Breathing on Serum TNF-α，IL-8，IL-6，IL-1β and Cys-C in Patients at Stable Stage of COPD / 中国实验方剂学杂志

Objective: To observe the effect and mechanism of modified Buzhong Yiqi Tang and pursed-lips breathing (PLB) on serum tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), IL-6, IL-1β and serum cystatin C (Cys-C) in patients of chronic obstructive pulmonary disease (COPD) at the stable stage. Method: Totally 120 cases of COPD treated at Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from September 2017 to March 2018 conformed to the inclusion criteria, and were randomly divided into treatment group (60 cases) and control group (60 cases). Cases of control group received Tiotropium (18 μg/time, qd). In addition to the therapy of control group, cases of treatment group were also given Buzhong Yiqi Tang and PLB. Both groups were treated for 6 months. Percent of forced expiratory volume in one second in predicted value (FEV1%), ratio of FEV1 to forced vital capacity (FEV1/FVC), six-minute walk distance (6MWD),TNF-α, IL-8, IL-6, IL-1β and Cys-C were compared between both groups. Result: After treatment, the clinical efficacy rate of observation group was 93.33%, which was evidently higher than 86.67%of control group (Pa,IL-8, IL-6,IL-1β, Cys-C but increases in FEV1%, FEV1/FVC (Pa, IL-8, IL-6, IL-1β, Cys-C but increases in FEV1%, FEV1/FVC (PConclusion: Buzhong Yiqi Tang and PLB has an anti-inflammatory effect on COPD by reducing levels of inflammation cytokines TNF-α, IL-8,IL-6, IL-1β and chronic inflammation markers serum Cys-C and inflammatory reaction, and alleviating airflow obstruction, promoting the levels of FEV1%, FEV1/FVC, pulmonary function control inflammatory factors, so as to improve pulmonary function and the quality of life in patients with COPD.

The Anti-Inflammatory Properties of Citrus wilsonii Tanaka Extract in LPS-Induced RAW 264.7 and Primary Mouse Bone Marrow-Derived Dendritic Cells.

'Zhique' (Citrus wilsonii Tanaka) is a traditional Chinese medicine. Its fruits have been used to treat inflammation-related symptoms, such as cough and sputum, though the underlying mechanism remains poorly understood. The aim of this study was to investigate the anti-inflammatory properties of 'Zhique' pulp extract (ZQE) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and primary mouse bone marrow-derived dendritic cells (BMDCs). The flavonoid profiles of the ZQE were determined by high performance liquid chromatography. The anti-inflammatory activity was evaluated in LPS-induced inflammatory RAW 264.7 macrophages and BMDCs through enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and Western blot assays. Naringin was a predominant flavonoid occurring in ZQE, followed by eriocitrin, hesperidin, neohesperidin, rhoifolin, naringenin, and poncirin. ZQE exhibited a very low cytotoxicity in LPS-stimulated RAW 264.7 macrophages. Meanwhile, ZQE significantly inhibited the production of prostaglandins E2 and secretion of cyclooxygenase-2 protein in LPS-stimulated RAW 264.7 macrophages, and markedly suppressed the mRNA expression of inflammatory mediators, such as cyclooxygenase-2, tumor necrosis factor alpha, interleukin-1 beta (IL-1ß), and IL-6 in LPS-induced RAW 264.7 macrophages and/or primary BMDCs. The ZQE inhibited the inflammatory responses in RAW 264.7 macrophages and BMDCs triggered by LPS. The results suggested that 'Zhique' has a high potential as a novel therapeutic agent to treat chronic inflammatory diseases.

Polycyclic Polyprenylated Derivatives from Hypericum uralum: Neuroprotective Effects and Antidepressant-like Activity of Uralodin A.

The isolation of the new polycyclic polyprenylated acylphloroglucinols uraliones A-K (1-11) together with five known analogues (12-16) from a whole Hypericum uralum plant was reported. The structures of these compounds were established through spectroscopic methods, and a single-crystal X-ray diffraction analysis was used to confirm the absolute configuration of 1. The protective effects of the isolates against corticosterone-induced PC12 cell injury were assessed. Except for compound 9, all tested compounds exhibited significant protective effects against induced injury in PC12 cells. Uralodin A (14), orally administered in doses of 13 and 26 mg/kg, exhibited antidepressant-like activity in the tail suspension and forced-swimming tests in mice.

Discovery of xanthine oxidase inhibitors and/or α-glucosidase inhibitors by carboxyalkyl derivatization based on the flavonoid of apigenin.

Three series of apigenin derivatives have been prepared by coupling the carboxyl alkyl group to 4'-, 5- or 7-hydroxyl groups of apigenin respectively. Preliminary biological evaluation in vitro revealed that xanthine oxidase inhibitory activity was improved by modifications at 4'-position and decreased by similar modifications at 5-, 7-positions while α-glucosidase inhibitory activity was maintained by modifications at 5-, 7-positions but lost by modifications at 4'-position. Administration (ip) of 7e markedly lowered serum uric acid levels in potassium oxonate induced hyperuricemic mouse model and administration (p.o.) of 11d or 11e effectively suppressed the elevation of serum glucose in the oral sucrose tolerance test in mice, while apigenin were not significantly effective in both tests.

Effects of Schisandra chinensis extracts on cough and pulmonary inflammation in a cough hypersensitivity guinea pig model induced by cigarette smoke exposure.

Schisandra chinensis (S. chinensis) is a traditional Chinese medicine commonly used in prescription medications for the treatment of chronic cough. However, the material basis of S. chinensis in relieving cough has not been completely elucidated yet. This study established a guinea pig model of cough hypersensitivity induced by 14 days of cigarette smoke (CS) exposure, to evaluate the antitussive, antioxidant, and anti-inflammatory effects of three S. chinensis extracts. And then the function of four lignans in reducing expression of TRPV1 and TRPA1 was examined using A549 cells induced by cigarette smoke extract (CSE). The results demonstrated that both ethanol extract (EE) and ethanol-water extract (EWE) of S. chinensis, but not water extract (WE), significantly reduced the cough frequency enhanced by 0.4M citric acid solution in these cough hypersensitivity guinea pigs. Meanwhile, pretreatment with EE and EWE both significantly attenuated the CS-induced increase in infiltration of pulmonary neutrophils and total inflammatory cells, as well as pulmonary MDA, TNF-α, and IL-8, while remarkably increased activities of pulmonary SOD and GSH. According to H&E and immunofluorescence staining assays, airway epithelium hyperplasia, smooth muscle thickening, inflammatory cells infiltration, as well as expression of TRPV1 and TRPA1, were significantly attenuated in animals pretreatment with 1g/kg EE. Moreover, four lignans of EE, including schizandrin, schisantherin A, deoxyschizandrin and γ-schisandrin, significantly inhibited CSE-induced expression of TRPV1, TRPA1 and NOS3, as well as NO release in A549 cells. In conclusion, S. chinensis reduces cough frequency and pulmonary inflammation in the CS-induced cough hypersensitivity guinea pigs. Lignans may be the active components.

Effects of nitrogen and phosphorus on arsenite accumulation, oxidation, and toxicity in Chlamydomonas reinhardtii.

We studied arsenite (iAs(III)) accumulation, oxidation, and toxicity in the freshwater green alga Chlamydomonas reinhardtii under nutrient-enriched (+NP), phosphorus-limited (-P), and nitrogen-limited (-N) conditions. The -P alga (55.1 µM) had a Michaelis constant (Kd) for uptake approximately one tenth of the +NP (419 µM) and -N (501 µM) cells, indicating iAs(III) uptake inhibition by extracellular phosphate. This conclusion was supported by the hyperbolic reduction in iAs(III) uptake rate (V) from 9.2 to 0.8 µmol/g-dw/h when the extracellular phosphate concentration went up from 0 to 250 µM. The maximal iAs(III) uptake rate (Vmax) of the -N alga (24.3 µmol/g-dw/h) was twice as much as that of the +NP (12 µmol/g-dw/h) and -P (8.1 µmol/g-dw/h) cells. It implies that more arsenic transporters were synthesized under the -N condition. Once accumulated, iAs(III) was oxidized and a higher proportion of arsenate (iAs(V)) was observed at lower [As]dis or under nutrient-limited conditions. Nevertheless, iAs(III) oxidation mainly occurred outside the cells with the extent of oxidation reciprocal to [As]dis. Based on the logistic modeling of the concentration-response curves in the +NP, -P, and -N toxicity tests, iAs(III) had an [As]dis-based EC50 of 1763, 13.1, and 1208 µM and an intracellular arsenic concentration based EC50 of 35.6, 28.8, and 195 µmol/g-dw, respectively. Higher iAs(III) toxicity to the -P cells occured because of their increased iAs(III) accumulation, whereas the underlying mechanisms why the -N alga was more tolerant need to be further revealed. Overall, both N and P had remarkable effects on the behavior and effects of iAs(III), which cannot be disregarded in the biogeochemical cycling research of arsenic.

Cytotoxic polycyclic polyprenylated acylphloroglucinols from Hypericum attenuatum.

Six new polycyclic polyprenylated acylphloroglucinols, attenuatumiones A-F (1-6), together with twelve known analogs (7-18) were isolated from the whole plant of Hypericum attenuatum. Their structures were elucidated by spectroscopic methods, and the absolute configuration of C-13 in attenuatumione C (3) was deduced via the circular dichroism datum of the in situ formed [Rh2(OCOCF3)4] complexes. All isolates were evaluated for the cytotoxic activities on three human cancer cell lines. Compound 3 showed moderate cytotoxic activities with IC50 values of 10.12 and 10.56 µM against SMMC7721 and U2OS, respectively.