Prevention of Deep Vein Thrombosis by Panax Notoginseng Saponins Combined with Low-Molecular-Weight Heparin in Surgical Patients / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy of deep vein thrombosis (DVT) prevention among real-world surgical inpatients who received panax notoginseng saponins (PNS) combined with low-molecular-weight heparin (LMWH).@*METHODS@#A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital, Capital Medical University, Beijing, China. Participants received LMWH alone or PNS combined with LMWH for preventing DVT. The primary outcome was incidence of lower extremity DVT, which was screened once a week. Participants in the LMWH group were given LMWH (enoxaparin) via hypodermic injection, 4000-8000 AxalU once daily. Participants in the exposure group received PNS (Xuesaitong oral tablets, 100 mg, 3 times daily) combined with LMWH given the same as LMWH group.@*RESULTS@#Of the 325 patients screened for the study, 281 participants were included in the final analysis. The cohort was divided into PNS + LMWH group and LMWH group with 134 and 147 participants, respectively. There was a significant difference of DVT incidence between two groups (P=0.01), with 21 (15.7%) incident DVT in the PNS + LMWH group, and 41 (27.9%) incident DVT in the LMWH group. Compared with participants without DVT, the participants diagnosed with DVT were older and had higher D-dimer level. The multivariate logistic regression model showed a significant lower risk of incident DVT among participants in the PNS + LMWH group compared with the LMWH group (odds ratio 0.46, 95% confidence interval, 0.25-0.86). There were no significant differences in thromboelaslography values (including R, K, Angle, and MA) and differences in severe bleeding between two groups. No symptomatic pulmonary embolism occurred during the study.@*CONCLUSION@#Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy, without increased risk of bleeding.

Therapeutic effect of Panax notoginseng saponins combined with cyclophosphamide in mice bearing hepatocellular carcinoma H22 cell xenograft / 南方医科大学学报

OBJECTIVE@#To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H22 cell xenograft.@*METHODS@#We examined the effects of treatment with different concentrations of PNS on H22 cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H22 cells. Mouse models bearing H22 cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-α), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate.@*RESULTS@#Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H22 cells (P < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF-α and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% (P < 0.01) and a life prolonging rate of 131.25% in the mouse models (P < 0.05).@*CONCLUSION@#PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H22 tumor-bearing mice.

Total Saponins of Panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage / 中国结合医学杂志

OBJECTIVE@#To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons.@*METHODS@#The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway.@*RESULTS@#MTT showed that TSPN (50, 25 and 12.5 µ g/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 µ g/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 µ g/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 µ g/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-II/LC3B-I, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 µ g/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 µ g/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01).@*CONCLUSION@#TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.

Treatment of Chronic Aplastic Anemia with Chinese Patent Medicine Pai-Neng-Da Capsule () for Replacing Androgen Partially: A Clinical Multi-Center Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA).@*METHODS@#A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol.@*RESULTS@#The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case.@*CONCLUSION@#The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].

Panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation / 中国天然药物

Colorectal cancer (CRC) is the third most lethal cancer and leading cause of cancer mortality worldwide. A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease (IBD). It has been proved that Panax notoginseng saponins (PNS) have anti-inflammatory, anti-oxidant and anti-tumor effects. The chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer (CAC) have not been evaluated.This present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against CAC. Our study showed that PNS significantly alleviated colitis severity and prevented the occurrence of CAC. Functional assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO1 mediated directly by signal transducer and activator of transcription 1 (STAT1) rather than phosphorylated STAT1. Ultimately, Rh1, one of the PNS metabolites, exhibited the best inhibitory effect on IDO1 enzyme activity. Our study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on CAC. It could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of CAC. These findings provided a promising approach for CAC intervention.

Tribulus terrestris for female sexual dysfunction: a systematic review / Tribulus terrestris para disfunção sexual feminina: uma revisão sistemática

Abstract Objective We performed a systematic review to assess the effectiveness and safety of Tribulus terrestris to treat female sexual dysfunction (FSD). Data sources We performed unrestricted electronic searches in the MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL, PsycINFO,WHO-ICTR, Clinicaltrials.gov and OpenGrey databases. Selection of studies We included any randomized controlled trials (RCTs) that compared T. terrestris versus inactive/active interventions. After the selection process, conducted by two reviewers, 5 RCTs (n = 279 participants) were included. Data collection Data extraction was performed by two reviewers with a preestablished data collection formulary. Data synthesis Due to lack of data and clinical heterogeneity, we could not perform meta-analyses. The risk of bias was assessed by the Cochrane Risk of Bias (RoB) tool, and the certainty of evidence was assessed with Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Results After 1 to 3 months of treatment, premenopausal and postmenopausal women randomized to T. terrestris had a significant increase in sexual function scores. Three months of treatment with T. terrestris showed a significant increase in the serum testosterone levels of premenopausal women. There was no report of serious adverse events, and none of the studies assessed health-related quality of life. The certainty of the evidence was very low, whichmeans that we have very little confidence in the effect estimates, and future studies are likely to change these estimates. Conclusion MoreRCTs are needed to supportor refute the use of T. terrestris. The decision to use this intervention should be shared with the patients, and the uncertainties around its effects should be discussed in the clinical decision-making process. Number of Protocol registration in PROSPERO database: CRD42019121130

Resumo Objetivo Nós realizamos uma revisão sistemática para avaliar a efetividade e a segurança do Tribulus terrestris no tratamento da disfunção sexual feminina (DSF). Fontes de dados Nós realizados uma busca eletrônica irrestrita nas seguintes bases de dados: MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL, PsycINFO, WHO-ICTR, Clinicaltrials.gov, e OpenGrey. Seleção dos estudos Nós incluímos todos os ensaios clínico randomizados (ECR) que comparou T. terrestris com controles ativos/inativos. Após o processo de seleção, conduzido por 2 revisores, 5 ECRs (n = 279 participantes) foram incluídos. Extração de dados O processo de extração de dados foi realizado por dois revisores, utilizando-se um formulário de extração de dados pré-estabelecido. Síntese de dados Devido à falta de dados disponíveis e à heterogeneidade clínica entre os estudos incluídos, nós não realizamos meta-análises. O risco de viés foi avaliado pela tabela de risco de viés da Cochrane e, a certeza do corpo da evidência foi avaliada pelo Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Resultados Após 1 a três 3 meses de tratamento, mulheres na pré e pós-menopausa randomizadas ao T. terrestris tiveram um aumento significante nos escores de função sexual. O grupo com 3 meses de tratamento com T. terrestris exibiu um aumento significante dos níveis séricos de testosterona emmulheres pré-menopausa. Não houve relato de eventos adversos graves, e nenhum estudo avaliou qualidade de vida das participantes. A certeza da evidência foi considerada muito baixa, o que significa que existe pouca certeza na estimativa dos efeitos e que é provável que futuros estudos mudem estas estimativas. Conclusão Mais ECRs são importantes para apoiar ou refutar o uso do T. terrestris. A decisão de usar essa intervenção deve ser compartilhada com pacientes, e as incertezas sobre seus efeitos devem ser discutidas durante o processo de decisão clínica.

Antidiabetic effect of Momordica charantia saponins in rats induced by high-fat diet combined with STZ

Background: The harmful effects of type 2 diabetes mellitus and its complications have become a major global public health problem. In this study, the effects of Momordica charantia saponins (MCS) on lipid metabolism, oxidative stress, and insulin signaling pathway in type 2 diabetic rats were investigated. Results: MCS could attenuate the tendency of weight loss of the model rats. It could also improve glucose tolerance; reduce fasting blood glucose, nonesterified fatty acid, triglyceride, and total cholesterol; and increase the insulin content and insulin sensitivity index of the rats. The activity of superoxide dismutase and catalase increased, and the content of malondialdehyde decreased in the liver and pancreas tissues of rats in MCS-treated groups significantly. In addition, the expression of p-IRS-1 (Y612) and p-Akt (S473) increased, and the expression of p-IRS-1 (S307) decreased in the liver tissues and pancreas tissues of rats in MCS-treated groups significantly. Conclusion: MCS has an antidiabetic effect, which may be related to its improving the lipid metabolism disorder, reducing oxidative stress level, and regulating the insulin signaling pathway.

Ophiopogonin D of Ophiopogon japonicus ameliorates renal function by suppressing oxidative stress and inflammatory response in streptozotocin-induced diabetic nephropathy rats

Ophiopogonin D (OP-D) is the principal pharmacologically active ingredient from Ophiopogon japonicas, which has been demonstrated to have numerous pharmacological activities. However, its protective effect against renal damage in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats remains unclear. The present study was performed to investigate the protective effect of OP-D in the STZ-induced DN rat model. DN rats showed renal dysfunction, as evidenced by decreased serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-β1, and kidney hypertrophy, and these were reversed by OP-D. In addition, STZ induced oxidative damage and inflammatory response in diabetic kidney tissue. These abnormalities were reversed by OP-D treatment. The findings obtained in the present study indicated that OP-D might possess the potential to be a therapeutic agent against DN via inhibiting renal inflammation and oxidative stress.

Astragaloside Ⅳ inhibits inflammation after cerebral ischemia in rats through promoting microglia/macrophage M2 polarization / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effects of astragaloside Ⅳ (AS-Ⅳ) on microglia/macrophage M1/M2 polarization and inflammatory response after cerebral ischemia in rats.@*METHODS@#Forty eight male SD rats were randomly divided into sham operation control group, model control group and AS-Ⅳ group with 16 rats in each. Focal cerebral ischemia model was induced by occlusion of the right middle cerebral artery (MCAO) using the intraluminal filament. After ischemia induced, the rats in AS-Ⅳ group were intraperitoneally injected with 40 mg/kg AS-Ⅳ once a day for 3 days. The neurological functions were evaluated by the modified neurological severity score (mNSS) and the corner test on d1 and d3 after modelling. The infarct volume was measured by 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining on d3 after ischemia. The expression of M1 microglia/macrophage markers CD86, inducible nitric oxide synthase (iNOS) and pro-inflammatory factors TNF-α, IL-1β, IL-6, M2 microglia/macrophages markers CD206, arginase-1 (Arg-1), chitinase-like protein (YM1/2) and anti-inflammatory factors interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) was detected by real-time RT-PCR. The expression of CD16/32/Iba1 and CD206/Iba1 was determined by double labeling immunefluorescence method in the peripheral area of cerebral ischemia.@*RESULTS@#Compared with model control group, AS-Ⅳ treatment improved neurological function recovery and reduced infarct volume after ischemia (@*CONCLUSIONS@#The findings suggest that AS-Ⅳ ameliorates brain injury after cerebral ischemia in rats, which may be related to inhibiting inflammation through promoting the polarization of the microglia/macrophage from M1 to M2 phenotype in the ischemic brain.

Anti-inflammatory Activity of Butanolic Extract of Albizia lebbeck.

Albizia lebbeck is a tree widely distributed in India and is also found in South Africa, South America and Australia. As in Indian traditional system as folk medicine, this plant is used to treat several inflammatory pathologies such as asthma, arthritis and burns. Study of other species this same genus has demonstrated an anti-inflammatory activity of crude extract, which, in some work has been attributed to the presence of saponins. In order to confirm these findings a study of phytochemical profile was realized and a rich extract in saponins, butanolic extract, was obtained and its anti-inflammatory activity was evaluated through measured by inhibition of carrageenan-induced mouse paw oedema, using dexamethasone as reference compound. The extract exhibited a moderate control of the both phase of inflammation, provoking an inhibition of edema formation. However, the butanolic extract exhibited lesser activity than reference compound dexamethasone. The results obtained suggest a significant antiinflamatory property of the butanolic extract of Albizia lebbeck, justifying the use of this plant in the traditional medicine for the treatment of inflammatory conditions and confirm their saponins as bioactive product.

Anti-proliferative effect of leaf extracts of Eucalyptus citriodora against human cancer cells in vitro and in vivo.

Six different extracts from Eucalyptus citriodora leaves were investigated for their anticancer effect. Extracts were prepared using a range of polar and non-polar solvents to leach out maximum active components. Phytochemical analysis of the extracts revealed the presence of anthraquinones, cardiac glycosides, flavonoids, saponins and tannins. Cytotoxic activity of different extracts was tested in vitro against seven human cancer cell lines from seven different tissues, such as SW-620 (colon), HOP-62 (lung), PC-3 (prostate), OVCAR-5 (ovary), HeLa (cervix), IMR-32 (neuroblastoma) and HEP-2 (liver). The ethyl acetate, chloroform and 50% methanolic extract displayed highest anti-proliferative effect in a dose-dependent manner. In vivo anti-tumor activity was evaluated against murine tumor (solid) model of Ehrlich ascites carcinoma and Sarcoma 180. The results showed that ethyl acetate and aqueous extracts suppressed the growth of Ehrlich ascites carcinoma (29.79% and 18.48%, respectively), but showed little growth inhibition in case of Sarcoma 180 (13. 86% and 8.57%, respectively). The activity might be due to the flavonoids, tannins and saponins that are present in all the extracts of the plant. Further investigation is required for the isolation of active principle(s) from the ethyl acetate extract, which has shown significant in vitro and in vivo anticancer potential.

Protective effect of total aralosides of Aralia elata (Miq) Seem (TASAES) against diabetic cardiomyopathy in rats during the early stage, and possible mechanisms

Total aralosides of Aralia elata (Miq) Seem (TASAES) from Chinese traditional herb Longya Aralia chinensis L was found to improve cardiac function. The present study was to determine the protective effects of TASAES on diabetic cardiomyopathy, and the possible mechanisms. Therefore, a single dose of streptozotocin was used to induce diabetes in Wister rats. Diabetic rats were immediately treated with low, medium and high doses of TASAES at 4.9, 9.8 mg/kg and 19.6 mg/kg body weight by gavage, respectively, for eight weeks. Cardiac function was evaluated by in situ hemodynamic measurements, and patch clamp for the L-type Ca2+ channel current (ICa2+-L) and transient outward K+ channel current (Ito). Histopathological changes were observed under light and electron microscope. The expression of pro-fibrotic factor, connective tissue growth factor (CTGF) was monitored using immunohistochemistry staining. Compared with diabetic group, medium and high doses, but not low dose, of TASAES showed a significant protection against diabetes-induced cardiac dysfunction, shown by increased absolute value of left ventricular systolic pressure (LVSP) and maximum rates of pressure development (+/-dp/dt(max)), and enhanced amplitude of ICa2+-L (P < 0.05). Histological staining indicated a significant inhibition of diabetes-caused pathological changes and up-regulation of CTGF expression (P < 0.05). The results suggest that TASAES prevents diabetes-induced cardiac dysfunction and pathological damage through up-regulating ICa2+-L in cardiac cells and decreasing CTGF expression.

Neuroprotective Effect of Ginseng Total Saponins in Experimental Traumatic Brain Injury

In the present study, we investigated whether ginseng total saponins (GTSs) protect hippocampal neurons after experimental traumatic brain injury (TBI) in rats. A moderate-grade TBI was made with the aid of a controlled cortical impact (CCI) device set at a velocity of 3.0 m/sec, a deformation of 3.0 mm, and a compression time of 0.2 sec at the right parietal area for adult male Sprague-Dawley rats. Shamoperated rats that underwent craniectomy without impact served as controls. GTSs (100 and 200 mg/kg) or saline was injected intraperitoneally into the rats immediately post-injury. Twenty-four hours after the injury, the rats underwent neurological evaluation. Contusion volume and the number of hippocampal neurons were calculated with apoptosis evaluated by TUNEL staining. 24 hr post-injury, salineinjected rats showed a significant loss of neuronal cells in the CA2 region of the right hippocampus (53.4%, p<0.05) and CA3 (34.6%, p<0.05) compared with contralateral hippocampal region, a significant increase in contusion volume (34 +/-8microliter), and significant increase in neurologic deficits compared with the GTSs groups. Treating rats with GTSs seemed to protect the CCI-induced neuronal loss in the hippocampus, decrease cortical contusion volume, and improve neurological deficits.

Utilizaçäo do Pó de Joá como método alternativo na reduçäo do índice de placa bacteriana na escovaçäo dentária / Utilization of the juá's powder as alternative method in reduction of the index of the bacterial plaque in dental brush

Com o propósito de analisar comparativamente a reduçäo do índice de placa bacteriana em crianças, através do uso do Pó de Juá, foi realizado o presente trabalho. Para tal, foram utilizados 30 crianças na faixa de 7 a 12 anos, de ambos os sexos, divididos em 3 grupos numericamente iguais: G1(grupo controle - pasta), G2(grupo experimental - Pó de Juá + pasta) e G3(grupo experimental - Pó de Juá). O trabalho foi realizado e supervisionado por um único operador em crianças atentidas na Faculdade de Odontologia de Camilo Castelo Branco de acordo com os resultados obtidos, o Pó de Juá utilizado individualmente ou associado ao creme dental, säo fatores que seguramente agem na reduçäo do índice de placa(G.V.S.)