Effects Of Panax Notoginseng Saponins Research Articles

Panax notoginseng Saponins Ameliorate Gamma Radiation-Mediated Damages in Human Peripheral Blood Monocytes and Swiss Albino Mice.

In this study, the protective effects of Panax notoginseng saponins (PNS) against gamma radiation-induced DNA damage and associated physiological alterations in Swiss albino mice were investigated. Exposure to gamma radiation led to a dose-dependent increase in cytokinesis-blocked micronuclei (CBMN) double-strand DNA breaks (DSBs), dicentric aberrations (DC), formation in peripheral blood mononuclear cells. However, pretreatment with PNS at concentrations of 1, 5, and 10 µg/mL significantly attenuated the frequencies of DC and CBMN in a concentration-dependent manner. PNS administration before radiation exposure also reduced radiation-induced DSBs in BL, indicating protection against reactive oxygen species generation and DNA damage. Notably, pretreatment with PNS at 10 µg/mL prevented the overexpression of γ-H2AX, proteins associated with DNA damage response, in irradiated mice. In addition, in vivo studies showed intraperitoneal administration of PNS (25 mg/kg body weight) for 1 h before radiation exposure mitigated lipid peroxidation levels and restored antioxidant status, countering oxidative damage induced by gamma radiation. Furthermore, PNS pretreatment reversed the decrease in hemoglobin (Hb) content, white blood cell count, and red blood cell count in irradiated mice, indicating preservation of hematological parameters. Overall, PNS demonstrated an anticlastogenic effect by modulating radiation-induced DSBs and preventing oxidative damage, thus highlighting its potential as a protective agent against radiation-induced DNA damage and associated physiological alterations. Clinically, PNS will be beneficial for cancer patients undergoing radiotherapy, but their pharmacological properties and toxicity profiles need to be studied.

Effects of Panax notoginseng saponins on alleviating low shear induced endothelial inflammation and thrombosis via Piezo1 signalling

Ethnopharmacological relevancePanax notoginseng saponins (PNS) are the major effective components of Panax notoginseng (burk) F.H.Chen which is one of the classic promoting blood circulation herbs in traditional Chinese medicine. PNS is widely used in China for the treatment of cerebral ischemic stroke. Pathological low shear stress is a causal factor in endothelial inflammation and thrombosis. However, the mechanism of PNS against low shear related endothelial inflammation is still unclear. Aim to the studyThis study aims to investigate the effects of PNS against endothelial inflammation induced by low shear stress and to explore the underlying mechanical and biological mechanisms. Materials and methodsMouse model of carotid partial ligation for inducing low endothelial shear stress was established, the pharmacodynamic effect and mechanism of PNS against endothelial inflammation induced by low shear stress through Piezo1 were explored. Yoda1-evoked Piezo1 activation and expression in human umbilical vein endothelial cells (HUVECs) were determined at static condition. Microfluidic channel systems were used to apply shear stress on HUVECs and Piezo1 siRNA HUVECs to determine PECAM-1, p-YAP and VCAM-1 expression. And platelet rich plasma (PRP) was introduced to low shear treated endothelial cells surface to observe the adhesion and activation by fluorescence imaging and flowcytometry. ResultsPNS attenuated endothelial inflammation and improved blood flow in a reasonable dose response pattern in carotid partial ligation mouse model by influencing Piezo1 and PECAM-1 expression, while suppressing yes-associated protein (YAP) nuclear translocation. We found Piezo1 sensed abnormal shear stress and transduced these mechanical signals by different pathways in HUVECs, and PNS relieved endothelial inflammation induced by low shear stress through Piezo1. We also found Piezo1 signalling has interaction with PECAM-1 under low shear stress, which were involved in platelets adhesion to endothelial cells. Low shear stress increased YAP nuclear translocation and increased VCAM-1 expression in HUVECs which might activate platelets. PNS inhibited low shear induced Piezo1 and PECAM-1 expression and YAP nuclear translocation in HUVECs, furthermore inhibited platelet adhesion and activation on dysfunctional endothelial cells induced by low shear stress. ConclusionPNS ameliorated endothelial inflammation and thrombosis induced by low shear stress through modulation of the Piezo1 channel, PECAM-1 expression, and YAP nuclear translocation. PNS might serve as a potential therapeutic candidate for ameliorating endothelial inflammation induced by abnormal blood shear stress.

The Synergistic Effect of Panax Notoginseng Saponins and Nicotinamide Mononucleotides on Anticoagulant

The Synergistic Effect of Panax Notoginseng Saponins and Nicotinamide Mononucleotides on Anticoagulant

Effects of Panax notoginseng Saponins Encapsulated by Polymerized Whey Protein on the Rheological, Textural and Bitterness Characteristics of Yogurt

Panax notoginseng saponins (PNSs) have been used as a nutritional supplement for many years, but their bitter taste limits their application in food formulations. The effects of PNS (groups B, C, and D contained 0.8, 1.0 and 1.2 mg/mL of free PNS, respectively) or Panax notoginseng saponin-polymerized whey protein (PNS-PWP) nanoparticles (groups E, F, and G contained 26.68, 33.35 and 40.03 mg/mL of PNS-PWP nanoparticles, respectively) on the rheological, textural properties and bitterness of yogurt were investigated. Group G yogurt showed a shorter gelation time (23.53 min), the highest elastic modulus (7135 Pa), higher hardness (506 g), higher apparent viscosity, and the lowest syneresis (6.93%) than other groups, which indicated that the yogurt formed a stronger gel structure. The results of the electronic tongue indicated that the bitterness values of group E (−6.12), F (−6.56), and G (−6.27) yogurts were lower than those of group B (−5.12), C (−4.31), and D (−3.79), respectively, which might be attributed to PNS being encapsulated by PWP. The results indicated that PWP-encapsulated PNS could cover the bitterness of PNS and improve the quality of yogurt containing PNS.

Anti-aging Effect of Panax notoginseng Saponins via Protecting Endogenous Antioxidant in Fruit Flies

Anti-aging Effect of Panax notoginseng Saponins via Protecting Endogenous Antioxidant in Fruit Flies

Efficacy and Safety of Panax notoginseng Saponins in the Treatment of Adults With Ischemic Stroke in China

Preclinical and clinical studies have suggested the neuroprotective effect of Panax notoginseng saponins (Xuesaitong soft capsules). However, robust evidence in patients with ischemic stroke is lacking. To assess the efficacy and safety of Xuesaitong soft capsules in patients with ischemic stroke. This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 67 tertiary health centers in China from July 1, 2018, to June 30, 2020. Included patients were aged 18 to 75 years with a diagnosis of ischemic stroke and a National Institutes of Health Stroke Scale score between 4 and 15. Eligible patients were randomly assigned within 14 days after symptom onset to receive either treatment with Xuesaitong soft capsules (120 mg orally twice daily) or placebo (120 mg orally twice daily) for 3 months. The primary outcome was functional independence at 3 months, defined as a modified Rankin Scale score of 0 to 2. Among 3072 eligible patients with ischemic stroke who were randomized, 2966 (96.5%) were included in the modified intention-to-treat cohort (median [IQR] age, 62 [55-68] years; 1982 male [66.8%]). The number of patients who achieved functional independence at 3 months was 1328 (89.3%) in the Xuesaitong group and 1218 (82.4%) in the control group (odds ratio, 1.95; 95% CI, 1.56-2.44; P < .001). In the safety cohort, serious adverse events occurred in 15 of 1488 patients (1.0%) in the Xuesaitong group and 16 of 1482 (1.1%) in the control group (P = .85). In this randomized clinical trial, Xuesaitong soft capsules significantly increased the likelihood of functional independence at 3 months in patients with ischemic stroke, indicating that this may be a safe and effective alternative therapy to improve prognosis in this population. Chinese Clinical Trial Registry Identifier: ChiCTR1800016363.

Self-Double-Emulsifying Drug Delivery System Enteric-Coated Capsules: A Novel Approach to Improve Oral Bioavailability and Anti-inflammatory Activity of Panax notoginseng Saponins.

In this work, self-double-emulsifying drug delivery system enteric-coated capsules (PNS-SDE-ECC) were used to enhance the oral bioavailability and anti-inflammatory effects of Panax notoginseng saponins (PNS), which are rapidly biodegradable, poorly membrane permeable, and highly water-soluble compounds. The PNS-SDEDDS formulated by a modified two-step method spontaneously emulsified to W/O/W double emulsions in the outer aqueous solution, which significantly promoted the absorption of PNS in the intestinal tract. The release study revealed that PNS-SDE-ECC exhibited sustained release of PNS within 24h and the stability study indicated that PNS-SDE-ECC were stable at room temperature for up to 3months. Furthermore, compared to PNS gastric capsules, the relative bioavailability of NGR1, GRg1, GRe, GRb1, and GRd in PNS-SDE-ECC was increased by 4.83, 10.78, 9.25, 3.58, and 4.63 times, respectively. More importantly, PNS-SDE-ECC significantly reduced OXZ-induced inflammatory damage in the colon by regulating the expression of TNF-α, IL-4, IL-13, and MPO cytokines. Overall, the prepared PNS-SDE-ECC may serve as a viable vehicle for increasing the oral bioavailability of PNS and its anti-inflammatory action on ulcerative colitis.

Study on the regulatory effect of Panax notoginseng saponins combined with bone mesenchymal stem cell transplantation on IRAK1/TRAF6-NF-κB pathway in patients with diabetic cutaneous ulcers

Panax notoginseng saponins (PNSs) have been found as the major active ingredient of Panax notoginseng (Burkill) F.H.Chen (PN) leaves, which has the effect of reducing inflammatory response, facilitating fibroblast proliferation, as well as promoting angiogenesis. This study aimed to investigate the molecular basis of PNS combined with bone mesenchymal stem cells (BMSCs) for treating diabetic cutaneous ulcers (DCU) and its mechanism of action. Methods. A total of 75 SD rats were selected to make diabetic cutaneous ulcers model. According random number table method, the rats were randomly divided into a control group, a DCU group, a BMSCs group, a PNS group and BMSCs + PNS group. Five groups of rats were given without treatment. After being treated for 7 days, the rats were anesthetized with pentobarbital, and granulation tissue was collected from the central point of the wound. They were used for pathological analysis, Western blot (WB) and polymerase chain reaction (PCR) assays. Results. The wound healing area was the largest in the BMSCs + PNS group. HE staining results showed that the PNS + BMSCs group could promote the formation of new epidermis and reduce the infiltration of inflammatory cells. Immunohistochemistry (IHC) results showed that the PNS + BMSCs group could up-regulate the expression of Ki67 protein and cell proliferation. In addition, PNS combined with BMSCs up-regulated the expression of miR-146-5p and down-regulated the expression of IL-1β, IL-6 and TNF-α, IRAK1, TRAF6 and p65 in the NF-κB signaling pathway (p < 0.05). Conclusions. PNS combined with bone mesenchymal stem cell transplantation up-regulated miR-146a-5p targeting and binding to IRAK1/TRAF6, inhibiting the activation of NF-κB pathway, which reduced the inflammatory response of DCU and facilitated the skin healing of DCU. Thus, this study provides a theoretical basis and a novel therapeutic option for the treatment of DFU with PNS combined with BMSCs.

Evaluation on the Efficacy and Safety of Panax Notoginseng Saponins in the Treatment of Stroke among Elderly People: A Systematic Review and Meta-Analysis of 206 Randomized Controlled Trials.

Evidence regarding the effect of Panax notoginseng saponins (PNS) on treating elderly stroke patients is scare and inconsistent. This study investigated the efficacy and safety of PNS by means of meta-analysis so as to provide an evidence-based reference for the treatment of elderly patients with stroke. We searched the PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, Wanfang, and China Biomedical Database to identify the eligible randomized controlled trials (RCTs) concerning using PNS to treat elderly people with stroke from their inception to first, May 2022. Meta-analysis was used for pool analysis of the included studies, whose quality was assessed via Cochrane Collaboration's RCT risk of bias tool. Altogether 206 studies published between 1999 and 2022 with a low risk of bias were included, covering 21,759 participants. The results showed that the improved neurological status shown in the intervention group with PNS alone was statistically significant (SMD = -0.826, 95% CI: -0.946 to -0.707) in contrast to the control group. The total clinical efficacy (Relative risk (RR) = 1.197, 95% Confidence interval (CI): 1.165 to 1.229) and daily living activities (SMD = 1.675, 95% C: 1.218 to 2.133) of elderly stroke patients were significantly improved as well. In addition, the invention group using PNS combined with WM/TAU displayed significant improvement in neurological status (SMD = -1.142, 95% CI: -1.295 to -0.990) and the total clinical efficacy (RR = 1.191, 95% CI: 1.165 to 1.217) compared with the control group. Single PNS intervention or PNS combined with WM/TAU significantly improves the neurological status, the overall clinical efficacy and daily living activities of elderly stroke patients. However, more multicenter RCT research with high quality is required in the future to verify the results in this study. The trial registration number: Inplasy protocol 202330042. doi:10.37766/inplasy2023.3.0042.

Retraction Note: Effects of Panax notoginseng saponins on severe acute pancreatitis through the regulation of mTOR/Akt and caspase-3 signaling pathway by upregulating miR-181b expression in rats

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12906-018-2118-8.

Effects of panax notoginseng saponins on pulmonary vascular remodeling in rats with pulmonary hypertension and its mechanisms

Objective: To investigate the effects of panax notoginseng saponins (PNS) on pulmonary vascular remodeling and SIRT1/FOXO3a/p27 pathway in pulmonary arterial hypertension (PAH) rats. Methods: Male SD rats weighing 200~250g were randomly divided into control group, monocrotaline group (MCT) and monocrotaline + panax notoginseng saponins group (MCT+PNS), with 10 rats in each group. The rats in control group were injected intraperitoneally with normal saline 3 ml/kg on the first day, then injected intraperitoneally with normal saline 2.5 ml/kg every day. The rats in MCT group were injected intraperitoneally with MCT 60 mg/kg on the first day, followed by daily injection of normal saline 2.5 ml/kg. In MCT+PNS group, 60 mg/kg MCT was injected intraperitoneally on the first day, and 50 mg/kg PNS was injected intraperitoneally every day. The above models were fed conventionally for 4 weeks. After the modeling was completed, the mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) of rats in each group were detected by right heart catheter method, weighed and calculated right ventricular hypertrophy index (RVHI), and the pulmonary vascular structure and morphological changes were observed by HE and Masson staining. The protein and gene expressions of SIRT1, FOXO3a, p27, PCNA and Caspase-3 were detected by qPCR and Western blot. Results: Compared with control group, mPAP, RVSP and RVHI in MCT group were increased significantly (P＜0.01), pulmonary vessels were thickened significantly and collagen fibers were increased, protein and gene expressions of SIRT1, FOXO3a, p27 and Caspase-3 were decreased (P＜0.05 or P＜0.01). The protein and gene expressions of PCNA were increased (P＜0.05). Compared with MCT group, the levels of mPAP, RVSP and RVHI in MCT+PNS group were decreased significantly (P＜0.05 or P＜0.01), pulmonary vascular thickening was alleviated and collagen fibers were reduced. The protein and gene expressions of SIRT1, FOXO3a, p27 and Caspase-3 were increased (P＜0.05 or P＜0.01), while the protein and gene expressions of PCNA were decreased (P＜0.05 or P＜0.01). Conclusion: Panax notoginseng saponins can relieve pulmonary vascular remodeling in rats with pulmonary hypertension by activating SIRT1/FOXO3a/p27 pathway.

Analysis of the Renal Protection and Antioxidative Stress Effects of Panax notoginseng Saponins in Diabetic Nephropathy Mice.

Objective Diabetic nephropathy (DN), a diabetes-induced chronic complication, is the major trigger of end-stage renal disease. As the main active ingredient of Panax notoginseng (PNG), Panax notoginseng saponins (PNS) are crucial in treating renal diseases. This study is aimed at investigating the role played by PNS in renal protection and antioxidative stress (OS) in DN mice. Methods A DN mouse model was constructed, and then low, medium, and high doses of PNS were used to intervene the model group mice. Eight weeks after intervention, the 24 h urine protein (UPro) and urinary albumin (UAlb) were quantitatively examined, and the related blood biochemical indices were measured. HE and PAS staining were performed for pathological changes of renal tissue. ELISA and western blotting were carried out to quantify the levels of OS indexes and inflammatory factors (IFs) in mouse kidney tissues and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), respectively. Results The weight of DN mice decreased first compared with control animals and then gradually increased after different doses of PNS treatment. Besides, DN mice presented elevated urine volume, UPro, and UAlb, all of which were reversed by PNS intervention. SOD activity and GSH content in renal tissues of the model group mice decreased markedly versus the control group, and MDA, CRP, IL-6, and TGF-β1 contents elevated statistically, while different doses of PNS effectively reduced the OS injury and IFs in mice. Compared with the model group, PNS dose-dependently increased Nrf2 and HO-1 levels in DN mice. Conclusions PNS is protective of HFF + STZ-induced DN mice against kidney tissue damage and can reduce the excretion of UPro and relieve the OS state of mice, possibly by activating Nrf2/HO-1 axis to play an antioxidant and anti-inflammatory role.

Panax Notoginseng Saponins Combined with Dual Antiplatelet Drugs Potentiates Anti-Thrombotic Effect with Alleviated Gastric Injury in A Carotid Artery Thrombosis Rat Model

ObjectiveTo observe the combination effects of Panax notoginseng saponins (PNS)and dual antiplatelet drugs (DAPT), and to explore the mechanism via cyclooxygenase /prostaglandin pathway. MethodsRight carotid artery thrombosis was induced in Wistar rats by infiltration with 70% FeCl3, and the animals were randomly divided into sham group, model group, DAPT group and PNS + DAPT group, intragastrically treated for 4 weeks. The cerebral pia mater microcirculation was observed in vivo after anesthetizing by anatomical microscope. The wet weight of carotid artery thrombosis was measured. Gastric mucosal injury was observed by hematoxylin and eosin staining. Platelet aggregation rate was detected with adenosine diphosphate -induced turbidimetry. Platelet CD62p expression was detected by flow cytometry. Concentrations of 6-Ketoprostaglandin F1 alpha, prostaglandin E2 in gastric mucosa and thromboxane B2, 6-Ketoprostaglandin F1 alpha, tissue plasminogen activator, plasminogen activator inhibitor, and fibrin fragment D in the plasma were measured by radioimmunoassay. ResultsPNS and DAPT increased the blood flow volume of cerebral pia mater and decreased erythrocyte aggregation and leukocyte adhesion of model rats. Compared to DAPT, PNS and DAPT further reduced the weight of carotid artery thrombosis with enhanced inhibition of platelet aggregation, increased tissue plasminogen activator levels and decreased fibrin fragment D levels. PNS and DAPT alleviated gastric injury induced by dual antiplatelet drugs and upregulated the expression of 6-Ketoprostaglandin F1 alpha in the gastric mucosa compared with DAPT. ConclusionsPNS combined with DAPT increased anti-thrombosis effects of DAPT and mitigated DAPT-related gastric injury. The underlying mechanisms may be associated with enhanced antiplatelet aggregation and activation of the fibrinolytic system and up-regulation of 6-Ketoprostaglandin F1 alpha expression in gastric mucosa.

Therapeutic effects of Panax notoginseng saponins in rheumatoid arthritis: network pharmacology and experimental validation

ABSTRACT Panax notoginseng saponins (PNS) have been reported to have good anti-inflammatory effects. However, the anti-inflammatory effect mechanism in rheumatoid arthritis (RA) remains unknown. The focus of this research was to investigate the molecular mechanism of PNS in the treatment of RA. The primary active components of PNS were tested utilizing the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Analysis Platform based on oral bioavailability and drug-likeness. The target databases for knee osteoarthritis were created using GeneCards and Online Mendelian Inheritance in Man (OMIM). The visual interactive network structure ‘active component – action target – illness’ was created using Cytoscape software. A protein interaction network was built, and associated protein interactions were analyzed using the STRING database. The key targets were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analyses. The effects of PNS on cell growth were studied in human umbilical vein endothelial cells (HUVECs) treated with various doses of PNS, and the optimum concentration of PNS was identified. PNS was studied for its implication on angiogenesis and migration. The active components of PNS had 114 common targets, including cell metabolism and apoptosis, according to the network analysis. The therapeutic effects of the PNS components were suggested to be mediated through apoptotic and cytokine signaling pathways. In vitro, PNS therapy boosted HUVEC proliferation. Wound healing, Boyden chamber and tube formation tests suggested that PNS may increase HUVEC activity and capillary-like tube branching. This study clarified that for the treatment of RA, PNS has multisystem, multicomponent, and multitargeted properties.

Therapeutic effect of Panax notoginseng saponins combined with cyclophosphamide in mice bearing hepatocellular carcinoma H22 cell xenograft

To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H22 cell xenograft. 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. 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). 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.

Effects and Mechanism of Action of Panax notoginseng Saponins on the Pharmacokinetics of Warfarin.

The interactions between Chinese herbs and drugs pose a great challenge to the combined clinical application of Chinese herbs and drugs. Chinese medicinal products contain complex pharmacologically active components that may influence the in vivo processes of drugs in a variety of ways. In China, drugs based on Panax ginseng total saponins (PNS) are often combined with warfarin for the treatment of cardiovascular diseases. To assess the effects of Panax notoginseng saponins (PNS) on the pharmacokinetics of warfarin and its mechanism. Blood was collected for the determination of the prothrombin time (PT) and international normalized ratio (INR) from rats treated with warfarin alone or with warfarin + PNS. The plasma concentration of warfarin was determined by high-performance liquid chromatography. Western blot was used to detect the expression of cytochrome P450 (CYP) enzymes. When warfarin and PNS were co-administered, the PT and INR increased compared to when warfarin was given alone. 72 hours after administration, compared to the warfarin alone group, the warfarin + low-dose PNS, warfarin + medium-dose PNS, and warfarin + high-dose PNS groups showed 110%, 122%, and 126% increases in PT, respectively (all P < 0.05), as well as 111%, 124%, and 128% increases in INR (all P < 0.05). Compared with the warfarin alone group, the clearance rate (CL/F) of warfarin in the warfarin + low-dose PNS, warfarin + medium-dose PNS, and warfarin + high-dose PNS groups was 10% (P > 0.05), 23% (P < 0.05), and 33% (P < 0.05) lower, respectively, while the systemic exposure (area under the concentration-time curve,AUC0-t) increased by 106% (P > 0.05), 119% (P < 0.05), and 134% (P < 0.05), respectively, and the blood concentration of warfarin incresed by 112%, 113%, and 114%, respectively (all P > 0.05). After combined treatment of HepG2 cells with warfarin + PNS, CYP1A2 expression was upregulated (P < 0.05) and CYP3A4 was downregulated (P < 0.05) but there was no effect on CYP2C9. In animal experiments, PNS had different effect on the expression of CYP1A2 in different doses. While a low dose of PNS resulted in downregulated CYP1A2 expression (P < 0.05), a medium dose resulted in upregulation (P < 0.05), and CYP1A2 expression was not significantly affected by a high dose of PNS (P > 0.05). Meanwhile, PNS at all doses downregulated the expression of CYP3A4 (P < 0.05) but had no effect on the expression of CYP2C9 (P > 0.05). PNS can increase the blood concentration of warfarin, as well as the exposure time, and it can enhance the anticoagulant effect of warfarin by inhibiting the expression of the liver enzyme CYP3A4.

Panax notoginseng saponins induce apoptosis in retinoblastoma Y79 cells via the PI3K/AKT signalling pathway

This study aimed to investigate the effects of Panax notoginseng saponins (PNS) on the proliferation, apoptosis, and PI3K/AKT signalling pathways of retinoblastoma Y79 cells to explore the possible mechanism of action of PNS on retinoblastoma. The effects of PNS and carboplatin on the proliferation of Y79 cells were examined using cell counting kit-8 assay. And the apoptosis rate, the mRNA and protein levels of apoptosis-related genes and the expression of PI3K/AKT pathway protein were assessed. PNS effectively inhibited the proliferation (P < 0.05) and increased apoptosis of Y79 cells (P < 0.05). Compared with the negative control, the Y79 cells treated with PNS had significantly increased (P < 0.05) mRNA and protein expression of Bax, caspase-3, caspase-8, and caspase-9 and elevated levels of cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 proteins (P < 0.05). The mRNA and protein expression of the apoptosis suppressor gene Bcl-2 was inhibited (P < 0.05), while the Bax/Bcl-2 values of the cells in the drug group were significantly higher than those in the negative group (P < 0.01). After treatment with PNS, the total protein expression of PI3K and AKT1 in the Y79 cells did not show significant differences compared with the negative group (P > 0.05), although the expression of phosphorylated proteins p-PI3K, p-AKT (Thr308), p-AKT (Ser473), and p-mTOR were significantly reduced (P < 0.05). Meanwhile, the antagonist protein of the pathway phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression was increased (P < 0.01). Cellular alterations following inhibition of the PI3K/AKT pathway using LY294002 were similar to those of PNS, the proliferation of Y79 cells was also inhibited, and cell apoptosis increased (P < 0.001). The expression of Bax, caspase-3, caspase-8, caspase-9, and activation proteins cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 was also significantly higher than that in the negative control (P < 0.05). Bcl-2 protein expression was decreased (P < 0.01), and the Bax/Bcl-2 ratio was higher than that in the negative control (P < 0.001). Overall, we demonstrated that PNS effectively inhibited the proliferation and promoted the apoptosis of retinoblastoma Y79 cells. The apoptosis-promoting effect of PNS may involve the inhibition of the PI3K/AKT signalling pathway, which subsequently regulates the expression of apoptosis-related genes.

Effects of Panax notoginseng Saponin on Neurons Based on Oxygen-Glucose Deprivation/Reoxygenation after Focal Cerebral Ischemia

We aimed to evaluate the effects of Panax notoginseng saponin on neuronal apoptosis and neuroprotection based on oxygen-glucose deprivation/reoxygenation in rats with focal cerebral ischemia. 100 rats were randomly divided into sham operation, middle cerebral artery occlusion model, low-dose Panax notoginseng saponin (10 mg/kg), medium-dose Panax notoginseng saponin (25 mg/kg) and high-dose Panax notoginseng saponin (50 mg/kg) groups. The model of focal cerebral ischemia was established by middle cerebral artery occlusion. For sham group, the right common, external and internal carotid arteries were only dissociated, without ligation or insertion. After modeling, Panax notoginseng saponin groups were intraperitoneally injected with Panax notoginseng saponin. Hippocampal neurons isolated from normal rats were randomly divided into control, oxygen-glucose deprivation/reoxygenation model, 1 μmol/l, 5 μmol/l and 20 μmol/l oxygen-glucose deprivation/reoxygenation+Panax notoginseng saponin groups. Neurological function was scored by Longa method and neuron morphology was observed. Neuronuclear antigen and neuroepithelial stem protein in brain tissues were detected by immunohistochemistry. The survival rate of neurons, lactate dehydrogenase leakage, neuronal apoptosis and expression levels of protein kinase B, phosphorylatedprotein kinase B and apoptosis-related proteins B-cell lymphoma 2, Bcl-2-associated X protein and caspase-3 were examined by cell counting kit-8 assay, lactate dehydrogenase kit, Hoechst 33 342 staining and Western blotting, respectively. Compared with model group, Panax notoginseng saponin groups had significantly lower neurological function scores (p<0.05). Panax notoginseng saponin significantly relieved neuronal injury and increased neuronuclear and neuroepithelial stem protein-positive cells (p<0.05). It significantly raised the survival rate of neurons, reduced lactate dehydrogenase leakage and inhibited neuronal apoptosis dose-dependently. Panax notoginseng saponin up-regulated the protein expressions of phosphorylated-protein kinase B/protein kinase B and B-cell lymphoma 2 and down-regulated those of Bcl-2-associated X protein and caspase-3 dose-dependently. It can protect against and repair neuronal injury caused by oxygen-glucose deprivation/reoxygenation, probably by activating the phosphatidylinositol 3-kinase/protein kinase B signaling pathway to suppress neuronal apoptosis.

Effect of Panax notoginseng Saponins on Atherosclerosis with Type 2 Diabetes Mellitus in Goto-Kakizaki Rats by Nuclear Factor-Kappa B Signaling Pathway

To explore the effect of Panax notoginseng saponins on atherosclerosis with type 2 diabetes mellitus in Goto-Kakizaki rats by nuclear factor-kappa B signaling pathway. Goto-Kakizaki rats fed with high fat diet and injected with N-nitro-L-arginine methyl ester for 8 w, were randomized into model group and Panax notoginseng saponins group (400 mg/kg/d). Another Goto-Kakizaki rats and Wistar rats were selected as Goto-Kakizaki group and control group which fed with normal diet and injected with saline. Serum lipid and inflammatory factors were measured. There were no statistical differences of lipid profiles between model group and Panax notoginseng saponins group (p>0.05). In Panax notoginseng saponins group, serum tumor necrosis factor-alpha, interleukin-6, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 were significantly decreased (p<0.01), messenger RNA expression and protein levels of interleukin-6, tumor necrosis factor-alpha, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemotactic protein-1 and nuclear factor-kappa B in the Panax notoginseng saponins group were significantly lower, compared with those in model group (p<0.05, p<0.01). Some inflammatory factors in model group were higher than those in Goto-Kakizaki group which were higher than those in control group. The inflammatory reaction with nuclear factorkappa B signaling pathway as core, occurs throughout type 2 diabetes mellitus and its atherogenesis and Panax notoginseng saponins improves nuclear factor-kappa B signaling pathway, decreasing its related inflammatory factors to achieve an improvement in the diabetic atherosclerotic process.

Regulatory effect of Panax notoginseng saponins on the oxidative stress and histone acetylation induced by porcine circovirus type 2.

Porcine circovirus type 2 (PCV2) exists widely in swine populations worldwide, and healthy PCV2 virus carriers have enhanced the severity of the infection, which is becoming more difficult to control. This study investigated the regulatory effect of Panax notoginseng saponins (PNS) on the oxidative stress and histone acetylation modification induced by PCV2 in vitro and in mice. In vitro, PNS significantly increased the scavenging capacities of superoxide anion radicals (O2•-) and hydroxyl radicals (•OH) and reduced the content of hydrogen peroxide (H2O2) induced by PCV2 in porcine alveolar macrophages (3D4/2). In addition, PNS decreased the protein expression level of histone H4 acetylation (Ac-H4) by increasing the activity of histone deacetylase (HDAC) in PCV2-infected 3D4/2 cells. In vivo, PNS enhanced the scavenging capacities of •OH and O2•− and reduced the content of H2O2 in the spleens of PCV2-infected mice. PNS also reduced the protein expression level of histone H3 acetylation (Ac-H3) by reducing the activity of histone acetylase (HAT) and increasing the activity of HDAC in the spleens of PCV2-infected mice. PCV2 infection activated oxidative stress and histone acetylation in vitro and in mice, but PNS ameliorated this oxidative stress. The research can provide experimental basis for exploring the antioxidant effect and the regulation of histone acetylation of PNS on PCV2-infected 3D4/2 cells and mice in vitro and in vivo, and provide new ideas for the treatment of PCV2 infection.