Gut microbiota: A new key of understanding for Panax notoginseng against multiple disorders and biotransformation.

The Gut Microbiome in Health and Disease

Transfer of Intestinal Microbiota From Lean Donors Increases Insulin Sensitivity in Individuals With Metabolic Syndrome

Comparative effectiveness of Panax notoginseng saponins-related agents and antiplatelet agents in ischemic stroke: A systematic review and network meta-analysis.

Objectives Chronic kidney disease (CKD) is a long-term condition characterized by poor prognosis and a high mortality rate. Panax notoginseng saponins (PNS) are the main active ingredient of the traditional Chinese herb Panaxnotoginseng(Burk.)F.H.Chen, which has been widely reported to have various pharmacological effects. Here, we examined the effect of PNS on renal function and the modulation of intestinal flora and intestinal barrier in a rat model of adenine-induced CKD. Methods Adenine was used to establish a rat model of CKD, biochemical testing, histopathologic examination, ELISA, immunohistochemical assay, western blot assay, and fecal microbiota 16s rRNA analysis was used to test the effect of PNS on CKD rats. Results Adenine induced a significant decrease in glomerular filtration rate, an increase in urinary protein excretion rate, and pathological damage to renal tissue in CKD rats. TNF-α, MCP-1, IL-1β, IL-18, TMAO, and endotoxin levels were increased in the blood of the model rats. Application of PNS countered the effects of adenine, restoring the above parameters to the level observed in healthy rats. In addition, activation of the inflammatory proteins NF-κB (p65) and NLRP3 and the fibrosis-associated proteins α-SMA and smad3 were inhibited in the kidneys of CKD rats. Furthermore, PNS promoted the expression of the tight junction proteins Occludin and ZO-1, increased SIgA levels, strengthened intestinal immunity, reduced mechanical damage to the intestine, was reduced levels of DAO and D-LA. Our data suggest PNS may delay CKD by restoring gut microbiota, and through the subsequent generation of a microbial barrier and modulation of microbiota metabolites. Conclusions In conclusion, PNS may inhibit the development of inflammation and fibrosis in the kidney tissue through regulation of intestinal microorganisms and inhibition of the activation of pro-inflammatory and pro-fibrotic proteins in the kidney.

Inhibiting adhesion events by Panax notoginseng saponins and Ginsenoside Rb1 protecting arteries via activation of Nrf2 and suppression of p38 – VCAM-1 signal pathway

ObjectiveWe investigated the effect of icariin (ICA) combined with Panax notoginseng saponins (PNS) on intestinal microbiota and hippocampal protein expression in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, a model of Alzheimer’s disease (AD).MethodsTransgenic mice were treated with icariin and PNS. The Morris water maze (MWM) was used to assess spatial memory, and the gut microbiota and differential protein expression in the hippocampus were investigated using high-throughput screening techniques. Differential protein expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.ResultsThe MWM results showed that the mice treated with the medium dose of ICA+PNS spent significantly more time in the target quadrant compared with the AD group. Bacterial diversity was the lowest in the AD group, with significantly greater diversity in the ICA + PNS treatment group. Three proteins were selected for proteomic analysis, and qRT-PCR and Western blot were used to detect the expression of 2ʹ-5ʹ-oligoadenylate synthetase ubiquitin like 1 (Oasl1), trichoplein keratin filament-binding protein (TCHP), and tumor necrosis factor receptor associated 3-interacting protein 1 (MIPT3). Compared with control mice, MIPT3 expression was increased and Oasl1 and TCHP were reduced in the AD group. These abnormal protein expressions tended to normalization after treatment with medium dose of ICA and PNS.ConclusionTreatment with ICA and PNS ameliorated memory impairment in an AD mouse model. The mechanisms may be related to modulation of the intestinal microbiota and expression of Oasl1, TCHP, and MIPT3.

Objective To investigate the effect of combined treatment with panax notoginseng saponins (PNS) and aminoguanidine (AG) on oxidative stress in kidney of diabetic rats as well as possible mechanism. Methods The rat diabetic model was induced by intraperitoneal injection of STZ in the left lower abdomen of the rats. A total of 48 model rats were randomly divided into diabetic group (n=12), PNS treatment group (n=12), AG treatment group (n=12), and PNS+ AG treatment group (n=12). Another 12 rats were used as normal controls. Serum and renal cortex superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by colorimetric assay. Advanced glycation end products (AGEs) were determined by spectrum law of fluorescence in the 4 and 8 weeks. The mean glomerular area (MGA) and mean glomerular volume (MGV) were measured by image analysis system. The changes of the blood glucose levels, urine amount, urine albumen, the renal function, body weight (BW), kidney weight (KW) and KW to BW ratio were observed. Results In comparison with the diabetic group, AGEs(F=36.017, P<0.01; F=8.213, P<0.01) and MDA(F=8.683, P<0.01; F=14.615, P<0.01) in serum and renal cortex, creatinine clearance rate (F=7.233, P<0.01), MGA(F=24.317, P<0.01), MGV(F=26.145, P<0.01), urinary excretion of protein(F=17.108, P<0.05), KW(F=5.182, P<0.05) and KW to BW ratio(F=50.169, P<0.01) were decreased significantly in the PNS+ AG treatment group , and SOD(F=6.260, P<0.01; F=7.666, P<0.01)in serum and renal cortex and BW were increased significantly (F=10.449, P<0.05). Decreased serum MDA was observed in PNS+ AG treatment group compared with AG treatment group(F=8.683, P<0.05), although renal cortex MDA was significantly lower than that of PNS treatment group and AG treatment group(F=14.615, P<0.05). Serum AGEs was decreased significantly in PNS+ AG treatment group compared with AG or PNS treatment group (F=36.017, P<0.01 or ﹤0.05), and renal cortex AGEs was significantly lower than that of AG or PNS treatment group(F=8.213, P<0.05). At 8 weeks, lower MGA(F=24.317, P<0.05)and MGV(F=26.145, P<0.05)were found in the PNS+ AG treatment group. Conclusion Combined treatment with PNS and AG may possess renoprotective effect on STZ-induced diabetic rats, and the possible mechanism could be associated with reduced oxidative stress and inhibited overproduction of AGEs in renal tissue. Key words: Diabetic nephropathy; Panax notoginseng saponins; Aminoguanidine; Oxidative stress; Nonenzymatic glycosylation

Quantification of Panax notoginseng saponins metabolites in rat plasma with in vivo gut microbiota-mediated biotransformation by HPLC-MS/MS

Objective To investigate the effects on extravascular lung water (EVLW) and mechanism by Panax notoginseng saponins (PNS) in intestinal ischeamia reperfusion (Ⅱ/R) induced acute lung injury (ALI) rat model.Methods Forty-eight Wistar rats were randomly assigned into four groups:(①sham-operated group,laparotomy without Ⅱ/R ( n =12);②sham+PNS group,identical to group one except for PNS treatment ( n =12) ;③Ⅱ/R group,one hour of intestinal ischemia followed by three hours of reperfusion ( n =12) ; ④Ⅱ/R + PNS group,injection of 100 mg/kg PNS,intravenously,15 minutes before reperfusion ( n =12).The effects of PNS administration on lung tissue histology,index of EVLW (EVLWI),expression of αENaC mRNA and protein,PaO2/FiO2 and PaCO2 were examined.Results Compared with Ⅱ/R group,pulmonary parenchymal damages and EVLWI were significantly reduced in Ⅱ/R + PNS group.The expressions of αENaC mRNA and protein in lung tissue were increased by PNS treatment.In addition,PaO2/FiO2 was improved remarkably in the Ⅱ/R+ PNS group compared with the Ⅱ/R group.Conclusions Administration of PNS berore reperfusion injury decreases EVLW of rat with ALI induced by Ⅱ/R,and this is partly attributable to prevention the decreases of expression of αENaC mRNA and protein. Key words: Panax notoginseng saponins; Acute lung injury; Extravascular lung water; Epithelialsodium channel

Gut morphology and gene expression in obesity: Short review and perspectives

Gut Microbiota and Its Possible Relationship With Obesity

Panax notoginseng saponins (PNS) are major components of Panax notoginseng, a herb with established clinical efficacy against vascular diseases. SHRSP.Z-Lepr(fa) /IzmDmcr (SHRSP.ZF) rats, a new animal model for metabolic syndrome, display an impaired vasorelaxation response in aortas and mesenteric arteries that is mediated by nitric oxide (NO). This study investigated whether PNS and its components can ameliorate this vascular dysfunction in SHRSP.ZF rats. In an in vitro study, in the presence or absence of PNS and its components, vasodilation in response to nitroprusside was determined from myographs under isometric tension conditions in aortas and mesenteric arteries from male SHRSP.ZF rats at 18-20 weeks of age. In an in vivo study, PNS (30 mg/kg per day) was orally administered to SHRSP.ZF rats from 8 to 20 weeks of age. In vitro treatment with PNS and Ginsenoside Rb1 increased nitroprusside-induced relaxation of aortas and mesenteric arteries in SHRSP.ZF rats. The PNS-induced increase was not affected by a nitric oxide (NO) synthase inhibitor or endothelium denudation. Relaxation in response to a cell-permeable cGMP analogue was increased by PNS, but cGMP accumulation by nitroprusside was not altered. In vivo treatment with PNS in SHRSP.ZF rats lowered blood pressure and increased relaxation and the expression of soluble guanylyl cyclase protein in arteries, without affecting metabolic abnormalities. These results indicate that PNS causes an increase in vasodilation in response to NO and a decrease in blood pressure, resulting in protection against vascular dysfunction in SHRSP.ZF rats. PNS might be beneficial in alleviating impaired vasodilation in metabolic syndrome.

Objective To observate the effects of panax notoginseng saponin （PNS） on restenosis of rat vein graft. Methods Jugular vein-to-artery bypass grafting was performed on 30 Sprague-Dawley rats. The rats were divided into three groups： sham gruup, model group and PNS group. Drugs were administered at the second day after the operation for 14 days. The grafts were harvested for histoehemieal staining to observe the hyperplasia of neointima, and proliferating cell nuclear antigen （PCNA） expression, and apoptosis of smooth muscle cells were detected by TUNEL. Results In sham group, model group and PNS group, the endometrial thickness was （4. 05± 0. 85 ）, （26. 30 ±1.15 ）, （ 10. 80 ± 0. 98 ） p.m; the intima/media was （ 0. 22 ± 0. 09 ）, （ 0. 76 ± 0. 27 ）, （ 0. 45±0. 23 ）, respectively. The neointimal thickness in PNS group was significantly less than in model group （ P 〈 0. 05 ）. The PCNA expression in model group （A value） was （23.6± 4. 3 ）, significantly higher than in PNS group （ 11.5±3.6 ） （ P 〈 0. 05 ）. The percentage of apoptotic cells in model group was （4. 3 ± 1.9 ） , significantly lower than in PNS group （20. 3 ± 3.5 ） （ P 〈 0. 05 ）. Conclusion PNS can inhibit the neointimal hyperplais of vein graft, which can prevente restenosis after bypass grafts. Key words: Vein graft ; Panax notoginseng saponin ; Vascular restenosis ; Neointima

RETRACTED: Borneol enhances the protective effect against cerebral ischemia/ reperfusion injury by promoting the access of astragaloside IV and the components of Panax notoginseng saponins into the brain

Panax notoginseng saponins protect PC12 cells against Aβ induced injury via promoting parkin-mediated mitophagy