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In this experiment, Panax notoginseng saponins chitosan nanoparticles(PNS-NPs) were prepared by self-assembly and their appearance, particle size, encapsulation efficiency, drug loading, polydispersity index(PDI), Zeta potential, and microstructure were characterized. The prepared PNS-NPs were intact in structure, with an average particle size of(209±0.258) nm, encapsulation efficiency of 42.34%±0.28%, a drug loading of 37.63%±0.85%, and a Zeta potential of(39.8±3.122) mV. The intestinal absorption of PNS-NPs in rats was further studied. The established HPLC method of PNS was employed to investigate the effects of pH, perfusion rate, and different drugs(PNS raw materials, Xuesaitong Capsules, and PNS-NPs). The absorption rate constant(K_a) and apparent permeability coefficient(P_(app)) in the duodenum, jejunum, ileum, and colon were calculated and analyzed. As illustrated by the results, the intestinal absorption of PNS-NPs was increased in the perfusion solution at pH 6.8(P<0.05), and perfusion rate had no significant effect on the K_a and P_(app) of PNS-NPs. The intestinal absorption of PNS-NPs was significantly different from that of PNS raw materials and Xuesaitong Capsules(P<0.05), and the intestinal absorption of PNS-NPs was significantly improved.
Subject(s)
Animals , Rats , Chitosan/pharmacology , Intestinal Absorption , Nanoparticles , Panax notoginseng/chemistry , Saponins/pharmacologyABSTRACT
Objective: To study the chemical constituents in acid hydrolysates of Panax notoginseng saponins (PNS). Methods: These compounds were separated and purified by column chromatography, and their structures were elucidated based on spectroscopic analyses (HR-ESI-MS, ESI-MS, 1H-NMR, 13C-NMR, HSQC and HMBC). Results: Eighteen compounds were obtained from the acid hydrolysates of PNS and characterized as dammar-25-ene-24-hydroperoxyl-3β,6α,12β,20S-tetraol (1), 6α,12β,20S-trihydroxy- dammarane-24-ene-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside (2), 6α,12β,20R-trihydroxy-dammarane-24-ene-3-O-β-D- glucopyranosyl-(1→2)-β-D-glucopyranoside (3), vina-ginsenoside-R8 (4), 24(S)-pseudo-ginsenoside-GQ (5), ginsenoside Rg5 (6), 20 (R)-ginsenoside Rg3 (7), 20(R)-ginsenoside Rk2 (8), 3β,12β-dihydroxy-dammar-(E)-20(22),24-diene-6-O-β-D-xylopyranosyl- (1→2)-β-D-glucopyranoside (9), 20(S)-ginsenoside Rg2 (10), ginsenoside SL1 (11), 20(R)-ginsenoside Rh1 (12), 20(22) E-ginsenoside Rh4 (13), 25-hydroxy-20(R) ginsenoside-Rh1 (14),3β,6α,12β,20(S)-20,25-epoxy-3,12-dihydroxy-dammarane-6-O-β-D-glucopyranoside (15), 20(R)-protopanaxadiol (16), 20(R)-protopanaxatriol (17), and 20(S)-protopanaxatriol (18). Conclusion: Compound 1 is a new triterpen saponin, and compounds 2-5 are isolated from P. notoginseng and acid dydrolysates of PNS for the first time.
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Objective:To explore the potential mechanisms of Panax Notoginseng Saponins （PNS） on growth inhibition of breast cancer cell line 4T1 in tumor-bearing mice by investigating the mitogen-activated protein kinase kinase kinase 1 （MEKK1）/stress activated protein kinase （SAPK）/extracellular regulated protein kinases （Erk） Kinase （SEK1）/c-Jun N-terminal kinase 1 （JNK1）/activator protein-1 （AP-1） signaling pathways. Method:The 4T1 breast cancer mice model was established. Forty-eight mice with successful modeled and randomly divided into the low， medium and high-dose PNS groups （10， 20， 40 mg·kg-1） and the model control group （12 mice in each group）. The PNS groups received intraperitoneal injection with dosage of 10 mL·kg-1， while the controlled group was given the same dosage of saline. After administration with PNS for 28 days， tumor tissues were isolated， weighed， sliced and homogenized. Tumor cell apoptosis was detected by TdT mediated-dUTP nick end labeling （TUNEL） staining. The mRNA expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissue were detected by Real-time polymerase chain reaction（Real-time PCR）. The protein expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissue were detected by immunofluorescence staining and Western blot. Result:Compared with model group， the tumor weights of medium-dose and high-dose PNS groups were decreased significantly （P<0.05）. TUNEL staining showed that the number of apoptotic tumor cells increased with the rise of dosage of PNS （P<0.05）. The medium-dose and high-dose PNS groups showed a significant increase in the mRNA expressions of MEKK1， SEK1， JNK1 and AP-1 as well as the protein expressions of MEKK1， SEK1， JNK1 and AP-1 in tumor tissues （P<0.05）， with statistically significant differences （P<0.05）. Conclusion:PNS could inhibit the tumor growth of breast cancer cell line 4T1 in tumor-bearing mice， which may be related to the activation of MEKK1/SEK1/JNK1/AP-1 signaling pathways.
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Objective To study the inhibitory effect of panax notoginseng saponins (PNS) on 3-nitrotyrosine (3-NT) formation in brain induced by heme/NO2 -/H2O2 or ONOO - pathways in vitro. Methods According to the two major pathways of 3-NT formation in vivo, the models of protein nitration induced by heme/NaNO2/H2O2 or ONOO-system were established, respectively, in vitro. Bovine serum albumin (BSA)/rat plasma protein or rat brain homogenate protein were utilized as reactive substrates in both systems. Samples were divided into blank-control group, 3-NT group and PNS group (including low-, medium-and high-concentration subgroups). In 3-NT group, samples were exposed to heme/NaNO2/H2O2 or ONOO-system, respectively, at 37℃for 30 min, whereas in PNS group, samples were pre-incubated with PNS (at final concentrations of 50 mg/L, 100 mg/L, and 200 mg/L) at 37℃for 5 min before the nitrating system exposure. The 3-NT level in each group was detected by Western blot assy. Results Compared with the blank-control group, both heme/NaNO2/H2O2 and ONOO-system can induce significant 3-NT generation in BSA/rat plasma protein or rat brain homogenate protein (P0.05). Medium- and high-concentrations of PNS pre-treatment markedly inhibited 3-NT accumulation, with maximum effect at the concentration of 200 mg/L (P<0.05). Conclusion Medium- and high-concentrations of PNS can inhibit 3-NT formation in brain tissue mediated by either heme/NO2-/H2O2 or ONOO-pathways, implying that potential neuroprotective action against 3-NT involves pathological conditions, like trauma, stroke, and neurodegenerative diseases.
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Aim To investigate the effects of panax nonstaining saponins ( PNS ) on the apoptosis of renal cells induced by cisplatin through the path of mitochon-drion . Methods Male Sprague-Dawley( SD) rats were randomized divided into normal control group, cisplatin model group and the cisplatin+PNS group,with 12 rats of each group. Animals were sacrificed to determine the N-acetyl-β-D-Glucosaminidase ( NAG ) in urine, blood urea nitrogen ( BUN) and serum creatinine ( Cr) concentrations after 8d of intraperitoneal injection. HE-staining was employed to observe renal pathologies. Transmission electron microscopy ( TEM ) was em-ployed to observe the mitochondria of the rats′ injured kidney region. TUNEL staining was employed to detect the distribution of apoptotic cells. Immunnohistochem-istry was used to detect Bax and caspase-9 expression, and expression of Bcl-2 protein was detected by West-ern blot. Results Compared with the normal control group, contents of BUN, serum Cr and urinary NAG levels of rat in the cisplatin model group were increased ( P <0. 01 ) , and some mitochondria of the epithelial cells of renal tubules got injured seriously. The apopto-sis rate of kidney cell was increased ( P<0. 01 ) . The expression of Bax,caspase-9 and Bcl-2 proteins was in-creased ( P < 0. 01 ) . Compared with the cisplatin model group, contents of BUN, serum Cr and urinary NAG levels of rats in the cisplatin model group were decreased ( P <0. 01 ) , and some mitochondria of the epithelial cells of renal tubules were significantly im-proved. The apoptosis rate of kidney cell was decreased ( P<0. 01 ) . The expression of Bax and caspase-9 pro-tein was decreased (P<0. 01),but Bcl-2 protein was increased ( P < 0. 01 ) . Conclusion PNS may in-crease the expression of Bcl-2 protein and decrease the expression of Bax and caspase-9 proteins, which may play a protective role in cisplatin nephritic damage.
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OBJECTIVE: To investigate the absorption kinetics of Panax notoginseng saponins (PNS) in rat small intestines and the effects of bioadhesive materials on the absorptive kinetics and appearance permeability. METHODS: HPLC was used to determine the concentrations of Panax notoginseng saponins. An in situ single pass intestinal perfusion was used to investigate the absorption of Panax notoginseng saponins in rat small intestines (duodenum and jejunum-ileum). RESULTS: In duodenum and jejunum-ileum, Panax notoginseng saponins at different concentrations (0.5-2 mg · mL-1) had no significant effect on the absorptive kinetics and appearance permeability of small intestines (P > 0.05), respectively. Some bioadhesive materials (include chitosan, carbomer 934P, 941P, Konjac glucan and HPMC K4M) could promote the absorption of Panax notoginseng saponins in small intestines, this effect was more obvious in duodenum area. HPMC K15M has no effect on the PNS absorption in small intestines(P > 0.05), pectin could even delay the absorption to some extent. CONCLUSION: Panax notoginseng saponins has a poor absorption in small intestines, the passive diffusion mechanism take great part in its transport progress. Some bioadhesive materials could enhance the permeability of Panax notoginseng saponins on the small intestine wall.
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Objective To evaluate the effectiveness and safety of treating active ankylosing spondylitis with total panax notoginseng saponins (PNS). Methods sixty-two patients were randomly recruited into a control group and a treatment group, with thirty-one patients in each group. All patients were treated with the routine therapy of NSAIDs and DMARDs. The treatment group was given PNS additionally, with 400mg PNS joined with 200ml normal saline being intravenously dripped daily. The therapeutic course was 14 days for both groups. The observation items for evaluation included symptoms, signs, and side effects. Results Compared with previous state before treatment, the lumbosacral portion pain and the count of joint pain was reduce, the time of morning stiffness was shortening, erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) were all significantly reduced (P<0.05) ; There were significant differences in the total effectiveness rates between the two groups (P<0.05) ; while no notable difference was found in adverse drug reaction between the groups (P>0.05). Conclusion It is effective that treating active ankylosing spondylitis with PNS plus NSAIDs.
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Objective To observe the effects of panax notoginseng saponins on the apoptosis and expression of C-myc of vascular VSMC in vitro.Methods VSMC derived from rabbit aorta were cultured in vitro and different concentrations of PNS were added in experimental groups.VSMC apoptosis was evaluated with cell ultrastructure under electron microscopy and flow cytometry.Expression of C-myc was observing by immunocytochemical method.Results The ratio of apoptosis and the expression of C-myc in PNS groups were high than control group.Conclusions PNS can increase the ratio of VSMC apoptosis which may be related the expression promoting of C-myc.
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Object To investigate the effects of Panax notoginseng saponins (PNS) on myocardial Gs? mRNA expression of seriously scalded rat. Methods A 30% skin full thickness scald model was produced by immersing rat in 95 ℃ water for 10 s. The effects of PNS on myocardial Gs? mRNA level were observed with dot blotting hybridization and in situ hybridization technique; effects on cAMP and adenyl cyclase (AC) activities were determined with radioimmunoassay. Results Myocardial Gs? mRNA, AC activity and cAMP content were reduced significantly 3 h after scalding. PNS (100, 200 mg/kg) could markedly increase the level of myocardial Gs? mRNA expression. The elevated quantity was correlated markedly with PNS dosage (r = 0.95, P
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Objective To investigate the effects of Panax notoginseng saponins(PNS)on both the excitatory and inhibitory synaptic transmission in the pyramidal neurons in hippocampal CA1 region of rats.Methods Wistar male rats(3—4 weeks)were killed by cervical dislocation and hippocampal slices(400 ?m)were prepared,blind whole-cell voltage-clamp recordings were performed on the CA1 pyramidal cells in hippocampal slices to examine and analyze the effects of PNS(0.05—0.4 g/L)on CA1 afferent fiber-evoked excitatory postsynaptic currents(EPSCs)and inhibitory postsynaptic currents(IPSCs),respectively.Moreover,the Schaffer collateral/commissural pathway was stimulated with paired pulses(interpulse interval was 50 ms)and the paired-pulse facilitation(PPF)was analyzed by EPSC2/EPSC1(P2/P1)ratio.Results PNS(0.1—0.4 g/L)significantly depressed amplitude of EPSCs in neurons in the hippocampal CA1 region(P0.05).Conclusion The inhibitory effect of PNS on EPSCs in hippocampal CA1 pyramidal neurons is not due to the reinforcement of the inhibiting interneurons.It may be a result of direct inhibition on excitatory synaptic transmission.The increasing of P2/P1 ratio after PNS application suggests that PNS depresses the excitatory synaptic transmission by presynaptic mechanism.
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Objective To investigate the regulatory effects of icariin (ICA) combined with the Panax notoginseng saponins (PNS) on immunological function in mice and provide some experimental evidences for the combination mechanism improving the spatial learning and memory abilities of Alzheimer's disease (AD) animal model. Methods Based on serum pharmacological method, the ICR mice were individually ig administrated with ICA+PNS [(40+320), (80+640), and (160+ 1 280 ) mg/kg] or ICA (80 mg/kg), and PNS (640 mg/kg) only for 7 d. Drug-containing serum was prepared and effects on spleen lymphocyte proliferation of Bable/c mice induced by concanavalin-A (ConA) or lipopolysaccharide (LPS) and on interleukin-2 (IL-2) secretion were observed in vitro. Meanwhile, the immunological organ indexes of treated mice were evaluated. Results Drug-containing serum of ICA+PNS [(80+640) and (160+ 1 280 ) mg/kg] could improve the spleen lymphocyte proliferation induced by ConA (P0.05). Drug-containing serum of ICA+PNS [(80+640) and (160+ 1 280) mg/kg] could improve IL-2 production (P0.05), respectively. Conclusion ICA combined with PNS could improve immunological function selectively and promote T cell function in mice.