Protective Effects Of Panax Notoginseng Saponins Research Articles

Panax notoginseng saponins inhibits oxidative stress- induced human nucleus pulposus cell apoptosis and delays disc degeneration in vivo and in vitro

Ethnopharmacological relevancePanax notoginseng (Burk) F. H. Chen has been a popular traditional Chinese medicine with a long history of treating low back pain. Its main active ingredient, Panax notoginseng saponins (PNS), can be found in several Chinese patent medicines that are frequently used to treat blood stasis type low back pain. Intervertebral disc degeneration (IDD) is the most common cause of back pain, and the injection of PNS has been used to relieve IDD-induced back pain in clinical practice. Despite its effectiveness, the exact mechanisms of action for PNS injections remain unclear. Aim of the studyIDD as a consequence of aging involves apoptosis of nucleus pulposus (NP) cells and imbalanced degradation of extracellular matrix (ECM) induced by several factors including oxidative stress. We hypothesized that PNS may have a therapeutic effect on IDD via inhibiting apoptosis of NP cells and degradation of ECM under oxidative stress. Materials and methodsIn this study, network pharmacology was initially employed to predict the targets of PNS against IDD. Subsequently, commercial PNS was analyzed by high-performance liquid chromatography to confirm the ingredients for in vitro and in vivo experiments. In vitro experiments were conducted on human nucleus pulposus (HNP) cells, including CCK-8, RT-PCR, Western blot, immunofluorescence staining, autophagic flux detection, and TUNEL assay. In vivo experiments were also performed on rats with IDD of tail discs induced by annular fibrosus needle puncture, which involved MRI, HE staining, and immunohistochemistry. ResultsOur study demonstrated the theoretical targets of PNS against IDD, including Caspase 3, MMP13, Akt, and autophagy, based on network pharmacology. Subsequently, in vitro experiments revealed that PNS attenuated cellular apoptosis of NP by suppressing the expression of cleaved-caspase 3 and the ratio of Bax/Bcl-2 under H2O2 stimulation. Autophagy was also inhibited by PNS treatment, and the protective effect was abolished with rapamycin, an autophagy inducer, indicating that autophagy inhibition was involved in the protective effect of PNS on IDD. Furthermore, Akt/mTOR pathway activation was observed in HNP cells responding to H2O2 with PNS treatment, which played a role in autophagy downregulation. PNS was also shown to promote the expression of anabolic genes such as COL2A1 and ACAN while inhibiting the expression of catabolic gene MMP13 in HNP cells. In addition, the in vivo study revealed that PNS treatment could ameliorate IDD in a puncture-induced rat tail model. The development of IDD was significantly reduced, and there was decreased MMP13 expression, as well as increased COL2A1 protein expression in NP tissues. ConclusionOur study showed that PNS could protect HNP cells against apoptosis via autophagy inhibition and ameliorate disc degeneration in vivo, indicating its potential to be a therapeutic agent for IDD.

Protective Effect of Panax Notoginseng Saponins on Apolipoprotein-E-deficient Atherosclerosis-prone Mice.

It is widely recognized that atherosclerosis (AS) is related to vascular inflammation. Panax notoginseng saponins (PNS) extracted from the roots of Panax notoginseng have been shown to possess anti-inflammatory activity. It is widely used in the clinical treatment of cardiovascular and cerebrovascular diseases, but the protective effect of PNS on atherosclerosis is not fully understood. This study was designed to test the effects of PNS administration in apolipoprotein (apo)-E-deficient (ApoE-/-) mice on the activation of NF-κB p65, IL-1β, IL-6, TNF-α and Calpain1 proteins. 24 ApoE-/- mice fed with high-fat diet for 8 weeks to create the AS model. PNS, dissolved in three distilled water, was administered orally to two treatment groups at dosages of 60 mg/kg/d/mice and 180 mg/kg/d/mice. After 8 weeks, peripheral blood was collected for assessing the levels of TG, TC, LDL-C and HDL-C in serum by Biochemical Analyzer. HE staining was used to observe pathomorphological changes in the aortic root. Oil Red O staining was used to observe the lipid deposition in the aortic root. ELISA kits were used to assess the levels of IL-1β and TNF-α in serum. The expression levels of NF-κB p65, IL-1β, IL-6, TNF-α, and Calpain1 proteins in the aortic root were identified by Western blot. After PNS administration for 8 weeks, the levels of TG, TC, LDL-C, IL-1β and TNF-α were decreased, the level of HDL-C was increased in apoE-/- mice. The arrangement of the tissue of aortic root tended to be normal, the cell morphology was restored, and the lipid depositions were reduced in apoE-/- mice treated with PNS. Moreover, PNS inhibited the expression levels of NF-κB p65, IL-6, IL-1β, TNF-α and Calpain1 proteins of aortic root tissues in apoE-/- mice. PNS may inhibit the progression of atherosclerotic lesions via their anti-inflammatory biological property. PNS suppress the NF-κB signaling pathway and inhibits the expression of pro-inflammatory factors such as NF-κB p65, IL-6, IL-1β, TNF-α and Calpain1 proteins in aortic root tissues of apoE-/- mice.

Panax notoginseng Saponins Modulate the Inflammatory Response and Improve IBD-Like Symptoms via TLR/NF-[Formula: see text]B and MAPK Signaling Pathways.

Panax notoginseng saponins (PNS) are the main active ingredients of Panax notoginseng (Burk) F. H. Chen, which are used as traditional Chinese medicine for thousands of years and have various clinical effects, including anti-inflammation, anti-oxidation, and cardiovascular protection. Inflammatory bowel disease (IBD) is a complex gastrointestinal inflammatory disease that cannot be cured completely nowadays. The anti-inflammatory and protective effects of PNS were analyzed in vitro and in dextran sulfate sodium (DSS)-induced colitis mouse model. PNS inhibited the release of nitric oxide (NO), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text], interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in Pam3CSK4-induced RAW 264.7 macrophages. In the animal study, compared with DSS-induced mice, PNS reduced the expression of pro-inflammatory cytokines (TNF-[Formula: see text], IL-6, and MCP-1) in the colon tissues. Furthermore, PNS treatment led to a remarkable reduction in the activation of the inhibitor of nuclear factor kappa-B kinase [Formula: see text]/[Formula: see text] (IKK[Formula: see text]/[Formula: see text], I[Formula: see text]B[Formula: see text] and p65 induced by DSS. On the other hand, PNS inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase 1/2 (ERK1/2). Taken together, our results suggested that PNS conferred profound protection for colitis mice through the downregulation of mitogen-activated protein kinase (MAPK) and NF-[Formula: see text]B signaling pathways, which were associated with reducing inflammatory responses, alleviating tissue damage, and maintaining of intestinal integrity and functionality.

Pananx notoginseng saponins attenuate CCL2-induced cognitive deficits in rats via anti-inflammation and anti-apoptosis effects that involve suppressing over-activation of NMDA receptors

HIV-associated neurocognitive disorders (HAND) are characterized by synaptic damage and neuronal loss in the brain, ultimately leading to progressive decline of cognitive abilities and memory. Chemokine CC motif ligand 2 (CCL2) is elevated in cerebrospinal fluid (CSF), and has been believed to contribute to HAND. Previous studies by our research team have shown that CCL2 enhances N-Methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) and causes nerve cell damage. However, there are few drugs currently available to treat nerve damage that is caused by CCL2. Panax notoginseng saponins (PNS) are isolated from Panax notoginseng and benefit the human body in various ways, including the neuroprotective effect. However, the protective effect of PNS on CCL2-induced neurotoxicity remains unknown. In this study, we found that PNS improved CCL2-induced learning and memory impairment, and inhibited CCL2-induced cell death. These effects may be due to inhibiting over-activation of NMDA receptors by alleviating the dysfunction of glutamate metabolism. Furthermore, PNS-modulated CCL2-inducd intracellular oxidative stress was found to attenuate cell inflammation. Additionally, PNS pretreatment evidently inhibited apoptotic pathways by reducing the Bax/BCL-2 ratio and caspase-3, 8, 9 expressions. In conclusion, this study demonstrates that PNS provides substantial neuroprotection against CCL2-induced neurotoxicity, and may be a novel therapeutic agent in CCL2-induced HAND or other neurodegenerative diseases.

Panax notoginseng saponins suppress lipopolysaccharide-induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF-κB inflammatory pathways.

Dysfunction of the blood-brain barrier (BBB) is a prerequisite for the pathogenesis of many cerebral diseases. Oxidative stress and inflammation are well-known factors accounting for BBB injury. Panax notoginseng saponins (PNS), a clinical commonly used drug against cerebrovascular disease, possess efficient antioxidant and anti-inflammatory activity. In the present study, the protective effects of PNS on lipopolysaccharide (LPS)-insulted cerebral microvascular endothelial cells (bEnd.3) were assessed and the underlying mechanisms were investigated. The results showed that PNS mitigated the decrease of Trans-Endothelial Electrical Resistance, increase of paracellular permeability, and loss of tight junction proteins in bEnd.3 BBB model. Meanwhile, PNS suppressed the THP-1 monocytes adhesion on bEnd.3 monolayer. Moreover, PNS prevented the pro-inflammatory cytokines secretion and reactive oxygen species generation in bEnd.3 cells stimulated with LPS. Mechanism investigations suggested that PNS promoted the Akt phosphorylation, activated Nrf2 antioxidant signaling, and inhibited the NF-κB activation. All the effects of PNS could be abolished by PI3K inhibition at different levels. Taken together, these observations suggest that PNS may act as an extrinsic regulator that activates Nrf2 antioxidant defense system depending on PI3K/Akt and inhibits NF-κB inflammatory signaling to attenuate LPS-induced BBB disruption and monocytes adhesion on cerebral endothelial cells in vitro.

Panax Notoginseng Saponins Attenuate Myocardial Ischemia-Reperfusion Injury Through the HIF-1α/BNIP3 Pathway of Autophagy.

Panax Notoginseng Saponins (PNS) is a formula of Chinese medicine commonly used for treating ischemia myocardial in China. However, its mechanism of action is yet unclear. This study investigated the effect and the mechanism of PNS on myocardial ischemia-reperfusion injury (MIRI) through the hypoxia-inducible factor 1α (HIF-1α)/bcl-2/adenovirus E1B19kDa-interacting protein3 (BNIP3) pathway of autophagy. We constructed a rat model of myocardial injury and compared among 4 groups (n = 10, each): the sham-operated group (Sham), the ischemia-reperfusion group (IR), the PNS low-dose group, and the PNS high-dose group were pretreated with PNS (30 and 60 mg/kg, respectively). Serum creatine kinase, malonaldehyde (MDA), lactate dehydrogenase, myocardial tissue superoxide dismutase, and reactive oxygen species were detected in rats with myocardial ischemia-reperfusion after the intervention of PNS. The rat myocardial tissue was examined using hematoxylin and eosin (H&E) staining, and the mitochondria of myocardial cells were observed using transmission electron microscopy. The expressions of microtubule-associated protein light chain 3 (LC3), HIF-1α, BNIP3, Beclin-1, and autophagy-related gene-5 (Atg5) in rat myocardial tissue were detected using Western blotting. The results showed that PNS was significantly protected against MIRI, as evidenced by the decreasing in the concentration of serum CK, MDA, lactate dehydrogenase, and myocardial tissue superoxide dismutase, reactive oxygen species, the attenuation of myocardial tissue histopathological changes and the mitochondrial damages of myocardial cells, and the increase of mitochondria autophagosome in myocardial cells. In addition, PNS significantly increased the expression of LC3 and the ratio of LC3II/LC3I in rat myocardial tissue. Moreover, PNS significantly increased the expression of HIF-1α, BNIP3, Atg5, and Beclin-1 in rat myocardial tissue. The protective effect of PNS on MIRI was mainly due to its ability to enhance the mitochondrial autophagy of myocardial tissue through the HIF-1α/BNIP3 pathway.

Panax Notoginseng Saponins attenuates sevoflurane‑induced nerve cell injury by modulating AKT signaling pathway.

General anesthesia in patients with or at risk for neuronal injury remains challenging due to the neurotoxic effects of volatile anesthetics. One inhalation anesthetic, sevoflurane, induces neuronal damage, including neuroapoptosis, and learning and memory impairment. Panax Notoginseng Saponins (PNS) is the active ingredient of Sanqui and has been reported to exert neuroprotective effects. In the current study, the protective effect of PNS on sevoflurane‑induced nerve cell injury was explored. Cell proliferation was significantly reduced in a dose‑dependent manner following stimulation with sevoflurane. Furthermore, cell apoptosis and the protein expression of caspase‑3, caspase‑9 and Bax were significantly increased, while the expression of Bcl‑2 was decreased in the sevoflurane group compared with normal control. Furthermore, the protein level of Bace‑1, APP and Aβ were elevated in the sevoflurane group compared with the control group. By contrast, PNS treatment significantly reduced the neurotoxicity induced by sevoflurane. Additionally, sevoflurane reduced activation of the AKT signaling pathway, which was activated by PNS treatment. In conclusion, the results suggested that PNS attenuates sevoflurane‑induced neurotoxicity through by stimulating cell proliferation and inhibiting cell apoptosis. These effects were mediated, at least in part, by activating the AKT signaling pathway.

Early Steroid-Induced Osteonecrosis of Rabbit Femoral Head and Panax notoginseng Saponins: Mechanism and Protective Effects.

Background. This study was aimed at investigating the pathogenesis of oxidative stress in steroid-induced avascular necrosis of the femoral head (SANFH) and at exploring the mechanism and protective effects of Panax notoginseng saponins (PNS) on early SANFH. Methods. 80 adult New Zealand rabbits were randomly divided into control group, model group, and PNS group. In model group, equine serum was injected into auricular vein; then methylprednisolone was injected into gluteus. In PNS group, PNS was applied for 14 consecutive days before methylprednisolone management. At different time points, serum and femoral heads were prepared for T-AOC, SOD, GSH-PX, ·OH, and MDA determination. Two weeks after steroid management, all femoral heads were assessed with MRI and HE staining. Results. Typical early osteonecrosis symptoms were observed in model group. Our results showed that PNS could significantly ameliorate the decrease of T-AOC level, improve SOD and GSH-PX activity, suppress ·OH ability, and augment MDA level. Besides, PNS improved MRI and pathological changes of the femoral head, markedly reducing the incidence of osteonecrosis. Conclusion. Based on our research, we found oxidative stress played a positive role in the occurrence of SANFH where reactive oxygen species was the direct cause. PNS could protect rabbits against early steroid-induced osteonecrosis of femoral head by its antioxidative effect.

Protective effects of panax notoginseng saponins on cardiovascular diseases: a comprehensive overview of experimental studies.

Panax notoginseng saponins (PNS) are one of the most important compounds derived from roots of the herb Panax notoginseng which are traditionally used as a hemostatic medicine to control internal and external bleeding in China for thousands of years. To date, at least twenty saponins were identified and some of them including notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were researched frequently in the area of cardiovascular protection. However, the protective effects of PNS on cardiovascular diseases based on experimental studies and its underlying mechanisms have not been reviewed systematically. This paper reviewed the pharmacology of PNS and its monomers Rb1, Rg1, and R1 in the treatment for cardiovascular diseases.

Effects of Panax notoginseng saponins on mRNA expressions of interleukin-1β, its correlative factors and cysteinyl-aspartate specific protease after cerebral ischemia-reperfusion in rats

To investigate the effects of Panax notoginseng saponins (PNS) on mRNA expressions of interleukin-1 beta (IL-1 beta), interleukin-1 receptor type I (IL-1RI), interleukin-1 receptor antagonist (IL-1ra), intercellular adhesion molecule-1 (ICAM-1), cysteinyl-aspartate specific protease-1 (caspase-1), caspase-3 and caspase-8 after cerebral ischemia-reperfusion in rats. Focal cerebral ischemia reperfusion in rats was induced by the method of nylon monofilament via the internal carotid artery. PNS was administered intraperitoneally respectively five minutes before cerebral ischemia and twelve hours after cerebral ischemia. After cerebral ischemia for two hours followed by reperfusion for twenty two hours, the mRNA expressions of IL-1 beta, IL-1RI, IL-1ra, ICAM-1, caspase-1, caspase-3 and caspase-8 in brain tissue were determined by reverse transcription polymerase chain reaction assay. After cerebral ischemia for two hours followed by reperfusion for twenty two hours, the mRNA expression levels of IL-1 beta, IL-1RI, IL-1ra, ICAM-1, caspase-1, caspase-3 and caspase-8 in brain tissue in the untreated group were obviously elevated as compared to those in the sham-operation group (P<0.05 or P<0.01). The mRNA expression levels of IL-1 beta, IL-1RI, IL-1ra in brain tissue in the PNS group were lower than those in the untreated group, but higher than those in the sham-operation group, and without statistical differences as compared to those in the sham-operation group and in the untreated group (P>0.05). The mRNA expression level of caspase-3 in brain tissue in the PNS group was significantly lower than that in the untreated group (P<0.05), but PNS had no effect on the mRNA expression levels of ICAM-1, caspase-1 and caspase-8 in brain tissue. PNS can inhibit the mRNA expression of caspase-3, slightly inhibit the mRNA expressions of IL-1 beta and its correlative inflammatory factors in brain tissue. The protective effects of PNS on cerebral injury induced by ischemia-reperfusion may be related to inhibiting the mRNA expressions of caspase-3, IL-1 beta and its correlative inflammatory factors in brain tissue.