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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. Significance Statement: Radiation induces DNA damage in human cells, posing risks to genomic integrity and cellular function. The study assessed Panax notoginseng saponins (PNS) for protection against gamma radiation‐induced DNA damage in human peripheral lymphocytes and Swiss albino mice. PNS reduced lymphocyte DNA damage markers, lowered lipid peroxidation, restored antioxidants, and maintained hematological parameters. It notably suppressed γ‐H2AX overexpression, indicating DNA damage response modulation. PNS demonstrated potential as an anticlastogenic agent, mitigating radiation‐induced DNA damage and oxidative stress, suggesting its suitability as a protective measure against radiation‐induced physiological changes. [ABSTRACT FROM AUTHOR]

Background: The neurovascular unit (NVU) and neurovascular trophic coupling (NVTC) play a key regulatory role in brain injury caused by ischemic stroke. Salvianolic acids (SAL) and Panax notoginseng saponins (PNS) are widely used in China to manage ischemic stroke. Neuroprotective effects of SAL and PNS, either taken alone or in combination, were examined in this research. Methods: Wistar rats were randomly divided into the following groups: Sham group (Sham), cerebral ischemia/reperfusion group (I/R), I/R with SAL group (SAL), I/R with PNS group (PNS), I/R with SAL combined with PNS (SAL + PNS), and I/R with edaravone group (EDA). Treatment was administered once daily for two days after modeling of middle cerebral artery occlusion/reperfusion (MCAO/R). Results: Compared with the I/R group, SAL, PNS, or SAL + PNS treatment reduced infarct size, improved neurological deficit score, reduced Evans blue extravasation, increased expression of CD31 and tight junction proteins (TJs), including zonula occludens‐1 (ZO‐1), zonula occludens‐2 (ZO‐2), and junctional adhesion molecule‐1 (JAM‐1). Furthermore, SAL, PNS, or SAL + PNS suppressed the activations of microglia and astrocyte and led to the amelioration of neuron and pericyte injury. Treatment also inhibited NVU dissociation of GFAP/PDGFRβ and Collagen IV/GFAP while upregulated the expression level of BDNF/TrkB and BDNF/NeuN. Conclusions: SAL and PNS have significantly remedied structural and functional disorders of NVU and NVTC in I/R injury. These effects were more pronounced when SAL and PNS were combined than when used separately. [ABSTRACT FROM AUTHOR]

Osteoporotic fractures seriously affect the quality of life of the elderly. Panax notoginseng saponins (PNS) have the potential function of preventing osteoporosis. The Phosphatidylinositol 3-kinase (PI3K)/protein kinase (AKT)/mammalian target of rapamycin (mTOR) pathway is involved in the regulation of osteoporosis and has been proven to be related to VEGF secretion and angiogenesis. Therefore, this study aimed to explore the effects of PNS on ovariectomized rats with osteoporotic fracture through the PI3K/AKT/mTOR pathway and angiogenesis-related factors. Female Sprague–Dawley rats were randomly divided into normal control, fracture model, ovariectomized fracture model, low-dose PNS (100 mg/kg/d), and high-dose PNS (200 mg/kg/d). The ovariectomized rat fracture model was established. In low and high dose groups, PNS was administered intraperitoneally. The vascularization of fracture ends was detected in vitro by micro-CT on the 7th, 14th, and 21st day after modeling, and the area and number of blood vessels in the unit field of vision of the callus healing plane were seen by hematoxylin-eosin staining. The expression levels of PI3K, AKT1, mTOR, hypoxia inducible factor-1; VEGF: vascular endothelial growth factor (HIF-1), VEGF, Ang-1, VEGFR2, and angiopoietin like 2 Gene (ANGPTL2) were determined using Western blotting. In the PNS treatment group, the area of cortical bone increased, the area of callus decreased, and the number and area of blood vessels increased significantly when compared with the ovariectomized fracture model group. PNS regulates the PI3K/AKT/mTOR signaling pathway and promotes the expression of vascular-related cytokines (VEGF, Ang-1, VEGFR2, and ANGPTL2) in osteoporotic fractures. PNS may regulate the expression of vascular-related factors through the PI3K/AKT/mTOR pathway and promote the healing of osteoporotic fractures in ovariectomized rats. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of basic fibro-blast growth factor (FGF-2) and Panax notoginseng saponins (PNS) alone or combined together on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cardiomyocytes (CMs) and the mechanism of action of PNS and FGF-2 in the differentiation. Methods BMSCs were isolated from 3-week-old SD rats (20~30 g) by whole bone marrow adherence, and then the purity of BMSCs was identified by flow cytometry. After the purity was qualified, PNS and FGF-2 alone or in combination, or combined with LY294002 (phosphatidylinositol 3 kinase inhibitor), were used to induce BMSCs to differentiate. According to the corresponding culture time, the cells were divided into control group, PNS group, FGF-2 group, and PNS+FGF-2 group. The expression levels of Desmin and Cx43 after induction were detected by immunohistochemical assay. Western blotting was used to measure the expression levels of myocardium-specific proteins, related pathway proteins, and apoptosis-related proteins. RT-qPCR was conducted to detect the expression of myocardial transcription factors. Results The expression levels of myocardium-specific proteins and genes were increased in each single induction group (PNS group and FGF-2 group) and combined induction group (PNS+FGF-2 group, P < 0.05), and the highest expression levels were observed in the combined group. PNS and FGF-2 combined with LY294002 decreased the expression levels of myocardium-specific proteins and genes, decreased the phosphorylation of pathway-related protein Akt, decreased the level of Bcl-2, increased the level of Bax, and decreased the ratio of Bcl-2/Bax when compared with the 2 single induction groups (P < 0.05). Conclusion Both PNS and FGF-2 can induce BMSCs to differentiate into CMs after induction, and the combined induction is more effective in the differentiation. The PI3K/Akt signaling pathway is involved in the differentiation process by PNS and FGF-2, and PNS and FGF-2 play a role in reducing apoptosis.

Background: With the prevalence of dietary supplements, the use of combinations of herbs and drugs is gradually increasing, together with the risk of drug interactions. In our clinical work, we unexpectedly found that the combination of Panax notoginseng and warfarin, which are herbs that activate blood circulation and remove blood stasis, showed antagonistic effects instead. The purpose of this study was to evaluate the drug interaction between Panax notoginseng saponins (PNS) and warfarin, the main active ingredient of Panax notoginseng, and to explore the interaction mechanism. Methods: The effects and mechanisms of PNS on the pharmacodynamics and pharmacokinetics of warfarin were explored mainly in Sprague–Dawley rats and HepG2 cells. Elisa was used to detect the concentrations of coagulation factors, HPLC-MS to detect the blood concentrations of warfarin in rats, immunoblotting was employed to examine protein levels, qRT-PCR to detect mRNA levels, cellular immunofluorescence to detect the localization of NR1I3, and dual luciferase to verify the binding of miR-214-3p and NR1I3. Results: PNS significantly accelerated warfarin metabolism and reduced its efficacy, accompanied by increased expression of NR1I3 and CYP2C9. Interference with NR1I3 rescued the accelerated metabolism of warfarin induce by PNS co-administration. In addition, we demonstrated that PNS significantly reduced miR-214-3p expression, whereas miR-214-3p overexpression reduced NR1I3 and CYP2C9 expression, resulting in a weakened antagonistic effect of PNS on warfarin. Additionally, we found that miR-214-3p bound directly to NR1I3 3′-UTR and significantly downregulated NR1I3 expression. Conclusion: Our study demonstrated that PNS accelerates warfarin metabolism and reduces its pharmacodynamics by downregulating miR-214-3p, leading to increased expression of its target gene NR1I3, these findings provide new insights for clinical drug applications to avoid adverse effects.

Panax notoginseng saponins (PNS) are a class of effective ingredients in Notoginseng Radix et Rhizoma, a well-known herbal medicine called San-Qi in Chinese. After oral administration, PNS inevitably interacts with gut microbiota, and thus affect the pharmacokinetic profiles and pharmacological effects. To date, studies concering gut microbiota-mediated metabolism of PNS have not been reviewed systematically. Herein, we outline the metabolic profiles of Panax notoginseng saponins mediated by gut microbiota, as well as its role in the pharmacokinetics and pharmacodynamics on the basis of reported data. The metabolic pathways of primary saponins are proposed, and step-by-step deglycosylation is found to be the primary degradation pathways of PNS mediated by gut microbiota. Specific microorganisms and enzymes involved in the metabolic processes were summarized. Gut microbiota is deeply involved in the metabolism of PNS, affects the pharmacokinetic profiles, and produces a series of active metabolites. These metabolites were documented to play an essential role in the efficacy of the parent compounds. Future studies should focus on strengthening the real-world evidence, defining the interaction between gut microbiota and PNS, and developing the strategy for modulating gut microbiota to enhance the bioavailability and efficacy of PNS. These information would be useful for further research and clinical application of PNS. [ABSTRACT FROM AUTHOR]

Abstract Panax notoginseng saponins (PNS) are the main active components of Panax notoginseng. But after oral administration, they need to be converted into rare ginsenosides by human gut microbiota and gastric juice before they can be readily absorbed into the bloodstream and exert their effects. The sources of rare ginsenosides are extremely limited in P. notoginseng and other medical plants, which hinders their application in functional foods and drugs. Therefore, the production of rare ginsenosides by the transformation of PNS using Aspergillus fumigatus was studied in this research. During 50 days at 25 ℃ and 150 rpm, A. fumigatus transformed PNS to 14 products (1–14). They were isolated by varied chromatographic methods, such as silica gel column chromatography, Rp-C18 reversed phase column chromatography, semi-preparative HPLC, Sephadex LH-20 gel column chromatography, and elucidated on the basis of their 1H-NMR, 13C-NMR and ESIMS spectroscopic data. Then, the transformed products (1–14) were isolated and identified as Rk3, Rh4, 20 (R)-Rh1, 20 (S)-Protopanaxatriol, C-K, 20 (R)-Rg3, 20 (S)-Rg3, 20 (S)-Rg2, 20 (R)-R2, Rk1, Rg5, 20 (S)-R2, 20 (R)-Rg2, and 20 (S)-I, respectively. In addition, all transformed products (1–14) were tested for their antimicrobial activity. Among them, compounds 5 (C-K) and 7 [20 (S)-Rg3] showed moderate antimicrobial activities against Staphylococcus aureus and Candida albicans with MIC values of 6.25, 1.25 μg/mL and 1.25, 25 μg/mL, respectively. This study lays the foundation for production of rare ginsenosides. Graphical abstract

Panax notoginseng saponins (PNSs) as the extracted bioactive components of Panax notoginseng, have a long history of application in prevention of thrombosis. PNSs down-regulate the expression of inflammatory factors, promoting endothelial cell growth, up-regulating the expression of anticoagulants and vasodilators, and regulating endothelial cell function; With multiple targets at which PNSs inhibit platelet adhesion, release, and aggregation; PNSs maintain the activity of the fibrinolytic system by regulating the dynamic balance of tissue type plasminogen activators and inhibitors; PNSs reduce blood viscosity, improve red blood cell indicators, and inhibit thrombosis through multiple pathways.

Panax notoginseng saponins (PNS) are the main active components of Panax notoginseng. But after oral administration, they need to be converted into rare ginsenosides by human gut microbiota and gastric juice before they can be readily absorbed into the bloodstream and exert their effects. The sources of rare ginsenosides are extremely limited in P. notoginseng and other medical plants, which hinders their application in functional foods and drugs. Therefore, the production of rare ginsenosides by the transformation of PNS using Aspergillus fumigatus was studied in this research. During 50 days at 25 ℃ and 150 rpm, A. fumigatus transformed PNS to 14 products (1–14). They were isolated by varied chromatographic methods, such as silica gel column chromatography, Rp-C18 reversed phase column chromatography, semi-preparative HPLC, Sephadex LH-20 gel column chromatography, and elucidated on the basis of their 1H-NMR, 13C-NMR and ESIMS spectroscopic data. Then, the transformed products (1–14) were isolated and identified as Rk3, Rh4, 20 (R)-Rh1, 20 (S)-Protopanaxatriol, C-K, 20 (R)-Rg3, 20 (S)-Rg3, 20 (S)-Rg2, 20 (R)-R2, Rk1, Rg5, 20 (S)-R2, 20 (R)-Rg2, and 20 (S)-I, respectively. In addition, all transformed products (1–14) were tested for their antimicrobial activity. Among them, compounds 5 (C-K) and 7 [20 (S)-Rg3] showed moderate antimicrobial activities against Staphylococcus aureus and Candida albicans with MIC values of 6.25, 1.25 μg/mL and 1.25, 25 μg/mL, respectively. This study lays the foundation for production of rare ginsenosides. [ABSTRACT FROM AUTHOR]

Panax notoginseng saponins (PNSs) as the extracted bioactive components of Panax notoginseng, have a long history of application in prevention of thrombosis. PNSs down-regulate the expression of inflammatory factors, promoting endothelial cell growth, up-regulating the expression of anticoagulants and vasodilators, and regulating endothelial cell function; With multiple targets at which PNSs inhibit platelet adhesion, release, and aggregation; PNSs maintain the activity of the fibrinolytic system by regulating the dynamic balance of tissue type plasminogen activators and inhibitors; PNSs reduce blood viscosity, improve red blood cell indicators, and inhibit thrombosis through multiple pathways. [ABSTRACT FROM AUTHOR]

Background: As a bioactive metabolite preparation widely used in acute ischemic stroke (AIS), the efficacy and safety of Panax notoginseng saponins injections (PNSI) in patients with AIS after intravenous thrombolysis remain to be evaluated. Methods: This study included randomized controlled trials published before 26 April 2024 in 8 databases. AIS patients who received intravenous thrombolysis were included. The control group receiving conventional treatment and the treatment group receiving additional PNSI. Primary outcomes were selected as mortality, disability, and adverse events. Secondary outcomes were selected as all-cause mortality, improvement of neurological deficit, quality of life, and cerebral injury indicators. The revised Cochrane Risk of Bias tool was used to assess risk of bias. Risk ratio (RR) and mean differences (MD) were calculated for binary variables and continuous variables, respectively, based on a 95% confidence interval (CI). Results: A total of 20 trials involving 1,856 participants were included. None of them reported mortality or disability. There was no significant difference in the adverse events [RR: 1.04; 95% CI: 0.60 to 1.81] and hemorrhagic transformation [RR: 0.99; 95% CI: 0.36 to 2.70] between the two groups. Compared to the control group, the treatment group had a better effect in neurological improvement assessed by National Institutes of Health Stroke Scale [MD: -2.91; 95% CI: -4.76 to -1.06], a better effect in activities of daily living changes in Barthel Index [MD: 9.37; 95% CI: 1.86 to 16.88], and a lower serum neuron-specific enolase level [MD: -2.08; 95% CI: -2.67 to -1.49]. Conclusion: For AIS patients undergoing intravenous thrombolysis, the use of PNSI improved neurological deficits and enhanced activity of daily living in the short term without increasing the occurrence rate of adverse events. However, due to the moderate to very low certainty of evidence, it is advisable to conduct highquality clinical trials to validate the findings of this study. [ABSTRACT FROM AUTHOR]

Objective: Panax quinquefolius saponins (PQS) and Panax notoginseng saponins (PNS) are key bioactive compounds in Panax quinquefolius L. and Panax notoginseng, commonly used in the treatment of clinical ischemic heart disease. However, their potential in mitigating myocardial ischemia-reperfusion injury remains uncertain. This study aims to evaluate the protective effects of combined PQS and PNS administration in myocardial hypoxia/reoxygenation (H/R) injury and explore the underlying mechanisms. Methods: To investigate the involvement of HIF-1α/BNIP3 mitophagy pathway in the myocardial protection conferred by PNS and PQS, we employed small interfering BNIP3 (siBNIP3) to silence key proteins of the pathway. H9C2 cells were categorized into four groups: control, H/R, H/R + PQS + PNS, and H/R + PQS + PNS+siBNIP3. Cell viability was assessed by Cell Counting Kit-8, apoptosis rates determined via flow cytometry, mitochondrial membrane potential assessed with the JC-1 fluorescent probes, intracellular reactive oxygen species detected with 2′,7′-dichlorodihydrofluorescein diacetate, mitochondrial superoxide production quantified with MitoSOX Red, and autophagic flux monitored with mRFP-GFP-LC3 adenoviral vectors. Autophagosomes and their ultrastructure were visualized through transmission electron microscopy. Moreover, mRNA and protein levels were analyzed via real-time PCR and Western blotting. Results: PQS + PNS administration significantly increased cell viability, reduced apoptosis, lowered reactive oxygen species levels and mitochondrial superoxide production, mitigated mitochondrial dysfunction, and induced autophagic flux. Notably, siBNIP3 intervention did not counteract the cardioprotective effect of PQS + PNS. The PQS + PNS group showed downregulated mRNA expression of HIF-1α and BNIP3, along with reduced HIF-1α protein expression compared to the H/R group. Conclusions: PQS + PNS protects against myocardial H/R injury, potentially by downregulating mitophagy through the HIF-1α/BNIP3 pathway. [ABSTRACT FROM AUTHOR]

Abstract Background The neurovascular unit (NVU) and neurovascular trophic coupling (NVTC) play a key regulatory role in brain injury caused by ischemic stroke. Salvianolic acids (SAL) and Panax notoginseng saponins (PNS) are widely used in China to manage ischemic stroke. Neuroprotective effects of SAL and PNS, either taken alone or in combination, were examined in this research. Methods Wistar rats were randomly divided into the following groups: Sham group (Sham), cerebral ischemia/reperfusion group (I/R), I/R with SAL group (SAL), I/R with PNS group (PNS), I/R with SAL combined with PNS (SAL + PNS), and I/R with edaravone group (EDA). Treatment was administered once daily for two days after modeling of middle cerebral artery occlusion/reperfusion (MCAO/R). Results Compared with the I/R group, SAL, PNS, or SAL + PNS treatment reduced infarct size, improved neurological deficit score, reduced Evans blue extravasation, increased expression of CD31 and tight junction proteins (TJs), including zonula occludens‐1 (ZO‐1), zonula occludens‐2 (ZO‐2), and junctional adhesion molecule‐1 (JAM‐1). Furthermore, SAL, PNS, or SAL + PNS suppressed the activations of microglia and astrocyte and led to the amelioration of neuron and pericyte injury. Treatment also inhibited NVU dissociation of GFAP/PDGFRβ and Collagen IV/GFAP while upregulated the expression level of BDNF/TrkB and BDNF/NeuN. Conclusions SAL and PNS have significantly remedied structural and functional disorders of NVU and NVTC in I/R injury. These effects were more pronounced when SAL and PNS were combined than when used separately.

Gastric precancerous lesion (GPL) is a crucial stage in the development of gastric cancer, characterized by incomplete intestinal epithelial chemotaxis and heterogeneous hyperplasia with high malignant potential. Early intervention in GPL is vital for preventing gastric cancer. Additionally, there are shared risk factors and pathogenesis between tumors and coronary heart disease (CHD), with an increasing number of tumor patients GPL complicated with CHD due to improved survival rates. Reperfusion therapy in CHD can result in myocardial ischemia-reperfusion injury (MIRI). Traditional Chinese medicine (TCM) has demonstrated unique advantages in treating GPL and MIRI by promoting blood circulation and removing blood stasis. Panax ginseng total saponin (PNS), a component of TCM known for its blood circulation benefits, has shown positive effects in inhibiting tumor growth and improving myocardial ischemia. This study utilized a GPL-MIRI mouse model to investigate the effects of PNS in treatment. Results indicated that PNS significantly improved typical GPL lesions in mice, such as incomplete intestinal epithelialization and heteroplasia, and also reduced myocardial infarction. At the molecular level, PNS exhibited a bidirectional regulatory role in the GPL-MIRI model. It enhanced the autophagic process in gastric mucosal cells by inhibiting the PI3K/Akt/mTOR signaling pathway, while suppressed excessive autophagy in cardiomyocytes. These findings offer new insights and treatment strategies for managing GPL and MIRI using the TCM compound PNS.

Abstract Background Mitochondrial dysfunction is one of the distinctive features of neurons in patients with Alzheimer’s disease (AD). Intraneuronal autophagosomes selectively phagocytose and degrade the damaged mitochondria, mitigating neuronal damage in AD. Panax notoginseng saponins (PNS) can effectively reduce oxidative stress and mitochondrial damage in the brain of animals with AD, but their exact mechanism of action is unknown. Methods Senescence-accelerated mouse prone 8 (SAMP8) mice with age-related AD were treated with PNS for 8 weeks. The effects of PNS on learning and memory abilities, cerebral oxidative stress status, and hippocampus ultrastructure of mice were observed. Moreover, changes of the PTEN-induced putative kinase 1 (PINK1)-Parkin, which regulates ubiquitin-dependent mitophagy, and the recruit of downstream autophagy receptors were investigated. Results PNS attenuated cognitive dysfunction in SAMP8 mice in the Morris water maze test. PNS also enhanced glutathione peroxidase and superoxide dismutase activities, and increased glutathione levels by 25.92% and 45.55% while inhibiting 8-hydroxydeoxyguanosine by 27.74% and the malondialdehyde production by 34.02% in the brains of SAMP8 mice. Our observation revealed the promotion of mitophagy, which was accompanied by an increase in microtubule-associated protein 1 light chain 3 (LC3) mRNA and 70.00% increase of LC3-II/I protein ratio in the brain tissues of PNS-treated mice. PNS treatment increased Parkin mRNA and protein expression by 62.80% and 43.80%, while increasing the mRNA transcription and protein expression of mitophagic receptors such as optineurin, and nuclear dot protein 52. Conclusion PNS enhanced the PINK1/Parkin pathway and facilitated mitophagy in the hippocampus, thereby preventing cerebral oxidative stress in SAMP8 mice. This may be a mechanism contributing to the cognition-improvement effect of PNS.

AbstractCOPD is an inflammatory lung disease that limits airflow and remodels the pulmonary vascular system. This study delves into the therapeutic potential and mechanistic underpinnings of Panax notoginseng Saponins (PNS) in alleviating inflammation and pulmonary vascular remodeling in a COPD rat model. Symmap and ETCM databases provided Panax notoginseng-related target genes, and the CTD and DisGeNET databases provided COPD-related genes. Intersection genes were subjected to protein-protein interaction analysis and pathway enrichment to identify downstream pathways. A COPD rat model was established, with groups receiving varying doses of PNS and a Roxithromycin control. The pathological changes in lung tissue and vasculature were examined using histological staining, while molecular alterations were explored through ELISA, RT-PCR, and Western blot. Network pharmacology research suggested PNS may affect the TLR4/NF-κB pathway linked to COPD development. The study revealed that, in contrast to the control group, the COPD model exhibited a significant increase in inflammatory markers and pathway components such as TLR4, NF-κB, HIF-1α, VEGF, ICAM-1, SELE mRNA, and serum TNF-α, IL-8, and IL-1β. Treatment with PNS notably decreased these markers and mitigated inflammation around the bronchi and vessels. Taken together, the study underscores the potential of PNS in reducing lung inflammation and vascular remodeling in COPD rats, primarily via modulation of the TLR4/NF-κB/HIF-1α/VEGF pathway. This research offers valuable insights for developing new therapeutic strategies for managing and preventing COPD.

AIM: To investigate the anti-fibrotic effect of Panax notoginseng saponins (PNS) in arecoline (ANE)-induced oral submucous fibrosis, and to analyze the effect of PNS on nuclear factor E2-related factor 2(Nrf2)/glutamate-cysteine ligase catalytic subunit (GCLC) signaling pathway. METHODS: CCK-8 assay was used to evaluate the effects of different concentrations of PNS and arecoline on the survival rate of human immortalized keratinocyte cell line HaCaT. The results of CCK-8 were used to select 75 mg/L arecoline, and 25，50 and 100 mg/L PNS as subsequent experimental concentrations. The cells were set as blank control group, model group, and low, medium and high doses (25，50 and 100 mg/L) of PNS groups. The protein and mRNA expressions of collagen type I (COL-I), E-cadherin, Nrf2, GCLC and glutathione reductase (GR) in each group were detected by Western blot and RT-qPCR. Immunofluorescence method was used to detect the entry of Nrf2 into the nucleus. Biochemical kits were used to detect the content of glutathione (GSH), nicotinamide adenine dinucleotide phosphate (NADPH) and malondialdehyde (MDA), and superoxide dismutase (SOD) activity in each group of cells. DCFH-DA fluorescent probe was used to detect the content of intracellular reactive oxygen species (ROS). RESULTS: Compared with the blank control group, the protein and mRNA expression of COL-I in the model group was up-regulated, and the protein and mRNA levels of E-cadherin, Nrf2, GCLC, nuclear Nrf2 and GR were down-regulated. The content of NADPH, MDA and ROS in the cells increased, and the content of GSH and the activity of SOD was significantly reduced. Compared with the model group, the protein and mRNA expression of COL-I was down-regulated, and the protein and mRNA expression of E-cadherin, Nrf2, GCLC, nuclear Nrf2 and GR were up-regulated in PNS 50 and 100 mg/L groups. Compared with the model group，the content of NADPH, MDA and ROS in cells decreased, and the content of GSH and the activity of SOD was significantly enhanced (P<0. 05 or P<0. 01). CONCLUSION:Panax notoginseng saponins have anti-fibrosis effects in HaCaT cells, and their mechanism may be related to the activation of Nrf2/GCLC signaling pathway, thereby resisting oxidative stress and improving oral submucosal fibrosis. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the efficacy and safety of Panax notoginseng saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI). Methods: Comprehensive searches were conducted in seven databases from inception until 28 September 2023. The search aimed to identify relevant randomized controlled trials (RCTs) focusing on PNS injection in the context of AMI. This meta-analysis adhered to the PRISMA 2020 guidelines, and its protocol was registered with PROSPERO (number: CRD42023480131). Result: Twenty RCTs involving 1,881 patients were included. The meta-analysis revealed that PNS injection, used adjunctively with CT, significantly improved treatment outcomes compared to CT alone, as evidenced by the following points: (1) enhanced total effective rate [OR = 3.09, p < 0.05]; (2) decreased incidence of major adverse cardiac events [OR = 0.32, p < 0.05]; (3) reduction in myocardial infarct size [MD = -6.53, p < 0.05]; (4) lower ST segment elevation amplitude [MD = -0.48, p < 0.05]; (5) mitigated myocardial injury as indicated by decreased levels of creatine kinase isoenzymes [MD = -11.19, p < 0.05], cardiac troponin T [MD = -3.01, p < 0.05], and cardiac troponin I [MD = -10.72, p < 0.05]; (6) enhanced cardiac function, reflected in improved brain natriuretic peptide [MD = -91.57, p < 0.05], left ventricular ejection fraction [MD = 5.91, p < 0.05], left ventricular end-diastolic dimension [MD = -3.08, p < 0.05], and cardiac output [MD = 0.53, p < 0.05]; (7) reduced inflammatory response, as shown by lower levels of C-reactive protein [MD = -2.99, p < 0.05], tumor necrosis factor-α [MD = -6.47, p < 0.05], interleukin-6 [MD = -24.46, p < 0.05], and pentraxin-3 [MD = -2.26, p < 0.05]; (8) improved vascular endothelial function, demonstrated by decreased endothelin-1 [MD = -20.56, p < 0.05] and increased nitric oxide [MD = 1.33, p < 0.05]; (9) alleviated oxidative stress, evidenced by increased superoxide dismutase levels [MD = 25.84, p < 0.05]; (10) no significant difference in adverse events [OR = 1.00, p = 1.00]. Conclusion: This study highlighted the efficacy and safety of adjunctive PNS injections in enhancing AMI patient outcomes beyond CT alone. Future RCTs need to solidify these findings through rigorous methods. Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/), identifier (CRD42023480131) [ABSTRACT FROM AUTHOR]

Panax notoginseng saponins (PNS), the primary medicinal ingredient of Panax notoginseng, mitigates cerebral ischemia–reperfusion injury (CIRI) by inhibiting inflammation, regulating oxidative stress, promoting angiogenesis, and improving microcirculation. Moreover, PNS activates nuclear factor erythroid 2-related factor 2 (Nrf2), which is known to inhibit ferroptosis and reduce inflammation in the rat brain. However, the molecular regulatory roles of PNS in CIRI-induced ferroptosis remain unclear. In this study, we aimed to investigate the effects of PNS on ferroptosis and inflammation in CIRI. We induced ferroptosis in SH-SY5Y cells via erastin stimulation and oxygen glucose deprivation/re-oxygenation (OGD/R) in vitro. Furthermore, we determined the effect of PNS treatment in a rat model of middle cerebral artery occlusion/reperfusion and assessed the underlying mechanism. We also analyzed the changes in the expression of ferroptosis-related proteins and inflammatory factors in the established rat model. OGD/R led to an increase in the levels of ferroptosis markers in SH-SY5Y cells, which were reduced by PNS treatment. In the rat model, combined treatment with an Nrf2 agonist, Nrf2 inhibitor, and PNS-Nrf2 inhibitor confirmed that PNS promotes Nrf2 nuclear localization and reduces ferroptosis and inflammatory responses, thereby mitigating brain injury. Mechanistically, PNS treatment facilitated Nrf2 activation, thereby regulating the expression of iron overload and lipid peroxidation-related proteins and the activities of anti-oxidant enzymes. This cascade inhibited ferroptosis and mitigated CIRI. Altogether, these results suggest that the ferroptosis-mediated activation of Nrf2 by PNS reduces inflammation and is a promising therapeutic approach for CIRI. [ABSTRACT FROM AUTHOR]

This study aimed to enhance the oral absorption of Panax notoginseng saponins (PNS) via nanoparticles modified with thiolated trimethyl chitosan (TMC-Cys) and wheat germ agglutinin (WGA), termed PP-WT NPs. In vitro investigations revealed that PP-WT NPs exhibited delayed release of PNS and a strong tolerance to the gastric acids and digestive enzymes. Moreover, PP-WT NPs exhibited efficient cellular uptake and transport capabilities in the Caco-2/HT29-co-cultured cell model. In vivo animal experiments demonstrated that PP-WT NPs effectively overcame the mucus layer barrier, with the effective permeability coefficients of R1, Rg1, and Rb1 in the small intestine being 1.68, 1.64, and 1.63 times higher than those of free PNS, respectively. Taken together, thiolated trimethyl chitosan and wheat germ agglutinin–modified nanoparticles hold significant potential for improving the oral absorption of PNS, representing an attractive strategy for enhanced therapeutic efficacy. [ABSTRACT FROM AUTHOR]

AbstractContext Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation.Objective To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2).Materials and methods Naive CD4+T cells were treated with IL-6, IL-23 and TGF-β to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 μg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 μM) and inhibitor (SAICAR, 2, 4, 8 μM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression.Results PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 μM) and SAICAR (4 μM), we demonstrated that PNS (10 μg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling.Discussion and conclusions PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA.

Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation. To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2). Naive CD4+T cells were treated with IL-6, IL-23 and TGF-β to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 μg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 μM) and inhibitor (SAICAR, 2, 4, 8 μM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression. PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 μM) and SAICAR (4 μM), we demonstrated that PNS (10 μg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling. PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA. [ABSTRACT FROM AUTHOR]

Ischemic stroke remains a major disease worldwide, and most stroke patients often suffer from serious sequelae. Endogenous neurogenesis matters in the repair and regeneration of impaired neural cells after stroke. We have previously reported in vivo that PNS could strengthen the proliferation and differentiation of neural stem cells (NSCs), modulate synaptic plasticity and protect against ischemic brain injuries in cerebral ischemia rats, which could be attributed to mTOR signaling activation. Next, to obtain further insights into the function mechanism of PNS, we evaluated the direct influence of PNS on the survival, differentiation and synaptic development of C17.2 NSCs in vitro. The oxygen glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemic brain injuries. We found that after OGD/R injuries, PNS improved the survival of C17.2 cells. Moreover, PNS enhanced the differentiation of C17.2 cells into neurons and astrocytes, and further promoted synaptic plasticity by significantly increasing the expressions of synapse-related proteins BDNF, SYP and PSD95. Meanwhile, PNS markedly activated the Akt/mTOR/p70S6K pathway. Notably, the mTOR inhibitor rapamycin pretreatment could reverse these desirable results. In conclusion, PNS possessed neural differentiation-inducing properties in mouse C17.2 NSCs after OGD/R injuries, and Akt/mTOR/p70S6K signaling pathway was proved to be involved in the differentiation and synaptic development of C17.2 cells induced by PNS treatment under the in vitro ischemic condition. Our findings offer new insights into the mechanisms that PNS regulate neural plasticity and repair triggered by NSCs, and highlight the potential of mTOR signaling as a therapeutic target for neural restoration after ischemic stroke.

Microangiopathy is the most basic pathological manifestation of lupus nephritis (LN), and glomerular endothelial cells (GECs) injury is an important pathological mechanism. LN patients with microangiopathy are prone to steroid resistance (SR). Our previous studies confirmed that Panax notoginseng saponins (PNS) could reverse SR by downregulating the expression of P-gp in SR lymphocytes of LN mice (SLCsL/S). However, the mechanism of how circulating lymphocytes transmit SR information to GECs and thus affect the efficacy of kidney treatment is not clear. Recent studies have found that exosomes (exos) are an important carrier for intercellular bioactive substance communication. But whether exosomes derived from SLCsL/S mediate SR in GECs and PNS interventions. To solve this problem, Exosomes isolated from SLCsL/S were characterized, and in vitro cell coculture was further conducted to investigate the effect of SLCsL/S-derived exosomes in the SR of GECs and PNS intervention. Sequencing was used to define the exosomal miRNA expression profiling of SR GECs. Moreover, the in vivo experiments were performed through the injection of exosomes extracted from SLCsL/S into the tail vein of mice.Our research results indicate that exosomes derived from SLCsL/S could transmit SR information to GECs and lead to the aggravation of inflammatory injury through conferring P-gp, which were negated by a P-gp inhibitor. Further, we identified higher levels of exosomal miR-125b-5p from SR GECs were associated with SR in LN and could serve as biomarker for the risk of developing SR. PNS could reverse the SR of GECs and alleviate inflammatory injury by suppressing exosomal P-gp levels from lymphocytes to GECs in vitro and in vivo. However, the specific molecular mechanism by which PNS regulates exosomes has not yet been elucidated, and we need to conduct more in-depth research in the future. Overall, Our findings suggest that exosomal transfer of SLCsL/S derived P-gp confer SR to GECs, and PNS can target exosome communication to reverse SR in LN, which provides new ideas and a scientific basis for improving the clinical efficacy of traditional Chinese medicine in the treatment of refractory LN.

Background: Stroke is the major cause of mortality and permanent disability and is associated with an astonishing economic burden worldwide. In the past few decades, accumulated evidence has indicated that Xuesaitong (XST) has therapeutic benefits in cases of acute ischemic stroke (AIS). Our study aimed to provide the best current body of evidence of the efficacy and safety of XST for patients with AIS. Methods: This is a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched eight electronic databases from inception to 17 July 2023 for relevant RCTs. The investigators independently screened trials, extracted data, and assessed the risk of bias. A meta-analysis was conducted using RevMan 5.3 and STATA 16.0 software. Results: In total, 46 RCTs involving 7,957 patients were included. The results showed that XST improved the long-term functional outcomes with lower modified Rankin Scale (mRS) scores (MD = -0.67; 95% CI [-0.92 to -0.42]; p < 0.00001) and a higher proportion of functional independence (mRS ≤2) (RR = 1.08; 95% CI [1.05 to 1.12]; p < 0.00001). Low-quality evidence indicated that XST improved the activities of daily living (MD = 10.17; 95% CI [7.28 to 13.06]; p < 0.00001), improved the neurological impairment (MD = -3.39; 95% CI [-3.94 to -2.84]; p < 0.00001), and enhanced the total efficiency rate (RR = 1.19; 95% CI [1.15 to 1.23]; p < 0.00001). No significant difference was found in the all-cause mortality or incidence of adverse events between the XST and control groups. The certainty of evidence was estimated as moderate to very low. Conclusion: Presently, the administration of XST within 14 days of AIS is associated with favorable long-term functional outcomes. In addition, XST can improve activities of daily living, alleviate neurological deficits, and has shown good tolerability. However, the current evidence is too weak, and the confidence of evidence synthesis was restricted by the high risk of bias. Given the insufficient evidence, appropriately sized and powered RCTs investigating the efficacy and safety of XST for patients with AIS are warranted. [ABSTRACT FROM AUTHOR]

AIM: To investigate the impact of Panax notoginseng saponins （PNS） on the Notch3 pathway and its subsequent effects on the proliferation and apoptosis of rat pulmonary artery smooth muscle cells （PASMCs） under hypoxic conditions. METHODS: Rat PASMCs were subjected to a 24-hour starvation period and then categorized into 6 groups: control （Con） group, hypoxia （Hypo） group, Hypo+PNS group, Hypo+DAPT ｛N-［N-（3, 5-difluorophenacetyl） -L-alanyl］-S-phenylglycine t-butyl ester; Notch3 pathway inhibitor｝ group, Hypo+Notch3 overexpression （Hypo+Notch3） group, and Hypo+Notch3+PNS group. The cells in Con group were cultured for 48 h in a normal oxygen environment （21% O2, 5% CO2 and 74% N2）. Meanwhile, the other five groups were treated with respective intervention treatment and cultured under hypoxic conditions （5% O2, 6% CO2 and 89% N2） for 48 h. The cell viability was assessed by CCK-8 assay, the cell proliferation was detected by EdU staining, and cell apoptosis was determined using TUNEL staining. The mRNA expression levels of Notch3, Hes-1, proliferating cell nuclear antigen（ PCNA） and caspase-3 were detected by RTqPCR, and corresponding protein levels were measured by Western blot. In addition, the effect of PNS on the proliferation of PASMCs with Notch3 overexpression was also investigated. RESULTS: The EdU and TUNEL assays revealed that compared with Con group, the rat PASMCs in Hypo group showed increased proliferation and reduced apoptosis （P<0. 01）. Both mRNA and protein levels of Notch3, Hes-1 and PCNA were elevated （P<0. 05）, while caspase-3 mRNA and protein levels were decreased （P<0. 05）. After PNS treatment, a decline in Notch3, Hes-1 and PCNA expression occurred （P< 0. 05）, and caspase-3 levels increased（ P<0. 05）. After Notch3 pathway inhibitor DAPT intervention, decreased levels of Notch3, Hes-1 and PCNA （P<0. 05）, and increased caspase-3 levels were observed （P<0. 05）. Subsequent findings demonstrated that Notch3 plasmids could counteract the anti-proliferative effect of PNS under Hypo （P<0. 05）. CONCLUSION: Panax notoginseng saponins may reduce Hypo-induced proliferation of rat PASMCs and bolster the apoptosis by suppressing the Notch3 expression. [ABSTRACT FROM AUTHOR]

Copyright of Modern Food Science & Technology is the property of Editorial Office of Modern Food Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AIM: To investigate whether Panax notoginseng saponins (PNS) attenuate arecoline (ANE)-induced human oral submucous fibrosis (OSF) by regulating ferroptosis, and to study its mechanism. METHODS: The OSF model was established by treating human immortalized keratinocyte cell line HaCaT with ANE. There were 6 groups created: blank group, model group(50 mg/L ANE), low-, medium- and high-dose (12. 5, 25 and 50 mg/L)PNS groups, and liproxstatin-1 (ferroptosis inhibitor) group. The morphological changes of the cells were observed under a light microscope. Cell viabilty was detected by CCK-8 assay. Collagen type I (Col-l), solute carrier family 7 member 11(SLC7A11) and glutathione peroxidase 4(GPX4)protein expression levels were detected by Western blot. The morphological changes of mitochondria were observed by transmission electron microscopy. The Fe2+ level was detected by FerroOrange fluorescent probe. The intracellular reactive oxygen species (ROS) content was detected by DCFH-DA fluorescent probe. The content of glutathione (GSH)was determined by colorimetry. RESULTS: Compared with blank group, the majority of the cells in model group displayed long spindle shape, fibrotic appearance, unstable adhesion, and obvious morphological changes. Under electron microscope, mitochondrial double membrane density increased, and cristae decreased significantly, presenting typical ferroptosis. The expression of Col-I increased, GPX4 and SLC7A11 protein expression decreased, Fe2+ and ROS levels increased, and GSH content decreased (all/><0. 05). Compared with model group, most of the cells in low-, medium- and high-dose PNS groups were round and epit he lo id, with decreased mitochondrial membrane density, increased ridge number and normal morphology, decreased Col-I expression and ROS level, and increased GSH content (all P<0. 05). Compared with model group, the protein expression levels of GPX4 and SLC7A11 in medium- and high-dose PNS groups were significantly increased, while the content of Fe2+ was significantly decreased (all P<0. 05). There were no significant differences in cell and mitochondrial morphology and indicator levels between liproxstatin-1 group and high-dose PNS group (all 05). CONCLUSION: Panax notoginseng saponins can alleviate OSF by preventing the ferroptosis of HaCaT cells induced by ANE. [ABSTRACT FROM AUTHOR]

Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety, particularly concerning the composition and content levels of trace ingredients. Panax notoginseng Saponins Injection (PNSI), widely used in China for treating acute cardiovascular diseases, contains low-abundance (10%–25%) and trace saponins in addition to its five main constituents (notoginsenoside R 1 , ginsenoside Rg 1 , ginsenoside Re, ginsenoside Rb 1 , and ginsenoside Rd). This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types. To achieve this, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method employing multiple ions monitoring (MIM) was developed. A "post-column valve switching" strategy was implemented to eliminate highly abundant peaks (NR 1 , Rg 1 , and Re) at 26 min. A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards, with digoxin as the internal standard. This study evaluated 119 batches of PNSI from seven vendors, revealing significant variability in trace saponin levels among different vendors and formulation types. These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety. Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Introduction: Panax notoginseng saponins (PNS), the main active ingredients extracted from Panax notoginseng, are chemical mixtures, with the five main active components of ginsenosides Rg1, Rb1, Re, Rd and notoginsenoside R1. Objectives: The present study investigated the effect of PNS on anti-aging in fruit flies, which represented as a natural physical organism aging model. Materials and Methods: After lifelong supplement of PNS in the culture medium at the concentration of 50, 100 and 200 mg/L, the reproduction and the lifespan were observed in fruit flies. The activity of total antioxidative capabilities (T-AOC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSHpx) were detected to evaluate oxidative stress levels. Results: Lifelong supplement of 50 mg/L PNS significantly prolonged the lifespan of fruit flies (Log rank X2=6.752, P=0.009); supplement of 100 mg/L PNS tendency increased the lifespan of fruit flies with no significance; while supplement of 200 mg/L PNS potentially accelerated the death of fruit flies with no significance. Supplement of 50 mg/L PNS protected the reproductive capacity (p<0.05 for 15 and 30 days) in fruit flies. The activity of T-AOC, CAT, total SOD (T-SOD) and GSH-px significantly or tendency increased by 50, 100 and 200 mg/L PNS. Conclusion: Supplement of 50 mg/L PNS prolonged the lifespan and protected the reproductive capacity of fruit flies. The mechanism might be, at least in part, through the anti-oxidative stress pathway by protecting the activity of T-AOC, CAT, T-SOD and GSH-px. Supplement of 200 mg/L PNS might be toxic for fruit flies. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of panax notoginseng saponins combined with cisplatin on renal injury in rats with gastric cancer and analyze the potential mechanism. Methods: 60 healthy male SD rats were divided into control group, gastric cancer model group, cisplatin group and panax notoginseng saponins group with 15 rats each. Except the control group, gastric cancer models were established by subcutaneous inoculation of gastric cancer BGC823 cell suspension in other groups. After successful modeling, rats in the control group and gastric cancer model group were given intraperitoneal injection and gastric perfusion of normal saline, rats in the cisplatin group were given intraperitoneal injection of 25 mg/kg cisplatin and gastric perfusion of normal saline, and rats in the panax nooginseng saponins group were given intraperitoneal injection of 25 mg/kg cisplatin and gastric perfusion of 30 mg/kg panax notoginseng saponins. Serum creatinine (SCR), urea nitrogen (BUN) and urine β-N-acetylglucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) levels were detected by enzyme-linked immunosorbent assay at the time of successful modeling and 28 days after drug treatment, respectively. After the rats were killed, the kidneys were taken, and the levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) in the renal tissue homogenate were measured respectively. The paraffin sections of kidney tissue were prepared and hematoxylin eosin staining was used to observe the pathological changes of the kidney tissue. TUNEL staining was used to detect apoptosis in renal tissue, and Western Blotting was used to detect LC3 and HIF-1α and Beclin1 protein ex pression in renal tissue. Results: The levels of serum SCR, BUN and urine NAG, KIM-1 in rats of cisplatin group and panax notoginseng saponin group were higher than those of control group and model group(P<0.05), and the levels of serum SCR, BUN, urine NAG, KIM-1 in rats of panax notoginseng saponin group were higher than those of cisplatin group (P<0.05). The levels of SOD and GSH in kidney tissue of rats in panax notoginseng saponins group were lower than those in the model group but significantly higher than those in the cisplatin group, MDA was significantly higher than those in the model group but lower than those in the cisplatin group (P<0.05), CAT had no difference from the model group(P<0.05), but higher than those in the cisplatin group(P>0.05). In the cisplatin group, the renal tubules were obviously expanded, the lumen was narrowed, and the epithelial cells in the basal layer were edematous, necrotic and formed vacuoles. The pathological changes of kidney in panax notoginseng saponins group were lighter than those in cisplatin group. The apoptosis index of renal tissue cells in cisplatin group and panax notoginseng saponins group was increased, while that in panax notoginseng saponins group was lower than that in cisplatin group(P<0.05). LC3 and HIF-1α and Beclin1 protein levels in kidney tissue of rats in cisplatin group were higher than those in the model group, but lower than those in the panax notoginseng saponins group (P<0.05). Conclusions: Panax notoginseng saponins may reduce the apoptosis of renal tissue cells by reducing the level of peroxy free radicals and peroxides, affecting the HIF-1α pathway to enhance the level of mitochondrial autophagy, and alleviate the renal injury of rats with gastric cancer caused by cisplatin. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Dalian Ocean University is the property of Journal of Dalian Ocean University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract 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

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.

Objectives This study aimed to observe the effect of the combination of astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) on cerebral ischaemia–reperfusion injury (CIRI) and explore the specific mechanism of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated combination of AST IV and PNS against CIRI based on ferroptosis and inflammatory response. Methods The therapeutic effect and mechanism of AST IV and PNS were evaluated by constructing a Sprague–Dawley rat middle cerebral artery ischaemia–occlusion–reperfusion model. The specific mechanism of the combination of AST IV and PNS against CIRI was revealed through the combined intervention of the Nrf2-specific inhibitor brusatol. Key findings After AST IV and PNS treatment, the cerebral infarction area of the rats was reduced; behavioural performance was improved; Fe2+, malondialdehyde, lipid peroxidation, interleukin-6, interleukin-1β, tumour necrosis factor-α and myeloperoxidase levels were reduced; and glutathione and glutathione peroxidase 4 levels were increased. In addition, the expression of Nrf2 was significantly increased, the combined treatment was more effective than the single treatment, and the Nrf2 inhibitor brusatol could reverse the effects of the combined intervention of AST IV and PNS. Conclusions The findings of this study suggest that combining AST IV and PNS attenuates CIRI by activating Nrf2 to inhibit ferroptosis and inflammatory responses. [ABSTRACT FROM AUTHOR]

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 24 h and the stability study indicated that PNS-SDE-ECC were stable at room temperature for up to 3 months. 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. [ABSTRACT FROM AUTHOR]

Objective　 To explore the potential therapeutic targets and mechanisms of action of panax notoginseng saponins （PNS） in the treatment of diabetic foot based on network pharmacology and molecular docking techniques. Methods　 The active ingredients and their related targets of PNS were collected through the HERB database and Pharm-Mapper platform, and the targets related to diabetic foot were collected in the GeneCards database and comparative toxicogenomics database to obtain the common targets of drugs and diseases. The common targets were imported into the STRING platform to construct a protein-protein interaction （PPI） network, and the core targets were identified by topological analysis. Gene ontology（ GO） and Kyoto Encyclopedia of Genes and Genomes（ KEGG） enrichment analyses were performed on the common targets using R software. Component-target-pathway networks were mapped using Cytoscape software, and topological analysis was performed to screen the core ingredients and core targets of PNS for the treatment of diabetic foot. Molecular docking simulations of the core targets and components were performed using AutoDock Vina software to validate the network pharmacological predictions. Results　 The main active ingredients of PNS were notoginsenoside R1, ginsenoside Rb1, ginsenoside Rd, ginsenoside Re and ginsenoside Rg1. Fifty-six common targets of PNS and diabetic foot were screened out, involving multiple biological processes and pathways, including wound repair, response to lipopolysaccharide, response to oxidative stress, regulation of smooth muscle cell proliferation, regulation of intercellular adhesion, regulation of neuronal death, and regulation of epithelial cell death, and diabetes complications AGE-RAGE signaling pathway, lipid and atherosclerosis pathway, Toll-like receptor signaling pathway, PI3K-AKT signaling pathway, and HIF-1 signaling pathway, etc. Four core targets, AKT1, MMP9, EGFR and HRAS, were screened out by PPI network and component-target-pathway network topology analysis, and molecular docking validation showed that all four targets were able to bind stably （binding energy <-5 kcal/mol） to the PNS active components. Conclusions　 The active ingredients of PNS play the role of promoting epithelial cell proliferation, regulating inflammatory response, antioxidant response, pro-angiogenesis and anti-neuronal cell death through targeting and regulating key targets such as AKT1, MMP9, EGFR and HRAS, so as to achieve the effect of treating diabetic foot. The core pathways mainly involve diabetic complications AGE-RAGE signaling pathway, lipid and atherosclerosis pathway, PI3K-AKT signaling pathway, Toll-like receptor signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway, etc. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of panax notoginseng saponins (PNS) regulating receptor for advanced glycation end products (RAGE) /mitogen activated protein kinase (MAPK) signaling pathway on inflammatory damage in rats with diabetic osteoporosis (DOP). Methods SD rats were divided into control group, model group, metformin (MET) group (100 mg/kg), PNS low dose group (PNS-L group, 10 mg/kg PNS), PNS high dose group (PNS-H group, 20 mg/kg PNS), PNS-H+empty vector plasmid group (20 mg/kg PNS+l5 µL empty vector plasmid), and PNS-H+RAGE overexpression group (20 mg/kg PNS+ 15 µL RAGE overexpression plasmid). Except for rats in the control group, the rats in other groups were fed with high sugar and high fat diet and intraperitoneal injection of streptozotocin to construct the DOP model. After successful modeling, rats in each group was treated with corresponding drug administration. Bone mineral density (BMD) of the rat femur was measured with dual energy X-ray absorptiometry. Fasting blood glucose (FBG), serum fasting insulin (FINS), tartrate resistant acid phosphatase (TRACP), alkaline phosphatase (ALP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured with blood glucose tester and enzyme-linked immunosorbent assay. Three-point bending test and hematoxylin eosin staining were used to detect the changes of femur biomechanics and pathological morphology. Western blotting was used to detect the expression of RAGE/MAPK pathway proteins. Results Compared with those in the model group, the femoral trabeculae in MET group, PNS-L group, and PNS-H group increased and the spacing decreased, and the fracture was alleviated, the femur BMD, FINS, ALP, maximum load and stiffness of femur significantly increased, and the expression levels of FBG, TRACP, IL-6, TNF-α, femoral tissue RAGE, and pp38 MAPK/p38 MAPK protein significantly decreased (P< 0. 05). RAGE overexpression could reverse the improvement effect of PNS-H on DOP rats (P <0. 05). Conclusion PNS alleviates the inflammatory damage in DOP rats by inhibiting the RAGE/ MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Ying Zhao,1,&ast; Shiyuan Lin,1,2,&ast; Ruiyue Fang,1 Yaling Shi,1 Wei Wu,1 Wei Zhang,1 Hui Chen1 1College of Pharmacy, Guilin Medical University, Guilin, 541199, People’s Republic of China; 2Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Chen; Wei Zhang, College of Pharmacy, Guilin Medical University, No. 1 Zhiyuan Road, Guilin, 541199, People’s Republic of China, Email chenhui_gl@163.com; 22437564@qq.comIntroduction: In the previous study, nanoparticles coated with trimethyl chitosan (TMC) derivatives (PPTT-NPs) could promote the oral bioavailability of panax notoginseng saponins (PNS). Herein, we chose PPTT-NPs as a model drug to study the property and mechanism of intestinal absorption in vitro and in vivo.Methods: The stability of PPTT-NPs was evaluated using simulated gastric fluid and simulated intestinal fluid. The uptake and transport of PPTT-NPs were investigated in Caco-2 and Caco-2&HT29 co-culture cells. The biosafety, intestinal permeability, adhesion, and absorption mechanism of PPTT-NPs were investigated using SD rats in vivo. The live imaging and biodistribution of PPTT-NPs were observed by IVIS. Furthermore, the effects on CYP3A4 of PPTT-NPs were investigated using testosterone as the probe substrate.Results: The results of the stability assay showed that PPTT-NPs had a strong tolerance to the pH and digestive enzymes in the gastrointestinal environment. In vitro cell experiments showed that the uptake of drugs exhibited a time-dependent. When the ratio of TMC-VB12 and TMC-Cys was 1:3, the uptake capacity of PPTT-NPs was the highest. PPTT-NPs could enhance the paracellular transport of drugs by reversibly opening a tight junction. Animal experiments demonstrated that PPTT-NPs have good biological safety. PPTT-NPs had good adhesion and permeability to small intestinal mucosa. Meanwhile, PPTT-NPs needed energy and various protein to participate in the uptake of drugs. The live imaging of NPs illustrated that PPTT-NPs could prolong the residence time in the intestine. Moreover, TMC-VB12 and TMC-Cys could reduce the metabolism of drugs by inhibiting CYP3A4 to a certain extent.Conclusion: The results show that TMC-VB12 and TMC-Cys are effective in the transport of PPTT-NPs. PPTT-NPs can increase the intestinal adhesion of drugs and exert high permeation by intestinal enterocytes which demonstrate significant and efficient potential for oral delivery of the BCS III drugs.Graphical Abstract: Keywords: Panax notoginseng saponins, TMC derivatives, nanoparticles, oral absorption, Caco-2&HT29 co-culture cells

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. [ABSTRACT FROM AUTHOR]

Glucocorticoids inhibit angiogenesis in the femoral head, which fails to nourish the bone tissue and leads to osteonecrosis. Restoring angiogenesis is not only essential for vessel formation, but also crucial for osteogenesis. Poly (L-lactic acid) (PLLA) is commonly used in the bone tissue engineering field. Panax notoginseng saponins (PNS) and osteopractic total flavone (OTF) promote angiogenesis and osteogenesis, respectively. We designed a sequentially releasing PLLA scaffold including PLLA loaded with OTF (inner layer) and PLLA loaded with PNS (outer layer). We assessed the osteogenic effect of angiogenesis in this scaffold by comparing it with the one-layered scaffold (PLLA embedded with OTF and PNS) in vivo. Results from the micro-CT showed that the data of bone mineral density (BMD), bone volume (BV), and percent bone volume (BV/TV) in the PO-PP group were significantly higher than those in the POP group (p < 0.01). Histological analyses show that the PO-PP scaffold exhibits better angiogenic and osteogenic effects compared with the one-layered scaffold. These might result from the different structures between them, where the sequential release of a bi-layer scaffold achieves the osteogenic effect of vascularization by initially releasing PNS in the outer layer. We further explored the possible mechanism by an immunohistochemistry analysis and an immunofluorescence assay. The results showed that the protein expressions of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1(CD31) in the PO-PP scaffold were significantly higher than those in the POP scaffold (p < 0.01); the protein expressions of osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) in the PO-PP scaffold were significantly higher than those in the POP scaffold (p < 0.05). Upregulating the expressions of angiogenic and osteogenic proteins might be the possible mechanism. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

[Display omitted] • RPM/DT is the first synthesized rosin adsorbent doped with diatomite. • DT acted as a pore-creating factor to increase the specific surface area of RPM/DT. • PNS's q e on RPM/DT is 3.3 times that of RPM and 6.5 times that of current adsorbents. • The PNS purity increased from 48.47% to 86.16%. Our current adsorbents have a limited capacity for adsorbing Panax notoginseng saponins (PNS). To address this issue, we synthesized a novel bioadsorbent called rosin polymer/diatomite microspheres (RPM/DT). This was done by doping diatomite (DT), an inorganic substance, with rosin-based organic compounds. PNS's adsorption capacity on RPM/DT is 427.96 mg·g−1, which is 6.5 times that of current adsorbents. RPM, without DT, displayed only 125.10 mg·g−1. This considerable difference in adsorption capacity can be attributed to the physical incorporation of DT into and onto the surface of RPM/DT. In addition, the incorporation plays a crucial role in creating pores, resulting in a remarkable increase in the specific surface area of RPM/DT (734.55 m2·g−1), surpassing that of RPM (405.17 m2·g−1). Additionally, using RPM/DT resulted in a significant increase in PNS purity, rising from 48.47 % to 86.16 %. We investigated the isotherm, kinetics, and thermodynamic properties of PNS on RPM/DT and found that the adsorption is spontaneous, endothermic, and predominantly chemisorptive. Quantum chemical calculations further revealed the adsorption mechanism of PNS on RPM/DT. The functional monomer molecules RPM/DT interacted with Rb1, involving van der Waals forces, H-bonds, and intermolecular electrostatic interactions. In summary, RPM/DT is an efficient and reusable biosorbent with the potential to be used in the separation and enrichment of PNS from crude solutions. [ABSTRACT FROM AUTHOR]

[Display omitted] • PNS ME penetrates skin capably, and promotes hair growth by comprehensive strategy. • D-panthenol as ME cosurfactant prevents skin from irritation caused by surfactants. • PNS ME has superior effects as well as safety due to plant-derived ingredients. • The multiple mechanisms of PNS ME include upregulation of β-catenin, VEGF and Ki67. The etiology of alopecia is so complex that current therapies with single-mechanism and attendant side-effects during long-term usage, are insufficient for treatment. Panax notoginseng saponins (PNS) is supposed to treat alopecia with multiple mechanisms, but difficult to penetrate skin efficiently due to water-solubility. Here, we designed water-in-oil microemulsion (PNS ME) using jojoba oil, fractioned coconut oil, RH 40 + Span 80 and cosurfactant D-panthenol, to help PNS penetrating the skin. Particularly, D-panthenol not only enlarges the microemulsion area, reduces the usage amounts of surfactants thus relieves skin irritation, but stimulates the migration of dermal papilla cells (DPCs), displaying cooperative effects on anti-alopecia. PNS ME penetrates through sebum-rich corneum via high-affinity lipid fusion, targets to hair follicles (HFs), where it resides in skin for sustained drug release, accelerates angiogenesis to build well-nourished environment for HFs, and facilitates the proliferation and migration of DPCs in vitro. PNS ME markedly improved hair density, skin pigmentation, new hair weight, skin thickness, and collagen generation of telogen effluvium mice. Moreover, PNS also took outstanding curative effects on androgenetic alopecia mice. Upon further exploration, PNS ME caused dramatic upregulations of β-catenin, VEGF and Ki67, suggesting it might function by triggering Wnt/β-catenin pathway, accelerating vessels formation, and activating the hair follicle stem cells. Notably, PNS ME indicated longer-term safety than minoxidil tincture. Together, PNS ME provides a comprehensive strategy for alopecia, especially it avoids defects by high-proportioned surfactants in traditional microemulsion, exhibiting milder and safer, which shows bright prospect of applying microemulsion in hair growth promotion. [ABSTRACT FROM AUTHOR]

Panax notoginseng saponins (PNS), as the main active component of Panax notoginseng , shows broad pharmacological effects but with low oral bioavailability. Borneol (BO) is commonly used as an adjuvant drug in the field of traditional Chinese medicine, which has been proven to facilitate the absorption of ginsenosides such as Rg1 and Rb1 in vivo. The presence of chiral carbons has resulted in three optical isomers of BO commercially available in the market, all of which are documented by national standards. This study aimed to investigate the role of BO in promoting the oral absorption of PNS from the perspective of optical configuration and compatibility ratios. In this study, an ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) method was validated and applied to determine the concentrations of five main saponins in PNS in rat plasma. The kinetic characteristics of PNS were compared when co-administered with BO based on optical isomerism and different compatibility ratios. The results showed that BO promoted the exposure of PNS in rats. Three forms of BO, namely d -borneol (DB), l -borneol (LB), and synthetic borneol (SB), exhibited different promotion strengths. SB elevated PNS exposure in rats more than DB or LB. It is also interesting to note that under different compatibility ratios, SB can exert a strong promoting effect only when PNS and BO were combined in a 1:1 ratio (PNS 75 mg/kg; BO 75 mg/kg). As a pharmacokinetic booster, the dosage of BO is worthy of consideration and should follow the traditional medication principles of Chinese medicine. This study shed new light on the compatible use of PNS and BO from the perspective of "configuration-dose-influence" of BO. The results provide important basis for the clinical application and selection of BO. [Display omitted] • Borneol (BO) promoted the oral absorption of Panax notoginseng saponins (PNS) in rat. • Dl -borneol (synthetic) increased PNS exposure in rats more than d - or l -borneol. • Compatibility ratio of BO and PNS at 1:1 can better promote the absorption of PNS. [ABSTRACT FROM AUTHOR]

Gastric precancerous lesion (GPL) is a crucial stage in the development of gastric cancer, characterized by incomplete intestinal epithelial chemotaxis and heterogeneous hyperplasia with high malignant potential. Early intervention in GPL is vital for preventing gastric cancer. Additionally, there are shared risk factors and pathogenesis between tumors and coronary heart disease (CHD), with an increasing number of tumor patients GPL complicated with CHD due to improved survival rates. Reperfusion therapy in CHD can result in myocardial ischemia-reperfusion injury (MIRI). Traditional Chinese medicine (TCM) has demonstrated unique advantages in treating GPL and MIRI by promoting blood circulation and removing blood stasis. Panax ginseng total saponin (PNS), a component of TCM known for its blood circulation benefits, has shown positive effects in inhibiting tumor growth and improving myocardial ischemia. This study utilized a GPL-MIRI mouse model to investigate the effects of PNS in treatment. Results indicated that PNS significantly improved typical GPL lesions in mice, such as incomplete intestinal epithelialization and heteroplasia, and also reduced myocardial infarction. At the molecular level, PNS exhibited a bidirectional regulatory role in the GPL-MIRI model. It enhanced the autophagic process in gastric mucosal cells by inhibiting the PI3K/Akt/mTOR signaling pathway, while suppressed excessive autophagy in cardiomyocytes. These findings offer new insights and treatment strategies for managing GPL and MIRI using the TCM compound PNS. [Display omitted] • PNS improves gastric precancerous lesions by enhancing autophagy via suppressing PI3K/Akt/mTOR pathway. • PNS mitigates myocardial ischemia-reperfusion injury via suppressing excessive autophagy. • PNS demonstrates therapeutic potential for gastric cancer complicated with MIRI. [ABSTRACT FROM AUTHOR]

In this paper, three kinds of rosin-based macroporous adsorption resins with carboxyl group (-COOH), ester group (-OR) and hydroxyl group (-OH) were synthesized. The adsorption characteristics of the three resins for Panax notoginseng saponins were investigated by static adsorption method. The results showed that the adsorption effect of the macroporous resin with -COOH as functional group was the best, the adsorption process accorded with the Langmuir model, and the adsorption kinetics was more consistent with the quasi-second order equation, the adsorption thermodynamic parameters ΔS was 159.46 J·mol−1·K−1, ΔH was 30.73 kJ·mol−1, indicating that the adsorption was a spontaneous endothermic process driven by entropy. When Panax notoginseng saponins were desorbed with 40% ethanol, the purity of Panax notoginseng saponins could be increased from 35.37% to 74.56%. The adsorption capacity of the resin was almost unchanged after being reused for 10 times. Through quantum chemical calculation, it was proved that the excellent performance of the macroporous adsorption resin with-COOH as functional group in the adsorption of Panax notoginseng saponins was mainly due to the role of hydrogen bond. The cytotoxicity test showed that the resin was safe and environmentally friendly, and the safety of the resin was better than that of the commercial resin D-101. Therefore, the prepared rosin-based macroporous resin with carboxyl groups was suitable for the separation and purification of Panax notoginseng saponins, and had certain application prospects.

Abstract Background P-glycoprotein (P-gp)-mediated steroid resistance (SR) has been suggested to play a significant role in lupus nephritis (LN) treatment failure. Panax notoginseng saponins (PNS), the main effective components of the traditional Chinese medicine notoginseng, exhibited potent reversal capability of P-gp-mediated SR, but its mechanism remains unknown. This study aimed to investigate the effect of PNS on reversing SR in lupus and its underlying mechanism in vivo and in vitro. Methods In this study, an SR animal and splenic lymphocyte model were established using low-dose methylprednisolone (MP). Flow cytometry was used to detect the effect of PNS on reversing P-gp-mediated SR and the expression of P-gp in different T-cells phenotypes. Serum levels of ANA and dsDNA in lupus mice were measured by ELISA. Apoptosis was identified by Annexin V-FITC/PI staining. RT–PCR and Western blotting were used to detect the protein and mRNA expression levels of SIRT1, FoxO1, and MDR1 in SR splenic lymphocytes from lupus mice (SLCs/MPs). Results PNS could reverse the SR in lupus mice. Simultaneously, PNS increased the apoptotic effect of MP on SLCs/MP cells. The increased accumulation of rhodamine-123 (Rh-123) indicated that intracellular steroid accumulation could be increased by the action of PNS. Moreover, PNS decreased the expression of P-gp levels. Further experiments elucidated that the SIRT1/FoxO1/MDR1 signalling pathway existed in SLCs/MP cells, and PNS suppressed its expression level to reverse SR. The expression of P-gp in Th17 from SLCs/MP cells was increased, while PNS could reduce its level in a more obvious trend. Conclusion The present study suggested that PNS reversed P-gp-mediated SR via the SIRT1/FoxO1/MDR1 signalling pathway, which might become a valuable drug for the treatment of SR in lupus. Th17 might be the main effector cell of PNS reversing SR.