Robust design space development for HPLC analysis of five chemical components in Panax notoginseng saponins

The fundamental principle of Quality by Design (QbD) is that the product quality should be designed into the process through an upstream approach, rather than be tested in the downstream. The keystone of QbD is process modeling, and thus, to develop a process control strategy based on the development of design space. Multivariate statistical analysis is a very useful tool to support the implementation of QbD in pharmaceutical process development and manufacturing. Nowadays, pharmaceutical process modeling is mainly focused on one-unit operations and system modeling for the development of design space across multi-unit operations is still limited. In this study, a general procedure that gives a holistic view for understanding and controlling the process settings for the entire manufacturing process was investigated. The proposed framework was tested on the Panax Notoginseng Saponins immediate release tablet (PNS IRT) production process. The critical variables and the critical units acting on the process were identified according to the importance of explaining the variability in the multi-block partial least squares path model. This improved understanding of the process by illustrating how the properties of the raw materials, the process parameters in the wet granulation and the compaction and the intermediate properties affect the tablet properties. Furthermore, the design space was developed to compensate for the variability source from the upstream. The results demonstrated that the proposed framework was an important tool to gain understanding and control the multi-unit operation process.

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Application of Design of Experiment and Design Space (DOE-DS) Methodology for the HPLC Separation of Panax Notoginseng Saponins

The Open Chemical Engineering Journal ◽

10.2174/1874123101509010047 ◽

2015 ◽

Vol 9 (1) ◽

pp. 47-52 ◽

Cited By ~ 1

Author(s):

Shengyun Dai ◽

Bing Xu ◽

Gan Luo ◽

Jianyu Li ◽

Zhong Xue ◽

...

Keyword(s):

Design Space ◽

Panax Notoginseng ◽

Hplc Method ◽

Experimental Result ◽

Quadratic Model ◽

Hplc Separation ◽

Panax Notoginseng Saponins ◽

Gradient Slope ◽

Optimal Separation ◽

Chromatographic Parameters

Panax Notoginseng Saponins (PNS), extracted from the roots of the common TCM Panax notoginseng (Burk.) F.H.Chen, consist of notoginsenoside R1, ginsenoside Rg1, Re, Rb1, Rd and many other chemicals which haven’t been identified. Due to its popular pharmacological effects, it is of importance to control the quality. This study combines design of experiments and design space methodology to optimize the HPLC separation of PNS. Three common chromatographic parameters (i.e. the temperature, the initial proportion of acetonitrile and the gradient slope) were selected to construct a Box-Behnken design which consisted of 17 experiments. A quadratic model that was built from the experimental result was used to construct the design space. The optimal separation was predicted at temperature 20°C;, with a gradient starting at 15% of acetonitrile and a gradient slope of 0.55%/min. Accuracy profile approach was employed to validate the established HPLC method. The results clearly showed that quality by design methodology could be effectively applied to optimize the HPLC chromatographic conditions for the analysis of PNS.

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Panax notoginseng saponins attenuate neuroinflammation through TXNIP-mediated NLRP3 inflammasome activation in aging rats

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021999201110204735 ◽

2020 ◽

Vol 21 ◽

Author(s):

Zhiyong Zhou ◽

Menghan He ◽

Qingqing Zhao ◽

Dongfan Wang ◽

Changcheng Zhang ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Panax Notoginseng ◽

Control Group ◽

Inflammasome Activation ◽

Panax Notoginseng Saponins ◽

Aging Rats ◽

Nlrp3 Inflammasome Activation ◽

Bv2 Microglia ◽

Old Rats

Introduction:: Microglia-mediated inflammatory responses play a crucial role in aging-related neurodegenerative diseases. The TXNIP/NLRP3 pathway is a key pathway leading to microglial activation. Panax notoginseng saponins (PNS) have been widely used for the treatment of stroke in China. Objective:: This study evaluates the anti-neuroinflammatory effect of PNS and investigates the mechanism via TXNIPmediated NLRP3 inflammasome activation in aging rats. Materials and Methods:: Eighteen-month-old Sprague-Dawley rats were randomly divided into the aging control group and PNS treated groups (n=15 each group). For PNS-treated groups, rats were administrated food with PNS at the doses of 10 mg/kg and 30 mg/kg for consecutive 6 months until they were 24-month old. Rats from the aging control group were given the same food without PNS. Two-month-old rats were purchased and given the same food until 6-month old as the adult control group (n = 15). Then, the cortex and hippocampus were rapidly harvested and deposited. H&E staining was used to assess histo-morphological changes. Western blotting was carried out to detect the protein expression. Immunofluorescence was employed to measure the co-localization of NLRP3, TXNIP and Iba-1. In vitro model was established by LPS+ATP coincubation in the BV2 microglia cell line. Results:: Aging rats exhibited increased activation of microglia, accompanied by a high level of IL-1β expression. Meanwhile, aging rats showed enhanced protein expression of TXNIP and NLRP3 related molecules, which co-localized with microglia. PNS treatment effectively reduced the number of degenerated neurons and reversed the activation of the TXNIP/NLRP3 inflammatory pathway. In vitro results showed that PNS up to 100 μg / ml had no significant toxicity on BV2 microglia. Discussion:: PNS (25, 50 μg/ml) effectively reduced the inflammatory response induced by LPS and ATP co-stimulation, thus inhibiting the expression of TXNIP/NLRP3 pathway-related proteins. Conclusion:: PNS treatment improved aging-related neuronal damage through inhibiting TXNIP mediated NLRP3 inflammasome activation, which provided a potential target for the treatment of inflammatory-related neurodegenerative diseases.

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Panax Notoginseng Saponins Promote Cell Death and Chemosensitivity in Pancreatic Cancer through the Apoptosis and Autophagy Pathways

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620999201110191459 ◽

2020 ◽

Vol 20 ◽

Author(s):

Li-Chao Yao ◽

Lun Wu ◽

Wei Wang ◽

Lu-Lu Zhai ◽

Lin Ye ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Panax Notoginseng ◽

Panax Notoginseng Saponins ◽

Transwell Assay ◽

Pancreatic Cancer Cells ◽

New Strategy ◽

Induced Apoptosis ◽

Promote Cell Death

Background:: Panax Notoginseng Saponins (PNS) is used as traditional Chinese medicine for ischemic stroke and cardiovascular disease, it has been proven to possess anticancer activity recently. Objective:: In this study, we aimed to explore the anticancer curative effect and potential mechanisms of PNS in pancreatic cancer cells. Methods:: Pancreatic cancer Miapaca2 and PANC-1 cells were treated with PNS and Gemcitabine (Gem), respectively. Then the cell viability was assessed by CCK-8 assay, cell proliferation was tested by colony formation assay and EdU cell proliferation assay, cell migration and invasiveness were tested by wound healing assay and transwell assay respectively, and cell apoptosis was detected by flow cytometry. Finally, we detected the expression levels of proteins related to migration, apoptosis and autophagy through Western blotting. Results:: PNS not only inhibited the proliferation, migration, invasion and autophagy of Miapaca2 and PANC-1 cells, but also induced apoptosis and promoted chemosensitivity of pancreatic cancer cells to Gem. Conclusion:: PNS may exhibit cytotoxicity and increase chemosensitivity of pancreatic cancer cells to Gem by inhibiting autophagy and inducing apoptosis, providing a new strategy and potential treatment option for pancreatic cancer.

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Preparation and Evaluation of Lecithin/Zein Hybrid Nanoparticles for the Oral Delivery of Panax Notoginseng Saponins

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2021.105882 ◽

2021 ◽

pp. 105882

Author(s):

Wen Fu ◽

Yiping Liang ◽

Zhonghui Xie ◽

Hangyi Wu ◽

Zhenhai Zhang ◽

...

Keyword(s):

Oral Delivery ◽

Panax Notoginseng ◽

Hybrid Nanoparticles ◽

Panax Notoginseng Saponins ◽

Preparation And Evaluation

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Panax notoginseng saponins promote endothelial progenitor cell angiogenesis via the Wnt/β-catenin pathway

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03219-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Peiqi Zhu ◽

Weidong Jiang ◽

Shixi He ◽

Tao Zhang ◽

Fengchun Liao ◽

...

Keyword(s):

Cell Proliferation ◽

Panax Notoginseng ◽

Tube Formation ◽

Optimal Concentration ◽

Mrna Levels ◽

Panax Notoginseng Saponins ◽

Endothelial Progenitor ◽

Angiogenic Potential ◽

Craniomaxillofacial Surgery ◽

And Migration

Abstract Background Distraction osteogenesis (DO) is an effective treatment in craniomaxillofacial surgery. However, the issue of sufficient blood supply at the regeneration tissue has limited its wide application. Panax notoginseng saponins (PNS) is a Traditional Chinese Medicine that is commonly used to treat a range of angiogenic diseases. However, the mechanisms whereby PNS alters angiogenesis in endothelial progenitor cells (EPCs) have yet to be clarified. Methods EPCs were identified by immunofluorescence, confirmed by their uptake of fluorescently labeled Dil-ac-LDL and FITC-UEA-1. EPCs were treated with different concentrations of PNS, and the effects of PNS on cell proliferation were measured on the optimal concentration of PNS determined. The effects of PNS on angiogenesis and migration, angiogenic cytokines mRNA expression and the proteins of the Wnt pathway were investigated. Then knocked down β-catenin in EPCs and treated with the optimum concentrational PNS, their angiogenic potential was evaluated in tube formation and migration assays. In addition, the expression of cytokines associated with angiogenesis and Wnt/β-catenin was then assessed via WB and RT-qPCR. Results We were able to determine the optimal concentration of PNS in the promotion of cell proliferation, tube formation, and migration to be 6.25 mg/L. PNS treatment increased the mRNA levels of VEGF, bFGF, VE-Cadherin, WNT3a, LRP5, β-catenin, and TCF4. After knocked down β-catenin expression, we found that PNS could sufficient to partially reverse the suppression of EPC angiogenesis. Conclusions Overall, 6.25 mg/L PNS can promote EPC angiogenesis via Wnt/β-catenin signaling pathway activation.

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