1.Targeted trace ingredients coupled with chemometric analysis for consistency evaluation of Panax notoginseng saponins injectable formulations.
Jingxian ZHANG ; Zijia ZHANG ; Zhaojun WANG ; Tengqian ZHANG ; Yang ZHOU ; Ming CHEN ; Zhanwen HUANG ; Qingqing HE ; Huali LONG ; Jinjun HOU ; Wanying WU ; Dean GUO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(8):631-640
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 R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, 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 (NR1, Rg1, 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.
Ginsenosides
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Saponins
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Chemometrics
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Panax notoginseng
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Cardiovascular Diseases
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Chromatography, Liquid
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Tandem Mass Spectrometry
2.Asponchimides A-E: new enantiomeric N-acetyldopamine trimers from Aspongopus chinensis.
Jinchun NIE ; Fang MEI ; Yueyuan ZHENG ; Qiuyi WEN ; Zhenwei LI ; Daidi ZHANG ; Wei LI ; Dean GUO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(11):859-867
Five new racemic N-acetyldopamine (NADA) trimers, asponchimides A-E (1-5), were isolated from Aspongopus chinensis, a prominent traditional Chinese medicinal insect employed for alleviating pain, treating indigestion, and addressing kidney ailments. Compounds 1-5 were successfully resolved by chiral high-performance liquid chromatography (HPLC), yielding five pairs of enantiomers: (+)- and (-)-asponchimides A-E (1a/1b-5a/5b). Their structural identities were discerned by extensive spectroscopic analyses, including high-resolution mass spectrometry (HRMS), ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR), and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. Compounds 1-5 are pioneering instances of NADA trimers featuring a Δ7 double bond. When subjected to a series of bioassays, a majority of the compounds exhibited weak inhibitory activity against nitric oxide (NO) production in LPS-induced RAW 264.7 cells.
Molecular Structure
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Magnetic Resonance Spectroscopy
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Dopamine
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Nitric Oxide
3.Offline two-dimensional liquid chromatography coupled with ion mobility-quadrupole time-of-flight mass spectrometry enabling four-dimensional separation and characterization of the multicomponents from white ginseng and red ginseng
Tiantian ZUO ; Chunxia ZHANG ; Weiwei LI ; Hongda WANG ; Ying HU ; Wenzhi YANG ; Li JIA ; Xiaoyan WANG ; Xiumei GAO ; Dean GUO
Journal of Pharmaceutical Analysis 2020;10(6):597-609
Inherent complexity of plant metabolites necessitates the use of multi-dimensional information to accomplish comprehensive profiling and confirmative identification. A dimension-enhanced strategy, by offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spec-trometry (2D-LC/IM-QTOF-MS) enabling four-dimensional separations (2D-LC, IM, and MS), is proposed. In combination with in-house database-driven automated peak annotation, this strategy was utilized to characterize ginsenosides simultaneously from white ginseng (WG) and red ginseng (RG). An offline 2D-LC system configuring an Xbridge Amide column and an HSS T3 column showed orthogonality 0.76 in the resolution of ginsenosides. Ginsenoside analysis was performed by data-independent high-definition MSE (HDMSE) in the negative ESI mode on a Vion TM IMS-QTOF hybrid high-resolution mass spectrometer, which could better resolve ginsenosides than MSE and directly give the CCS information. An in-house ginsenoside database recording 504 known ginsenosides and 58 reference compounds, was estab-lished to assist the identification of ginsenosides. Streamlined workflows, by applying UNIFI TM to auto-matedly annotate the HDMSE data, were proposed. We could separate and characterize 323 ginsenosides (including 286 from WG and 306 from RG), and 125 thereof may have not been isolated from the Panax genus. The established 2D-LC/IM-QTOF-HDMSE approach could also act as a magnifier to probe differ-entiated components between WG and RG. Compared with conventional approaches, this dimension-enhanced strategy could better resolve coeluting herbal components and more efficiently, more reli-ably identify the multicomponents, which, we believe, offers more possibilities for the systematic exposure and confirmative identification of plant metabolites.
4.Pigment epithelium——derived factor is involved in the vascular endothelial cells dysfunction induced by arsenic
Wei ZHANG ; Lijun ZHAO ; Dean LI ; Xiangnan GUO ; Jingqiu WANG
Chinese Journal of Endemiology 2019;38(2):107-110
Objective To explore the role of pigment epithelium-derived factor (PEDF) in vascular endothelial cells dysfunction induced by sodium arsenite (NaAsO2).Methods Human umbilical vein endothelial cells (EA.Hy926 cells) were treated with different levels of NaAsO2 [0 (control),1,2,5,10,20,50 μmol/L] for 24 hours.The cell viability was determined using CCK8.Colorimetric assay was used to detect the activity of inducible nitric oxide synthase (iNOS) in culture supematants,PEDF content in the supematant of EA.Hy926 cells was detected by enzyme-linked immunosorbent assay (ELISA),and nitric oxide (NO) content in cells was detected by flow cytometry.Results Compared with the control group [(101.08 ± 3.22)%],the cell viability of 20 μ mol/L group [(80.69 ± 7.95)%] and 50 μmol/L group [(69.87 ± 10.54)%] decreased significantly,and the differences were statistically significant (P < 0.05).The activity of iNOS increased significantly in 10,20,50 μmol/L groups [(829.1 ± 68.2),(772.3 ± 37.1),(874.6 ± 43.5) U/L],respectively,in comparison with that of the control group [(397.5 ± 43.5) U/L] in the cell culture supematant (P < 0.01).Similarly,PEDF levels in the groups of 10,20,50 μmol/L [(12.06 ± 0.55),(11.97 ± 0.39) and (13.89 ± 0.26) mg/L respectively] were higher than that of the control group [(10.70 ± 0.35) mg/L,P < 0.01],and the highest content of PEDF was found in 50 μmol/L group.The NO level in 50 μmol/L group (11 558.99 ± 397.43) was significantly lower than that of the control group (14 131.49± 262.61,P < 0.01).Conclusion PEDF is involved in the vascular endothelial cells dysfunction induced by arsenic.
5.Novel C-17 spirost protostane-type triterpenoids from with anti-inflammatory activity in Caco-2 cells.
Qinghao JIN ; Jianqing ZHANG ; Jinjun HOU ; Min LEI ; Chen LIU ; Xia WANG ; Yong HUANG ; Shuai YAO ; Bang Yeon HWANG ; Wanying WU ; Dean GUO
Acta Pharmaceutica Sinica B 2019;9(4):809-818
Twenty-one protostane-type triterpenoids with diverse structures, including nine new compounds (-), were isolated from the of Linn. Structurally, alisolides A‒F (-), composed of an oxole group coupled to a five-membered ring, represent unusual C-17 spirost protostane-type triterpenoids. Alisolide H () is a novel triterpenoid with an unreported endoperoxide bridge. Alisolide I () represents the first example of 23,24-acetal triterpenoid. Their structures were elucidated based on spectroscopic analysis, wherein the absolute configurations of ‒, were further confirmed by the Mo(OAc)-induced ECD method. Furthermore, all isolates were evaluated for their inhibitory effects on LPS-induced NO production in Caco-2 cells, and all the compounds showed remarkable inhibitory activities, with IC values in the range of 0.76-38.20 μmol/L.
6.Approaches to establish Q-markers for the quality standards of traditional Chinese medicines.
Wenzhi YANG ; Yibei ZHANG ; Wanying WU ; Luqi HUANG ; Dean GUO ; Changxiao LIU
Acta Pharmaceutica Sinica B 2017;7(4):439-446
Traditional Chinese medicine (TCM) has played a pivotal role in maintaining the health of Chinese people and is now gaining increasing acceptance around the global scope. However, TCM is confronting more and more concerns with respect to its quality. The intrinsic "multicomponent and multitarget" feature of TCM necessitates the establishment of a unique quality and bioactivity evaluation system, which is different from that of the Western medicine. However, TCM is investigated essentially as "herbal medicine" or "natural product", and the pharmacopoeia quality monographs are actually chemical-markers-based, which can ensure the consistency only in the assigned chemical markers, but, to some extent, have deviated from the basic TCM theory. A concept of "quality marker" (Q-marker), following the "property-effect-component" theory, is proposed. The establishment of Q-marker integrates multidisciplinary technologies like natural products chemistry, analytical chemistry, bionics, chemometrics, pharmacology, systems biology, and pharmacodynamics, etc. Q-marker-based fingerprint and multicomponent determination conduce to the construction of more scientific quality control system of TCM. This review delineates the background, definition, and properties of Q-marker, and the associated technologies applied for its establishment. Strategies and approaches for establishing Q-marker-based TCM quality control system are presented and highlighted with a few TCM examples.
7.Comparative study of two prediction scoring systems on patients with suspected coronary heart disease
Zhiming ZHOU ; Yonghe GUO ; Dean JIA ; Linlin ZHANG ; Bin HU ; Minjie ZHAO ; Yujie ZHOU
Chinese Journal of Interventional Cardiology 2017;25(2):82-86
Objective To investigate and compare the predictive value of 2 prediction scoring systems for diagnosis of coronary heart disease (CHD) in patients with suspected symptom, and provide information for diagnosis and therapy. Methods By prospectively studying a database of 272 patients with suspected CHD,the total score was calculated by prediction scoring system including PROCAM (The Prospective Cardiovascular Munster Study) and SCP(Suspected CHD Prediction Scoring System) with the data of clinic parameters and risk factors. All patients received coronary angiography and they were categorized into the CHD group (n =94) and non CHD group ( =178) according to the angiography result. The relationship between total scores and the SYNTAX score was evaluated by Spearman analysis and the value of the prediction scoring system was evaluated by the ROC (receiver operating characteristic) system. Results The score of PROCAM was from 6. 00 -77. 00(41. 76 ± 19. 91), and the score was significantly correlated with the extent and severity of coronary artery atherosclerosis (rs = 0. 420,P = 0. 023). The score of SCP was from 1. 00 - 13. 00(8. 64 ± 3. 42), and it was significantly correlated with the SYNTAX score (rs = 0. 482,P = 0. 016). The areas under ROC was 0. 770 (P = 0. 007) in PROCAM and that was 0. 733 (P = 0. 012) in SCP. Conclusions The nature and extent of coronary artery atherosclerosis could be evaluated by the scoring system effectively,which had a good correlation with CAG result.
8.General Situations and Several Thoughts on Japanese Pharmacopoeia, Korean Pharmacopoeia and Taiwan Herbal Pharmacopoeia
Wanying WU ; Juan DA ; Tingting WU ; Lin YANG ; Dean GUO
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(7):1258-1265
Through comparative analysis on the quality standards in Japanese Pharmacopoeia Seventeenth Edition,Korean Pharmacopoeia,Taiwan herbal Pharmacopoeia and pharmacopoeias of neighboring countries and regions,thoughts and suggestions are proposed on how to use the advantages of them,and research thoughts for available reference are provided for the construction of more scientific and feasible quality standards of traditional Chinese medicine.
9.Progress on Post Traumatic Epilepsy and Its Forensic Evaluation.
Yun Ge ZHANG ; Chun Xiao LI ; Guo Fu GUAN ; Ming LÜ ; He Ying CHENG ; Huan CHEN
Journal of Forensic Medicine 2016;32(3):200-203
Post traumatic epilepsy (PTE) refers to the epileptic seizures after traumatic brain injury. Organic damage can be found by imaging examination, and abnormal electroencephalogram can be detected via electroencephalogram examination which has the similar location of the brain injury. PTE has the characteristics of low incidence, absence of case reports, and easy to exaggerate the state of illness, which add difficulties to the forensic identification. This paper reviews the status of epidemiology, pathogenesis, clinical treatment and forensic identification for PTE.
Brain Injuries, Traumatic/physiopathology*
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Electroencephalography
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Epilepsy
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Epilepsy, Post-Traumatic/pathology*
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Forensic Pathology
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Humans
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Incidence
10.Metabolic pathway and metabolites of total diterpene acid isolated from Pseudolarix kaempferi.
Peng LIU ; Hongzhu GUO ; Jianghao SUN ; Man XU ; Hui GUO ; Shifeng SUN ; Dean GUO
Acta Pharmaceutica Sinica 2014;49(8):1169-74
The preliminary metabolic profile of total diterpene acid (TDA) isolated from Pseudolarix kaempferi was investigated by using in vivo and in vitro tests. Pseudolaric acid C2 (PC2) was identified as the predominant metabolite in plasma, urine, bile and feces after both oral and intravenous administrations to rats using HPLC-UV and HPLC-ESI/MS(n), and demethoxydeacetoxypseudolaric acid B (DDPB), a metabolite proposed to be the glucoside of PC2 (PC2G), as well as pseudolaric acid C (PC), pseudolaric acid A (PA), pseudolaric acid A O-beta-D glucopyranoside (PAG), pseudolaric acid B O-beta-D glucopyranoside (PBG) and deacetylpseudolaric acid A (DPA) originated from TDA could also be detected. It was demonstrated by tests that the metabolism of TDA is independent of intestinal microflora, and neither of pepsin and trypsin is in charge of metabolism of TDA, TDA is also stable in both pH environments of gastric tract and intestinal tract. The metabolites of TDA in whole blood in vitro incubation were found to be PC2, DDPB and PC2G, which demonstrated that the metabolic reaction of TDA in vivo is mainly occurred in blood and contributed to be the hydrolysis of plasma esterase to ester bond, as well as the glucosylation reaction. These results clarified the metabolic pathway of TDA for the first time, which is of great significance to the in vivo active form and acting mechanism research of P. kaempferi.

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