Phytochemical analysis of Panax species: a review

Yuangui Yang,Zhengcai Ju,Yingbo Yang,Yanhai Zhang,Li Yang,Zhengtao Wang 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.1

Panax species have gained numerous attentions because of their various biological effects on cardiovascular, kidney, reproductive diseases known for a long time. Recently, advanced analytical methods including thin layer chromatography, high-performance thin layer chromatography, gas chromatography, high-performance liquid chromatography, ultra-high performance liquid chromatography with tandem ultraviolet, diode array detector, evaporative light scattering detector, and mass detector, two-dimensional high-performance liquid chromatography, high speed counter-current chromatography, high speed centrifugal partition chromatography, micellar electrokinetic chromatography, high-performance anion-exchange chromatography, ambient ionization mass spectrometry, molecularly imprinted polymer, enzyme immunoassay, <SUP>1</SUP>H-NMR, and infrared spectroscopy have been used to identify and evaluate chemical constituents in Panax species. Moreover, Soxhlet extraction, heat reflux extraction, ultrasonic extraction, solid phase extraction, microwave-assisted extraction, pressurized liquid extraction, enzyme-assisted extraction, acceleration solvent extraction, matrix solid phase dispersion extraction, and pulsed electric field are discussed. In this review, a total of 219 articles published from 1980 to 2018 are investigated. Panax species including P. notoginseng, P. quinquefolius, sand P. ginseng in the raw and processed forms from different parts, geographical origins, and growing times are studied. Furthermore, the potential biomarkers are screened through the previous articles. It is expected that the review can provide a fundamental for further studies.

Stem-leaf saponins from Panax notoginseng counteract aberrant autophagy and apoptosis in hippocampal neurons of mice with cognitive impairment induced by sleep deprivation

Cao, Yin,Yang, Yingbo,Wu, Hui,Lu, Yi,Wu, Shuang,Liu, Lulu,Wang, Changhong,Huang, Fei,Shi, Hailian,Zhang, Beibei,Wu, Xiaojun,Wang, Zhengtao The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.3

Backgroud: Sleep deprivation (SD) impairs learning and memory by inhibiting hippocampal functioning at molecular and cellular levels. Abnormal autophagy and apoptosis are closely associated with neurodegeneration in the central nervous system. This study is aimed to explore the alleviative effect and the underlying molecular mechanism of stem-leaf saponins of Panax notoginseng (SLSP) on the abnormal neuronal autophagy and apoptosis in hippocampus of mice with impaired learning and memory induced by SD. Methods: Mouse spatial learning and memory were assessed by Morris water maze test. Neuronal morphological changes were observed by Nissl staining. Autophagosome formation was examined by transmission electron microscopy, immunofluorescent staining, acridine orange staining, and transient transfection of the tf-LC3 plasmid. Apoptotic event was analyzed by flow cytometry after PI/annexin V staining. The expression or activation of autophagy and apoptosis-related proteins were detected by Western blotting assay. Results: SLSP was shown to improve the spatial learning and memory of mice after SD for 48 h, accomanied with restrained excessive autophage and apoptosis, whereas enhanced activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in hippocampal neurons. Meanwhile, it improved the aberrant autophagy and apoptosis induced by rapamycin and re-activated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling transduction in HT-22 cells, a hippocampal neuronal cell line. Conclusion: SLSP could alleviate cognitive impairment induced by SD, which was achieved probably through suppressing the abnormal autophagy and apoptosis of hippocampal neurons. The findings may contribute to the clinical application of SLSP in the prevention or therapy of neurological disorders associated with SD.

Stem-leaf saponins from Panax notoginseng counteract aberrant autophagy and apoptosis in hippocampal neurons of mice with cognitive impairment induced by sleep deprivation

Yin Cao,Yingbo Yang,Hui Wu,Yi Lu,Shuang Wu,Lulu Liu,Changhong Wang,Fei Huang,Hailian Shi,Beibei Zhang,Xiaojun Wu,Zhengtao Wang 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.3

Backgroud: Sleep deprivation (SD) impairs learning and memory by inhibiting hippocampal functioningat molecular and cellular levels. Abnormal autophagy and apoptosis are closely associated with neurodegenerationin the central nervous system. This study is aimed to explore the alleviative effect and theunderlying molecular mechanism of stemeleaf saponins of Panax notoginseng (SLSP) on the abnormalneuronal autophagy and apoptosis in hippocampus of mice with impaired learning and memory inducedby SD. Methods: Mouse spatial learning and memory were assessed by Morris water maze test. Neuronalmorphological changes were observed by Nissl staining. Autophagosome formation was examined bytransmission electron microscopy, immunofluorescent staining, acridine orange staining, and transienttransfection of the tf-LC3 plasmid. Apoptotic event was analyzed by flow cytometry after PI/annexin Vstaining. The expression or activation of autophagy and apoptosis-related proteins were detected byWestern blotting assay. Results: SLSP was shown to improve the spatial learning and memory of mice after SD for 48 h,accomanied with restrained excessive autophage and apoptosis, whereas enhanced activation of phosphoinositide3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in hippocampalneurons. Meanwhile, it improved the aberrant autophagy and apoptosis induced by rapamycinand re-activated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling transductionin HT-22 cells, a hippocampal neuronal cell line. Conclusion: SLSP could alleviate cognitive impairment induced by SD, which was achieved probablythrough suppressing the abnormal autophagy and apoptosis of hippocampal neurons. The findings maycontribute to the clinical application of SLSP in the prevention or therapy of neurological disordersassociated with SD.

Biosynthesis of rare 20(R)-protopanaxadiol/protopanaxatriol type ginsenosides through Escherichia coli engineered with uridine diphosphate glycosyltransferase genes

Yu, Lu,Chen, Yuan,Shi, Jie,Wang, Rufeng,Yang, Yingbo,Yang, Li,Zhao, Shujuan,Wang, Zhengtao The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.1

Background: Ginsenosides are known as the principal pharmacological active constituents in Panax medicinal plants such as Asian ginseng, American ginseng, and Notoginseng. Some ginsenosides, especially the 20(R) isomers, are found in trace amounts in natural sources and are difficult to chemically synthesize. The present study provides an approach to produce such trace ginsenosides applying biotransformation through Escherichia coli modified with relevant genes. Methods: Seven uridine diphosphate glycosyltransferase (UGT) genes originating from Panax notoginseng, Medicago sativa, and Bacillus subtilis were synthesized or cloned and constructed into pETM6, an ePathBrick vector, which were then introduced into E. coli BL21star (DE3) separately. 20(R)-Protopanaxadiol (PPD), 20(R)-protopanaxatriol (PPT), and 20(R)-type ginsenosides were used as substrates for biotransformation with recombinant E. coli modified with those UGT genes. Results: E. coli engineered with $GT95^{syn}$ selectively transfers a glucose moiety to the C20 hydroxyl of 20(R)-PPD and 20(R)-PPT to produce 20(R)-CK and 20(R)-F1, respectively. GTK1- and GTC1-modified E. coli glycosylated the C3-OH of 20(R)-PPD to form 20(R)-Rh2. Moreover, E. coli containing $p2GT95^{syn}K1$, a recreated two-step glycosylation pathway via the ePathBrich, implemented the successive glycosylation at C20-OH and C3-OH of 20(R)-PPD and yielded 20(R)-F2 in the biotransformation broth. Conclusion: This study demonstrates that rare 20(R)-ginsenosides can be produced through E. coli engineered with UTG genes.

Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non–Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis

조병철,김동완,Ullas Batra,박근칠,김상위,Cheng-Ta Yang,Pei-Jye Voon,Virote Sriuranpong,K. Govind Babu,Khalid Amin,Yingbo Wang,Paramita Sen,Khemaies Slimane,Sarayut Geater 대한암학회 2023 Cancer Research and Treatment Vol.55 No.1

Purpose Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial.Materials and Methods Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events.Results At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively.Conclusion Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.