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Untargeted metabolomics analysis to unveil ......
ABSTRACT
Precise identification and differentiation among those congeneric Traditional Chinese Medicines (TCMs) or derived from the same plant trend to be more challenging, particularly in the absence of appearance characteristics. Three TCMs, involving Gleditsiae Sinensis Fructus (GSF), Gleditsiae Fructus Abnormalis (GFA), and Gleditsiae Spina (GS), recorded in Chinese Pharmacopoeia (2020 edition) are derived from Gleditsia sinensis, but prescribed for different clinical uses. The documents aimed to compare their chemical differences are rare, to date.
An untargeted metabolomics approach, based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS), was elaborated to unveil the potential chemical markers to differentiate among GSF, GFA, and GS. Good chromatographic separation of all the GSF/GFA/GS components was achieved within 33 min by utilizing a BEH C18 column, while data-independent MSE in the positive mode was selected for profiling the metabolic features.
Chemicals and reagents
forsythin (22), were purchased from Chengdu Desite Biotechnology Co., Ltd. (Chengdu, China).
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A multi-evaluating strategy for Weikangling capsules: ……
Abstract
Weikangling capsules (WKLCs), a Chinese patent medicine consisting of 8 Chinese drugs, have been widely used in clinic to treat gastrointestinal diseases for more than 30 years. The current “Chinese Pharmacopoeia” (2020 Edition, ChP2020) uses paeoniflorin content (≥ 1.0 mg per capsule) as the standard of quality control, but it is insufficient to evaluate the overall quality of WKLCs. An efficient and economic method for quality control is urgently needed to ensure the quality consistency and clinical effects of WKLCs. Herein, a systematic and reliable method for the rapid analysis of chemical components in WKLCs was established for the first time based on ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A total of 115 components covering 7 herbs in WKLCs were preliminarily identified by comparison with standard substances or literature. To evaluate the quality of 26 batches of WKLCs, a new method of fingerprinting combined with quantitative analysis was established, and 16 common peaks were selected to establish the fingerprint similarity model (similarity>0.90). Simultaneously, the contents of albiflorin, paeoniflorin, dactylorhin A, militarine, and glycyrrhizic acid were determined to be 0.82 ± 0.22, 2.09 ± 0.24, 1.15 ± 0.40, 3.73 ± 0.76 and 0.99 ± 0.20 mg/capsule, respectively. The transfer rates and dissolution curves of the five compounds were successfully detected in WKLCs, and the average transfer rates were 67.2%, 33.0%, 68.3%, 54.7%, and 33.7%, respectively. Notably, the dissolution profiles of different manufacturers presented remarkable differences in pH 1.2 hydrochloric acid solution. This method not only qualitatively identified the chemical components of Chinese patent medicines at the microlevel but also evaluated the quality consistency between batches at the macrolevel, which provided a comprehensive reference for the quality consistency of Chinese patent medicines between batches.
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2. Materials and methods
2.1. Chemicals and materials
…… The detailed information of all samples is listed in Table S1. The standard substances, including liquiritin, isoliquiritin, liquiritin apioside, isoliquiritin apioside, ononin, gly-cyrrhizic acid, glycyrrhetinic acid, paeoniflorin, albiflorin, oxypaeo-niflorin, benzoylpaeoniflorin, militarine, corydaline, tetrahydropalmatine, protopine, ginsenoside Rg1, ginsenoside Rb1, and ginsenoside Re were purchased from Chengdu Desite Biological Technology Co., Ltd. (Sichuan, China);
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原文链接：https://doi.org/10.1016/j.jpba.2021.114347
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Caffeic Acid, an Allelochemical in Artemisia argyi……
Artemisia argyi is widely distributed in Asia, and it often becomes the dominant population in the field because of its strong ecological niche competitiveness. Allelochemicals secreted by plants are generally considered an important reason for their dominance in ecological competition. In this study, the allelochemicals in A. argyi were screened by a series of experiments and their mechanisms were explored via transcriptomics. First, the inhibitory effects of A. argyi on Echinochloa crusgalli, Setaria viridis, Portulaca oleracea and Amaranthus retroflexus were evaluated. Then, we carried out a qualitative and quantitative analysis of the chemical composition of the aqueous extract of A. argyi to screen for potential allelochemicals that can inhibit weed growth. Four potential allelochemicals were quantified: neochlorogenic acid (5-CQA), chlorogenic acid (3-CQA), cryptochlorogenic acid (4-CQA), and caffeic acid (CA). …………
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Materials and Methods
Plant Materials and Chemicals
……Neochlorogenic acid (5-CQA, 99.6%), chlorogenic acid (3-CQA, 99.5%), cryptochlorogenic acid (4-CQA, 98.7%), and caffeic acid (CA, 99.7%) were provided by Chengdu Desite Bio-Technology Co., Ltd. (Chengdu, China). …………
原文链接：https://doi.org/10.3389/fpls.2021.802198
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姜黄提取物固体分散体的制备及体外评价
姜黄为姜科姜黄属植物姜黄 Curcuma longa L.的干燥根茎，常用来治疗胸胁刺痛、闭经等疾病。姜黄提取物（Curcumae Longae Rhizoma extract，CLRE）是从姜黄中分离得到的 β-二酮类多酚提取物，其中主要包括姜黄素、去甲氧基姜黄素和双去甲氧基姜黄素[1]。有研究表明 CLRE 可以通过抑制代谢途径改善肾纤维化症状，保护肾功能，改善肾损伤，治疗糖尿病肾病[2-4]。但 CLRE 水溶性差，生物利用度低，成为限制其临床应用的主要因素[5]。因此，提高 CLRE 溶解度及生物利用度的研究有利于 CLRE 的利用和临床使用。近几年，不少研究者通过把姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素制备成其他剂型来解决溶解度差的问题[6-8]。
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1.2 试药与试剂
……对照品姜黄素（质量分数≥98%，批号 DST200412-014）、去甲氧基姜黄素（质量分数≥98%，批号 DST190910-030）、双去甲氧基姜黄素（质量分数≥98%，批号 DST191009-021），均购自成都德思特生物科技有限公司。
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DOI: 10.7501/j.issn.0253-2670.2022.01.013
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Discovery of a novel megakaryopoiesis enhancer, ingenol,……
Abstract
Thrombocytopenia, a most common complication of radiotherapy and chemotherapy, is an important cause of morbidity and mortality in cancer patients. However, there are still no approved agents for the treatment of radiation- and chemotherapy-induced thrombocytopenia (RIT and CIT, respectively). In this study, a drug screening model for predicting compounds with activity in promoting megakaryocyte (MK) differentiation and platelet production was established based on machine learning (ML), and a natural product ingenol was predicted as a potential active compound. Then, in vitro experiments showed that ingenol significantly promoted MK differentiation in K562 and HEL cells. Furthermore, a RIT mice model and c-MPL knock-out (c-MPL-/-) mice constructed by CRISPR/Cas9 technology were used to assess the therapeutic action of ingenol on thrombocytopenia. The results showed that ingenol accelerated megakaryopoiesis and thrombopoiesis both in RIT mice and c-MPL-/- mice. Next, RNA-sequencing (RNA-seq) was carried out to analyze the gene expression profile induced by ingenol during MK differentiation. Finally, through experimental verifications, we demonstrated that the activation of PI3K/Akt signaling pathway was involved in ingenol-induced MK differentiation. Blocking PI3K/Akt signaling pathway abolished the promotion of ingenol on MK differentiation. Nevertheless, inhibition of TPO/c-MPL signaling pathway could not suppress ingenol-induced MK differentiation. In conclusion, our study builds a drug screening model to discover active compounds against thrombocytopenia, reveals the critical roles of ingenol in promoting MK differentiation and platelet production, and provides a promising avenue for the treatment of RIT.
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2.2. Chemicals
Ingenol (purity = 99.99%, as determined by HPLC) were purchased from Chengdu DeSiTe Biological Technology Co., Ltd. (Chengdu, China) and reconstituted according to manufacturers’ instructions.
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原文链接：https://doi.org/10.1016/j.phrs.2022.106096
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Zafirlukast inhibits the growth of lung adenocarcinoma ……
Lung cancer has the highest mortality among cancers worldwide due to its high incidence and lack of the effective cures. We have previously demonstrated that the membrane ion channel TMEM16A is a potential drug target for the treatment of lung adenocarcinoma and have identified a pocket of inhibitor binding that provides the basis for screening promising new inhibitors. However, conventional drug discovery strategies are lengthy and costly, and the unpredictable side effects lead to a high failure rate in drug development. Therefore, finding new therapeutic directions for already marketed drugs may be a feasible strategy to obtain safe and effective therapeutic drugs. Here, we screened a library of over 1400 Food and Drug Administration–approved drugs through virtual screening and activity testing. We identified a drug candidate, Zafirlukast (ZAF), clinically approved for the treatment of asthma, that could inhibit the TMEM16A channel in a concentration-dependent manner. Molecular dynamics simulations and site-directed mutagenesis experiments showed that ZAF can bind to S387/N533/R535 in the nonselective inhibitor binding pocket, thereby blocking the channel pore. Furthermore, we demonstrate ZAF can target TMEM16A channel to inhibit the proliferation and migration of lung adenocarcinoma LA795 cells. In vivo experiments showed that ZAF can significantly inhibit lung adenocarcinoma tumor growth in mice. Taken together, we identified ZAF as a novel TMEM16A channel inhibitor with excellent anticancer activity, and as such, it represents a promising candidate for future preclinical and clinical studies.
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Experimental procedures
Drug screening
The calcium-bound structure of TMEM16A (PDB ID: 5OYB) (38) was used as a docked receptor, and the missing short loops were complemented using the SWISS-MODEL program (39, 40). Virtual screening of drugs was performed using the molecular docking program Vina (41). The database contains 1435 FDA-approved drug molecules. Autodock tool (42) was used to prepare the PDBQT files of TMEM16A and drugs. The receptor was programmed to remain rigid, while the ligand was flexible. The grid center was determined according to the center of the upper inhibitor binding pocket of the pore, with a searching space size of 24 Å3. The global search exhaustiveness value was set to 50. The maximum energy difference between the optimal binding mode and the worst case was set to 5 kcal/mol to ensure diverse docked poses. Conivaptan and Zafirlukast were purchased from DeSiTe (Chengdu, China).
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DOI：https ://doi.org/10.1016/j.jbc.2022.101731
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